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·Obesity ITS CAUSE, CLASSIFICATION, AND CARE by E. PHILIP GELVIN, M.D., F.A.C.P. Associale in Afedicine, New York Meducal College, Floreer and Firth Arenue Hospital, Physician-in- Charge Oberty Clinic, Afelropolitan Ffospital, New York and THOMAS II. MCGAVACK, M.D., F.A.C.P. Professor of Clinical Medicine, New York Med. ical College, Florder and Fifth Avenue Hospital, New York (HİH 110EWIN-TARPER BOOK

·OBESITY ITS CAUSE, CLASSIFICATION, AND CARE
Copyright © 1957, by Paul B Hoeber, Inc
Medical Book Department of Harper & Brothers
Printed in the United States of America
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Library of Congress catalog card number 57-7162

·Contents PREFACE 1 1 Definition and Clinical Features Measurements of Obesity--Height Weight Tables- Estimation of Body Fat-Direct Chemical Analysis Skunfold Measurements-Densitometry--Dilution Tests Clinical Evaluation of Fatness --Incidence--Hazards Morbidity-Mortality 2 12 Adipose Tissue Cell Origin-Innervation-Blood Supply—Mature of Stored Fat-Source of Stored Fat 3 16 Intermediary Metabolism of Carbohydrates and Fats Fats-Carbohydrates --Interrelationships of Lipid and Carbohydrate Metabolism 4 22 Lipogenesis and Fat Mobilization Lipogenesis--Fat Mobilization 5 Classification of Obesity 26 6 33 The Normal Regulation of Intake of Food Hunger and Appetite-Mechanisms of Regulation of Food Intake-Thermostatic Mechanista Theory-Clu costatic Vlechanism Theory-Conclusions ·OBESITY ITS CAUSE, CLASSIFICATION, AND CARE 7 38 Etiology Hereditary, Psychological, Nervous, and Dietary Factors Heredity-Psychological Factors—The Hypothalamus -Dietary Factors 8 48 Etiology Metabolic Factors Increased Efficiency of Digestion and Absorption- Nitrogen Exchange--Respiratory QuotrentBasal Met abolic Rate--Specific Dynamic Action--Rebound of Metabolism-Luxury Consumption-ketosis—Physical Activity-Lipophilia 9 59 Etiology Endocrine Factors Thyroid-Gonads--Pituitary-Adrenal--Pancreas Summary 10 Obesity in Childhood 67 11 69 Management General Considerations Psychological Factors in the Patient--Role of the Physician 12 73 Management Increasing Energy Expenditure Exercise Drugs 13 78 Management Decreasing Energy Intake (Diet) Functions of a Diet-Factors Involved in Planning a Diet--High Protein Diet-Protein Powders--High Fat Diet-The Dietary Prescription-Dietary Modifications for Children-Presentation of Dietary Instructions to the Patient 96 14 Management Anorexigenic Agents Amphetamine Preparations-Addiction to Amphet ammes-Metamphetamine (Desoxphedrine)-Discus Sion and Use of Anorexigenic Agents ·CONTENTS 15 109 Management Endocrine Preparations Thyroid-Anterior Pituitary--Posterior Pituitary--Sex SIormones-11 Oxycorticoids 16 113 Management Miscellaneous Medications, Physio therapy, Surgery Bulh-Vitamin Preparations-Belladonna Preparations --Dehydration--Combinations of Drugs-Massagem Surgery 17 119 Course and Follow Up The Rate of Loss of Weight-Termination of Treat ment-Return Visits-Unsatisfactory Loss of Weight- The Management of a CaseTypes of Patients and the Results obtained ---Those with Strong Incentive Children-Others--Results obtained in an Average Croup-Results of Successful Weight Reduction DIALIOCRAPETY 233 INDEX 141

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·Preface IN TINS BOOL we have attempted to present a practical program for the management of obesity It stems from personal experience primarily at the Obes. Clinic at Metropolitan Hospital, New York. The Obesity Clinic was organized some ten years ago as a specialized unit in the Metabolism and Endocrine Clinic because we felt that centralizing the managernent of our overweight patients in one place would bring about better care, more intensive follow-up and improved results Overweight is one of the major medical problems of our day Most chnicians see in their practice some patients who should reduce Many different types of diets have been advocated for the treatment of obesity Compler methods for calculating caloric requirements on an individual basis have been devised The resulting confusion has often been a deterrent to active treatment of the overweight patient Yet it is the family physician who is best qualified to identify and treat the obese individual, not reducing salons, food faddists, and the purveyors of patent medicines Patients are or crawed by long lists of foods and suggested substitutions They resent being forced to memorize tables of caloric values, they do not enjoy the necessity for dctailed planning of each meal. From the start, we wondered just how much individual- ·OBESITY ITS CAUSE, CLASSIFICATION, AND CARE ization of the dietary prescription was necessary We felt that if the diet could be standardized so that with only slight modification it could be used for most patients, the work of the physician would be greatly simplified We realized that the diet should be composed of ordinary foods, easily available under most circumstances in order to encourage cooperation on the part of the patient The patient must not be required to perform intricate calculations of calories or to become involved in the detailed planning of menus However, some latitude of choice must be left to the individual Daily prescribed menus are impractical, incon venient, and monotonous Many drugs have been recommended as helpful in the management of obesity With the cooperation of several pharmaceutical companies, we were able to study the effects of some of the more commonly used medications under controlled conditions The progress of the work at the chinic toward our objecu tives resulted in the development of a program which is simple yet effective Experience acquired in the clinic was applied to private patients and to a group of employees of a large industrial organization with even more gratifying results Our success with these methods led us to the thought of sharing our technics with others Great advances in the knowledge of the basic chemistry and physiology of fat metabolism deposition, and mobilizaton have been made recently Most of these studies have been publshed in specialized journals not ordinarily read by most physicians We have attempted to describe those findings that we feel are basic to the understanding of the problem, have practical applications, or tend to dispel pop ular misconceptions The bibliography, consisting mainly of ·PREFACE references in the English language, and the use of review articles whenever possible can serve as a springboard for more detailed readings in this fascinating field It is not our intention to present a basic text on the physiology of obesity or the science of dietetics and nutrition We have no panacea to offer, nothing sensational nor magical. We do feel that the program for the management of obesity as presented in these pages is safe, effective, and consistent with principles of good nutrtion, yet simple for the physician to prescnbe and convenient for the patient to observe

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·CHAPTCR 1 Definition and Clinical Teatures ANY_INCREASE in weight above the ideal, unless caused by pregnancy, pathological skeletal overgrowth, or retention of Qud, such as is seen in certain cardiovascular, renal, he patic, or endocrine diseases, is caused by the deposition of fat tissue Such an accumulation of adipose tissue beyond the Tange of normal for the individual constitutes obesity (35) Obesity, then, depends upon an increase in the amount of fot tissue When the increased amount of fat tissue causes an increase in weight in excess of 10 per cent of the optrmum weight of an individual, the chnical diagnosis of obesity is justified However, it is obvious that the optimum weight must be established before a 10 per cent increment can be ascertained. This has not been a very sumple thing to do MEASUREMENT OF OBESITY Ieight Weight Tables The most common tables i usc are those based upon the Medico Actuarial Investigation which was published in 1912 (5) These consist of two tables, one for men and on Women, and Give the average body weight of individuals 3 ·2 OBESITY ITS CAUSE, CLASSIFICATIOY, AND CARE ار of different height and age They refer to measurements obtained from subjects as they were ordinarily dressed according to the fashion of about 1900 The reliability of these tables is open to serious question Was the group studied a representative section of the adult population? What do the words ordinarily dressed mean, and how do fashions of about 1900 compare with those of today? Height was determined with shoes on How much of a variable was introduced thereby? Also, these tables represented average weight, not optimum, showing progressive increase with age Thus, the weight of the average man increased about twelve pounds between the ages of 25 and 50 However, experience has indicated that this age trend is not desirable from the standpoint of mortality (79] Maximum development and growth is completed at about the age of 30 Any significant continued increase of weight beyond that age, unless caused by factors men tioned above, is usually the result of the deposition of fat The decrease in activity with advancing age, coupled with the maintenance of eating habits of younger years by many individuals probably caused this average increase for the a entire group Recently, other tables have been prepared which give a range of desirable weights, at each inch of height, for different body builds—slight, medium, and heavy These tables make no distinction in relation to age, but apply to all persons over age 25 These tables also refer to measurements 'as ordinarily dressed " They are based upon meas urements made upon policy holders with the Metropolitan Life Insurance Company (Tables 1 and 2) [79] However, The same criticisms regarding representativeness and definition of the term 'as ordinarily dressed that were leveled ·DCFINITION AND CLINICAL FEATURES 3 TABLE 1 DESIRABLE WEICITS FOR MEN, AGES 25 AND OVER Herght (truth ahoca) Jaght in Pounds (as ordinanly dressed) Feet Inches Small Frame Bredium Frame Large Frame 5 5 5 5 5 5 5 5 6 5 6 6 6 6 2 3 4 5 6 7 8 9 10 11 0 1 2 3 116-125 119-128 122-132 126-136 123-139 133-143 136-147 140-151 141-155 148-159 152-164 157-169 163-175 168-180 121-133 127-136 130-140 131-144 137-147 141-151 145-156 149-160 153-164 157-168 161-173 166-178 171-184 176-189 131-142 133-144 137-143 141-153 145-157 149-162 153-166 157-170 161-175 165-180 169-185 174-190 179-196 181-202 SOURCE Metropolitan Life Insurance Co , Statistical Bureau, 1943 TABLE 2 DESIRABLE WEICISTS FOR WOVEN ACES 25 AND OVER Ilerghi (with shoes) leghe in Pounds (as ordinarily dressed) Feet Inches Small Frame Medium Frame Large Frams 4 5 5 5 5 5 5 6 5 8 3 5 $ 0 2 2 3 4 5 6 7 8 9 10 11 101-111 105-113 107-115 110-118 113-121 116-125 119-128 123-132 126-138 129-133 133-143 136-147 139 150 110-118 112-120 111-122 117-125 120-128 121-132 127-135 130-140 131-144 137-147 141-151 145-155 148-158 117-127 119-129 121-131 124-135 127-138 131-142 133-145 138-150 142-151 145-159 149-162 152-166 155-169 SOLRCE Metropolitan Lafe Insurance Co , Statutical Buresu, 1943 ·4 OBESITY ITS CAUSE, CLASSIFICATION, AND CARE at the older tables apply to these In addition, many of these examinations were performed in the field where the height and weight of the applicant were estimated and not measured The accuracy of many of these estimations 15 questionable Finally, no criteria are given for the definition of the term "frame" This depends solely on the subjective im. pression of the examiner The desirable weight of a man whose height is 5 feet 10 inches could vary from 144 to 175 pounds, depending upon the opinion of the examiner as to the "frame" of the individual It has been interesting (and amusing) to observe how different physicians, depending upon their own weight, categorize individuals Even a superficial examination of these standards shows errors The average line of a college football team consists of a group of young men somewhat under 6 feet tall, weighing 190 to 200 pounds According to these tables, these athletes would be considered overweight The question has been raised as to whether we are at all justified in estimating fatness by measunng height and weight It has been demonstrated that heavy muscled athletes and laborers may be poor in fat, although the body weight is above normal as measured by height-weight tables Conversely, inactive individuals with subnormal muscle mass may be obese, even though the tables indicate they have a body weight which is normal for their height [22, 61] The human body is composed of several major components which are metabolically distinct, and which may vary independently to a large extent (1) fat, which may represent as much as 70 per cent of the gross weight, (2) extracellular water, which may represent from 10 to 60 per cent ·DEFINITION AND CLINICAL FEATURES 5 of the gross weight (3) cells or "active tissue" (4) bone mineral In an average "normal" man these components represent something like 15 23 58 and 4 per cent respectively of the total body weight [61] It has been estimated that frank obesity is present when the fat content of th organism reaches 30 per cent of the body weight [78] ESTIATION OF Body Fat Direct Chemical Analysis This method is perhaps the most accurate but since it presupposes that the subject will be sacrificed it is not applicable to clinical studies in the human being Skinfold Mcasurements This is a simple method and depends upon the estima tion that about half the total body fat is superficial and therefore directly accessible for clinical eramınation [62] A rather rough estimate of fatness can be made by pinching the skin at various locations Refinements of this technic involve the use of special calipers or demonstration in soft tissue roentgenograms of the thickness of the fat layer at the sides of the ray silhouette This skinfold measurement method is not completely re liable The thickness of the subcutaneous fit layer at dif ferent sites varies with age and ser ind from individual to individual It is also difficult to estimate the total body fat from the fraction in the subcutaneous deposits meas ured at a limited number of sites (60 62) Densitometry Human fat has a density of about 092 while the fat free portion of the body has a density of about 11 (62) This ·6 ORESITY ITS CAUSE, CLASSIFICATION, AND CARE fat free portion represents the average of the density of bones whose density is about 29, of cells whose density is about 12, and of extracellular fluids with a density of slightly over 10 The mineral content of bone represents only about 4 per cent of the total weight of the average adult, and the extracellular fluid content tends to be a rather constant fraction of the lean body mass Thus, if the density of the body is known the fat content may be calculated (9, 122] The density of the body can be measured by weighing it under water and making corrections for the residual air in the lungs, and the gases in the intestinal tract Inaccuracies in weighing under water, variations in the degree of hydration, and individual differences in the amount of bone mineral will introduce errors into the final results Although this procedure is not too difficult to carry out, it is still essentially a research laboratory study, and not readily adapted to routine clinical use Dilution Tests Since the total body water tends to represent a constant fraction of the lean body mass, its estimation provides a basis for the calculation of the lean body mass provided neither dehydration nor edema exists (50] An intravenous injection of a nontoxic, stable, water sol uble substance that penetrates all body tissues is made, and, after allowing time for its diffusion throughout all the water in the body, the concentration of this substance is measured in a sample of the blood serum Some of the test substances used include thirourea, sulfanilamide, urea, antipyrine, deuterum oxide, and tritium water The accuracy of this meth od is limited by variations in hydration It is also timeconsuming and analytically difficult, and is not readily adaptable to ordinary clinical use ·DEFINITION AND CLINICAL FEATURES 7 Clinical Evaluation of Fatness Fortunately, in clinical practice the degree of accuracy claimed for the above methods is not required Variations of as much as 10 per cent of the desirable body weight are not excessive We have found the use of a combination of the latest height weight tables (Tables 1 and 2) and skinfold measurements to be a useful guide in determining satisfactory weight of subjects The tables afford a rough indication as to the degree of overweight skin thickness judged over several sites, such as upper arm, chin, abdomen, lower chest in the axıllary line region hips, and thighs offers help. ful corroborative information It must be emphasized that the tables serve merely as a guide If the physical examination does not reveal any excessive amount of subcutaneous fat, no further weight reduction is encouraged, no matter what the tables predict Conversely, if examination reveals ercess subcutaneous fat, weight reduction is continued even though the individual Falls within normal range according to these tables With a little practice and experience, surprisingly good guesses can be made as to the degree of overweight INCIDENCE The incidence of obesity is difficult to estimate, because there is no sharp dividing line between normal weight and overweight Using the tables of the Metropolitan Life In. surance Company, Armstrong estimates that about 15 million persons in this country are 10 per cent overweight, and at least 5 millon are 20 per cent or more above the normal [4] Another estimate is that 28 per cent of the population is overweight 10 per cent or more, and 12 per cent are at least 20 per cent overweight Thus, obesity represents prob- ·OBESITY ITS CAUSE, CLASSIFICATION, AND CARE ably the most common danger to the life and health of the adult population of this country HAZARDS Morbidity Numerous studies have brought out the association of obesity with many serious physical impairments Abnor malities of the cardiovascular system are considerably more frequent in overweight individuals than in those of normal weight Thompson found that in the 35 to 44 year old age group, a diastolic blood pressure of 90 mm of mercury or over was found in 26 per cent of those classified as heavy build, 15 per cent of those of medium build and 9 per cent of those of light body build In older age groups, the inci dence of hypertension was higher, but the differences according to body type persisted [116] Master, Dublin and Marks in a sample of 74 000 industrial workers, showed a steady progression in average blood pressure (systolic and diastolic) with increase in body weight for all age groups and for both sexes [75] In a study of a group of Army offi cers, it was found that sustained hypertension developed more than twice as frequently in the obese as it did in those of normal weight [67] Wilens, in a study based upon autopsy material found that the incidence of advanced atherosclerosis was about three times as frequent in the obese as in those of poor nutritional status (20 per cent of obese, 67 per cent of those poorly nourished) [127] Coronary atherosclerosis was also more commonly observed in the overweight in dividual Electrocardiographic abnormalities were found to exist in 15 per cent of men who were more than 25 per cent over- ·DEFINITION AND CLINICAL FEATURES 9 weight as compared with 85 per cent of those of normal weight and 2 per cent of those of underweight [103] Gallbladder disease is more frequent in the obese A study of the weight of insurance applicants with a history of gall MEN WOMEN 180% 169% 150% 52% 152% 50% 147% 130% 131% 134% ALL AGES 20 29 30 39 40 49 50 64 (20-64 YEARS) ALL AGES 20 29 30 39 40-49 50-64 120-64 YEARS) Fic 1 P'er cent actual of expected deaths among men and women limited to substandard insurance because of overweight By age at issue of insurance Issues of 1925- 1931 traced to policy anniversary in 1950 Death rates of standard roaks in each sex = 100% (From Metropolitan Life Insurance Co , Statistical Bulletin, Vol 32, 1951 ) stones revealed that 41 per cent of the men and 53 per cent of the women were overweight [33] The increased incidence of diabetes in association with obesity has long been known Joslın found that 60 per cent of patients over age 10 were at least 20 per cent overweight at the time of onset of diabetes An additional 25 per cent were moderately Oserweight, makng a total of 85 per cent ·10 OBESITY ITS CAUSE, CLASSIFICATION, AND CARE TABLE 3 PRINCIPAL CAUSES OF DEATH AMONG MEN AND WOVEN LIMITED TO SUBSTAND 4RD INSURANCE BECAUSE OP OVERWEIGHT ATTAINED AGES 25 TO 74 YEARS ISSUES OF 1925 TO 1934 TRACED TO POLICY ANNIVERSARY IN 1950 (Death Rates of Standard Risks in Each Sex = 100%) Men Iomen to Actual of Actual of No of Expected No of Expected Deaths Deaths Deaths Deaths Cause of Death 149 1 103 177 Principal cardiovascular renal diseases 1 867 Organic heart disease diseases of the coronary arteries and angina pectoris 1 377 Cerebral hemorrhage 247 Chrono zephrit29 243 Cancer--all forms 385 Leukemia and Hodgkın s disease 26 Diabetes mellitus 205 Tuberculosis--all forms 24 Pneumonia all forms 98 Cirrhosis of the liver 96 Appendicitis 76 Bilary calculi (gallstones) 19 Ulcers of stomach and duodenum 30 Suicide 63 Accidents--total 142 159 192 97 100 383 21 102 249 223 206 67 78 111 697 226 280 476 23 235 20 78 32 41 50 10 23 74 175 162 212 100 110 372 35 129 147 195 284 * 73 135 177 * Deaths too few to warrant calculation of mortality ratio Note Italics denote that the deviation from the Standard 19 not atstistically significant SOURCE Metropolitan Life Insurance Co Statistical Bulletin Vol 32 Oct 1951 who were overweight Only 5 per cent were underweight Osteoarthritis, especially appreciably more frequent In a 611 and Nerd an it be ,36] rot of ·DEFINITION AND CLINICAL FEATURES 11 normal presentations, prolonged labor, and postpartum hemorrhage Operative intervention was required twice as frequently as in women of average weight Infant mortality was increased, as were puerperal maternal morbidity and mortality (76, 86] In the presence of obesity, the surgical risk is high and embolic phenomena common (7, 36) Carcinoma of the uterus is apparently more frequent among obese than among normal women [52] Mortality Statistics of the Metropolitan Life Insurance Company Indicate clearly that life expectancy is shortened in the obese (Fig 1) Contrary to the older belief that some degree of overweight is desirable in younger individuals, these findings indicate that the mortality ratio for overweight men was hughest in the 20 to 29 age group For all ages mortality among fat men was 150 per cent and for overweight women 147 per cent of that expected The principal causes of death in the obese group are indicated in Table 3 Degenerative diseases of the heart, brain, and kidney, and diabetes were the most common factors in this increased mortality rate [32] the ·CHAPTER 2 Adipose Tissue IN 1940, H G Wells entitled an article "Adipose Tissue, A Neglected Subject" (123) In the years following there has been considerable revival of mterest in thus subject Al though a great deal is yet to be understood and explained, there have been tremendous advances in our knowledge of the anatomy, physiology, formation, and breakdown of fat tissue In the following three chapters, the results of a few of these investigations will be mentioned with the idea that some understanding of our present knowledge of the anatomy, chemistry, and physiology of adipose tissue may lead to a more rational approach to the therapy of obesity, and dispel the misconceptions advanced by faddists and cultists CELL ORICIN Adipose tissue is not merely connective tissue loaded with fat and having no other function than that of fat storage It develops from special primitive fat cells, and has a specific structure distinct from the fibroblasts of connective zssue This cell structure is more evident when the stored fat is depleted [124] The fatty depots furta an organ system composed of it dividual lobules that develop chiefly during fetal life inde- 12 ·ADIPOSE TISSUE 13 pendently of the degree of lipid storage in the cells In the development process these depots are intimately related to the vascular apparatus At one point during fetal life there is beginning differentiation of hitherto undifferentiated con nective tissue around the blood vessels At first the imma ture fat cell cannot be distinguished from other connective tissue cells Later however the young fat cells take up lipid as they lie alongside the capillaries of a thick network of blood vessels The reaction to vital staining helps distinguish developing adipose tissue from other mesodermal derivatives When newborn rats were injected with trypan blue and trypan red, weight and growth were retarded but the development of adipose tissue was not disturbed On the other hand fol lowing the administration of lithuum carmine the primitive fat cells were cheched but the blood vessels and connective tissuc flourished These studies lend additional evidence to the view that adipose tissue is not lipid bearing connective tissue (95) INNERVATION An abundant network of nerves is found in fat tissue the larger units being in the connective tissue septa which subdivide the adipose tissue into lobes and lobules. The acrves are essential because they regulate the functional activity of the adipose tissue Growth of the fat tissue is apparently controlled by ef ferent fibers of the autonomic nenous system which run to the periphery together with branches of the spinal nerves Increased storage of lipid follows nene resection Whether this reaction is effected through direct ner ous regulation of the blood vessels or by the production of acetylcholine- ·CHAPTER 3 Intermediary Metabolism of Fats and Carbohydrates FATS INGESTED FATS are not stored directly, but are first metabolized to 2 carbon units and rebuilt into fatty acids for storage A brief review of the mtermediary metabolism of fats may assist in the understanding of some of the processes involved in Lipogenesis The Knoop ß oxidation theory, formulated in 1904, was the one accepted for many years This postulated a suc cessive splitting at the ß carbon atom of the long fatty acid chain, leaving a 4 carbon molecule which was converted to acetoacetic acid, ß hydroxybutyric acid, and ultimately, to acetone These male up the so called "Letone bodies' (63) However, when the amount of acetone was calculated, it was discovered that an impossible amount of fat must have been metabolized to have formed the quantity of acetone that was found The acetone production was far in excess of that expected from successive 8 oxidations Thus, the ß 011- dation theory became untenable as the sole mechanism In 1916, Hurtley proposed the hypothesis that the fatty acid was attacked at alternate carbon atoms simultaneously along the entire carbon chain [55] This hypothesis was 16 ·INTERMEDIARY METABOLISM OF FATS AND CARBOLTYDRATES 17 supported by the studies of Jowett and Quastel in 1935 [58] Similar results were reported by Stadie in 1940 and 1911 (105, 106] He postulated a multiple altemate oxidation mechanism and a splitting of the long chain at alternate B carbon atoms Although this concept accounted for the formation of the relatively large amount of ketone bodies found several other questions remained unanswered In support of the successive B-oxidation theory, degradation products of the long-chain fatty acids ie, shorter chain fatty acids had been identified The presence of these degradation products could not be explained on the basis of the multiple alternate oridation theory It was also difficult to explain why the splitting should occur regularly at alternate B carbon atoms Mackay and his co-workers in 1910 offered another con cept of the intermediary metabolism of fatty acids (72, 73) They accepted the B-oudation theory of the successive for mation of a shorter chain fatty acid and a molecule of acctic acid As this degradation process continued two molecules of acetic acid condensed to form acetoacetic acid and the other Actone bodies This hypothesis explained both the amount of Letonc bodies formed and the identification of shorter chain fatty acids MacKay found that when acetic icid was fed to phlorhızınızed dogs or fasting rats there as a marked nse in the excretion of acetone bodies demon rating that the animal organism can synthesize ketone dies from acctic acid (69) It is likely that perhaps other reactions are involved in the metabolic degradation of long-chain fatty acids At the present state of our knowledge, the B-ondation multiple condensation theory appears to offer the best explanation for most of the observed phenomena ·20 OBESITY: ITS CAUSE, CLASSIFICATION, AND CARE 8C 2 GLUCOSE-S-PROSPHATE +2 TPN +2 HO 6C 26-PHOSPHOGLUCONIC ACID 2 TPNH. CARBOXYLASE2 TPN 5C 2 ROOSE-S PHOSPHATE 2 RIBULOSE 5 PHOSPHATE 20.2 TPNH T 7C SC SEDOREPTOLOSE-7 PHOSPRATE. TRKOSEPHOSPRATE I 6C 4C FRUCTOSE-6-PHOSPHATE , ERYTHROSE PHOSPHATE 6C GLUCOSE 8 PROSPHATE + TPN HO 6C 6 PHOSPHOGLUCONIC ACID. TPNH8* TPN CARBOXYLASE SC RIBUTOSE 3 PHOSPHATE TPNN. .Com [2C - FRAGMENT) TRIOSE PHOSPHATE GLUCOSE POL START WITH 2 6C COMPOUNDS END WITH 1 8C 13C 3 CO, 3 TPNHI Fig. 3. The hexosemonophosphate shunt.

·INTERVIEDLANY METABOLISSI OF FATS AND CARBOETYDRATES 21 A schematic illustration of the intermediary metabolism of carbohydrates and fats and their interrelationshup is presented in Figure 2 Another pathway has recently been described It is called the "Hexosemonophosphate Shunt," or "Glucose Shunt" (Fig 3) By this mechanism 2-carbon fragments may again be synthesized to carbohydrate and not fat (96] Carbohydrate is a normal precursor and the chief source of stored fat Animals on a fat free diet deposit fat in their tissues About 10 to 15 per cent of Clabeled glucose fed to rats on a fat free diet was recovered as fatty acids (11] The metabolism of carbohydrate supplies energy for building fatty acids from 2-carbon units Variations in carbohydrate metabolism will affect this formation of fatty acids Tat metabolism is subject to the control of hormones which exert their primary effect on carbohydrate metabolism Two carbon units are produced in the metabolism of fats and carbohydrates At this stage, their metabolism is identi cal The citric acid cycle which effects the oxidation of 2 carbon units to CO, and water is the mechanism of both fat and carbohydrate oridation (11) ·CHAPTER 4 Lipogenesis and Fat Mobilization THE CONVERSION of carbohydrates to fats has been known for many years Although some of the intermediate meta bolic processes have been identified, knowledge in this field is still relatively scanty LIPOGENESIS It is probable that only those substances capable of being degraded biologically to 2-carbon fragments can be syn. thesized into long chain fatty acids It has been demon strated that the carbon atoms of glucose, lactate, pyruvate, acetone, acetaldehyde, and acetic acid can be synthesized into fatty acids The active 2 carbon unit is probably acety! Co A It is apparent that carbohydrate must undergo glycolysis before it can be utilized for fatty acid synthesis [47] Acetyl Co A can be oxidized to CO, and water, or be synthesized to cholesterol, fatty acids, or ketone bodies, (Fig 2) Which of these occurs depends to a great extent upon hormonal and nutritional factors Liver slices of normal rats can readily convert acetate to fatty acids This is not true of liver slices obtained from alloran diabetic, fasting, or depancreatectomized rats The same results prevail whether acetate or glucose is used. 22 ·LIPOCENESIS AVD FAT MOBILIZATIOY 23 Although the addition of insulin to liter slices of normal ani mals stimulates the synthesis of fatty acids no in citro effect can be demonstrated with liver slices of diabetic animals [47] However lipogenesis in her slices of fasting rats can be stimulated by the addition of large amounts of glucose, or even more effectively glucose plus insulin [6] Liver slices obtained from cats which have been pan createctomized can convert labeled acetate into fat at a normal rate The addition of insulin accelerates this re action wlule the administration of a purified growth hor mone inhibits lipogenesis (47) The oxidation of fatty acids is unimpeded or even accel crated in experimental diabetes Chabeled fatty acids are readily converted by such slices to cetoacetate The fast ing state is also characterized by an accelerated hepatic ori dation of fatty acids and increased Letogenesis It is apprent that under these conditions there must be an abund ance of 2-carbon units formed It has been demonstrated that the oridation of lactate and the decarbory lation of pyruvate proceeds in the dia betic state thus indicating that the glycolytic and oxidative enzymes are intact Since laser slices of fasted rats can od dize acetate it appears that the activation of acetate is not Impured in such animals It would appear then that for coupling of actnc2-carbon units to form fatty acids an acetate activating system alone is inadequate It is likely that energy derived from glicol ysis is necessars to drac these reictions in the direction of synthesis A common feature of diabetes and the fasting state is a diminished availability of intracellular substrates for glucolisis (r) Glycolysis is accelerated by insulin probably by means of ·24 OBESITY ITS CAUSE, CLASSIFICATION, AND CARE a stimulating effect upon hexokinase activity The eract way in which the effects of insulia are brought about is not known The Coris postulated that insulin influences the rate of hexokinase activity by overcoming the inhibitory effect of a pituitary factor (93) More recently, Levine has suggested that insulin exerts its effect by accelerating the permeation of glucose into the cell, and its metabolic effects are secondary to its entry into the cell No effect upon the hexokinase system by insulin was found in the absence of cells (66) No matter which explanation is correct, the diabetic and fasting states are characterized by an accumulation of 2 carbon fragments in the liver If their condensation to fatty acids as blocked there is a greater diversion of these 2 carbon units to acetoacetate, thus explaining the hetosis of diabetes and fastıng Since the direct conversion of acetoacetate to cholesterol has been observed, the accumulation of acetoacetate could result in the accelerated formation of cholesterol observed in diabetes FAT MOBILIZATION A striking increase in total liver lipids was found to follow the administration of small amounts of purified growth hormones [87, 121) Choline and other lipotropic agents did not influence this response to the fat mobilizing factor [87] Payne studied va 10us types of anterior pitutary hormones in an attempt to establish whether the fat mobilizing factor was a function of one of the known antenor pituitary hormones, or distinct from them He studied the effects of the growth, thyrotropic, adrenotropic, lactogenic, follicle stimulating, and lutemizing hormones All these preparations showed some activity, though their potency varied [87] ·LIFOCENESIS AND FAT MOBILIZATION 25 Adrenalectomy completely inhibited this response The administration of cortisone restored it The effect of des ory corticosterone was variable The administration of corti sone alone to adrenalectomized or intact animals had no cffect upon thc fat content of the liver Neither thyroidectomy nor thiouracil, thyroxine, nor posterior pituitary hormones were able to induce fatty anfiltration of the Liver It was thus concluded that neither the adrenotropic nor the thyrotropic hormone was the fat mobılızıng factor Likewisc, the inability to correlate the fat mobilizing factor with the potency of any of the other better known tropic hor moncs indicated that it is distinct from them There are apparently at least two hormonal factors in volved in fat mobilization an anterior pituitary factor and an adrenocortical factor [87] Lovin and Farber postulated that the pituitary factor triggers the reaction This triggering is not mediated by the adrenal corter. The adrenal cortical hormones act directly on the fut tissue presumably on the enzyınc systems It conditions the tissue thus rendering it responsive to the Inggering factor which sets off the release of fat from the depots (65) Two-carbon units are produced in the metabolism of fats and carbohydrates At this stage, their metabolism is identical The citric acid cycle which effects the oxdation of 2 carton units to CO, and water is a mechanism of both fat and carbohydrate oridation ·CHAPTER 5 Classification of Obesity TO BE of value any classification of disease must guide us to therapeutic procedures From this standpoint, there has thus far been no satisfactory classification of the obesities The common division into endogeneous and exogeneous, or into endocrine and nonendocrine, has, as far as we can determine, served no useful purpose Indeed, by definition, it is possible to place all obesities in the endogeneous class, or in the exogeneous class as one may desire For example, all overweight is exogeneous in the sense that the individual consumes more calories than he needs to maintam a normal weight Such an explanation fails to take into account any underlying factors which predetermine his needs or the reasons why he maintains an energy intake which is greater than his output At the other extreme, one may speak of all overweight as endogeneous, in that the individual ingests more food than he requires because of some inward compulsion or disease On this basis, on the one hand the cause of the fat may be found in a poorly adjusted personality which finds escape from reality in the pleasant pastime of eating, or on the other hand, the overweight may represent a severe glandular dyscrasia Between and including these two extremes lie many categories which will enable us to 26 ·CLASSIFICATION OF OBESTTY 27 place all subjects with obesity in the endogeneous class should we so desire The ideal classification of obesity would be one based upon etiology In experimental physiology, one may speak of hypothalamic obesity, gold thioglucose obesity, or hereditary obesity [78] However, such an etiological classification of obesity is still of no practical clinical value in the present state of our knowledge The difficulties inherent in such a classification will be discussed further in the chapters dealing with the etiology of obesity Another classification of obesity is essentially descriptive In this connection it should be emphasized that fat may be commonly distributed in one of four ways (1) about the head, neck, and upper body, an accentuation of the mas. culine configuration, and in more extreme forms often alluded to as the bullfrog or buffalo type, (2) about the lower abdomen, hps, and thighs, an accentuation of the feminine configuration, and in its extreme form resembling or corresponding to familial lipodystrophy, (3) in a girdle fashion with so-called "rolls" of fat about the chin, the arillae, the bust, the abdomen, the hips, the thighs, and, in extreme forms, also about the knees In this form, the overall height of the individual may be short, and the hands and fcet relatively small and (4) generalized obesity, in which the entire body and extremities share rather evenly in the distribution of fat The essential types, as summarized by LeRay, are as follows (61] 1 Android type, where the obesity is concentrated on the upper liall of the body and, secondanly, on the abdomen 2 Gynod tyre, where the fat is found predominantly at the level of the hips and lower half of the body ·28 OBESITY ITS CAUSE, CLASSIFICATION, AND CARE 3 Endocrine type, characterized the coexistence of recognized endocrine disorders The endocrine disorder is not necessarily the cause of the obesity, but may denote two manifestations of an underlying common etiology The following classification of overweight has some etiological implications and simultaneously affords us at least a partial key to therapeutic procedures (Table 4) As TABLE 4 TYPES OF OBESITY IN RELA TION TO THEIR ORICIN I Nervous Obesity Hypotbalamic II Endocrine Obesity A Hypothyroid (?) B Adrenal C Overran D Patuito-hypothalamic (1) III Hereditary or Familial Obesity (7) IV Habit Obesity is true in most classifications, the rubrics in this one overlap each other to a greater or lesser extent For instance, the nervous or hypothalamic type of obesity might well include many cases of "habit obesity," where an abnormalappetite or lack of normal satiety is associated with or arises from disturbed nervous pathways The familial type of obesity may represent habitually abnormal eating customs within the confines of a single group of individuals On the other hand, it may indicate an unborn type of bodily_build with which fat is unusually or abnormally distributed It is not uncommon, for instance, to find all of the men of a single family with exceptionally wide pelves, and abnormally heavy hips and thighs However, maleness is not disturbed in any of its essential characteristics By the same token, in some families, there is a tendency for the men to show an ·CLASSIFICATIOV OF OBESITY increased distribution of fat about the head, neck, and shoulders, and for the women to display evidence of masculine configuration with relatively broad shoulders and narrow hips Thuis we have termed the "adrenal type” of obesity, but it might just as easily have been included as a subgroup of the familial or hereditary form It is not difficult to see that every arrangement of the obesities has its shortcomings Our own classification has proven of some use to us in selecting and directing therapy, it has no further justification At thus point, it should be made clear that medicines will not substitute for the basic role which diet must play in the management of all obesities Nevertheless, we are convinced that the judicious and well indicated use of drugs in selected cases is of tremendous help in carrying out the dietary regimen and in reversing the underlying physiological disturbances which have led to the deposition of unwanted fat In the hypothalamic, or nervous, group of patients we in. clude all cases of Frohlich's disease and Frohlich's syddrome, some of the children with so called adolescent obesity," and a majority of the individuals with a girdle type of obesity whether they do or do not show the rather delicate fcatures and small hands and fect commonly associated with such a distribution of fat For the purposes of therapy it seems that we must also consider here those in- Vividuals, particularly women, who periodically losc and gain weight rapidly in relation to episodes of water tetention and durcsis, and in whom such phenomen are as. sociated with moderate to marhed over eight These people appear to be subject to a considerable degree of emotional and outonomic nen ous system lability, which may initiate or at least be associated with abnormal impulses arising in 3 ·30 OBESITY ITS CAUSE, CLASSIFICATION, AND CARE the hypothalamic nucles that regulate appetite and/or the storage of fat To carry thus thought one step further, it is difficult to say just how often the excessive ingestion of food in people of normal weight has its origin in mental or emotional disturbances which subject the hypothalamic centers, and through them probably the pituitary, to stimuli capable of altering metabolic balances and of favoring the deposition of adipose tissue In other words, we include in thus hypothalamic group of cases, some, if not all, of the individuals who have established faulty eating habits not connected with the familial patter of food consumption into which they were born Hypothyroid obesity has been included in our classification with a question mark, because it would appear that underfunction of the thyroid per se does not lead to obesity A slight increase in weight, rarely greater than five is present as a result of myxedema While the lowered metabolism undoubtedly could favor the deposition of adıpose as well as myxedematous tissue, it appears that appetite is lowered as the hypothyroid state appears Thus a satisfactory balance between energy intake and outgo is main tamed Rarely does appetite stay at the previous level, an such instances obesity may result, which will respond to specific medication with thyroid hormone Obesity in association with the adrenal is due to an overactivity of the cells of the adrenal cortex, and is seen in cases of Cushing's syndrome This is a rare cause of obesity It should be treated specifically by control of the hyperfunction whuch induced it It is not easy to explain the so-called "ovarian_type” of obesity in which the deposition of fat is chiefly if not exclusively confined to the lower abdomen, hips, and thighs per cent, ·CLASSIFICATION OF OBESITY 31 So-called "familial lipodystrophy and closely allied condi tions probably should be included in this category of ovarian obesity The middle-age sprcad of the menopausal woman is the chief clinical example of so called "ovapan obesity Hence in the minds of most individuals the condi tian is believed to be due to a diminution in or cessation of ovarian activity If this is true it seems strange that the feeding of ovarian hormone tends to exaggerate the condi tion Furthermore of decreased ovarian activity were the sole factor involved it is surprising that individuals with ovarian agenesis not only do not show this type of body build but on the contrary are rather short stochy in dividuals with relatively broad shoulders and narrow hips It seems to us doubtful that a disturbance of the pituitary gland en cause olesity lo sindrome has as yet been described in which either underfunction or overfunction solcly of this gland or of any part of it has led to obesity The majority of the cases in which obesity has been ascribed to the hypophysis have actually been instances of hypothalamic obesity Ilowever without any conclusnc evi dence not only Truhlich s syndrome but also such condi tions as the Lawrence Voon Biedl syndrome Dercums disease and the Vorgagni Morel syndrome have been ascribed to or believed to be associated with lesions in this gland It seems better to recognize the endocrine disturb ances If any as secondary to the nen ous dysfunction as far as the several diseases just mentioned arc concerned concnital and hereditary factors may play a major role The pituntary crstainly does not In the hereditary congenital or familial causes of olsesity We might well consider the Lawrence lfoon Biedl sin drome Vorgagni Stewart Vorels disease and similar prob- ·30 OBESITY ITS CAUSE, CLASSIFICATION, AND CARE the hypothalamic nucles that regulate appetite and/or the storage of fat To carry this thought one step further, it is difficult to say just how often the excessive ingestion of food in people of normal weight has its origin in mental or emotional disturbances which subject the hypothalamic centers and through them probably the pituitary, to stimuli capable of altering metabolic balances and of favoring the deposition of adipose tissue In other words, we include in this hypothalamic group of cases, some, if not all, of the individuals who have established faulty eating habits not connected with the familial pattern of food consumption into which they were born Hypothyroid obesity has been included in our classi fication with a question mark, because it would appear that underfunction of the thyroid per se does not lead to obesity A slight increase in syeight, rarely greater than five is present as a result of_myxedema While the lowered metabolism undoubtedly could favor the deposition of adıpose as well as myxedematous tissue, it appears that appetite is lowered as the hypothyroid state appears Thus a satis factory Kance between energy intake and outgo is main. tained Rarely does appetite stay at the previous level, in such instances obesity may result, which will respond to specific medication with thyroid hormone Obesity in association with the adrenal is due to an overactivity of the cells of the adrenal cortex, and is seen in cases of Cushing's syndrome This is a rare cause of obesity It should be treated specifically by control of the hyperfunction which induced it It is not casy to explain the so called "ovarian_type” of obesity in which the deposition of fit is chiefly if not exclusively confined to the lower abdomen, hips, and thighs per cent, , ·CLASSIFICATION OF OBESITY 31 So called "famılal lipodystrophy” and closely allied conditions probably should be included in this category of ovarian obesity The middle age spread of the menopausal woman is the chief clinical example of so called "ovarian obesity " Hence, in the minds of most individuals, the condition is believed to be due to a diminution in or cessation of ovarian activity If this is true, it seems strange that the feedmg of ovarian hormone tends to exaggerate the condition Furthermore, if decreased ovarian activity were the sole factor involved, it is surprising that individuals with ovarian agenesis not only do not show this type of body build, but on the contrary are rather short, stocky individuals with relatively broad shoulders and narrow hips It seems to us doubtful that a disturbance of the pituitary gland can cause obesity No syndrome has as yet been described in which either underfunction or overfunction solely of this gland or of any part of it has led to obesity The majority of the cases in which obesity has been ascribed to the hypophysis have actually been instances of hypothalamic obesity However without any conclusive evidence, not only Frohlich's syndrome but also such conditions as the Lawrence-Moon Biedl syndrome, Dercum's disease, and the Morgagni Morel syndrome have been ascribed to or believed to be associated with lesions in this gland It seems better to recognize the endocrine disturbances, if any, as secondary to the nervous dysfunction As far as the several diseases just mentioned are concerned, congenital and hereditary factors may play a major role The pituitary certainly does not In the hereditary congenital or familial causes of obesity we might well consider the Lawrence-Moon-Bredl syndrome, Morgagni Stewart-Aforels disease, and similar prob- ·32 OBESITY ITS CAUSE, CLASSIFICATION, AND CARE lems as developmental disturbances For most of these conditions, no satisfactory or specific therapeutic regimen exists Habit obesity has already been discussed at some length ✓One of us leans to the view that most of the cases of habit obesity have developed as a result of abnormal nervous and mental stimuli while the other looks upon this condition as purely exogeneous in origin, the result of following a pattern land down by others as a simple mechanism for escape from reality In any event, abnormal appetite exists, and must have some mediation via glandular or nervous structures within the body, irrespective of the extraneous forces which may have played a role in bringing it about In summary, no classification of obesity is wholly satis factory Justification for the present one resides chiefly in the fact that it affords some useful guides to the selection and pursuit of therapeutic procedures ·CHAPTER 6 The Normal Regulation of Intake of Food HUNCER AND APPETITE HUNGER AND appetite are terms used to describe sensations leading to the ingestion of food Hunger is an unpleasant sensation described as an empty feelug in the epigastrium Cannon and Washburn have shown that sensations of hunger pains coincide with waves of contraction of the empty stomach. Appetite is a pleasant desire for food It is based upon previous acquaintance with food, impressions of sight and smell, and is conditioned by habit and training Hunger and appetite are interdependent in regulating the intake of food An individual may eat in spite of the absence of hunger, for example, the partaking of a rich dessert following a sumptuous meal Conversely, unpleasant sensations can completely eliminate the desire for food, although the individual was hungry prior to exposure to the unpleasant stimulus Although the two probably differ physiologically, an exact differentiation between them is dif. ficult However, such differentiation is unnecessary clinically Both result in eating, and it is the excessive intake of food that results in obesity 33 ·34 OBESITY ITS CAUSE, CLASSIFICATION, AND CARE MECHANISMS OF REGULATION OF Food INTALE Many theories have been advanced to explain the regulatron of intake of food energy Early concepts held that the taking of food was the result of (1) stimulation of afferent nerves by some local changes in the tissues, mainly in the stomach, (2) a hunger center in the brain was sensitive to a starvation state of the blood, and (3) a hunger center in the brain was stimulated directly by a hunger state of the blood and also indirectly by afferent impulses from all organs of the body [78] After it was demonstrated that hunger sensations coin cided with contractions of the empty stomach, Carlson sug. gested that hypoglycemia, acting upon the stomach, might be responsible for inducing these contractions [26] However, this theory became untenable when it was demon strated that total denervation and surgical removal of the stomach did not fundamentally alter the characteristics of the regulation of the intake of food. THERMOSTATIC MECHANISM THEORY In the process of assimilation of food, there is a rise in the total production of body heat This extra heat is termed * specific dynamic action, and varies with the different types of foodstuffs, proteins having the highest, and fat, the lowest Booth and Strang observed a rise in skın temperature following eating They correlated this with the onset of satiety They found that the subjects were unable to continue eating when there was a fise in shin temperature of 0 9°C in 22 minutes (12] Strang and McCluggage found that a considerable difference in the rate of heat production eusted between thin obese, and normal people The greatest rate ·reasonable to suppose that the specific dynamic artion 1 play a role in selectively altering the drive from the feed However there are several contradictions to the static theory It does not explain the hyperpha mia card that in acclimatized hypothalamic animals, i not depressed by high environmental teme Tre central temperature of hyperphagic animals Lethaa that of nonhyperphagic controls and finally Le sottott GLUCOSTATIC MECHANISM TEL 11 Recently Mayer has returned to the couro center and thus cut off or otherwise alter the feedinra causes an increased intake of food while allo deprivation of food increases the central to tie 7 glucose is the main factor regulating the food THE NORMAL REGULATION OF LYTAKE OF FOOD 33 of heat production was found in underweight indiduals and the lowest rate in the obese They admitted the d. ficulty of trying to establish a relationship between saliety and the physiological stress resulting from the specific lynamic action of food However assuming such a rela tonship the rapid rate of heat production in the thin person rused an early feeling of satisfaction The slower rate of at production in the obese caused the individual to reach 'uration much later if at all so a normal brake on eating s damaged (108) Brobeck stated that animals eat to keep warm and stor eating to prevent hyperthermia Since the hypothal.oms is known to contain temperature sensitive cells it seems flexes (15) by insulin or diabetes Thyroxine a thyroidectomy causes a decrease It has been designed hyperthe camera in 78] ·36 OBESITY ITS CAUSE, CLASSIFICATION, AND CARE reasoning behind this theory, as stated by Mayer, is as follows "The regulation of food wtake proceeds by relatively frequent partaking of food (meals) It is improbable that the hypothalamic centers are sensitive to decrease of the body content of proteins or fats, since during the short interval between meals, the decrease is proportionally very small On the other hand, the body stores of carbohydrate are limited The postprandial liver glycogen in man is only about 75 Gm In the postabsorbtive period, these stores are rapidly depleted The nervous system depends exclusively on glucose Thus, it would appear possible that the nervous system contains glucoreceptors' sensitive to fluctuations of available blood glucose' (77,78] A crude test of this hypothesis was provided by a survey of the effects of various metabolites on the effect of intake of food of normal animals Increase in levels of blood sugar was obtained by wjections of glucose, fructose, or epine phrine Decreases were obtamed with insulin Hypoglycemuc levels were avoided It was found that temporary increases in blood glucose levels corresponded to decreases in food intake, and vice versa, even when the caloric equivalent of injected metabolites was taken into account Substances with out effect on blood glucose did not influence food intake Over and beyond the caloric value of these substances [77] The absolute values of blood glucose, however, could not be the determining factor, else how could the hyperphagia of diabetes mellitus, hyperthyroidism, or that existing in obesity where there is a tendency to hyperglycemic blood levels be explained for variation of blood sugar levels to mfluence hypothalamic glucoreceptors, glucose has to cross the membranes of these cells, thus, utilization of available blood glucose is of major importance (77,78] ·TEDE NORMAL REGULATION OF INTAKE OF FOOD 37 This concept was tested in human subjects by measuring the concentration of glucose in simultaneously obtained specimens of blood from an antecubital vein and a finger tip (venous and capıllary blood) The difference was desig nated as a glucose A Glucose values were found to correspond closely with the calonc intake of the individual, and with hunger feelings Adequate diets were associated with large a glucose values, while submaintenance diets were associated with rapidly decreasing a glucose values after meals Values of 15 mg per 100 cc were associated with satiety, those near zero with hunger (83) In diabetes mellitus since glucose is not adequately utilized the concentration of blood sugar had to be forced up through ingestion of food to levels were arteriovenous differences were introduced for hunger to be satisfied In hyperthyroidism glucose is metabolized very rapidly It is possible that the increased food intake of food characteristic of hyperthyroidism may be related to a metabolic hypoglycemia CONCLUSIONS It is evident that the physiological regulation of intake of food is erceedingly complicated No matter what metabolic factors are involved, other factors such as habits, environment physical characterstics or prlatability of food, emotional associations social stimuli and reactions to stress are involved to a variable degree and cannot be quantita tively measured (78) ·CHAPTER 7 Etiology : Hereditary, Psychological, Nervous, and Dietary Factors Excess fat can come from only one source, ingested food In an otherwise healthy individual, food intake in excess of the energy requirements of the body is converted into and stored as fat If the amount of food eaten us in balance with the energy expended, there can be no accumulation of fat Any deviation from this concept contradicts fundamental physical laws of conservation of energy In the average healthy person, the amount of food eaten is nicely attuned to the energy requirements of the body, and the weight remains fairly constant at a satisfactory level Anything which disturbs this equilibrium will cause a deviation from the desirable weight Thus, obesity may be caused by increased intake of food, decreased work output, or decreased rate of heat production, acting singly or in combination In this connection, we asked 108 consecutive obese pa. tients why they thought they were fat Fifty four (50 per cent) admitted frankly that they ate too much, while an additional 17 (15 per cent) although blaming their obesity primanly on other factors, admitted they overate Thus 65 per cent of these patients implicated faulty dietary habits 38 ·ETIOLOCY TIEREDITY, PSYCHIOLOGICAL, NERVOUS DIET FACTORS 39 as the cause of their obesity Popularly held reasons for obesity, such as pregnancies, the menopause, heredity, and glandular disturbances, not accompanied by admissions of overeating accounted for only 18 per cent of the answers 17 per cent of the patients stated they did not know why they became obese [43] The disproportion between energy intake and output as the immediate cause of obesity is almost universally accepted But what mechanisms operate to bring about this disproportion? Why should the homeostatic mechanisms which operate so efficiently in most people to enable them to maintain a desirable weight without their giving a second thought to what they eat, break down in the obese? The final answer, or answers to these questions are unfortunately still lacking A wide variety of factors have been implicated as the fundamental abnormality leading to obesity Some of these will be discussed in the ensuing sections HEREDITY It has been observed that obesity in many instances is familial Gurney in a study of 75 obese women, found that 82 per cent had one or both parents who were obese, while in only 38 per cent of individuals of normal weight did such a situation exist He noted that if both mother and father were markedly overweight, 73 per cent of the offspring were abnormally fat, if only one parent was overweight 59 per cent of the offspring were excessively heavy, while if both parents were of normal weight, only 9 per cent of the offsprog were obese [49] In a similar study of 39 obese patients, we found that in 87 per cent, one or both parents were overweight (39] Hereditary obesity has been studied in different animals ·OBESITY ITS CAUSE, CLASSIFICATION, AND CARE The yellow strain of mice, and the obese hyperglycemic syndrome of mice have been extensively investigated The obesity of the Danforth strain of yellow mice is transmitted by a dominant gene These mice attam a weight two to three times greater than nonyellow littermates Both males and females develop obesity The mtake of food of these obese mice is increased, while activity is diminished These animals will lose weight as calculated when their diets are restncted (99) The obese hyperglycemic syndrome of mice is also char acterized by extreme obesity, and has been demonstrated to be controlled by a single recessive gene This syndrome has been intensively studied by Mayer and associates The average consumption of food by these animals is about 20 per cent greater than those of normal weight However, measurements of activity reveal that normal mice are 50 to 100 times more active than the obese mice The inactivity precedes the development of obesity Thus even when a genetic factor can be positively implicated in the etiology of obesity, a disproportion between every intake and output must exist before obesity can develop When these factors are controlled so that the disproportion is eliminated there is no excess accumulation of fat [78] On the other hand, unless exceptional genetic conditions were present, it has not been possible to produce excessive deposition of fat in experimental animals by purely dietary means Fenton and Carr observed the weight response of four different strains of mice to variations in the fat content of the diet An increase in the rate of gain in weight was noted in only two of the strains, thus suggesting that genetic factors are involved. Whether these results obtained with ·ETIOLOGY HEREDITY, PSYCHOLOCICAL, NERVOUS, DIET FACTORS 41 mice can be applied to the problem of obesity in man is uncertain (37] There is no disputing the fact that individuals are built differently Some are much larger than others However, mere size, or a large frame, does not constitute obesity It is the amount of padding on the framework that determines that, and such padding must be acquired While the matter is not definitely settled, we feel that the tendency for obesity to run in families depends more upon environmental than hereditary factors It has been found that the body weight showed greater variation than any other characteristic in identical twins who were separated at an early age and subjected to different environments (35) Children eat at the same table as their parents, and imitate and learn the same eating habits Since faulty eating habits were concerned in the obesity of the parents, duplication of these habits in the offspring will result Gurney found that among the overweight patients he studied 43 per cent had an obese mother, whule 15 per cent had an obese father [48] In our group, the ratio was 46 per cent and 18 per cent respectively Since the mother has the greater control of the childs diet during the formative years, it is likely that she tries to force her methods of eating upon her children The separation of the relative influence of heredity and environment is as difficult for obesity as for many other characteristics Much of the evidence points to the domi nance of environmental factors in most individuals In any case, the hazards of overweight are essentially the same in both groups, and both will respond to a properly controlled ·OBESITY ITS CAUSE, CLASSIFICATION AND CARE weight reducing regunen That one is a member of an obese family should be no deterrent to a desirable loss of weight PSYCHOLOGICAL FACTORS Eating, is a popular outlet for anxieties and frustrations It substitutes a pleasurable sensation for the unpleasant feelings engendered by emotional strain Obesity affords some individuals an excuse for other inadequacies It pro tects them from being forced to do hard work or other unpleasant tasks Their appearance is used as an excuse for failing to indulge in normal social activities and as a re sult normal responsibilities of marriage parenthood and community obligations are often avoided A Freudian concept sees obesity as the result of arrested sexual development the libido remaining at the oral stage The mouth is the erotogenic zone and the partaking of food is the gratification Once obesity has become established the individual feels himself different from others and he may tend to isolate himself Emotional problems are thus increased and a vicious circle is set up This type of individual looks for some factor beyond his control as the cause of his obesity as a face saving mecha nism Any implication by the physician that his obesity is caused by glands or heredity is just what the patient is seeking and can result in irreparable harm This patient must be told bluntly that his overweight is caused by overeating By using food as the solution for his problems a habit pattern becomes established This habit must be broken and the patient must be re educated in proper eating habits (See chapter on diet management) ·ETIOLOGY HEREDITY, PSYCHIOLOGICAL, NERVOUS, DET FACTORS 13 Psychic stress, however, does not invariably result in overeating Mfany individuals react quite the opposite, a loss of weight caused by a reduction of appetite will ensue It is impossible to state whether increased or decreased intake of food will result from psychic stress in different individuals, or in the same individuals at different times Patients with anorexin nervosa may demonstrate alternate periods of obesity and leanness THE HYPOTHALAMUS Destruction of specific portions of the hypothalamus will result in obesity [53] The exact locations of these lesions vary in different species These lesions can be made at will in experimental animals by means of the Horsley-Clarke stereotauc needle In rats, the ventrolateral bodies of the ventromedial nuclei must be destroyed These lesions will produce obesity whether the anterior pituitary is present or not No amount of pituitary damage will cause obesity if the hypothalamus is intact Animals in whom such lesions were made develop an enormous voracious appetite They may be said to attach their food The term 'hyperphagua" best expresses their abnormal appetites and methods of eating Many studies have been made on animals in whom obesity was induced by hypothalamic injury to see whether there were any changes in normal physiological functions The outstanding characteristic of these animals was their voracious appetite These animals showed an increase in average meal size, and ate more frequently This abnormal appetite came on immediately after the lesion was made Surgical reduction of the size of the stomach did not prevent the development of obesity The animals merely ate ·OBESITY ITS CAUSE, CLASSIFICATION, AND CARE smaller amounts more frequently The hyperphagia was not abolished by long continued limitation of food [20] When animals in whom the medial hypothalamic nuclei have been destroyed are pair fed with normals, the operated anımals, m some cases, gain weight slightly faster It is thought that the method of eating of the operated animals is responsible for this Brobeck found that when normal animals are taught to devour their food rapidly, they gain equally with their operated pair [15] In the obese anımals, blood lipids are high and fat in the liver is excessive [15] However, a comparison of the dry weight of the feces with the dry weight of the food ingested by normal and obese rats shows no significant difference, indicating no change in intestinal absorption [21] Chemical analysis of the accumulated fat in the obese animals reveals nothing remarkable Obese animals utilize their stored fat when they are starved The respiratory quotient (RO) during starvation is the same as that observed in normal animals (14 15, 17, 19) Recent studies utilizing deuterium oxide have demon strated that there is no excessive rate of absorption of food or deposition of fat in hypothalamic animals The fraction of depot fat mobilized per day is extremely small . The quantity of depot fat mobilized is likewise small but it could not be determined definitely that it was less than normal [74] Immediately following the destruction of the ventral hypothalamic nuclei there is some decrease in activity However, activity gradually increases in frequency and in tensity The greater weight of the animal requires more energy for movement, and the weight shift inyolved in such activities as eating and washing becomes significant The ·ETTOLOGY TIEREDITY, PSYCIIOLOGICAL, NERVOUS, DIET FACTORS 45 recorded activity finally exceeds the preoperative activity of the individual even before weight gain has ceased Thus, the great increase of weight of these anuals cannot be attributed to inactivity (18] In some animals, there is an increase in the RQ during the period of rapid weight gain (dynamic phase) Only those few animals that demonstrated this rise in RQ outgained normals in pared feeding experiment This increased RQ has been attributed to the voracious method of eating of the hyperphagic animals The administration of thyroxın to hypothalamic animals to elevate the metabolic rate retarded, but did not completely abolish the gain in weight (15, 18, 211 In some animals with such hypothalamıc lesions, there are noted hypoplasia of the gonads and genitalia and ab normalities of the estrous cycle This is independent of pituitary damage, and is not necessarily related to such damage Brobeck suggested that the ingestion of large quantities of food and the rapid deposition of fat require large amounts of accessory food factors (vitamins), and that the above findings may be a result of deficiencies of these (14] However, since it has been noted that adjacent lesions in the hypothalamus which do not cause hyperphagia frequently lead to disturbances of the sexual proc esses, these changes may have been caused by the extent of the lesion and are, therefore, independent of the hyperphagra [78] Since the centers for many vital functions lie close together in the hypothalamus, and it is difficult exactly to control the extent of the destructive lesion, the latter explanation seems the more likely Insulin is required for storage of fat Relatively large amounts are needed in the rapid deposition of fat caused ·44 OBESITY ITS CAUSE, CLASSIFICATION, AND CARE smaller amounts more frequently The hyperphagia was not abolished by long continued limitation of food (20] When animals in whom the medial hypothalamic nucles have been destroyed are pair fed with normals, the operated animals, in some cases, gain weight slightly faster It is thought that the method of eating of the operated animals is responsible for this Brobeck found that when normal animals are taught to devour their food rapidly, they gain equally with their operated pair (15) In the obese animals, blood lipids are high and fat in the liver is excessive (15] However, a comparison of the dry weight of the feces with the dry weight of the food ingested by normal and obese rats shows no significant difference indicating no change in intestinal absorption [21] Chemical analysis of the accumulated fat in the obese animals reveals nothing remarkable Obese animals utilize their stored fat when they are starved The respiratory quotient (RO) during starvation is the same as that observed in normal animals (14, 15, 17, 19) Recent studies utilizing deuterium orde have demon strated that there is no excessive rate of absorption of food or deposition of fat in hypothalamic animals The fraction of depot fat mobilized per day is extremely small . The quantity of depot fat mobilized is likewise small but at could not be determined definitely that it was less than normal [74] Immediately following the destruction of the ventral hypothalamic nucle there is some decrease in activity However activity gradually increases in frequency and in tensity The greater weight of the animal requires more energy for movement, and the weight shift involved in such activities as eating and washing becomes significant The ·ETIDLOGY HEREDITY PSYCHIOLOGICAL, NERVOUS DET FACTORS 45 recorded activity finally exceeds the preoperative activity of the individual even before weight gain has ceased. Thus the great increase of weight of these animals cannot be attributed to inactivity (18) In some animals there is an increase in the RQ during the period of rapid weight gain (dynamic phase) Only those few anunals that demonstrated this rise in RQ Out gained normals in paved feeding experiment Thus in creased RQ has been attbuted to the voracious method of cating of the hyperphagic animals The administration of thyrorin to bypothalamic animals to elevate the metabolic rate retarded but did not completely aboush the gaja in weight (15 18 21) In some animals with such hypothalamic lesions there are noted hypoplasia of the gonads and genitalia and ab normalities of the estrous cycle This is independent of pituitary damage and is not necessarily related to such damage Brobeck suggested that the ingestion of large quantities of food and the rapid deposition of fat require large amounts of accessory food factors (vitamins) and that the above findings may be a result of defciencies of these (14} However since it has been noted that adjacent lessons in the hypothalamus which do not cause hyper phaga frequently lead to disturbances of the sexual proc esses these changes may have been caused by the extent of the lesion and are therefore independent of the hyper phagia [78] Since the centers for many vital functions lie close together in the hypothalamus and it is difficult etactly to control the extent of the destructive lesion the latter ex planation seems the more hkely Insula is required for storage of fat Relatively large amounts are needed in the rapid deposition of fat causna ·46 OBESITY IS CAUSE, CLASSIFICATIOV, AND CARE by the hyperphagia Glycosuria is more common in the obese animals It is possible that adequate amounts of insulin are not available to take care of all metabolic requirements (151 Both Brobeck and Brooks conclude that the major cause of experimentally produced obesity is the breakdown of the balance between food intake and energy utilization The metabolic effects of hypothalamic injury are probably secondary to the hyperphagia [16, 19) Recently, this view has been challenged Some investigators feel that the problem is more complex, and involves a general metabolic disturbance Disturbances in calcum, phosphorus, and iron metabolisin have been noted in hypothalamıc animals [54] The intake of food varies with the type of diet, being greatest when a high fat diet is offered Very little hyperphagia is observed when the animals are fed a high protein diet [68] Mayer found that during the active phase of weight gain, an excellent degree of correlation could be established between the lowering of the non fasted blood sugar levels and the hyperphagia He sug gested, in keeping with his glucostatic theory, that the increased rate of lipogenesis prevented satiety glucose levels to be reached [78] When hypothalamic animals are forced to work to obtain their food, it has been found that they eat less than control animals Thus, it would seem that hypothalamıc animals eat excessively not because of an overwhelming urge to eat, but rather because of a failure of satiety 'The lesions interfere seriously with the mechanism of stopping eating and somewhat less seriously with the mechanism of hunger [80] Bilateral destruction of a small region in the lateral hypothalamus will result in complete anorexia Rats and cats so ·ETIOLOCY HEREDITY, PSYCHOLOCICAL, NERVOUS DIET FACTORS 47 operated upon die of starvation although food is present in their cages When the regions causing hyperphagia and anorexia are simultaneously destroyed, inanition will result Hyperphagic animals in whom the lateral centers were destroyed at a later date ceased to eat It has been concluded that the lateral regions are the locations of the appetite center, the location of the receptor cells and effector neurons The medial centers are the inhibitors of the appetite center [3] Whether this effect of the medial on the lateral centers is mediated by a direct neural inhibition, as suggested by Anand (3] or acts indirectly through some underlving metabolic disturbance, as advocated by Mayer [78], has not as yet been established DIETARY FACTORS Many dietary factors have been implicated as to why some people become obese Thus, it has been suggested that_fat people eat excessive amounts of carbohydrates, fats or fat rich foods, or normal amounts accompanied by decreased activity Also, such individuals are said to eat large amounts at one sitting, have an excessive amount of snacks, or eat most of their food at the evening meal Using a special Type of dietary history method, Beaudoin and Mayer found that the average intake of food by obese individuals was derived from the same proportions of fat (37 per cent) and carbohydrates (49 per cent) as that of normal persons Both obese and normals were found to have snacks in similar proportions [8] Apparently there is not a great deal of difference qualitatively between the diets of obese and normal individuals It would appear that the main difference is quantity ·CHAPTER 8 Etiology: Metabolic Factors OBESITY is the result of a chronic disproportion between caloric intake and energy output Derangements of either or both of these factors by some metabolic error could cause such a disproportion Vanous abnormalities of energy exchange have been suggested as the cause of obesity Some early studies attempted to show that no significant change in weight would ensue in some thin and obese per sons no matter what modifications were made in their diet or activity Strouse and Dye studied five cases One was very thin A 50 per cent increase in food intake and reduce tion of activity caused no increase in weight after four weeks Conversely, four obese persons whose caloric intake was markedly reduced showed negligible weight loss after one week to four months [112] All these individuals, however, were followed on an outpatient basis We have found that no reliance can be placed on patients' reports as to how much they ate A group of obese individuals were instructed to keep daily score cards as to what and how much they ate The daily caloric intake was then calculated for each patient It was found that most subjects maintained their weight, and even gained weight on admitted caloric intakes of less than 1000 calories a day, ·ETIOLOGY METABOLIC FACTORS some as low as 400 or 500 calories a day for penods of at least two weeks This is a most unusual findung [39] In a study of eight obese patients who were hospitalized and allowed a free choice of food, Strang, McCluggage and Evans found an average intake of 2570 calories a day Moreover, even on such a relatively high caloric intake, a loss of weight averaging two pounds in four days was observed [111] It has repeatedly been demonstrated in careful metabolic studies where the intake of food can be controlled and measured, that changes in weight can be predicted with considerable accuracy [84, 85, 125] Practically every physician is familiar with the obese patrent who insists he is a very small eater Part of the explanation for this is the confusion that exists in the minds of many between bulk and food value Small amounts of butter, or pastry will afford considerably more calories than a much larger amount of lettuce, but be much less filling An excess of 100 calones a day will result in the deposition of ten pounds of fat in a year Since 100, or even 200 calories is so small when compared to the total daily intake, it is easy to understand why so many obese patients insist they do not eat more than the average One patient was observed who requested treatment for underweight A high caloric diet, frequent feedings, and various food supplements caused only a very slight gain in weight after two months The patient insisted that he fol lowed the dietary instructions, and was eating more than he ever did This same patient developed a duodenal ulcer year later He was then forced to indulge in frequent feedings, and he drank large quantities of milk in order to be free of his ulcer symptoms The resultant gain about a ·CHAPTER 8 Etiology: Metabolic Factors OBESITY is the result of a chronic disproportion between caloric intake and energy c or both of these factors b cause such a disproportion Various abnormalities of energy exchange have been suggested as the cause of obesity Some early studies attempted to show that no significant change in weight would ensue in some thin and obese persons no matter what modifications were made in their diet or activity Strouse and Dye studied five cases One was very thin A 50 per cent increase in food intake and reduction of activity caused no increase in weight after four weeks Conversely, four obese persons whose caloric intake was markedly reduced showed negligible weight loss after one week to four months [112] All these individuals, however, were followed on an outpatient basis We have found that no reliance can be placed on patients' reports as to how much they ate A group of obese individuals were instructed to keep daily score cards as to what and how much they ate The daily caloric intake was then calculated for each patient It was found that most subjects maintained their weight, and even gained weight on admitted caloric intakes of less than 1000 calories a day, ·ETIOLOGY METABOLIC FACTORS some as low as 400 or 500 calories a day for periods of at least two weeks This is a most unusual finding [39] In a study of eight obese patients who were hospitalized and allowed a free choice of food, Strang, McCluggage and Evans found an average intake of 2570 calories a day Moreover, even on such a relatively high caloric intake, a loss of weight averaging two pounds in four days was observed [111] It has repeatedly been demonstrated in careful metabolic studies where the intake of food can be controlled and measured, that changes in weight can be predicted with considerable accuracy (84, 85, 125] Practically every physician is familiar with the obese patient who insists he is a very small eater Part of the explanation for this is the confusion that exists in the minds of many between bulk and food value Small amounts of butter, or pastry will afford considerably more calories than a much larger amount of lettuce, but be much less filling An excess of 100 calories a day will result in the deposition of ten pounds of fat in a year Since 100, or even 200 calories is so small when compared to the total daily intake, it is easy to understand why so many obese patients insist they do not eat more than the average One patient was observed who requested treatment for underweight A high caloric diet, frequent feedings, and vanous food supplements caused only a very slight gain in weight after two months The patient insisted that he fol lowed the dietary instructions and was eating more than he ever did This same patient developed a duodenal ulcer about a year later He was then forced to indulge in frequent feedings, and he drank large quantities of milk in order to be free of his ulcer symptoms The resultant gain ·50 OBESITY, ITS CAUSE, CLASSIFICATION, AND CARE in weight was so rapid that it was necessary to institute dietary restrictions to prevent excessive gain of weight INCREASED EFFICIENCY OF DIGESTION AND ABSORPTION It is obvious that if one individual absorbs more of a similar meal than another, his caloric intake is greater However, it has been found that the caloric value, nitrogen, and fat content of the feces are the same for obese and normal individuals on comparable diets Similar findings have been described when underweight subjects were compared to normal persons (109] In their studies on rats made obese by hypothalamıc lesions, Brooks and his co-workers could find no difference between obese and control animals when the dry weight of the feces was compared to the dry weight of the food (21) NITROGEN EXCHANGE Strang, McCluggage and Evans found that the level of nitrogen exchange in obese individuals on a restricted diet was normal if 0 16 Gm of nitrogen per kilogram of ideal body weight was furnished, and that this was no different from that observed in normal individuals (110) The nitrogen output in undernourished individuals under going treatment with a high caloric diet is less than normal at the outset, and after treatment It is the undernourished individual who handles energy conservatively and with little body waste (109) RESPIRATORY QUOTIENT The respiratory quotient represents the relationship be tween oxygen intake and CO, Output Expressed mathemat.

·ETIOLOGY METABOLIC FACTORS 51 ucally, RQ = COME The respiratory quotient of carbohydrate is 10, of protein 080 and of fat 0 71 When an oxygen-rich substance is converted to an oxygenpoor substance, which occurs in the conversion of carbohydrate to fat, the respiratory quotient will rise On the other hand, when fat is metabolized, the respiratory quotient will be low Because of these facts, the respiratory quotient has been exhaustively studied in order to determine whether any metabolic difference existed between obese and normal individuals Hagedorn found the respiratory quotient in the postprandial state higher in the obese than in normals This was interpreted as proving an increased conversion of carbohydrates to fats in the obese He also found a lower respiratory quotient in obese individuals in the post absorptive phase [49] Brooks found that there was an elevation of the respiratory quotient after eating during the dynamic phase of obesity (period of rapid gain of weight) in animals with hypothalamic lesions This was attributed to the ravenous way these animals ate and the rapid deposition of fat secondary thereto During the static phase of obesity, these animals had normal respiratory quotients [17] During dietary restriction, there is no difference in the respiratory quotient between obese and normal individuals, indicating that the obese can metabolize their fat in the same manner as normal persons [107] The finding of an elevated respiratory quotient following a meal does not necessarily mean the conversion of carbohydrate to fat The oxidation of carbohydrates and the for mation of acid metabolites, such as lactic acid, increases the output of carbon dioxide and thus the respiratory quo tient The occasional finding of a decreased fasting respua- ·50 OBESITY ITS CAUSE, CLASSIFICATIOV, AND CARE in weight was so rapid that it was necessary to institute dietary restrictions to prevent excessive gain of weight INCREASED EFFICIENCY OF DIGESTION AND ABSORPTION It is obvious that if one individual absorbs more of a similar meal than another, his caloric intake is greater How ever, it has been found that the caloric value, nitrogen and fat content of the feces are the same for obese and normal individuals on comparable diets Similar findings have been described when underweight subjects were compared to normal persons [109] In their studies on rats made obese by hypothalamıc lesions, Brooks and his co workers could find no difference between obese and control animals when the dry weight of the feces was compared to the dry weight of the food [21] NITROGEN EXCHANGE Strang McCluggage and Evans found that the level of nitrogen exchange in obese individuals on a restricted diet was normal if 0 16 Gm of nitrogen per kilogram of ideal body weight was furnished, and that this was no different from that observed in normal individuals (110) The nitrogen output in undemnourished individuals under going treatment with a high caloric diet is less than normal at the outset and after treatment It is the undernourished individual who handles energy conservatively and with little body waste (109) RESPIRATORY QUOTIENT The respiratory quotient represents the relationship be tween oxygen intake and CO, Output Expressed mathemat ·ETIOLOGY METABOLIC FACTORS 53 to 30 Strang and Evans, on the basis of their own data and calculations based upon data obtained by others, found a 25 per cent increase in the basal metabolic rate (107] The excess fat is what causes the increase in surface area Adipose tissue is not merely an inert storage depot It is part of the reticuloendothelial system with a definite, active function, and a specific carbohydrate metabolism However, it has been calculated that the metabolic activities of fat tissue contribute probably less than 10 per cent to the excess heat production (98] The excessive rate of metabolism may contribute to the greater incidence of degenerative diseases in overveight individuals (Chapter 1) They burn themselves out faster During weight reduction by dietary means, the basal metabolic rate remains within normal limits an adequate amount of protein is provided Some studies demonstrated a lowering of the basal metabolic rate during weight reduction This was probably caused by an inadequate intake of protein [99] During weight reduction the rate of heat production dımınıshes to a greater extent than either the weight or surface area, but never goes below the theoretical normal level (107] SPECIFIC DYNAMIC ACTION The specific dynamic action of food refers to the increased metabolism above the basal rate caused by the metabolism of food The increase caused by protein is 30 per cent, that caused by carbohydrate 6 per cent, and that caused by fat 4 per cent The determination of the specific dynamic action is difficult Since it measures the increase in metabolisin over the basal level, the establishment of a true baseline is impera.

·52 OBESITY ITS CAUSE, CLASSIFICATION AND CARE tory quotient in the obese represents an increased metabo. lısın of fat This may be necessary because of decreased glycogen stores, and is consistent with the usual findings of pathological changes in the liver in obesity plus the possi bility that the increased level of metabolism in the obese depletes glycogen stores more rapidly [99] There have been no consistent and significant differences noted in the respiratory quotients of obese and normal ındı viduals that would indicate fundamental variations in me tabolism Changes noted in some studies may be just as well explained by other factors The respiratory quouent is at best difficult to measure accurately It represents the total of a great number of compler reactions going on at the same time As Long has stated, it is probable that too much emphasis has been placed on the level of the respiratory quotient as evidence that a certain single process is or is not occurring [35] L. BASAL METABOLIC RATE The basal metabolic rate represents the basal heat pro duction of the body in relation to the surface area Strouse and Dye (113) found that 10 ont achf nor underweight was associates the basal metabolic rate that the basal metabolic rate was within normal limits in the obese The vast majority of patients in our clinic presented no abnormality in their basal metabolic rate (39, 40 411 While the basal metabolic rate is usually normal in obes ity, the total basal heat production per hour is excessively hugh since the surface area is relatively greatly increased When heat production was related to the ideal surface area, ·ETIOLOGY METABOLIC FACTORS 55 about 200 calories would represent the specific dynamic action If obesity depended upon this specific dynamic action, it would have to drop 30 to 50 per cent in mild cases, and completely disappear in severe cases Such changes should be demonstrable The failure to be able to do so is in opposition to the suggested causal relationship of reduced specific dynamic action to obesity [108] REBOUND OF METABOLISM A decrease in metabolic rate to below the baseline after the rise caused by the ingestion of food was found in obese individuals by Bernhardt This decrease was also thought to follow exercise This saying in metabolism could account for an increase in weight after a prolonged time However, neither Wilder, nor Strang and McCluggage were able to demonstrate this rebound effect in their studies (108, 125) LUXURY CONSUMPTION This is a term for a mechanism whereby normal individuals compensated for an increased caloric intake by an increase in metabolism Grafe postulated that such a mechanism was absent in the constitutionally obese [46] It is true that undernourished persons will respond to an adequate diet with an increase in metabolism However, this is no proof that such happens in normally nourished individuals nor has this been demonstrated. An increase in metabolism will occur in superalimentation only when there is also protein overfeeding and is probably caused by the specific dynamic action of the protein [98] KETOSIS MacKay and Shernll, in their studies on metabolic changes, found that some obese subjects, while fasting, de- ·54 OBESITY ITS CAUSE CLASSIFICATION AND CAPE tive Considerable training and practice are necessary be fore any individual becomes a satisfactory subject Deter minations must be carried on for a sufficient length of time Since the stomach may not completely empty itself for three or more hours the study must be continued for several hours beyond that The method of expressing the increase in metabolism is also important If it is represented as the per cent increase the specific dynamic action in the obese will be relatively low, since they start with a high baseline caused by their increased rate of heat production It is better to express the specific dynamic action as the total increase in heat production rather than the per cent increase [35] Using a group of trained subjects, and contmung the study for eight hours Strang and McCluggage found no significant quantitative difference between obese, normal, and thin individuals in the total increase of heat production They used a diet which supplied 610 calories The addı tional heat produced was 57 calories The cost of digestion was, then, 9 per cent [108] Benedict found it to average about 6 per cent in his series, using a different diet Wilder stated that, at best, it is no more than 10 per cent (125) Wilhelmj in a comprehensive summary of the problem of specific dynamic action quotes studies demonstrating no change in the specific dynamic action in pituitary disease after hypophysectomy in dogs, in exophthalmic goiter and hypothyroidism, and in adrenalectomized dogs He also noted that the specific dynamic action is not a function of the amount of food ingested, but of the amount metabolized and varies with the state of nutrition (128] It has been demonstrated that an intake of about 100 calories a day in excess of requirements will result in a gan of ten pounds in a year On a diet of 2500 calories a day, ·ETIOLOGY METABOLIC FACTORS 57 weight with age noted in the older tables of standard weight Chapter 1) is probably a result of this However, this increase in weight is relatively small, and normally does not result in clinical obesity Mayer found that abnormality of energy exchange in the hereditary obese hyperglycemic syndrome in mice was associated with a marked decrease of activity by these anı mals [78] However, it is questionable whether inactivity is important in the etiology of most cases of human obesity In our study of the subjective impressions of overweight individuals as to the cause of their obesity, only two of the 108 patients questioned attributed their obesity to inactivity [43] Enforced inactivity, such as the result of accident, illness, or surgery is probably accompanied by a great deal of psychic stress which may concomitantly pervert the nor mal appetite mechanism Conversely, the same emotional disorders which might cause a voluntary decrease of activity could also cause an increase in the intake of food In other words, mactivity is not necessarily the cause of obesity, both may be the result of some common situation LIPOPHILIA This is a term used by Bergman to describe an abnormal tendency of obese individuals to fix fats, and an increased difficulty in losing fats from their depots Hetenyı made several observations in support of this concept He found that in undernutrition, the blood lipid level in individuals of normal weight remained unchanged, but decreased in the obese Obese individuals given a fatty meal had a lesser increase in blood lipids than normals He also found that if olive oil were injected into the lean upper extremities of persons with lipodystrophy, absorption was normal, but ·56 OBESITY ITS CAUSE, CLASSIFICATION, AND CARE veloped a greater ketosis than normal individuals, and some had very little ketosis They believed that the obese became ketotic during starvation because they burned a greater amount of fat Those subjects that showed a diminution in ketone bodies were thought not to have a simple obesity Their fat was considered locked in storage depots and was not available for metabolism An endocrine basis was sug gested for this phenomenon [71] If the above were correct, what sort of metabolic mature were these individuals utılızıng? Energy is derived from the metabolism of carbohydrates, proteins, and fats Those indı viduals who had decreased ketosis were believed not to be metabolizing fats If proteins were being utilized to supply the energy which the locked fats could not, there should have been a distinctly greater negative nitrogen balance in this group Unfortunately, such balance studies were not included There was no previous dietary control in any of these studies It is possible that the difference in the nutritional status between these groups caused the variation in the amount of ketosis rather than any peculiarity of the stored The entire subject of the ketosis present in obesity is confused Some investigators have and some have not found increased ketosis a constant finding during the dietary cor rection of obesity The absence of any consistency in these various experimental studies casts considerable doubt on the causal relationship between ketogenesis and obesity PHYSICAL ACTIVITY A decrease in activity will, of course, result in an increase of weight of the diet remains constant The increasing ·CHAPTER 9 Etiology: Endocrine Factors DYSFUNCTION OF one or another of the endocrine glands has often been considered a cause of obesity Not only have many glands been thus implicated but even when a gland has been singled out as the etiological factor in a particular case, there has been no agreement as to whether hypofunc tion or hyperfunction exists The incidence of frank evidence of endocrine dysfunction in overweight individuals (other than their obesity) is small Of 200 unselected cases of obesity studied by Rony, only 13 had definite evidence of endocrine disease [98] Even this small number may be somewhat exaggerated, since it is sometimes difficult to determine whether the endocrine disturbances are independent lesions, the cause of the obesity, or manzfestations secondary to it It is likely that endocrine diseases cause obesity in only a relatively small number of cases Some of the glands which, because of some abnormality of function, have been thought to cause obesity, are discussed below THYROID Hypofunction of the thyroid gland is one of the most frequently implicated endocrine causes of obesity The gain 59 ·58 OBESITY IT'S CAUSE, CLASSIFICATION, AND CARE when injected into the fat lower extremities, absorption fol lowed the pattern observed in the obese [35] Increased lipogenesis and difficulty in mobilizing fat reserves has been demonstrated in the obese hyperglycemic syndrome of mice [78] However, no increase in the rate of lipogenesis could be demonstrated animals made obese by hypothalamic lesions In these latter animals, it could not be established with certainty that there was a decreased ability to mobilize depot fats [74] The concept of lipophilia has not been established in hunan obesity In controlled studies where obese individ vals have been observed on submaintenance diets, the rate of loss of weight has been as calculated If an adequate amount of protein were allowed, the patients remained in nitrogen balance This should not be the case if there were any impairment of fat mobilization In addition the BMR has almost always been normal in obese human beings whereas hypometabolism has been characteristic of the obese hyperglycemic syndrome of mice In conclusion, it can be stated that no peculiar mecha nism for controlling energy, as is implied in the concept that the amount of food intake has no effect upon the weight of some individuals, can be demonstrated Subjective impressions of the amount of food eaten are unreliable and ínısleading Careful, controlled studies have been un able to confirm the conclusion drawn from data based upon such unpressions ·ETIOLOGY ENDOCRINE FACTORS 61 obesity followed castration in some animals However, this is probably a species reaction Castrated humans are not necessarily obese Eunuchs may be of normal weight, or even lean In some civilizations where castration is performed in all males above a certain age, the incidence of obesity is not found to be excessive | Many individuals date their obesity to a time when major gonadal changes occur, such as puberty, pregnancy, or the climacterium However, changes in hormonal functions at these times are completely different There increasing gonadal function at puberty while the climacterium represents waning glandular function We are again faced with attributing the same phenomenon (obesity) to hypo and hyperfunction of the same gland Aside from the differences of endocrine changes, there is no constancy regarding the development of obesity at these various times Actually, some individuals lose weight then Obese children frequently lose weight at the time of puberty A loss of weight following the menopause is also not uncommon Weight tables show no rapid changes in those age groups in which these variations in gonadal function occur, suggesting that there is no startling deviation of weight for the average ndividual coincident with these changes Menstrual disorders and sterility are frequently present in the obese women Their correction, which frequently occurs after weight reduction, makes it hkely that they are secondary to the obesity, rather than a cause of it PITUITARY In the early part of this century, Frohlich described a syndrome consisting of trophic disturbances such as infan- ·60 OBESITY ITS CAUSE CLASSIFICATION AND CARE in weight has been attributed to the low level of metabo lism In a study of 53 patients with mild hypothyroidism Seward found that 14 patients under 40 years of age, and I over 60 complained of weight loss, while 12 patients over age 40 gained weight. Sixteen patients under age 35 were underweight and 2 were overweight of those over age 40 12 were overweight and 2 were underweight [100] Plummer analyzed 200 cases of spontaneous myxedema Sixty-one and one half per cent were overweight, and 38% per cent were underweight There was no quantitative rela tionship between weight and the level of the basal meta bolic rate The average loss of weight after thyroid therapy was instituted was about 13 pounds The greater the degree of myxedema, the greater was the loss of weight, suggesting that it was edema fuid that was eliminated, not body tissue When all the excess fluid was eliminated, the average weight for the group was somewhat below normal He suggested that there appears to be a loss of body flesh which is replaced by edema flud in well established cases of myxedema (91) Hypothyroid and myxedematous patients are not neces sarıly obese Conversely, most obese individuals do not have a low basal metabolic rate (See section on oxygen er. change ) GONADS The distribution of fat is obviously different in men and women However, mere differences in the distribution of fat do not consitute obesity There must be an excess amount of fat deposited Several observations have led to the belief that obesity was associated with gonadal dysfunction The first was that ·ETIOLOCY ENDOCRINE FACTORS sulted in a marked increase of the circulating neutral fat which is ordinarily absorbed and metabolized by the liver Posterior pituitary hormone had no effect upon the level of the circulating neutral fat when injected into dogs in whom such lesions of the nervous system were made Raab concluded that "Pituitrin promotes the absorption and destruction of circulating fat by the liver through nervous pathways starting in the tuber cinereum and running through the cervical cord and the abdominal splanchnic nerves to the liver Any disturbance of the cooperative pituitary mesencephalic system would lead to a retention of excess amounts of fat in the body and thus lead to obesity" ADRENAL Cushing's disease is caused by hyperfunction of the adrenal cortex Obesity is one of the most constant findings in this disease being noted in 97 per cent of all cases The appetite stimulating effect of the corticord hormones un. doubtedly contributes to the development of this obesity There is a characteristic distribution of the fat it is most prominent in the upper part of the body, the cheeks, supraclavicular and neck regions over the spines of the upper vertebral column, and the trunk The appearance of the patient has given rise to the descriptive term 'buffalo obesity" However, some cases show pseudoobesity, that is, the characteristic obesity of the upper part of the body is apparent, although there is no abnormal increase in the total body weight [90] Undernutrition in a verified case of Cushing's disease resulted in a loss of weight exactly as predicted for a normal person This led Frey berg and Newburgh to conclude that ·62 OBESITY ITS CAUSE CLASSIFICATION AND CARE tilism genital dystrophy and adiposity in the presence of a tumor at the base of the brain [25] On the basis of his description the condition of untold numbers of fat children had been diagnosed as Frohlich s syndrome and they have been subjected to courses of hormonal therapy The normal development of puberty belies the diagnosis in most of these youngsters As a descriptive term "Frohlichs syn drome can be accepted However there is no evidence to prove that obesity and distribution of fat in this disease are caused by hypofunction of the anterior pituitary Frohlich himself admitted in 1940 that the obesity in his original case was secondary to hypothalamic damage caused by the tumor rather than by any destruction of the pituitary itself Hetherington has shown that no amount of pituitary damage will cause obesity of the hypothalamus is intact [54] Sunmonds disease is a process associated with failure of the anterior pitwtary Individuals with this disease are often thin and cachectic Thus we have the situation in which the obesity of Frohlich s syndrome and the cachexia of Sum monds disease are attributed to the same dysfunction of the pituitary gland Cushing's disease is an endocrinopathy which is usually associated with obesity This is probably mediated through adrenal cortical hormones and will be discussed further under that heading The ability of posterior pituitary extract to cause a de crease of the neutral fat in the blood and to prevent a rise of blood lipids following a fatty meal led Raab to postulate a fat regulating center in the hypothalamus In dogs de struction of the tuber cinereum or interruption of the nerv ous pathways between the hypothalamus and the liver re ·ETIOLOCY ENDOCRINE FACTORS 65 tolerance after weight loss If the excess weight were regained diabetes again developed, only to disappear a sec ond time after satisfactory weight reduction When the weight of these patients was normal, glycosurea was not present even though they were under no restrictions or treatment These authors postulated that excess fat in the liver interfered with normal glycogen formation [82, 83] The development of diabetes was related to the duration of the obesity, and not its extent A recent study utilizing liver biopsies confirmed pathologically abnormalities of the liver in all of 20 individuals who were 50 to 100 per cent overweight The severity of the lesion was directly related to the duration of the obesity [131] The excess of insulin required for the deposition of fat in the obese may also contribute to the relative hypoinsulinism and decreased carbohydrate tolerance Fındıngs relevant to carbohydrate metabolism in obesity are variable and contradictory Some cases of obesity are associated with hyperinsulinism However, it has been noted that functional hyperinsulinism is frequently associated with psychoneurotic disorders A correlation between the duration and activity, that is, dynamic or static, of the obesity and an increase in glucose tolerance has been suggested in a study of two groups of obese women, one representing active," and the other "static' obesity, Beaudoin and co workers found that the former had a markedly increased tolerance to carbohydrate after ingestion of meals and after test doses of glucose [8] SUMMARY The preceding chapters dealing with the etiology of obes. ity started with the premise that the unmediate cause of the condition was a chronic disproportion between the intake ·64 OBESITY ITS CAUSE, CLASSIFICATION, AND CARE there was a normal energy exchange, and no unusual meta bolic feature was apparent as a cause of the obesity [38] PANCREAS The pancreas, through its hormone insulin, exerts a profound effect upon the intermediary metabolism of fats and carbohydrates (Chapter 2) Insulin is also required for lipo genesis (Chapter 3) Prolonged administration of protamine zinc insulin to rats has produced hyperphagia and obesity However, regular insulin has not had this effect [70] Recently, another hormone of the pancreas which causes hyperglycemia has been identified (glucagon) An excessive production of this hormone has been suggested as one of the causes of the obese hyperglycemic syndrome in mice Increased secretion of the hyperglycemic factor would in turn cause an increase in insulin secretion, hence an m crease in lipogenesis [78] • Obesity in some individuals has been attributed to a low blood sugar, or an increased tolerance to carbohydrates as manifested by a flat glucose tolerance curve, or one with a pronounced dip in the level of blood sugar after several hours It is argued that a low concentration of blood sugar is a stimulus to the appetite However, the usual finding in obesity, especially in the middle aged, is a decreased carbohydrate tolerance Diabetes is much more frequent in obese persons It is almost axiomatic that an obese individ ual who develops diabetes after the age of 45 will not re quire insulin if he loses his excess weight Newburgh and Conn found that two thirds of persons between the ages of 30 and 65 admitted to their diabetic chuc were overweight. Thirty five patients were followed. All except one showed reversion to a normal carbohydrate A great many raore recent studies fail to support this concept ·CHAPTER 10 Obesity in Childhood FOR SOVE reason, obesity in childhood is frequently considered apart from the problem in general Special classıfications, etiologies, and methods of treatment have been advocated for this group It is true that certain modifications in the general plan of treatment must be made because of different nutritional requirements necessitated by the need for maintaining growth and development (see section on management), but we do not feel that any fundamental differences exist between obesity in children and adults It is unfortunate that the obese child is often considered an endocrine problem Rony, who found only 13 frank endocrinopathies in 200 obese adults, stated there were definite endocrine abnormalities in 34 of 50 obese children [98] Why this discrepancy should exist is difficult to understand Most obese children live to adulthood, and, of endocrine factors are responsible for their obesity while young, why are they not the same in adult life? If there is such a high incidence of spontaneous cure of endocrine abnormal. ities, the problem has been magnified out of all proportion to its importance Obesity in children probably does not differ from that 67 ·66 OBESITY ITS CAUSE, CLASSIFICATION, AND CARE and output of energy An attempt to explore possible ab normalities responsible for this disproportion has failed to reveal any consistent differences between obese and normal individuals as regards genetic, metabolic, or endocrine factors Contradictory results have been reported, and contra dictory conclusions from similar data were derived by dif ferent investigators Recently the question has been raised as to whether obes ity per se is a disease entity, or merely a symptom of a vari ety of abnormalities differing both etiologically and path ologically [45, 78] It has also not been established what effects such factors as the duration of the obesity, or its dynamic status (active or static) may have on metabolism It is possible that the ultimate cause of the energy imbal ance may be any one or a combination of seyeral factors such as (1) disturbances in carbohydrate metabolism, medi ated through abnormalties in the enzyme systems or through some endocrine imbalance involving the pancreas pituitary adrenal system, the thyroid, or gonads, (2) in creased lipogenesis or impairment of fat mobilization (3) inactivity, (4) disturbances in the central nervous system, probably hypothalamic in origin, (5) psychosomatic fac tors, operating either through the autonomic nervous sys tem or at the cortical level, (6) genetic factors [78] ·CHAPTER 11 Management: General Considerations SINCE THE cause of obesity is always an imbalance between the caloric intake and energy output or as stated differently, a state of positive caloric balance, the principle of treatment becomes obvious In simplest terms, it implies correcting this caloric imbalance There must be instituted a state of negative caloric balance during the stage of active weight reduction Following this, the patient must be trained to live in isocaloric balance so that the excess weight is not regained A state of negative caloric balance can be accomplished by either increasing the energy output, decreasing the caloric intake, or both PSYCHOLOGICAL FACTORS IN THE PATIENT Overeating as an outlet for psychic stress is well recog nized However some individuals react in exactly the opposite fashion Worrying oneself thin is more than just a saying Anorexia nervosa is a disease of emotional tension, but its manifestations are completely different from obesity It is obvious that overeating is not the only outlet for emotional conflicts However, to some individuals, eating as an outlet becomes a fixed habit pattern It is this habit ·68 OBESITY ITS CAUSE, CLASSIFICATION, AND CAF observed in older age groups Talbot stated that over 95 pe cent of such cases were caused by simple overeating [115] In his group the cases of obesity associated with menta retardation and other bodily defects, such as seen in the Laurence-Moon-Biedí syndrome, or those caused by hypo glycemia were rare He also stated that it was unusual to find an associated hypothyroidism, since the appetite ap peared to be dımınıshed in proportion to the lowered meta bolic level Slow growth and/or mental retardation, an invariable accompaniment of diminished thyroid activity in childhood, was not apparent in most obese children Bruch has demonstrated the difficulties attendant upon determining the basal metabolic rate for children She did observe that there was no relationship between the level of blood cholesterol and the basal metabolic rate in obese children Thyroid administration and withdrawal did not influence either the serum cholesterol level or the rate of loss of weight [24] In careful studies of obese children, Bruch found that their growth in stature was in excess of the average normal rate, but in harmony with the height and development of children who mature early She found that the menarche appeared early in obese girls Since the weight of normal children who mature early was higher than those who mature later, the weight of the obese patients represented an exaggeration of a normal trend [23] It is obvious that these findings of intensive growth and early maturation are not consistent with theories which attempt to explain childhood obesity on the basis of hypothyroidism and hypopituitarism They are more in agree. ment with observations of the growth promoting effects of abundant nutrition ·DEANACELENT GENERAL CONSIDERATIOVS 71 take advantage of him Too soft an attitude will soon result in many excuses but no loss of weight The patient that is honestly interested in losing weight will soon appreciate the wisdom of such an approach The individual who consults a physician for weight reduction merely to salve his own conscience that he is trying to do something for himself, but is unwilling to make any sacrifices toward that end, will not lose weight under any circumstances Of course, the physician must make every effort to enlist this patient's complete cooperation A description of the hazards of obesity will usually impress the patient with the serious nature of his condition Flowever, if it does not there will be only a waste of the physician's time and the patients time and money There will be no significant loss of weight In essence a bad habit must be broken and a desirable one substituted This requires among other things a consider. able amount of self discipline The patient must realize that although the physician can give him some help, he must do most of the work himself will power cannot be administered in capsules The role of the physician and the importance of return visits at regular intervals are illustrated by the comments of a patient who also happened to be a psychiatrist She admitted frankly that she was overweight because of the use of an improper diet She also stated that she did not need a physician to prescribe a diet, as dietitian colleagues could do that equally well as a physician, she had access to any medication she might desưe ller objective in placing herself under treatment was to have someone to whom she was responsible It gave her someone to impress Since another would be aware of her short comings should she not lose weight as anticipated, she made every effort to be a ·70 OBESITY ITS CAUSE, CLASSIFICATION AND CARE pattem which must be changed Sometimes, other more desirable reactions to stress can be substituted just as other habits, such as excessive smoking or drinking can be broken, so can abnormal eating It is seldom necessary to resort to formal psychiatric therapy to accomplish these changes in habits A careful and sympathetic discussion and explanation of the problems involved are usually all that are needed for the patient to gain some insight into his condition We have been rather disappointed with the results ob tained in some of our patients who were referred for formal psychiatric therapy An extremely obese young woman of superior intelligence and education had a highly responsible position which necessitated her making platform appear ances before large audiences She felt she made an unsightly appearance because of her weight of around 300 pounds Careful and complete endocrine studies done on two occasions revealed no significant abnormalities After almost a year of psychiatric treatment, she lost no weight at all However she was pleased with the results, because this course of treatment taught her how to live with her obesity While that was quite a commendable achievement the menace to her health and life was just as great as before therapy It was at best only partial treatment, comparable to a patient with tuberculosis who has learned to make an excellent mental adjustment to his disease, but whose disease itself remains untreated ROLE OF THE PHYSICIAN The physician must endeavor to remain in complete control of the patient at all times He should be understanding and sympathetic, but not to the extent that the patient may ·CHAPTER 12 Management: Increasing Energy Expenditure EXERCISE EXERCISE IAS always had great popular appeal as a means of losing weight Familiar to all is the middle age business man tending to corpulence who says he will have to start playing golf again However, Newburgh has shown that the energy consumed in walking one mile equals 100 calories An individual must walk about 36 miles at average speed to lose one pound of fat tissue [84, 85) Of course, hard physical labor can result in a tremendous energy output, as much as 2000 calories or more a day in excess of basal requirements, but how practical is this as a common procedure to effect weight reduction? The physical efforts of most adults are usually fixed in rather narrow limits by their occupational commitments Any major modification of this is usually impractical, if not impossible Also, since exercise usually increases the appetite, it is of dubious value in effecting a loss of weight unless there is a concomitant, proportionate reduction in food mtahe There is also a real danger in imposing an increased burden upon cardiovascular, renal, and respiratory systems operating under a load of increased metabolism, perhaps even already anatomically or physiologically damaged. 73 ·72 OBESITY ITS CAUSE, CLASSIFICATION AND CARE model patient During her period of regular revisits, she had a satisfactory rate of loss of weight When circumstances made it impossible for her to continue regular visits for an extended period of time, her rate of loss dropped precipitously Upon resuming regular supervision, this retumed to its previous level She stated she realized the importance of the diet, but in the absence of supervision, a certain in centive was lacking Dietary lapses became more frequent The excuses she manufactured, which were not acceptable to her physician while she was under supervision were readily accepted by her In short there was a breakdown of the discipline that is so essential to successful reduction of weight Some patients will question the need for frequent revisits They cannot understand why they should retum when nothing new is done for them They feel that since the primary therapy is the diet, why cant they be permitted to follow it by themselves? The above illustration is the answer to that question They usually will not It must be carefully explained to such patients that if they are sincere about wanting to lose weight, constant supervision will effect a much more rapid attainment of a desirable weight, and will be less costly in the long nin Several patients who discontinued their visits returned and admitted the wisdom of and necessity for constant supervision ·BEANAGEMENT INCREASING ENERGY EXPENDITURE 75 function The basal metabolic rate in obesity is normal when calculated for the actual weight of the individual [107, 113) More recently, thyroid has been used as a metabolic stimulant to try to burn up excess fat The consistent, predictable effect of thyroid in increasing metabolism is well known in myxedema Relatively small doses are sufficient to bring about this effect Usually no more than two to four grains of thyroid daily is required to maintain an euthyroid state after total ablation of the thyroid gland Actually, hypothyroid patients are relatively intolerant to thyroid medication The calorigenic effect of thyroid in the euthyroid in dividual, however, is not so certain In a long range experurnent, Johnston, Squires and Farquharson studied the effect of increasing increments of thyroid [57] They found that it was extremely difficult to bring about a permanent elevation in the basal metabolic rate On a dose of two grains a day, there was an early rise in the basal metabolic rate, then a gradual fall When the dose was increased to four grains daily the metabolic rate again rose, on prolonged administration it again fell but not to the original level A few instances of toxicity were noted On six grains daily, there was again an increase in metabolic rate This again declined, but became stabilized above the control level Toxic symptoms were frequent At this dosage level, some subjects began to lose weight Those who did suffered from increased fatiguability, malaise, and palpitation Then thyroid was discontinued, the above workers noted that there was quick relief of toxic symptoms However, there was also a rapid drop in the basal metabolic rate indicating that the thyroid gland was depressed, probably ·74 OBESITY ITS CAUSE CLASSIFICATION AND CARE While activity alone cannot be the entire solution to the problem of obesity moderate exercise_should be en couraged as part of the redueng regimen Although it is unreasonable to ask an individual to walk 36 miles to lose one pound walking one mile a day a not too difficult task will result in an expenditure of energy equivalent to ten pounds of fat in a year Similiarly regular indulgence in other forms of activity and sports to a reasonable extent can result in the expenditure of a considerable amount of caloric equivalents when calculated on a long term basis provided there is no simultaneous increase in the amount of food eaten (78 118] Exercise is also of great value in creating a feeling of well being maintaining muscle tone and helping take up loose skin DRUGS Several drugs are reputed to cause an increase in the metabolic rate thereby resulting in the consumption of excess tissue Dinitrophenol is one of these However the high incidence of serious toxic effects such as agranulocytosis cataracts neuntis and skin rashes makes its use ex tremely hazardous and it should never be employed Thyroid hormone has enjoyed great popularity as a weight reducing agent for many years Originally it was thought that diminished thyroid activity was a frequent cause of obesity and therefore the administration of the thyroid hormone would act as a specific remedy in correct. ing this However more recent studies have demonstrated that hypothyroid and even myxedematous patients are not necessarily obese indeed they may be undersseight [100] Conversely most obese individuals have normal thyroid ·MANAGEMENT CREASIC ENERGY EXPENDITURE 77 that this drop in basal metabolic rate does not appear if the diet contains an adequate amount of protein (125) We have noticed no significant change in the basal metabolism of patients successfully losing weight on a low calorie diet contaming 75 Gm of protein a day (39, 41, 42] We do not mean to imply that thyroid should not be used when indicated It certainly should be prescribed for obese patients who are also hypothyroid However, it should be realized that its use is to correct a coincidental disease, just as digitalis or insulin would be used where indicated rather than as a specific treatment for the obesity itself ·76 OBESITY ITS CAUSE, CLASSIFICATIOV AND CA because of an inhibition in the formation of the thyrotrop hormone of the anterior pituitary Fortunately, this depresion was only temporary, and there was a return to contre levels in about two to six months There was great individual variation in the tolerance thyroid among euthyroid individuals found in the abov studies Some could not tolerate three grains a day, whil one patient noticed no ill effects while taking ten grains day This latter patient, incidentally, gained weight whul taking such an enormous dose of thyroid (57] The effect of thyroid on loss of weight in the norma person is inconstant and unpredictable When it does occur it is apparently secondary to the toxic effects of the drug As a result of these studies, it is obvious that there is no indication whatsoever for the routine use of thyroid in the management of obesity There is no physiological basis for its employment, since hypothyroid persons are not neces sarily obese, nor are obese individuals with rare exception, hypothyroid Although the basal metabolic rate of obese patients is normal when calculated for their actual weight, computations based upon their ideal weight indicate that their energy output is high Thus, not only is thyroid in effective in moderate dosage, but potentially extremely dangerous when used in sufficiently large dosage to cause weight reduction since such action is mediated through its toxic effects After an extensive trial, and except with proven hypothyroidism we have abandoned the use of thyroid at our clinic for the simple reason that it is in cases ·MANAGEMENT DECREASING ENERGY INTAKE (DIET) 79 subjects on a diet of 444 calories per day, containing 09 Gm of protein per kg of ideal body weight These patients remained in nitrogen equilibrium, felt well, and retained ther usual vigor No ketosis developed in spite of an average weight loss of 21 Kg in 100 days (110, 111) Such extreme restrictions of calories, however, can only be attained in a hospital, where all portions of food are weighed and measured It is not necessary to enforce so marked a deprivation of food in the clinical management of the average case of obesity What other factors aside from total calones must be given consideration? The diet must (17 contain an adequate amount of protein (1 Gm of protein per kg of ideal weight is satisfactory), (2) contain sufficient carbohydrate to act as a protein sparer and to prevent hetosis, (3) be adequate in minerals and vitamins, or such deficiencies should be made up by supplements and (4) be acceptable to the patient It is useless to try to force on an individual foods that are repulsive to him The second important function of a diet is to teach the patient proper eating habits This is every bit as important as effecting a loss of weight and is much more difficult to iccomplish of what avail is it to have a patient lose 40 bunds in six months only to have him regain it three onths after supervision is discontinued? Yet this happens all too frequently because this very important function of dietotherapy is not taken into account The patient becomes obese because he ate improperly If this is not corrected through re education, any reducing regimen is doomed to fallure, since the aim of both the physician and patient should be not only the elimination of obesity, but the maintenance of a desirable weight ·CHAPTER 13 Management: Decreasing Energy Intake (Diet) mpractical, but SINCE ACCOMPLISHING weight reduction by increasing the energy output is not only ineffective and may even be dangerous, the management of obesity, for the most part, must be concerned with the reduction of caloric intake through proper dietary regulation There is con siderable controversy as to the type of diet both qualitatively and quantitatively that will best accomplish a reduction of weight Evaluation of some of the problems involved may help to clanfy our own position FUNCTIONS OF A DIET What are the functions of a weight-reducing diet? (1) The patient should lose weight, and (2) he should establish proper eating habits lest the weight be regained after termination of treatment FACTORS INVOLVED IN PLANNING A DIET In order to effect a loss of weight, the diet must provide less calories than the individual expends How much less depends upon how rapid a loss of weight is desired The caloric intake can be reduced to extremely low levels with safety Strang, McCluggage and Evans observed a group 78 ·MANACEMENT DECREASEC ENERGY INTAKE (DIET) 79 subjects on a diet of 414 calories per day, containing 09 Gm of protein per kg of ideal body weight. These patients remained in nitrogen equilibrium, felt well, and retained their usual vigor No hetosis developed in spite of an average weight loss of 21 Kg in 100 days (110, 111] Such extreme restrictions of calories, however, can only be attained in a hospital where all portions of food are weighed and measured It is not necessary to enforce so marked a deprivation of food in the clinical management of the average case of obesity What other factors aside from total calories must be given consideration? The diet must (14contain an adequate mount of protein (1 Gm of protein per kg of deal weight satisfactory), (2) contain sufficient carbohydrate to act as a protein sparer and to prevent hetosis, (3) be adequate in mincrals and vitamins, or such deficiencies should be made up by supplements, and (4) be acceptable to the patient It is useless to try to force on an individual foods that are repulsive to him The second important function of a diet is to teach the patient proper eating habits This is every bit as important as effecting a loss of weight and is much more difficult to accomplish of what aval is it to have a wounds in six months only to have him regain it three months after supervision is discontinued? Yet this happens all too frequently because this very important function of dietotherapy is not taken into account The patient becomes obese because he ate improperly If this is not corrected through re-education, any reducing regimen is doomed to fallure, since the aim of both the physician and patient should be not only the elimination of obesity, but the main tenance of a desurable weight. patient lose 40 ·80 OBESITY ITS CAUSE CLASSIFICATION AND CARE סת It is to accomplish this purpose that we use and aduocale a general diet, made up of ordinary everyday foods with an average distribution of proteins, carbohydrates, and fats It encourages cooperation by the patient since the adjust ment he has to make is only quantitative, not qualitative also Patients who are sincere about wanting to lose weight make this adjustment readily in about three to five weeks Thereafter, the problem of dietary adherence is not too great When satisfactory weight reduction has been accom plished, a firm foundation has been laid for the maintenance of proper eating habits Adjustment of this basic diet by the addition of sufficient foods to make it isocaloric is simple for the physician and patient and places no addstional strain upon the patient Many types of diet combinations have been advocated the proponents of each proclaiming its superiority Aside from a few which are faddıst and nutritionally inadequate most diets are satisfactory, and will accomplish one of the functions of a diet that is, a loss of weight But will the patient develop proper eating habits? HICH PROTEIN DIET The high protein diet is probably the most popular of the special type drets It was onginally advocated to take adran tage of the presumably greater specific dynamic action of protein foods The specific dynamic action of protein is 30 per cent, as compared to 6 per cent for carbohydrate How ever, the 30 per cent applies to the ingestion of protein only Even high protein diets contain some carbohydrate and fat It is almost impossible to separate these elements from protein since they coexist in the natural state of foods The ·f 81 ALAA ACEMENT DECREASNG ENERGY INTAKE (DIET) specific dynamic action of an average meal us about 9 per cent Thus caloric savings accruing to the high protein diet will be about 150 calories a day 1 relatively insignificant amount when compared to the caloric deficit in a usual reducing diet Some disadvantages of a high protein diet more than outweigh these slight energy savings It is what might be termed an unnatural diet The average individual does not ordinarily eat meat three times a day nor is he accustomed to consuming large numbers of eggs These foods are the essentials of the usual high protein diet As a result the diet soon becomes monotonous and unpalatable 1 addition to being rather costly Since it is unacceptable the patient it is extremely difficult to maintain his co operation Even if the patient has erceptional will power and ad heres to the diet long enough to reach a desirable weigha what is the next step? The actual reduction of weight but a part of the treatment The maintenance of this los weight is equally if not more important It is unreasonab. to expect an individual to exist on an unnatural diet fo the rest of his life On the other hand it is difficult to return him to the usual type of mixed diet for the only one he Inous as the one that resulted in his obesity Consequently he early use of the high protein diet means starting all over at the end of the reducing period and then teaching hum what a properly balanced diet is and how to use it. Is It not more sensible to use a low caloric mired diet at the outset? Then when the desired weight is reached no drastic change is necessary and the transition from hypocaloric to an isocaloric diet is made ensih and smoothk with little add tional effort on the part of the patient ·82 OBESITY ITS CAUSE, CLASSIFICATIOV AND CARE PROTEIN POWDERS These are widely advertised for use in weight reduction with the recommendation that they be used in place of meals, or sprinkled on food It is thus antıcıpated that the high specific dynamic action of the protein will in some way cause a consumption of excess fat As has been shown the specific dynamic effect of food is a small factor in the total energy exchange We studied the effects of one of these preparations in the following experiment Alternate patients were assigned to one of two groups A 1200 calorie diet was prescribed for the patients in one group The patients in the other group were given a protein powder preparation They were in structed to use two teaspoonsful of this powder dissolved in water for breakfast and lunch, eating nothing else for those two meals No restrictions were placed on their dinner or evening meal It was found that there was practically no dif ference in the rate of weight loss between the two groups The experiment was then modified as follows No change was made for the group that received the 1200 calorie diet The other group continued to use only the protein powder for breakfast and lunch However, a diet was prescribed for their dinner This diet was calculated to contain the dif ference between the calories contained in the powder used for breakfast and lunch and 1200 calories Thus their total daily intake was also 1200 calories When the caloric intake of this group was also controlled, a slightly greater rate of weight loss than that attamed by the control group ensued. The average weekly weight loss for the control group was 09 pounds, while that of the group using the protein powder was 12 pounds (Table 5) However, 38 per ·BLANAGEMENT DECREASING ENERGY INTAKE (DIT) TABLE 5 TILE RATE OF Loss of WEICHT OF A GROUP OF PATIENTS RECEIYING A 1200 CALORDE DIET COMPARED TO STILIAR GROUP RECEIVING A PROTEIN POWDER PREPARATION FOR BREAKFAST AND LUNCH, AND A DIET FOR DINNER TO ALLOW A TOTAL Darty CALORIC INTAKE OF 1200 CALORIES & 1800 Calore Diet Alone Protein Powder Plus Food to Mfake 1200 Calories Po of patients verage time observed (wks ) verage weight loss (bs per wk) cidence of side effects (.) 15 13 09 0 13 81 12 38 cent of the patients who used the protein powder complained of unpleasant side effects These side effects were almost exclusively referable to the gastrointestinal tract and consisted of gastric uitation, nausea, vomiting, and constipation (39) These studies indicate that protein powders are most effective in conjunction with dietary restrictions, but are at best only slightly more effective than diet alone Is there then any distinct advantage in the use of such preparations? A few teaspoonsful of a rather unpleasant tasting powder is hardly a satisfactory substitute for even a small meal An indication of patient resistance to such preparations is that a considerably larger number of individuals in this group as compared to the control group did not retum to the clinic Furthermore, the appearance of undesirable side effects in 38 per cent of the patients using this preparation was ercesshe It is bad enough that a patient on a reducing regimen must suffer some discomfort from hunger Cooperation can hardly be expected when he is subjected to additional unpleasant symptoms ·84 OBESITY ITS CAUSE CLASSIFICATION AND CARE A further problem arises in conjunction with the use of protein supplements Should the weight loss be satisfactory how is the patient to maintain it? He certainly cannot be expected to substitute an unpalatable powder for food for the rest of his life Moreover he has received no traming in proper eating habits Since dietary restriction in addition to the use of protein powders is required for optimum re sults it is no more difficult for the patient if a general low caloric diet is prescribed for all his meals HIGH FAT DIET Recently Pennington has advocated a diet high in fat content and low in carbohydrate foods-less than 20 Gm per meal (88 89] According to this diet about 80 per cent of calories should be derived from fats and about 20 per cent from proteins Fluids are encouraged but salt is re stricted Pennington explains the physiological basis of his diet as follows In obese individuals there is a defect in the ability of the tissues to metabolize carbohydrates beyond the pyruvic acid stage The accumulated pyruvic acid in hibits the utilization of fat and thus reduces the rate of mobilization of fat from its depots Since the body is unable to use carbohydrates or fats in customary amounts a larger intake of food is necessary to serve energy needs According to Pennington much of this ingested food is rapidly con verted to fat and stored in the fat depots [88] By restricting the intake of carbohydrates the inhibitory effect of pyruvic acid is decreased The ingestion of large amounts of fat results in a mild ketonemia This ketonemia stimulates the mobilization of fat The tissues receive a con siderable quota of their energy needs from the mobilized ·ALAXACEBIENT DECREASING ENERGY INTAKE (DIET) fat which is released from depots faster than it is deposited thus resulting in a loss of weight (88) In Pennington's regimen, there is no restriction of total calories He states that some people can reduce their weight on an intale in excess of 3000 calones a day The difference between this type of diet and a low calorie diet is, according to Pennington, that low calorie diets limit he formation of new fat by withholding necessary materials, phile his diet produces a loss of weight through increased utilization of stored fat (89] Pennington has reported ercellent results using the above therapeutic regimen However set eral questions arise re garding the physiological basis of this concept Does pyruvic acid inhibit the utilization of fat? If carbohydrates can be metabolized only to pyruvic acid from what is the excess amount of fat synthesized since it is probable that only those substances capable of being degraded biologicall to 2 carbon fragments can be synthesized into long chain fatty acids? (47] The actre 2 carbon unit is probabli acetyl Co A, the next step bevond the pyruvic acid stage And finally, the effect of ketonema on fat mobilization has not been established There have been many conflicting results and conclusions regarding ketosis in obesity (See Chapter 8 ) The lack of need for restricting the intake of calories is ko unusual Thus far there have been no careful studies of the dietary histories or measurements of the actual caloric intake of these patients Until such is done it is dillicult to disregard the mass of evidence to the contrary This concept of the cause and management of obesity offers a new and different approach to the problem Hos ever, until such time as the biochemical background ·TABLE 6A BASIC REDUCING DIET (Approumately 1000 calories) Menu Pattern Sample Drenu Breakfast Breakfast I serving of fruit, no sugar added 4 oz glass orange juice 1 egg, soft cooked, hard cooked, or 1 soft cooked egg poached 23 slice enriched bread Kalice bread or toast Black coffee 1 cup skummed milk (beverage) 4 cup skimmed milk Plain coffee or tea Lunch Lunch 2 oz lean meat or equal (see 2 slices liverwurst Meat below) cup cole slaw beasoned with 35 to 1 cup of any vegetable on salt, pepper, and vinegar List A 34 cup stewed tomatoes 23 Blice bread 39 slice enriched bread I pat of butter 1 pat of butter I serving of frut 1 small pear 8 oz of skimmed milk 8 oz glass skimmed muk Plain coffee or tea Supper Supper 3 oz lean meat or equal (see 1-3 oz broiled hamburger Meat below) 16 cup canned string beads 22 to I cup of any vegetable on 34 cup raw carrot and celery sticks List A 3 Bhce enriched bread 38 cup of any Vegetable on List B 1 pat of butter 3 slice bread % grapefruit I pat of butter 8 02 glass skimmed milk I serving of fruit 8 oz skimmed milk Plain coffee or tea. Meat Two ounces of meat or substitute is Three Ounces of meat or substitute u equal to one of the following equal to one of the following I medium veal chop 2 slices of processed cheese 1 cutlet (13" X 4" X 7 34 cup cottage cheese 2 emall lamb chops 6 medium sardines (draia off oil) 2 medium meat patties 15 cup canned fish (drain off oil) 1 slice roast meat (X" X 4" X 2 slices cold cut (434" X 18") 2 frankfurters (8-9 per lb) 2 elices liver (3" X 2' X 16") 4 tbs peanut butter 14 lb fish 2 oz lean meat or poultry, bones ¥4 chicken (broiler, 145 to 2 removed lbs) Cold plate 1 egg, 1 slice cheese, 1 slice cold cut 2 eggs ·TABLE 6A BASIC REDUCING DIET (Continued) Vegetable LIST A LIST B Use freely of served raw Use one cup You may 129e these vegetables rew at a meal if cooked if taken in excess or cooked 34 cup of this amount calculate as a List B Beets Pimpkin vegetable Lumit tomatoes or tomato Carrots Rutabagas juice to 4 cup at one meal Onions Winter squash Asparagus Lettuce Pess green Turnip Broccoli Mushrooms Brussels Okta sprouts Peppers Cabbage Radishes Cauliflower Sauerkraut Celery Young string Chicory beans Cucumbers Summer Squash Escarole Tomatoes Eggplant Watercress Greeng beet grecas ap nach collarda 14 cup 36 cup Frutt Apple 1 small Applesauce Apricots dried 4 halves Banana 34 anal! Blackberr eg 1 cup Blueberries 34 cup Cantaloupe X (6 diam) Chernice 10 large Grapefruit 3 small Grapefruit ju ce cup Grapes 12 Grape Juice Iloneydew melon lá medium Mango 1 small Orange 1 small Orange Juice Peach 1 medium Perr 1 small Pineapple 34 cup Pineapple juice 34 cup Plums 2 medium Prunes dried 2 medium Raisins 2 tbs Strawberries Tangerine 1 large Watermelon 1 cup 1 cup 1 cup Do NOT EAT 1 Sugar candy cake pre Pastry ice cream cookies, buts malteds 2 Gravies sauces fred and greasy fools salad dressings 3 Smoked meats such as ham corned beef pork 4 Sodas beer aleobol 5 Starches such as potatoes rice noodles spagbetti Courtey Vetropolitan Hospital Clinic ·TABLE 6B BASIC REDUCING DIET (Approximately 1200 calories) Aenu Pattern Sample Menu Breakfast Breakfast 1 serving of fruit, no sugar added 4 oz glass orange juice 1 egg, soft cooked, hard cooked, or 1 soft cooked egg poached 136 slices enriched bread 1 blice bread or toast Black coffee 4 cup skimmed milk (beverage) 44 cup skimmed milk Plain coffee or tea Lunch Lunch 3 oz lean meat or equal (see 2 slices liverwurst Meat below) 3 cup cole slaw seasoned with 35 to 1 cup of any vegetable on salt, pepper, and vinegar List A 35 cup stewed tomatoes 1 slice bread 1 blice enriched bread 1 pat of butter 1 pat of butter 1 serving of fruit 1 small pear 8 oz of skimmed milk 8 oz glass skimmed milk Plain coffee or tex Supper Supper 3 oz lean meat or equal (see Meat 1-3 oz broiled bamburger below) 35 cup canned string beans 33 to 1 cup of any vegetable on 33 cup raw carrot and celery sticks List A 1 slice enriched bread 34 cup of any vegetable on List B 1 pat of butter 1 slice bread 36 grapefrut 1 pat of butter 8 oz glass skimmed milk 1 serving of fruit 8 OZ skimmed milk Plain coffee or tea Aleet Two ounces of meat or substitute 19 Three ounces of meat or eubstitute equal to one of the following 19 equal to one of the following 2 eggs 1 medium veal chop 2 slices of processed cheese 1 veal cutlet X4'X 4") cup cottage cheese 2 small lamb chops 6 medium sardines (drain off oil) 2 medium meat patties 34 cup canned fish (drain off oil) 1 blice roast meat (14" X 4" X 2 slices cold cut (474" X 38"') 4'') 2 frankfurters (8-9 per lb) 2 slices liver (3" X 2' X 8") 4 tbs peanut butter 14 Ib fish 2 oz lean meat or poultry, bones & chicken broiler, 116 to removed Iba ) Cold plate 1 egg, 1 slice cheese, 1 slice cold cut ·TABLE 6B BASIC REDUCINC Drer (Continued) Vegetable List A LIST B Use freely of served raw Use one cup You may use these vegetables raw or at & meal i cooked, if taken in er cooked 34 cup cess of this amount calculate as a Beets Pumpkin Lust B vegetable Limit tomatoes or Carrots Rutabag99 tomato juice to 1 cup at one meal Onions Winter squash Asparagus Lettuce Pess, green Turnips Broccoli Mushrooms Brussels Okrs sprouts Peppers Cabbage Radisbes Cauliflower Sauerkraut Celery Young string Chicory beans Cucumbers Summer squash Escarole Tomatoes Ergplant Watercress Greens beet greens, spinach, collards Fruit Apple I small Applesauce 1 cup Apricots, dried 4 halves BADADA 35 small Blackberries 1 cup Blueberries 4 cup Cantaloupe (G' diam ) Cherries 10 large Grapefruit 3 small Grapefruit juice 34 cup Grapes 12 Grape juice 4 cup lloneyden toelong medium Mango Orange Orange juice Peach Pear Pneapple Pineapple juice Pumps Prunes dried Rajas Strawberries Tangerine Watermelon 1 small I amall 15 eup 1 medium 1 small 15 cup 1 cup 2 medium 2 medium 2 tbs 1 cup 1 large Ieup Do Nor L.AT Sugar, candy, cake, pie pastry, ice cream cookies nuls, malteds 2 Gravies, sauces, fried and greasy foods, salad dressings 3 Smoked meats such as ham, corned beef, pork Sodas, beer, alcohol 3 Starches such as potatoes, nice, noodles, spaghetu Courtesy, Metropolitan llospital Clinic ·90 OBESITY IS CAUSE, CLASSIFICATION, AND CARE definitely established, caloric balance studies done, and the therapeutic results repeated and duplicated, it must be regarded more as an interesting hypothesis rather than an established fact TILE DIETARY PRESCRIPTION The caloric allowance of the diet is governed almost er clusively by how rapid a weight reduction is desired. How ever, two points must be given consideration in the ordinary clinical management of obesity It is almost impossible to maintain a diet of less than 900 to 1000 calories outside a hospital where all foods can be weighed and measured Caloric allowances in excess of 1500 calories usually result in too slow a weight loss, and the patient becomes dis couraged We have employed diets of_1000_and_1200 calories Because the rate of weight loss is satisfactory when such diets are used and because variety and palatability are easily accomplished, the patient's cooperation is not too dif ficult to secure Since no diet can be successful unless the patient adheres to it, the method of presentation and the instructions given to the patient are extremely important It must be remem bered that eating is a pleasurable experience It must be maintained as such if continued cooperation by the patient is to be obtained Instructions encumbered by many “don ts" cannot be expected to add to the happiness of the patient Also, people enjoy eating food, not calories When each meal becomes an exercise in mathematics, the pleasures of eating are soon gone, and usually the patient also Our patients are given a diet sheet contaming the types and amounts of foods they are permitted to eat No mention is usually made of any forbidden foods unless the patient ·ALANACEMENT DECREASING ENERGY NTAKE (DIET) 91 specifically asks about them We have found this positive approach (telling the patient what he should eat) much more acceptable than the negative approach (telling him what he must not eat) Tables 6A and B illustrate basic diets that allow approximately 1000 and 1200 calories Easily made variations and additions to these diets permit any modification the physician may deem necessary for a specific case An additional slice of bread can be added for those individuals forced to eat a sandwich for lunch TAPLE 6C APPROXIMATE CONTENT OF FOOD FACTORS PRESENT IN THE BASIC 1000 CALORE DIET 100 Gm 75 Gm 40 Gm 950 Gm 1500 mg Carbohydrates Proteins Fats Calcrum Phosphorus Iron Vitamin A in excess of Thiamin Riboflavin Niacin Ascorbic acid in excess of 11 mg 5000 1 U 1 mg 2 mg 4 5 mg 100 mg The content of the diets as regards proteins carbohydrates, fats, minerals and vitamins will vary somewhat depending upon what foods are selected from the different groups In general the 1000 calorie diet will allow appror imately 100 Gm of carbohydrates, 75 Gm of proteins and 40 Gm of fats (Table 6C) Several points about the dietary instructions should be emphasized. The total intake of food is divided into the three usual meals breakfast lunch and dinner The patient must not be permitted to continue with a cup of coffee for ·92 OBESITY ITS CAUSE, CLASSIFICATION, AND CARE breakfast, a sandwich for lunch, and a too big dinner Train ing in proper eating habits must begin at the time of the first visit It has also been demonstrated that there is a greater increase in weight when all the food is eaten at one time than when the same total quantity of food is taken in duided portions throughout the day This may be caused by an inability of the body to handle large amounts of food talen at one time, with the result that the excess is diverted to storage It has also been found that large feedings de creased specific dynamic action as compared to smaller, more frequent feedmgs The patient is not given daily menus, as this makes for monotony Rather, he is given a choice of several foods from each group, and he can make his selection as deter mined by his tastes, desires, and convenience at the time of eating It is rather difficult and embarrassing to ask your hostess to prepare a special menu for you because that is what your diet demands for that meal The diet must contain a sufficient vanety of common, easily obtainable foods to satisfy everyone, no matter what his social or economic position may be It should be capable of being followed as well by the social lion who attends dinner parties several times weekly as by the harried busi ness man who must grab a quick meal at whatever restau rant may be near, by the affluential as well as by those less fortunate financially No mention is made of the caloric content of foods If the patient, as so many bave, has bought a book, he is ad vised to hide it The science of dietetics is much too com plex for one to expect the average person, after reading a book, to be adept at planning meals on the moment Even if the patient can master tables of caloric spur of the ·ALANAGEMENT DECREASING ENERGY INTAKE (DIET) 93 values, he knows little about the qualitative differences in food values among, for example, potatoes, pie, and butter In his ignorance, he thus makes unwise substitutions in his self planned diet, with the result that such a diet frequently is nutritionally inadequate In the diet here ullustrated (Table 6), the patient is allowed free substitutions within any group, but no substitutions between groups are permitted To re emphasize what was stated above, people like to eat food, not calories, and an exercise in mathematics offers no particular pleasure The calculations should be made by one capable of making them properly The patient should devote his energies to following the diet, rather than be called upon to plan it DIETARY MODIFICATIONS FOR CHILDREN As previously mentioned (Chapter 10), some modifications are made in the basic diet (Table 6) when it is prescribed for children Unless the child is grossly overweight, we do not attempt to effect an actual loss of weight Rather, our efforts are aimed at preventing a further gain in weight, thus allowing the chid "to grow into his present weight In addition, it is usually wisc to prescribe supplementary vitamnins, and increase the allowance of milk to one and one half pints a day It is frequently possible to allow as much as 1800 calories a day PRESENTATION OF DIETARY INSTRUCTIONS TO THE PATIENT Adherence to the diet is the one essential of a reducing regimen Without it, there can be no loss of weight. The diet must be explained to the patient most carefully, and 10 ·94 OBESITY ITS CAUSE, CLASSIFICATIOY, AND CARE the greatest detail This is not the place for time saving devices The patient must be impressed with the importance and seriousness of the matter Each of the meals is discussed. The selection of foods within groups must be erplained It is surprising how frequently a patient will ask, *Do I have to eat everything in that group for each meal?" This is the time to take into account individual dislikes, idiosyncrasies, and allergies The importance of some of the components of the diet, such as salads and fresh fruits for bowel regularity, and milk for its calcium content, is ex plamed Should necessity require that any important con stituent of the diet be eliminated, replacement by a proper supplement or medication must be made All questions, no matter how welevant or foolish they may seem to the physician must be fully and thoughtfully answered, for they are not irelevant or foolish to the patient Calories are not mentioned The relative size of portions is described, using measurements and comparisons that are familiar to the patient For example, we describe the size of a portion of meat or fish as being equivalent to the size of a dollar bill and about one quarter inch thick That he will readily identify, whereas telling him a portion should be 100 Gm means nothing at all to him Salt and fluid intake are not restricted unless some specific indication such as hypertension or congestie cardiac failure coexists We rely on the homeostatic mechanisms of the body to maintain fluid and sodium equilibrium In the presence of normal cardiac and renal functions, the body will retain what is needed and eliminate the excess Newburgh has shown that although salt and water retention may influence the day to day weight, it has little or no effect in long range experiments [84] ܝܗ ·MANAGEMENT DECREASAC ENERGY NTAKE (DIET) 95 The patient should be gren definite goals toward which he should strre Various types of food pomograms have been described With them, one can predict the rate of weight loss with remarkable accuracy—if, and only if, the measurements of food intale are made with equal accuracy If they are not, the patient's morale suffers when he discovers that his actual loss of weight is less than the predicted loss Consequently, precise, quantitative predictions of weight loss, while indispensable in metabolic studies, are of less value in the clinical management of obesity We do not mean to imply that the patient should be allowed to drift along losing very slowly and irregularly, if at all With the above described diet the patient is told he is expected to lose an average of six to eight pounds a month Since a loss of two to three pounds a week would be realized of such caloric intakes were adhered to quantı tatively, one can see that some leeway is allowed the patient The patient should also be given a longer range goal toward which to strive lle is told of definite goals that he is expected to reach in a specified time For example, a patient who has weighed well over 200 pounds for some time is told that he is expected to break out of the 200 pound class by a specified date As each goal is reached, a new one is set, always using the critena described above The goal that is set should be attainable by adherence to the diet prescribed It should not be made too casy That wall cause the patient to loaf Nor should it be so difficult to reach that the patient becomes discouraged at the outset ·CHAPTER 14 Management: Anorexigenic Agents AMPHETAMINE PREPARATIONS A loss of weight associated with a decrease in voluntary food intake has been noticed since the earliest studies with amphetamine During the treatment of narcolepsy and de pressed states with this drug, a loss of weight was observed in most of the patients [30, 117] Since then, there have been many reports describing the value of this drug as an adjunct to weight reducing regimens The mechanism of appetite depression by these drugs is obscure It has been found that there is an increase in the emptying tune of the stomach This is probably caused by a decreased tonus of the stomach and an increased tonus of the pylorus [10, 119) There is no apparent decrease in absorption or assimilation as the dry weight of the stool is not diminished (114) However the effect of these drugs is probably not on the stomach since surgical denervation of the gastrointestinal tract does not influence the anorexia and weight loss This would suggest that the effects are central. In this regard, it it interesting to note that amphetamine did not influence the voluntary intake of food of a small group of patients who had undergone a surgical prefrontal lobotomy [51] 36 ·MANAGEMENT ATORESIGEVIC ACENTS 97 Afassive doses of amphetamine sere administered intravenously to dogs These animals practically staned to death, although adequate amounts of food were made available to them (51) In most clinical studies with these drugs, they have been used in conjunction with a low calorie diet Albrecht however, claimed he was able to accomplish satisfactory reduction by the use of amphetamine alone (2) If this were $0, weight reduction could be made very simple But the following is typical of what we have observed le administered an amphetamine preparation to a group of 30 patients No dietary restrictions of any kind were imposed An inurl dose of 5 mg three times a day was used If this dose were tolerated, it was rapidly increased to 25 or 30 mng daily Twenty-seven patients lost weight on this regmen However, only 13 patients lost an average of one pound a week or more, the standard we had set for a satis factory rate of reduction of these ten were under observation for a period of eight wecks or less (40) The suggestion that satisfactory loss of weight occurred only during the early phase of treatment with amplietamiae led us to examine the data for each individual more carefully During the first eight scels, 14 patients (47 per cent) lost weight satisfactorily After ten weeks, & patients (27 per cent), and after twelve weeks, 7 patients (23 per cent) fell into this category Beyond this time, the number of patients averaging a weekly weight loss of one pound den creased rapidly (Fig 4) The average weekly weight loss per subject was then cal culated for the entire group It was found that a loss of one pound per seek for the entre group could be mamtamed for only eight weels (rig 5) Two possible explanations for ·99 OBESITY ITS CAUSE CLASSIFICATION AND CARE this can be offered The most obvious one is the development of a tolerance to the anorexigenic effect of the medi cation while this probably did occur, it is unlikely that it is the only factor If it were simply a matter of tolerance, the 26 24 22 20 18 16 NUMBER OF SUBJECTS 12 0 6 4 2 36 40 0 4 B 2 6 20 24 28 32 NUMBER OF WEEKS FIG 4 Number of subjects maintaining a loss of weight of one pound a week while receiving d-amphetamine but under no dietary restrictions (From NY State J Med 19 279, 1919) patient should return to his original caloric intake, and thus regain weight. This was not observed Rather, most of the subjects continued to lose weight, but at a decreasing rate It has been shown on repeated occasions that the number of calories required by an individual in the basal state is ·DLANACATENT ANOREXIGENIC AGENTS 99 proportional to the surface area In undernutrition, there is a loss of weight to that figure which the lower calone intake would support However, the rate of loss is not constant, but gradually decreased as the lesser weight is approached 36 33 27 24 POUNDS 65 12 09 05 03 00 0 4 32 36 40 12 15 20 24 28 NUMBER OF WEEKS Fic 5 The average weekly wesght loss per *ubject in 30 subjects treated with d-amphetamine (From MI State ) Ved 49 279, 1919 ) The curve of the nite of loss is similar to that obtained in our study To apply these findings of the subjects in our study, let Us assume that each lad a daily intake of a calones at the time he entered the study The amphetamine caused a de ·100 OBESITY ITS CAUSE CLASSIFICATION AND CARE minus Y crease of calories a day Thus with a total intale of x calories there was a gradual but decreasing rate of loss as the weight which the lessened caloric intake would support was approached Whether the decreasing rate of loss observed in this study was caused by development of a tolerance to the medication or by an insufficient decrement in caloric intake the use of amphetamine alone even in rather large dosage was in adequate to bring about satisfactory reduction in patients more than slightly overweight Subsequent studies in which amphetamine was combined with a low calorie diet re vealed that a satisfactory rate of loss could be maintained for much longer periods (41, 42] It is believed by some investigators that d amphetamine is superior to the racemic form as an anorexigenic agent They state that the desirable appetite depressing effects are a property of the dextrorotatory form while the undesirable excitatory effects are caused by the levorotatory form [28] In a small group of patients in the above study who were given both the dextrorotatory and racemic form of ampheta mine in rotation we could notice no such distinction The rate of loss and incidence of side effects were similar Subjectively most patients did not notice any difference A few preferred the dextrorotatory form while an equally small number preferred the racemic form The anorexigenic effects of d amphetamine were studied in some detail All the patients in this experiment were given a similar diet which allowed 1000 calories a day Each patient was then observed for a period of six to eight weeks while taking a placebo and a similar period of time while taking d amphetamine Patients were rotated as to which was presenbed initially Thus each patient served as his or ·BLAXACESTEXT ANOREXICENIC AGENTS 101 her own control. These patients were markedly obese, the entire group averaging 45 to 50 per cent above standard weight It was found that with d amphetamine, the average wechly loss was about twice that observed with placebo (Table 7) (41,42] TABLE 7 COMPARISOY OF AYERACE VEICIIt Loss ODSERVED WITT A PLACERO VYHODIFIED d ANPHETAYINE, AND SUBSTANED RELEASE AMPHETAMINE No of Aledicalion No of trials Aretage time Average treight obacroed (us) Loss (lho per erk) subjects Macebo 64 64 60 06 Unmodified stophetamine 103 118 fustaiped release d-amphetamine 101 101 62 12 • The total daily dosage of each d-amphetamine preparation was 15 mg These results require some explanation We do not mean to imply that patients lost weight more rapidly when damphetamine was used because of any direct effect of the drug It is obvious that the rate of loss sbould have been the same with either medication of the prescribed dict had been followed equally well. This study was carried out on A group of clinic patients, where cooperation as far as ad. herence to the diet was not ideal Consequently, it is felt that the more rapid rate of weight loss while using a amphetamine was caused by an anorerigenic effect of this drug thus making it easier for the patient to adhere more closely to the diet as prescribed All the patients were carefully checked for objective and subjecte evidence of sido effects The blood pressure and pulse rate were determined at each visit, and blood counts, ·102 OBESITY ITS CAUSE, CLASSIFICATION, AND CARE urinalyses, and determinations of the basal metabolic rate were done on a representative group while on each of the medications No change in any of these attributable to do amphetamine was found (Table 8) This group included TABLE 8 AVERACED LABORATORY AND CLINICAL DATA ON THE SAME SUBJECTS WHILE USING A PLACEBO UNODIFIED D AMPHETAMINE AND SUSTAINED-RELEASE AMPHIETAMINE Average Polys Blood pressure Pulse rale HB (Gm) Medication WBC (%) BUR 137/85 83 13 8 8390 57 +5 2 137/86 Placebo Uamodified d-amphetamine Sustained release d-emphetamine 81 13 6 8340 55 +51 136/85 83 13 5 7810 +53 55 some patients with a marked hypertension, systolic and diastolic At first, d amphetamine was prescribed with caution to such patients Subsequent observations led us to use this drug without hesitation At no time did we observe any deleterious effect upon the hypertension Actually, in many instances when loss of weight was satisfactory, the level of the blood pressure declined, the usual observation when excess weight is lost Although it has been found that amphetamine causes a slight rise in the metabolic rate, this effect is transient There is no cumulative effect of this drug Subjective symptoms occurred in about 17 per cent of the patients using d amphetamine These consisted of ercitatory effects such as insomnia, nervousness, and palpitation, and muld gastrointestinal disturbances such as nausea and epi ·MLANACEMENT ANOREXIGENIC AGENTS 103 "gastric distress (Table 9) In moderate dosage (up to 15 mg daily) these subjective symptoms were mild and usually easily controlled by mild sedation Only rarely was it necessary to adjust the dosage of this drug downward, or to discontinue it TABLE 9 INCIDENCE OF SWE EFFECTS OBSERVED IN PATIENTS USING A PLACERO, UNIODIFIED D-AIPHETAMINE, AND SUSTAINED- RELEASE L AMPHETAMINE Unmodified Placebo d amphetamine Sustained-release d-amphetamina 64 103 10+ 3 1 No of patients Character and frequency Epigastric distress Nervousness Insomnia Duzinesa Headache Palpitation Constipation Nausea and vomiting 1 0 0 2 0 0 9 11 2 3 1 2 8 5 2 4 1 0 3 1 0 7 Totalt No of patients with side effects 30 24 6 (90) 18 (17) 15 (14) * The total daily dosage of each d-amphetamine preparation was 15 mg 1 The discrepancy between the total number of side effects and the number of patients with side effects is due to the fact that esch of smeral patients bad multiple arde effects The action of a single dose of d amphetaminc persists for & relatively short time Consequently, this drug must be taken several times dunng the day in order to be effectue We have found that this drug eterts its optimal anorexigenic efect if taken 20 to 30 minutes before cach meal. Although the appetite is depressed for the ensuing meal, there are periods during the day when the drug effect is absent This ·104 OBESITY ITS CAUSE CLASSIFICATION AND CARE results in a feeling of hunger by the patient He may then indulge in food thus exceeding his prescribed caloric allowance Recently a sustained release d amphetamine preparation has been made available It consists of a capsule containing many small pellets of d amphetamine Each pellet is in dividually coated The coatings are designed to disintegrate at varying times in the gastrointestinal tract Thus the en tire daily dose can be incorporated into one capsule and because of the gradual disintegration of the capsule and continuous absorption of the medication a sustained thera peutic effect can be maintained during the entire day The advantages of such a preparation are the convenience of a single daily dose and the avoidance of periods of no drug effect Although such a preparation seemed superior to orduary d amphetamine theoretically two important questions re main to be answered Would such a preparation be as effec tive as ordinary d amphetamine as an anorexigenic agent and would any increase in undesirable side effects be caused by the maintenance of a continuous drug effect? To answer these questions a group of patients was ob served while taking ordinary d amphetamine sustained release d amphetamine and a placebo Again each patient was observed while using each of these drugs thus serving as his or her own control The diet remained constant during the entire study for each patient It was found that the average weekly rate of loss of weight was similar while using either d amphetamine preparation and about twice that observed when a placebo was employed There was noted no increase in undesirable side effects when the sustained release form was used (Tables 7 8 9) Sub- ·BIASAGNENT ALOREXICENIC ACENTS 105 jectively most of the patients preferred the sustained re lease preparation because of the convenience of a single dally dose and avoidance of periods of hunger especially during the late afternoon A preparation consisting of 15 mg, of d amphetamine so constituted as to allow a gradual release and absorption of the drug over a period of eight to ten hours was found to one the optimal results with a minimum of side effects (41 42) ADDICTION TO AMPHETAMINES Addiction to amphetamine preparations has been rc ported (101) This ss rare and occurs almost exclusively in psychopaths Some of our patients have been gnen such preparations for extended periods of time a sear or longer In no instance have we obsersed any addiction to this gro ip of drugs in the dosages prescribed or any untos ard symptoms when such drugs were discontinued ET1IAPILETAMINF (DesoxyEPIEDRINE) Methamphetamme was desveloped in Germany during World War II and was used there as amphetamine was used here at the time mainly as a stimulant It was reputed to be the drug used by the Luftwaffe early in the war to enable them to perform so well Pharmacological studies of the drug here revealed that methamphetamine had about twice the stimulators effect of amphetamine (6 mg of the former cquivalent to 10 to 15 mg of the latter) Its appetite-curbing effect was about the same as that of amphctamine milligram for milligram The conclusion was that methamphetamine was more toric thin amphetamine (56) Vethamphetamine has been used extensivel 25 an anor ·106 OBESITY ITS CAUSE, CLASSIFICATION, AND CARE exigenic agent and there have been several favorable reports concerning its action (31] In our hands, this drug has not yielded favorable results In an experiment set up in an identical fashion to our studies of amphetamine (see above), we found that there was no difference in the rate of loss of weight between methamphetamme and a placebo (Table 10) Thirty four per cent of our patients developed TABLE 10 COMPARISON OF WEIGHT LOSS ATTAINED WITH METHAMPHETAMINE AND A PLACERO Methamphetamine Placebo NO Ay time Av teiphl No Ar time Ad weight of observed change of observed change Group* subjects trials (eks) (ibs per uk ) trials (oks ) (lbs per nok ) No of 27 61 -08 30 14 B2 57 -05 -1 2 I 27 II 14 It1 9 Average of all trials 9 5 3 -09 60 -07 36 58 -07 * Group I Patients observed while using methamphetamine and placebo Group II Patents observed only while using methasophetamine Group III Patients observed oply while using & placebo side effects on a dosage of 25 mg three times a day When the dose was increased to 5 ing three times a day, 58 per cent of the subjects reported unpleasant reactions (Table 11) Methamphetamine in the dasage employed had no significant effect upon the blood pressure or pulse rate Four subjects had a significant elevation of their basal metabolo rate while taking methamphetamme Because of their faul ure to lose weight, and the high incidence of side effects considerable patient resistance to this medication was en countered during this study (39) ·MANACELLENT AVORETICENIC ACENTS 107 TABLE 11 SIDE EFFECTS NOTED WIMLE USING METHAMPHETAVINE 41 Total no of subjects Character and frequency Dusiness Ileadache Nauses vortiog epigastric distress Somnolence and listlessness Pulpitation Insomous Nervousness Constipation 13 9 7 6 3 1 1 1 Total No of Patients with multiple symptoms Total on ol patients with aide effects No of patients with side effects while taking 3 tablets daily No of patients who developed side effects when dosage increased to & tablets dady 41 12 21 (58) 14 (34%) 10 (21) Consists of 1 patient displaying 4 symptomas 3 patients with 3 nymp toms and 8 patients with 2 symptoms DISCUSSION AND Use op ANOREXICENIC AGENTS It has been stated that the amphetamine preparations act as placebos, and that their effect is largely psychological (29) We find it dificult to accept this on the basis of our studies We attempted to eliminate psychic influences by having each patient serve as his or her own control The patient never knew what medication was being administered at any given time We insanably found a statistically significant greater rate of loss of weight when an amphetpreparation was used than when an identically appearing placebo was used Amphctamine preparations hasc a place in the manage ment of obesity When an individual is required to change eating habits to which he has conformed for years to a dict allowing less calories some discomfort, both physical and amine ·110 OBESITY ITS CAUSF, CLASSIFICATION, AND CARE ment of Simmonds' cachexia Such preparations have also been used in the therapy of Frohlich's syndrome The idea of using similar preparations for the treatment of opposite conditions apparently caused by similar path ology is rather confusing POSTERIOR PITUITARY Raab, experimenting with dogs, postulated a fat regulating center in the hypothalmus, the function of which de pended upon a normal supply of the posterior pituitary hormone He found that the subcutaneous injection of pituitrin caused the disappearance of neutral fat from the blood (91) Blotner, quoted by Werner (129), found that the injection of posterior pituitary extracts prevented a rise, or caused a decrease in the plasma cholesterol levels following a fat meal consisting of 500 cc of 20 per cent cream Werner (129), on the basis of these findings, has used pituitrın for the treatment of obesity He cites a series of 77 patients treated with pituitrin and thyroid (one to three grains daily) These patients were on diets which allowed 1350 to 1500 calories a day The average duration of treat A 20 tained with the use of diet and amphetamine, and indicates that pitutrin is certainly not a specific We used pitutrin in a small group of cases Several of these patients lost weight satisfactonly However, our enthusiasm was rather d when we found that those patients who lost pitutru did just as well with a saline placebo antly, those patients in our series who did well 14 ·111 MANAGEDIENT ENDOCRIYE PREF ARATIOS did so because of the adherence to the diet, rather than because of any effect of the pituutrin SEX HORMONES --Both estrogens and testosterone have been suggested for the treatment of obesity While many women date the onset of their obesity to the menopause, this does not mean that there is any causal relationship between obesity and cessation of ovarian function Estrogens cause retention of sodium and water, hence a temporary gain in weight will ensue Testosterone will cause nitrogen retention Consequently, it has been advocated for use in the treatinent of underweight It can hardly be espected that it is effective for both leanness and obesity 11-OXYCORTICOIDS from observations made during the past five years on approximately 30 obese patients there are two groups which will probably respond to treatment with a ngidly observed diet and an 11 ory corticoid Here we must place those individuals with familial lipodystrophy and those who, because of ovanan dysfunction show a distribution of fat mainly to the lower abdomen, hips thighs, and legs In both of these groups it is quite common to have the patient tell you that no matter how hard she tries to maintain a dict, the end result is always the same--loss of weight i the thinnest parts of the body, with little, if any, change in the lower abdomen, hips, and legs These are the peoplet who look tlun and haggard about the face and neck fri lowing the loss of a few pounds, but who never appear rid themselves of weight below the waistline £ of t* ** ·ment of Simmonds' cachexia Such preparations have also been used in the therapy of Frohlich's syndrome The idea of using similar preparations for the treatment of opposite conditions apparently caused by similar pathology is rather confusing POSTERIOR PITUITARY Raab, experimenting with dogs, postulated a fat regu. lating center in the hypothalmus, the function of which depended upon a normal supply of the posterior pituitary hormone He found that the subcutaneous injection of pituitrin caused the disappearance of neutral fat from the blood [94] Blotner, quoted by Wemer [129), found that the injection of posterior pituitary extracts prevented a rise, or caused a decrease in the plasma cholesterol levels following a fat meal consisting of 500 cc of 20 per cent cream Werner (129), on the basis of these findings, has used pituítrın for the treatment of obesity He cites a series of 77 patients treated with pıtustria and thyroid (one to three grams daily) These patients were on diets which allowed 1350 to 1500 calories a day The average duration of treatment was 46 months, and the average weight loss was 303 pounds, an average weekly weight loss of about 15 pounds This is not significantly different from the results we obtamned with the use of diet and amphetamine, and indicates that pituitrın is certainly not a specific We used pituitrun in a small group of cases Several of these patients lost weight satisfactorily However, our enthusiasm was rather short lived when we found that those patients who lost rapidly with pituitrin did just as well with a salıne placebo [39] Apparently, those patients in our series who did well ·BLANACEVEXTENDOCRINE PREPARATIONS did so because of the adherence to the diet, rather than be. cause of any effect of the pituitrin 111 Sex HORMONES -Both estrogens and testosterone have been suggested for the treatment of obesity While many women date the onset of their obesity to the menopause thus does not mcan that there is any causal relationship between obesity and cossa. tion of ovarian function Estrogens cause retention of sodiym_and seater hencc a temporary gain in weight will ensue Testosterone will cause nitrogen retention Conse quently, it has been adi ocated for use in the treatment of underweight It can hardly be expected that it is effective for both leanness and obesity 11 OXYCORTICOIDS From observations made during the past five ycars on approximately 30 obese patients there are two groups which will probably respond to treatment with a riguly obscreed diet and an ll-on corticoid Ilere we must place those individuals with familial lipodystrophy and those who, because of ovarian dysfunction show a distrbution of fat mainls to the lower abdomen hips thighs, and legs In both of these groups it is quite common to have the patient tell you that no matter hoss hard she tries to maintun a diet, the end result is always the same loss of weight in the thinnest parts of the body with little, if any, change in the lower abdomen hips and legs These are the people who look thun and laggard about the face and neck fol lowing the loss of a few pounds but who never appear to rid themselves of weight below the waistline These people ·112 OBESITY ITS CAUSE, CLASSIFICATION, AND CARE will reduce quite satisfactorily when given a modest te striction of calories and an 11-oxycorticoid In fact, the diet should contain about 1500 calories, which we apportion somewhat as follows carbohydrates, 125 Gm, proteins, 85 Gm, and fat, 75 Gm We have not been able to decide which of the 11 ory corticoids is best for the purpose in hand Our experience is limited to the use of cortisone acetate and prednisone Our dosages have been 125 mg of the former four times daily or 5 mg of the latter twice or three times daily In these doses, there is no tendency for the appearance of side effects, provided the patient adheres strictly to the sub caloric diet Nor is it necessary to give supplements of potassium If the patient does not adhere to the diet, edema and acne are more commonly seen in those taking cortisone than in those using prednisone However, when the regimen is carefully followed, weight will disappear from all parts of the body This is least noticeable about the face, neck and upper torso which is directly in contrast to the former ergroup of patients, who have always found it impossible to remove any fat from the lower parts of the torso and lower extremities without excessive, unbecoming, and uncomfortable loss of weight from the waist up Again, it should be emphasized that this relocation of fat will not occur unless there is an over all reduction in weight Moreover, side effects from the corticoids are common in these types of obesity unless a subcaloric diet is eaten periences of this ·CIIAPTER 16 Management: Miscellaneous Medications, Physiotherapy, and Surgery BULK VIV ONDER to prevent the sensation of hunger when low caloric diets are used, or as a substitute for food when no defimitc diet is prescribed, certain products, notably those containing methyl-cellulose, have been used all these preparations have certain qualities in common They are inert, have no food value, and expand in volume when moistened Because of these properties, it is claimed that thev gue the patient a sensation of satiety and fullness without contributing any calories It is questionable as to whether methyl-cellulose has any cliect on the stomach at all in the dosage usually employed (about 150 mg per tablet) Larger doses have a bull laratic effect In any case, it is not the stomach that controls the amount of food that is ingested, since denervation, and even total removal of the stomach have no lasting effect upon the intake of food. Expenmentally, it has been found that dilution of the dict of rats by the addition of an inert substance such as haolin had no lasting effect upon their total caloric intale These animals adjusted to this dilution by increasing the 113 ·OBESITY ITS CAUSE, CLASSIFICATION, AND CAPE amount of food ingested so as to maintain a constant caloric consumption (1) The use of inethyl cellulose is not completely without danger Although rare, cases of esophageal impaction and intestinal obstruction have been reported. VITAMIN PREPARATIONS Vitamin C has been used to promote the elimination of flud It has been used in the treatment of congestive cardiac failure Because of thus property of ascorbic acid it has been mcorporated into various types of reducing pills How ever, there are two important fallacies inherent in the rationale behind such preparations Firstly, large doses of as corbic acid (in the region of 2 or 3 Gm a day) have been needed to demonstrate the diuretic action Such large doses are not nearly approximated in these widely advertised "reducing pills Secondly, the treatment of obesity is concerned with a loss of fat not fluid One of the vitamin C preparations was studied in the following experiment This product contained 30 mg of vitamin C shim milk powder, and dextrose, and allowed five and one half calories per tablet Patients were assigned in rotation to one of three groups All the patients were given an identical 1200 calorie diet Patients in group one were also given this vitamin C preparation Those in group two were given a placebo tablet, and those in group three received no medication of any kind The number of pa tients, the average duration of treatment, and average per cent overweight were similar for all three groups The average weekly weight loss for groups one and two was similar and slightly less than that attained by patients in group three The vitamin C preparation used in this study ·PANACENIENT MEDICATIONS, PJIYSIOTHERAPY, SURGERY 115 was completely ineffective The results of this experiment are summarized in Table 12 [39] TABLE 12 THE RATE OF Loss OF WEICHT OF TIIREE SINOLAR GROUPS OF PATIENTS EACII RECEIVIAC A 1000 CALORIE DIET AND OVE Group RECEIVING IN ADDITION, A VITAMIN C PRE PARATION Group 1 Group 11 Group III Bled cations No of patients Average tunc observed (wks ) Average logg of weight (lbs per wk) Vitamis 15 Noge 17 Placebo 17 4 8 05 04 BELLADONNA PREPARATIONS Preparations of belladonna have been recommended for their effect in reducing gastric motihty It is belicsed that lly keeping food in the stomach longer, the desire for addı tional food is lessened While drugs of the belladonna group do diminish gastric motility, large doses are required to do so Other effects of the drug, such as my drasis and dryness of the mouth, become manifest before there is any signif scant sedative effect on the stomach In any casc appetite is not a local phenomenon of the stomach Vagotomy does not appreciably affect food intake Complete surgical dcnervation of the gastrointestinal tract in dogs does not cause Anorexia For these reasons we cannot rationalize the use of belladonna and its derivatives in the management of obesiły Finally, in our hands, its clinical application lias been a failure DFYDRATIOY Under this heading are included such therapies as d!1 retics, salt and water restriction purges, Turkish baths, and ·114 OBESITY ITS CAUSE, CLASSIFICATION, AND CARE amount of food ingested so as to maintain a constant calonc consumption (1) The use of methyl cellulose is not completely without danger Although rare, cases of esophageal mpaction and intestinal obstruction have been reported. VITAMIN PREPARATIONS Vitamin C has been used to promote the elimination of fud It has been used in the treatment of congestive car. diac failure Because of thus property of ascorbic acid, it has been incorporated into various types of reducing pills How ever, there are two important fallacies inherent in the rationale behind such preparations Firstly, large doses of as. corbic acid (in the region of 2 or 3 Gm a day) have been needed to demonstrate the diuretic action Such large doses are not nearly approximated in these widely advertised "reducing pills * Secondly, the treatment of obesity is concerned with a loss of fat, not fluid One of the vitamin C preparations was studied in the following experiment This product contained 30 mg of vitamin C, shum milk powder, and dextrose, and allowed five and one-half calories per tablet Patients were assigned in rotatron to one of three groups All the patients were given an identical 1200 calorie diet Patients in group one were also given this vitamin C preparation Those in group two were given a placebo tablet, and those in group three recened no medication of any kind The number of patients, the average duration of treatment, and average per cent overweight were sınılar for all three average weekly weight loss for groups one and two was similar and slightly less than that attained by patients in group three The vitamin C preparation used in thus study groups The ·MANAGEMENT MEDICATIOYS PHYSIOTHERAPY SURGERY 115 was completely ineffective The results of this experiment are summarized in Table 12 [39] TABLE 19 THE RATE OF Loss OF WEICIIT OF THREE SIMILAR GROUPS OF PATIENTS EACH RECEIVING 1000 CALORIE DIET AND ONE GROUP RECEIVING IN ADDITION A VITAMIN C PREPARATION Group 1 Group II Group IIT None 17 Medication No of pat ents Average time observed (wks ) Average logs of we ght (lbg per wk) Vitam ac 15 46 04 Placebo 17 48 0 5 07 BELLADONNA PREPARATIONS Preparations of belladonna have been recommended for their effect in reducing gastric motility It is believed that by keeping food in the stomach longer the desire for addi tional food is lessened While drugs of the belladonna group do diminish gastric motility, large doses are requued to do so Other effects of the drug such as mydriasis and dryness of the mouth become manifest before there is any signif icant sedative effect on the stomach In any case appetite is not a local phenomenon of the stomach Vagotomy does not appreciably affect food intake Complete surgical de nervation of the gastrointestinal tract in dogs does not cause anorexia For these reasons we cannot rationalize the use of belladonna and its derivatives in the management of obesity Finally in our hands its clinical application has been a failure DEHYDRATION Under this heading are included such therapies as diu retics salt and water restriction purges Turkish baths and ·OBESITY ITS CAUSE, CLASSIFICATI0Y, AND CARE amount of food ingested so as to maintain a constant caloric consumption (1) The use of methyl cellulose is not completely without danger Although rare, cases of csophageal impaction and intestinal obstruction have been reported VITAMIN PREPARATIONS Vitamin C has been used to promote the elimination of Sud It has been used in the treatment of congestive cardiac failure Because of this property of ascorbic acid, it has been incorporated into various types of reducing pills However, there are two important fallacies inherent in the sa tionale behind such preparations Firstly, large doses of ascorbic acid (in the region of 2 or 3 Gm a day) have been needed to demonstrate the diuretic action Such large doses are not nearly approximated in these widely advertised "reducing pills" Secondly, the treatment of obesity is conccrned with a loss of fat, not fluid One of the vitamin C preparations was studied in the following experiment This product contained 30 mg of vitamin C, shim milk powder, and dextrose, and allowed five and one half calories per tablet Patients were assigned un rotation to one of three groups All the patients were given an identical 1200 calorie diet Patients in group one were also given this vitamin C preparation Those in group two were given a placebo tablet, and those in group three received no medication of any kind The number of patients, the average duration of treatment, and average per cent overweight were similar for all threc groups The average weekly weight loss for groups one and two was similar and slightly less than that attained by patients in group three The vitamin C preparation used in this study ·ALANAGEMENT MEDICATIONS, PHYSIOTHERAPY, SURGERY 117 MASSAGE This is advocated to remove fat selectively from specified sites However, it has been demonstrated that massage of one limb will not change its size in comparison to the other nor will it mobilize enough fat to affect the concentration of blood lipids significantly [59] On close examination, it will be found occasionally that the prominence of certain parts, especially the hip region, is not caused by an accumulation of fat but rather some peculiarity of bone structure such as a flared pelvis Diet, of course, cannot be expected to influence this Sometimes adipose tissue accumulates in certain regions probably because of some hormonal influences which govern the site of fat deposition However, without an intake of food greater than the needs of the body, there can be no excess to be converted into fat Dietotherapy wall frequently effect a removal of such localized fat deposits However in these cases, treatment should proceed cautiously lest fat be rernoved from other sites, such as the face and neck regions Frequent observation of the patient and repeated meas urements are necessary in this type of case Treatment must be discontinued if the general appearance of the patient so indicates, as for instance, if she develops a gaunt, haggard look with lines in her face and neck SURGERY Surgical removal of masses of fat is rarely done Aside from the hazards of surgery in obese individuals, with the risk of fat embolisin and delayed healing, the basic cause of the obesity is not corrected Unless the dietary habits of ·116 OBESITY ITS CAUSE, CLASSIFICATION, AND CAI heat cabinets All these have one thing in common, the cause a loss of weight by eliminating water However, th loss is temporary, as the body will tend to remain in flur equilibrium It is the long-range change in weight that mus be observed, not day-to day changes While adipose tissu has an affinity for fluid, the amount of fluid cannot be toc great, as any fluid retention in excess of 12 to 15 pounds re sults in manifest edema The average obese individual is no edematous What is desired is the elimination of fat, not water If excessive fat is eliminated, the fluid which was re tained is also eliminated with it Elimination of fluid without the fat results in the rapid reaccumulation of the fluid In addition to the meffectiveness of dehydration, certain dangers exist with some forms of this therapy The most commonly used diuretics are ammonium chloride and the mercurials The prolonged use of ammonium chloride can result in a severe acidosis The mercurial diuretics are neph rotoxic Fatalities following their use have been reported Purging will completely derange the normal bowel habits of the individual Since most purges irritate the bowel, an Irritative colitis can result COMBINATIONS OF DRUGS Many proprietary brands of reducing drugs are avulable For the most part, they consist of varying muxtures of several or all of the following amphetamine or methamphetamine, thyroid, cathartics, vitamins, belladonna, and a sedative Their individual actions have already been discussed There is no evidence that their action in combination is more adequate or effective than that obtained by use of the individual preparations ·MANAGEMENT MEDICATIONS, PHYSIOTHERAPY, SURGERY 117 MASSAGE This is advocated to remove fat selectively from specified sites However, it has been demonstrated that massage of one limb will not change its size in comparison to the other nor will it mobilize enough fat to affect the concentration of blood lipids significantly [59] On close examination, it will be found occasionally that the prominence of certain parts, especially the hip region, is not caused by an accumulation of fat but sather some peculiarity of bone structure such as a flared pelvis Diet, of course, cannot be expected to influence this Sometimes, adipose tissue accumulates in certain regions, probably because of some hormonal influences which govern the site of fat deposition However, without an intake of food greater than the needs of the borly there can be no excess to be converted into fat Dietotherapy will frequently effect a removal of such localized fat deposits However, in these cases, treatment should proceed cautiously lest fat be removed from other sites, such as the face and neck regions Frequent observation of the patient and repeated measurements are necessary in this type of case Treatment must be discontinued if the general appearance of the patient so indicates, as for instance, if she develops a gaunt, haggard look with lines in her face and neck SURGERY Surgical removal of masses of fat is rarely done Aside from the hazards of surgery in obese individuals, with the risk of fat embolism and delayed healing, the basic cause of the obesity is not corrected Unless the dietary habits of ·118 OBESITY IS CAUSE, CLASSIFICATIOY, AND CARE the patient are corrected the same factor that caused the obesity will continue to operate after the surgery, and the fat will reaccumulate Surgical excision of redundant skin, such as a large abdominal apron, could be done after the weight has become stabilized by dietotherapy This is of value not only for cosmetic reasons but also to eliminate the severe dermatitis which develops on the adjacent surfaces of skin under such an apron ·CHAPTER 17 Course and Follow-up THE RATE OF LOSS OF WECHT THE RATE of loss of weight, as was discussed above, is not constant It is usually more rapid at the outset of the reducing regimen Plateaus occur during which time no weight is lost at all These sometimes last as long as two weeks and are caused by water and salt retention A spontaneous diuresis always follows The use of diuretics is not indicated However, patients should be told of these plateaus, lest their morale suffer because of a period of stationary weight even though they adhere to the diet Women should also be informed that no loss, or possibly even a slight gain of weight may occur immediately prior to menstruation, because of the retention of water Spontancous diuresis with consequent satisfactory weight reduction occurs shortly after the onset of the period Just as patients are not permitted to loaf and lose weight slowly and iregularly, they are dissunded from losing Height too rapidly Some patients try to be heroic and lose Weight raprdly by semistarvation Aside from the effects of malnutrition and vitamin deficiencies, cosmetically the end results are not too lappy These patients frequently end up with unwanted lines in their faces, and a gaunt, haggard 119 ·120 OBESITY ITS CAUSC, CLASSIFICATION, AND CARE expression For the first month of therapy, the patient is allowed to lose as much as he can After that, a maximum loss of eight to ten pounds a month is all that is permitted If necessary, dietary adjustments are made so that the maximum allowable monthly loss is not exceeded TERMINATION OF TREATMENT When can a satisfactory reduction of weight be considered accomplished? This is a difficult question to answer Theoretically, it can be stated that the patient should be reduced to his ideal weight However, ideal weights are difficult to determine Tables of desirable weights (see Chapter 1) are a useful guide and afford us an approximate ultimate goal The simplest answer to this question is to terminate active reduction when the patient looks and feels well Personal desires, within reason, must be respected Thus, a woman may want to stop reducing when she is about 8 to 10 per cent above the desirable level because that is the way her husband prefers her to look On the other hand, a model who had gained 60 pounds during a pregnancy required reduction to 10 to 15 per cent below her desirable weight before she could resume employment After reduction has proceeded to desirable level, the patient must be told how this weight is to be maintained Tortunately, this is not difficult when the above regimen has been employed He is told to remun within three or four pounds of his weight at the time of discharge, thus giving him a six to eight pound leeway It is explained to him that were he to maintain the prescribed diet, he would continue to lose, and that such a decreased caloric intake could not support his desirable weight Consequently, he must increase his intake of food Using the prescribed diet as a ·COURSE AND FOLLOW UP 121 foundation, since it already allows him the essentials of a well balanced, mixed diet, he can increase the size of his portions, and add previously forbidden foods such as bread, butter, cream, and desserts in moderation He is told to weigh himself weekly and if he continues to lose, to m. crease his intake of food If his weight exceeds the maximum allowed him, he is to decrease his intake toward the original diet „By a process of trial and error, the patient quickly learns what he can eat and yet maintain a desirable weight The transition from a hypocaloric to an isocaloric diet is made simply, quickly, and pleasantly He is urged to return should he have any problems, or should his weight begin to get out of hand RETURN Visits Regular and frequent return visits are important We have used various time intervals between appointments It was found that if too much time intervened between appointments, three or four weeks for example the patient would do as he pleased the first two weeks then try to lose all that was expected for the entire interval in the next week or two It just did not work At the clinic we have had to compromise our wishes with practicability and convenience and see our patients every two weeks Our private patients are seen weekly at the outset, and never less frequently than biweekly At each retum visit, after the weight has been recorded, the patient is encouraged to discuss any problem that may have arisen Even though the diet has been carefully erplained at the initial visit, many questions regarding it Invanably crop up once the patient actually starts living with it These are carefully answered ·122 OBESITY ITS CAUSE CLASSIFICATION AND CARE Minor modifications of the regimen may have to be made but these are kept to a minimum One of the most frequent allowances is a bedtime fceding Many people have become accustomed to a snack before retiring and they claim they cannot fall asleep without it. They are advised to eliminate their desserts or milk at supper and eat or drink it at bed time UNSATISFACTORY Loss or WEIGHT If the weight loss has been unsatisfactory the cause should be explored The patient is impressed with the fact that his failure to lose weight satısfactorily is caused by his straying from the prescribed diet and that every effort should be made to discover and correct these deviations Many and varied are the excuses made by patients for their failure to lose weight Some will vehemently deny any dietary excesses but blame their failure on other factors Such excuses must be dealt with firmly It must be made clear to him that you cannot create something out of nothing It is extremely rare that an obese individual will maintain his weight or even gain weight on a submain tenance diet of less than 1500 calories It is like trying to run an automobile without gasoline Usually after firm refutation of such excuses the patient will sheepishly admit straying from the diet Such an admission is an important victory for the physician since it could bring about a com plete change in the patients concept of his disease Other patients will frankly admit overeating but offer excuses for so dong The usual excuses are hunger and social obligations The problem of hunger is extremely im portant While he can be given some help to lighten this burden it usually cannot be eliminated completely It is ·COURSE AND FOLLOW UP 123 obvious that an individual who has been accustomed to eating excessively will not be completely satisfied with a drastically reduced intake of food However, it must be carefully explained to him that his discomfort will be temporary He should be told that his former eating habits were just that, habit Just as he developed faulty eating habits, he can educate himself to proper habits Ilowever, in order to do so, he must conscientiously adhere to the prescribed diet The patient who does well usually states after three to five weeks that he has no further difficulties or discomfort with the diet However, he must be willing to make this initial sacrifice Should he indulge his hunger, the results will-be unsatisfactory on two counts tie will not lose weight satisfactonly, nor will be ever become accustomed to a dimiushed intake of food The individual who will not adhere to the diet because of social obligations must be impressed with the importance of the diet The analogy of diabetic patients is used frequently It should be explained that although the immediate effects of his dietary indiscretions are not as dramatic or serious as with a diabetic, the ultimate barm as regards his health and longevity is just as real THE MANAGEMENT OF A CASE Although each patient must be treated as an individual, the general plan of management is fairly constant. At the first visit, a careful history is obtained It is important to know why treatment is being instituted Did the patient come for weight reduction, is a reducing regunen being recommended as an ancillary treatment for some other disease process, or is it prophylactic therapy in an otherwise healthy, normal individual? If either of the latter, the ·124 OBESITY ITS CAUSE, CLASSIFICATIOV AND CARE reasons for weight reduction must be carefully explained The history should bring to light any unsuspected patho logical process We routinely ask each patient why he be came obese The patient who readily admits to eating er cessively must be handled differently from the one who eats like a bird but has gland troubles The duration of obesity is important, especially as regards irreversible patho logical changes Sometimes, valuable information regarding emotional conflicts is elicited while the history is being taken In thus regard, we question the patient as to any factor which he feels caused him to start gaining weight A discussion of the patient's eating habits, although fre quently unreliable, is important A menstrual and obstetrical history is taken in women The physical examination is also performed carefully Evidences of vitamin deficiencies are sought Cardiovascular function is carefully evaluated Measurements, in addition to height and weight include span, lower measurements (pubis to floor), and the circumference at the neck chest waist, hips, and thighs In addition to the undressed weight the patient is weighed dressed without shoes, in order to have a comparison reference for future visits when it is not necessary to undress completely Routine laboratory examinations include a complete urinalysis and blood count It is surprising how frequently an obese patient is anemic Other tests are done only of indicated We have found the basal metabolic rate to be abnormal so rarely as to dispense with tlus examination unless other findings suggest dysfunction of the thyroid gland [40, 41, 42] This examination however, may be neces sary to convince an occasional patient that there really is nothing wrong with the function of his thyroid ·COURSE AND FOLLOW-UP 125 The findings arc then discussed with the patient Therapy for other pathological processes is prescribed The nature of obesity is explained to the patient He is made to under stand that fat can come only from the food he eats, and the only way fat can be eliminated is by regulation of his intake of food He is gren a diet and instructions as to its use as described in Chapter 13 A suitable anorexigenic agent, usually one of the sympathomimetic amines, is prescribed However, the patient is impressed with the fact that he will not lose an ounce through the use of the drug itself, loss of weight will be brought about only by a decreased intake of food The anorexigenic dnig will only make it easier for him to adhero to the prescribed diet He is instructed to return in one weck At subsequent visits, the weight is recorded, the blood pressure is checked, and he is again examined for evidences of vitamın deficiencies He is questioned regarding how he got along in the interim Changes in the regimen, as de. scribed above, are made if necessary If the loss of weight has not been satisfactory, reasons for this are sought The importance of the diet is continuously re emphasized The patient is seen weekly at least twice, and as many times thercafter as necessary until the physician feels that the patient is fully acquainted with the prescribed regimen and can follow it easily When this occurs, the patient is seen every sccond week After about tio weeks the dose of the anorexigenic agent is gradually decreased, and is completely eliminated in three to five weeks The patient is seen at least every second weel during the entire course of treatment Encouragement, praise, or reprimand is given as indicated After about fiftcen pounds tre lost, measurements at the above described sites are repeated It is excellent en- ·126 OBESITY ITS CAUSE, CLASSIFICATION, AND CARE couragement, and good for the patient's morale to be given objective evidence of a decrease in size These measure ments are repeated regularly When a desirable weight has been attained, the patient is advised how to maintain this weight by dietary changes as described above Types OF PATIENTS AND THE RESULTS OBTAINED Those with Strong Incentive Since the patient's active participation in the treatment of obesity is necessary, the reason for his requesting treat ment will materially influence the result We have ob served several categories of patients where the incidence of therapeutic success is high These include girls of about 15 to 18 years of age who are just developing a social con sciousness, but find themselves left out of things because of their appearance, single women in their early 30's (old enough to worry, but not old enough to have become reconciled to spinsterhood) who feel they are losing their chance for mange, ind men who cannot get insurance on standard terms Children We are extremely discouraged about our failure to obtain satisfactory results with young people for the most part they are themselves not interested in losing weight They allow treatment at either their parents' or physicians' in sistence Even when it is at parental insistence, prental co operation is not wholehearted Mothers frequently can't see that their child is obese because he eats too much, and feel they are starving him by keeping him on even a lberal diet Also, the child, who isn't particularly interested in ·COURSE AND FOLLOW UP 127 losing weight, is not going to deprive himself of the candy, ice cream, and sodas that he usually gets outside the home between his meals Others Between these opposite groups is the large number of patients who must be convinced of the hazards of obesity Here the results of therapy will depend upon how well the physician can impress these upon each patient The average individual is not interested in obesity as an abstract term He must be made to understand the relationship between his excess weight and his arthritis, diabetes, or hypertension Even if no other abnormalities are found, the danger to his future health, and the potentially more rapid development of degenerative diseases, must be explained to him RESULTS OBTAINED IN AN AVERACE GROUP Recently, one of us has had the opportunity to observe a rather large group of patients under close supervision [39] The individuals in this group were employees at a large industrial organization, and could be considered comparable to the average patient seen in private practice About half the group were comprised of individuals who were found to be obese on routine examination and for whom weight reduction was advised The remainder came in voluntarıly for weight reduction Treatment was instituted on a total of 96 persons Of these, 16 are still under active treatment, 34 reduced to a desirable weight and were discharged, 44 discontinued treatment on their own (that is, did not return for further follow up), and 2 were dismissed A to cooperate of the 41 who discon- Nithin the first three weeks ·126 OBESTTY ITS CAUSE, CLASSIFICATION AND CARE couragement, and good for the patient's morale to be given objective evidence of a decrease in size These measure ments are repeated regularly When a desirable weight has been attained the patient is advised how to maintain this weight by dietary changes as described above TYPES OF PATIENTS AND THE RESULTS OBTAINED Those with Strong Incentive Since the patient's active participation in the treatment of obesity is necessary, the reason for his requesting treat ment will materially influence the result We have ob served several categories of patients where the incidence of therapeutic success is high These include girls of about 15 to 18 years of age who are just developing a social con sciousness, but find themselves left out of things because of Morten their appearance single women in their early 30's (old vugh to worry but not old enough to have become conciled to spinsterhood) who feel they are losing their chance for marriage and men who cannot get insurance on standard terms Children We are extremely discouraged about our failure to obtai satisfactory results with young people for the most part they are themselves not interested in losing weight They allow treatment at either their parents' or physicians' in sistence Even when it is at parental insistence, parental co operation is not wholehearted Mothers frequently can t see that their child is obese because he eats too much and feel they are "starving" hy keepi him on even a liberal diet Also, then ly interested in 1 1 ·COURSE AND FOLLOW UP 127 losing weight, is not going to deprive himself of the candy, ice cream, and sodas that he usually gets outside the home between his meals Others Between these opposite groups is the large number of patients who must be convinced of the hazards of obesity Here the results of therapy will depend upon how well the physician can impress these upon each patient The average individual is not interested in obesity as an abstract term He must be made to understand the relationship between his excess weight and his arthritis, diabetes, or hypertension Even if no other abnormalities are found, the danger to his future health and the potentially more rapid development of degenerative diseases, must be explained to hum RESULTS OBTAINED IN AN AVERAGE GROUP Recently, one of us has had the opportunity to observe a rather large group of patients under close supervision [39] The individuals in this group were employees at a large industrial organization and could be considered comparable to the average patient seen in private practice About half the group were comprised of individuals who were found to be obese on routine examination and for whom weight reduction was advised The remainder came in voluntarily for weight reduction Treatment was instituted on a total of 96 persons Of these, 16 are still under active treatment, 34 reduced to a desirable weight and were discharged, 41 discontinued treatment on their own (that is, did not return for further follow up), and 2 were dismissed for failure to cooperate of the 44 who discontinued therapy, 18 did so within the first three weeks ·26 OBESITY ITS CAUSE, CLASSIFICATION AND CARE ouragement, and good for the patient's morale to be given bjective evidence of a decrease in size These measure nents are repeated regularly When a desirable weight has been attained the patient s advised how to maintain this weight by dietary changes s described above TYPES OF PATIENTS AND THE RESULTS OBTAINED Those with Strong Incentive Since the patients active participation in the treatment f obesity is necessary, the reason for lus requesting treat nent will materially influence the result We have ob erved several categories of patients where the incidence of therapeutic success is high. These include girls of about 5 to 18 years of age who are just developing a social con ciousness but find themselves left out of things because of heir appearance single women in their early 30s (old nough to worry but not old enough to have become econciled to spinsterhood) who feel they are losing their hance for muriage and men who cannot get insurance on tandard terms "Tuuldren We are extremely discouraged about our failure to obtaid atisfactory results with young people for the most part hey are themselves not interested in losing weight. They low treatment at either their parents' or physicians in istence Even when it is at parental insistence parental com peration is not wholehearted Mothers frequently cant see hat their child is obese because he eats too much, and feel hey are starving him by Leeping him on even a liberal liet Also, the child, who isnt particularly interested in ·COURSE AND FOLLOW UP 127 losing weight, is not going to deprive himself of the candy, ice cream, and sodas that he usually gets outside the home between his meals Others Between these opposite groups is the large number of patients who must be convinced of the hazards of obesity Here the results of therapy will depend upon how well the physician can impress these upon each patient The average individual is not interested in obesity as an abstract term He must be made to understand the relationship between his excess weight and his arthritis diabetes, or hypertension Even if no other abnormalities are found, the danger to his future health and the potentially more rapid development of degenerative diseases must be explained to him RESULTS OBTAINED IN AN AVERAGE GROUP Recently, one of us has had the opportunity to observe a rather large group of patients under close supervision [39] The individuals in this group were employees at a large industrial organization and could be considered comparable to the average patient seen in private practice About half the group were comprised of individuals who were found to be obese on routine examination and for whom weight reduction was advised the remainder came in voluntarily for weight reduction Treatment was in stituted on a total of 96 persons Of these, 16 are still under active treatment, 34 reduced to a desirable weight and Stere discharged, 44 discontinued treatment on their own (that is, did not return for further follow up), and 2 were dismissed for failure to cooperate of the 44 who discontinued therapy, 18 did so within the first three weeks ·126 OBESITY ITS CAUSE, CLASSIFICATION, AND CARE couragement, and good for the patient's morale to be guien objective evidence of a decrease in size These measurements are repeated regularly When a desirable weight has been attained, the patient is advised how to maintain this neight by dietary changes as described above TYPES OF PATIENTS AND THE RESULTS OBTAINED Those with Strong Incentive Since the patient's active participation in the treatment of obesity is necessary, the reason for his requesting treat ment will materially influence the result We have ob served several categories of patients where the incidence of therapeutic success is high These include giris of about 15 to 18 years of age who are just developing a social con sciousness, but find themselves left out of things because of their appearance single women in their early 30's (old enough to worry, but not old enough to have become reconciled to spinsterhood) who feel they are losing their chance for marriage and men who cannot get insurance on standard terms Children We are extremely discouraged about our failure to obtain satisfactory results with young people for the most part they are themselves not interested in losing weight They allow treatment at erther their parents' or physicians ansistence Even when it is at parental insistence, prental.com operation is not wholehearted drothers frequently can't see that their child is obese because he eats too much, and feel they are "starving him by keeping him on even a liberal diet Also, the child, who isn't particularly interested in ·COURSE AND FOLLOW-UP 127 losing weight, is not going to deprive himself of the candy, ice cream, and sodas that he usually gets outside the home between his meals Others Between these opposite groups is the large number of patients who must be convinced of the hazards of obesity Here the results of therapy will depend upon how well the physician can impress these upon each patient The average individual is not interested in obesity as an abstract term He must be made to understand the relationship between his excess weight and hus arthritis, diabetes, or lıypertension Even if no other abnormalities are found, the danger to his future health, and the potentially more rapid development of degenerative diseases must be explained to him RESULTS OBTAINED IN AN AVERACE GROUP Recently, one of us has had the opportunity to observe a rather large group of patients under close supervision [39] The individuals in this group were employees at a large industrial organization, and could be considered comparable to the average patient seen in private practice About half the group were comprised of individuals who were found to be obese on routine examination and for whom weight reduction was advised The remainder came in voluntarily for weight reduction Treatment was in stituted on a total of 96 persons Of these, 16 are still under active treatment, 34 reduced to a desirable weight and were discharged, 44 discontinued treatment on their own (that is, did not return for further follow-up), and 2 ucre dismissed for failure to cooperate of the 44 who discontinued therapy, 18 did so within the first three weeks ·130 OBESITY ITS CAUSE, CLASSIFICATION, AND CARE two patients The results of this analysis are summarized in Table 14 TABLE 14 EFFECT OF STATUS OF OSESITY (Acrive or STATIC) UPOY RESULTS OF TREATMENT Static Active 23 13 3 21 wk, 9 3 wks 4 13 wks 7 6 uke Number Time observed Range Average Total weight lost Range Average Logg per week Range Average Time medication prescribed Range Average 10-64 lbs 22 5 lbs 10-50 lbs. 18 lbs 174 2 Ibe 2 5 lbs 104 0lbs 2 6 Ib3 18 ks 2 5 wk8 1wks 2 5 W From the data recorded in this table, it can be concluded that in this study neither the method of therapy nor the results obtained were influenced by the status of the obesity of the individual patient RESULTS OF SUCCESSFUL WEICUT REDUCTION The most obvious result of successful weight reduction is an improvement in appearance This gives a tremendous psychological lift to the patient orale is unproved, and his whole outlook on hfe is There is a creased feeling of well being ostered feeling of vict difficult A lowerin ressur Loss of weig ratar obese hypert cardi to see ·COURSE AND FOLLOW UP 131 breathlessness on mild erertion are relieved Cardiovascular disease complicated by congestive failure is no contraindica tion to reduction of weight on the contrary, removal of excess weight eliminates a considerable load from the already overworked, failing heart Joint pains, particularly in the weight bearing joints as noted in osteoarthritis are frequent in overweight middle age individuals Removal of the excess weight almost ivariably results in improvements in these arthritic manifestations Intertrigo and hyperhidrosis are decreased and frequently completely eliminated by the removal of ercess fat Glucose tolerance is greatly increased when excess weight is lost The necessity for insulin can be eliminated in most obese patients whose diabetes started after the age of 40 Newburgh has suggested that glycosuria in the obese middle age individual is not true diabetes, but a result of fatty infiltration of the liver interfering with normal gly cogen formation [83] Menstrual disturbances such as irregularities and dys menorrhea are frequently relieved or entrely eliminated when obesity is corrected Occasionally, sterility is corrected after weight loss However, so varied are the causes of sterility that this should not be promised a patient A recent study has demonstrated that the serum con centration of high molecular lipoproteins considered by many to be concerned with development of atherosclerosis, is reduced after successful dietary treatment of obesity (120) There is abundant endence demonstrating that mor bidity and mortality are increased in the oversieight com pared to those of normal weight A recent report by Dublin ·130 OBESITY ITS CAUSE, CLASSIFICATION AND CARE two patients The results of this analysis are summarized in Table 14 TABLE 14 EFFECT OF STATUS OF OBESITY (ACTIVE OR STATIC) UPON RESULTS OF TREATMENT Static Active 18 13 3 24 wks 9 3 wks 4-13 kg 7 6 wks Number Tume observed Range Average Total weight lost Range Average Long per week Range Average Time medication prescribed Range Average [0-64 lbs 22 5 lbs 10-50 lbs 18 lbs 1 7 4 2 lbs 2 5 lbs 10-4 0 lbs 2 6 lbs 1 8 wkg 2 5 wks 1-4 kg 2 5 wks From the data recorded in this table, it can be concluded that in this study neither the method of therapy nor the results obtained were influenced by the status of the obesity of the individual patient RESULTS OF SUCCESSFUL WEIGHT REDUCTION The most obvious result of successful weight reduction is an improvement in appearance This gives a tremendous psychological lift to the patient His morale is improved, and his whole outlook on life is changed There is an in creased feeling of well being This is also fostered by the feeling of victory over a difficult problem A lowering of blood pressure is frequently seen after a loss of weight Reduction of weight is imperative in the obese hypertensive Other cardiovascular symptoms such as ·Bibliography 1 ADOLPII C F Urges to eat and dnnk m rats Am | Plysiol 151 110 19:47 2 ALBRECIT FK The use of Benzedrmne Sulfate in obesity Ann Int Med 21 983 1944 3 ANAND B. Hypothalamic control of obesity Food intake in rats and cats Yale 1 Biol ( Med 24 141 1951 4 ARMSTRONG D B DUBLIN LIWHEATLEY GM and MARKS H H Obesity and its relation to health and disease T.AM A 147 1007 1951 5 Association of Life Insurance Med cal Directors and the Actuarial Society of America Medico-Actuarial Mortal ty In vestigation Vol 1 1912 (New York) 6 BARKER N CHAIKOFF I Land SCHUNDEK A Effect of fructose n lipogenesis from lactate and acetate in duabetic liver J Bol Chem 194 435 1952 7 BARKER NV NYC LARD KA WALTERS W and PRIESTLEY JT A statistical study of post operative venous thrombosis and pulmonary embolism II Predisposing factors Proc Staff Meet Afayo Clin 161 1941 8 BEAUDOIN R VAN ITALLIE TB and MAYER 1 Carbohydrate metabolism in active and static human obesity Clin Nutrition 1 91 1953 9 BELINKE A R Phys ologic stud es pertaining to deep sea diving and aviat on especially in relation to the fat content and composition of the body Harrey Lecture Series (New York) 37 198 1941-2 10 BEYER K II and AfEEK W ] Effect of Benzedrine Sulfate on gastric emptying and ntestinal activ ty Arch Int Med 63 752 1939 11 BLOGII I Interrelationships of 1 pid and carbohydrate metabolisit Ann Rev Bochem 21 273 1952 12 Boorur G and STRANG J M Change in temperature of skin following mgestion of food Arch Int Afed 57 533 1936 133 ·132 OBESITY ITS CAUSE CLASSIFICATION, AND CARE per cent indicates that a loss of the excess weight will correct this He studied the experience of the Metropolitan Life Insurance Company with persons accepted for insurance at a substandard rate solely beciuse they were overweight, and who later lost their excess weight and reapplied either for reduction of their rating, or for new insurance A total of about 2300 persons were included in this study He found that among men in the lower substandard group who reduced, the number of deaths recorded was 113 per cent of the expected as comprred with a ratio of 142 per cent of the expected in the entire experience from which they were originally drawn Among women, the ratio for those who reduced their weight was 90 compared with 142 per cent in the entire group For men in the higher sub standard group, who reduced their weight, the mortality ratio was only 109 per cent as compared with 179 per cent in the entire group from which they were drawn while among women, the ratios were 135 per cent and 161 re spectively (34) While morbidity and mortality are higher in the overweight than in the population at large, Correction of the obesity increases the life expectancy to normal. What stronger incentive to reduction can the abnormally fat person havel What more rewarding effort can he makel What goal in life affords the same degree of assurancel This is the optimistic note upon which the physician can always make his plea for the cooperation of the obese individual ·BIBLIOGRAPHY 135 31 DOUCLAS, HS Obesity The problem and treatment, West I Surg, Obstet and Gyn 59 238, 1951 32 DUBLIN, L I The nfluence of weight on certain causes of death, Human Biol 2 159, 1930 33 DUBLIN, L I. JOAN, A 0, and MARKS, H H Factors in the selection of risks with a history of gall bladder disease, Proc Assoc Life Ins Med Dir Amcrica 21 34, 1934 34 DUBLIN, L I, and MARES H Mortality among insured overweights in recent years Proc Assoc Life Ins Med Dir America 4 1951 35 Evans, F In Descascs of Metabolism, edited by Garfield Duncan, Philadelphia, WB Saunders Co 19:12 36 Faust, R A Complications of obesity, New Orlcans AS] 99 502, 19:16 37 FENTOV, PW, and CARR, CI The nutrition of the mouse Response of four straws to diets differing in fat content, Nutrition 45 225, 1951 38 FREYBERG, HH, and NEWBURCI LH The obesity and energy exchange in a verified case of pituitary basophilism, Arch Int Med 58 229, 1930 39 GeLVIN E P Unpublished data 40 GELVIN, E P, and McGAVACK T H Devedrine and weight reduction New York State ) Med 49 279 19:19 41 GELVIN, E P, MCGAVACK, T H, and XENICSDERG S The anorexgenic effect of sustained release Dexedrine preparations Am I Digest Dis 20 307, 1953 42 GELVIN, E P, MCGAVACK TH and KENICSBERG, S Sus tamned release Dexedrine A comparison of various preparations in the management of obesity, New York State ) Med 54 1310 1951 43 CeLVIN, E P, MCGAVACK TH, and KENIGSBERC S Observa tions on obesity Subjective impressions of 108 consecutive pa tents as to the causes of their obesity, Am Digest Dis 20 200, 1953 44 CEORCE F BAKER CLINIC AND METROPOLITAN LIFE INS Co Diabetes in the 1940's, New York, Metropolitan Life Ins Co Press, 1940 45 COLD ZIEHEN, MA Endoctine aspects of obesity, Am I Digest Du 13 40, 1946 46 CRAFE, E Metabolic Discases and Their delpha, Lea and Febiger, 1933 47 GURIN, S Lipogenesis New 48 CUPNET, R The hereditary 51 557, 1938 14 ·134 OBESITY ITS CAUSE, CLASSIFICATION, AND CARE 18 BRAM, I Therapeutic hyperthyroidism, Internat Clin 1 18, 1937 14 BROBECK J R Mechanism of the development of obesity in animals with hypothalamic lesions, Physiol. Rev 26 54, 1946 15 BRODECK JR Food intake as mechanism of temperature regulation, I ale / Biol ( Aled 20 545, 1948 18 DROBECK , R, TEPPERMAN, J and LONG, C NH Experi mental hypothalamic hyperphagia in the albino rat Yale ) Brol Med 15 830 1943 17 BROOKS, Mc. A study of the respiratory, quotient in 18 Peri rat Am / Physiol 147 708 1916 19 BRODES, Mc, and LAMBERT E F A study of the effect of limitation of food intake and the method of feeding rate of weight gain during hypothalamic obesity in the albino rat, Am J Physiol 1 17 695, 1916 20 BROOKS, CMC, LOCKWOOD RA, and Wiccovs, M L A study of the effect of hypothalamic lesions on the eating habits of the albino rat, Am J Physiol 147 735 1946 21 Brooxs, C MC, MARINE, D N, and LAMBERT, E F A study of the food feces ratios and the oxygen consumption of albino rats during various phases of experientally produced obesity, Am J Physiol 147 717 1946 22 BROZEK ), and LEYS, A Limitations of the "normal" body weight as a criterion of normality, Science 112 788, 1950 23 BRUCH, H Obesity in childhood I Physical growth and de velopment of obese chuldren Am ſ Dus Child 58 457, 1939 24 BRUCH H Obesity in childhood II Basal metabolism and serum cholesterol of obese children Am ] Dus Child 58 1001, 1939 25 BROCH H The Frohlich Syndrome Report of the original case Am J Dis Child 58 1282 1939 26 CARLSON, A Į The Control of Hunger in Health and Disease, Chicago University of Chicago Press 1916 27 CECIL, R L A Textbook of Medicine by American Authors 6th ed, Philadelphia, WB Saunders Co, 1913 28 COLTON N H SEGAL H I STEINBERG, A, SCHECHTER, F R, y with emphasis 1 ity, Am J Aled 29 13 478, 1952 30 DAVIDOFF E and REIFENSTEIN, E e The stunulating action of Benzedrine Sulfate, I AMA 108 770 1937 ·137 BIBLIOCHAPITY hexoses, as studied by its effect on the distribution of galactose, Am ] Physiol 163 70, 1950 67 LEVY, RL, WHITE, PD, STROUD, WD, and HILLATAN, CC Ovenveight Its prognostic significance in relation to hypertension and cardiovasculs renal diseases JAMA 131 951, 19:16 83 LUNBAEK, K, and STEVENSON, J AF Reduced carbohy drate intake after fat feeding m normal rats and rats with hypo thalamic hyperphaga Am | Physiol 151 530, 1947 69 Mackay, E A1, BARNES, RI, CAINE H 0, and WICK, AN Ketogenic activity of acetic acid, 1 Biol Chem 135 157, 1940 70 MACKAY, E M, CALLAWAS Į w, and BARNES R H Hyper alimentation in normal animals produced by protamie insulin J Nutrition 20 59, 1940 71 MACKAY, E M, and SHERRILL J W A comparison of the ke tosis developed during fasting by obese patients and normal subjects, Endocrinology 21 677, 1937 72 MACKAY, E M, WICK A N, and BARNU), C P ketogenic action of short chain even numbered carbon fatty acids in carbohydrate fed anunals, J Biol Chem 135 183, 1940 18 MACKAY, E M, WICK A. N, and BARNUA CP Ketogenic action of odd numbered carbon fatty acids, / Brol Chem 136 503, 1940 74 MANKIN, H, STEVENSON, T R BROBECK, I R, LONG, CNH, and STETIIN, DEW JR The turnover of body fat in obesity resulting from hypothalamic injury studied with the aid of deu tertum, Endocrinology 47 443, 1950 75 MASTER, A M, DUBLIN, L I, and MARKS, H H The normal blood pressure range and its clmical implications, JAM A 143 1464, 1950 78 MATTHEWS, HB, and DERBRUCKE, M G Normal expectancy in the extremely obese pregnant woman JAMA 110 551, 1938 77 MAYER, ) Clucostatic mechanism of regulation of food intake, New England J Med 249 13, 1953 78 MAYER, ) Genetic, traumatic and environmental factors in the etiology of obesity, Physiol Rev 33 472 1953 79 METROPOLITAN LIFE ÎNs Co Statistical Bulletin 246, 1943 80 MOLLER, N E, BAILEY, CJ and STEVENSON, Į AF De creased "hunger" but increased food intake resulting from hypo thalmic lesion, Science 119 256, 1950 82 Alisa, A Metabolism of adipose tissue in vitro, Biochem I 36 232, 1942 ·136 OBESITY TTS CAUSE, CLASSIFICATION, AND CARE 49 HAGEDORN, H C, HOLTEN, C, and JOHANSEN, A H The path ology of metabolism in obesity, Arch Int Med 40 30 1927 50 HARDY, J D, and DRABKIN, D L Measurement of body water, techniques and practical implications, JANA 149 1113, 1952 51 HARRIS, S C, Ivy, A C, and SEARLE, L M The mechanism of amphetamine-induced loss of weight, JAMA 134 1468, 1947 52 HERTIC, AT, and SOAIMERS SC Genesis of endometrial carcinoma Summary of prior biopsies, Cancer 2 946, 1949 53 HETTIERINGTON, AW, and RANSON, S W Hypothalamic le sions and adiposity in rats, Anat Rec 78 149 1940 54 HETHERINGTON, AW, and WEIL, A The lipoid calcium, phosphorus and iron content of rats with hypothalamic and hypophyseal damage Endocrinology 26 723, 1940 55 HURTLEY, WH "The four carbon atom acids of diabetic urine, Quart J Med 9 301 1915-16 56 Ivy, A C, and COETZL F R d Desoxyphedrine, a review, War Mcd 3 60 1943 57 JOHNSTON, M W SQUIRES, A H, and FARQUHARSON RF The effect of prolonged administration of thyroid Ann Int Med 35 1008, 1951 58 T 59 LALE, SW The fallacy of massage in the treatinent or gues ity J M Soc New Jersey 41 406, 1944 60 Keys, A Obesity measurement and the composttion of the body In Overeating, Overweight and Obesity, Nutrition Sym posium Series No 6 New York, The National Vitamin Founda tion, Inc, Jan 1953 61 KEYS, A Handbook of Nutrition, 2nd ed, Philadelphia The Blakuston Co 1951 62 Keys, A, and BROZEK, J Body fat in adult man, Physiol Rev 33 245, 1953 63 KNOOP, F Der abbau aromatischer fettsäuren im terkorper, Bertr Chem Physiol Path 6 150 1904 64 LERAY, I Considerations Actuelles sur les Obesites et lcurs Traitements 2nd ed, Paris, Libraire E LeFrancois, 1951 65 LEYIN, L., and FARBER, R K The endocrine mechanism con trolling the mobilization of depot fat, Tr New York Acad Sc 3 260, 1951 66 LEVINE, R, GOLDSTEIN, MS, HUDDLESTON, B, and KLEIN, S P Action of insulin upon permeability of cells to free ·BELIOGRAPITY 139 cator in the study of intermediary metabolism III The role of fat tissues, J Biol Chem 111 175, 1935 Srina Tha 12 ܝ ܟܬ. ܝ ܠܐܫܚܗ ܬܝܝ 105 SCADIE, V C, ZAPP, J A, and LUKENS, F P The effect of insulin upon the ketone metabolism of normal and diabetic cats, 1 Biol Chem 132 423, 1940 106 STADIE, W C, ZAPP, J A, and LUXENS, F P Intermediary metabolism in diabetes mellitus- The non formation of acetic acid and the ratio of ketone body increase to fatty acid decrease • AY IM obes. mamic action of food in abnormal states of nutrition, Am I MSc 182 49, 1931 109 STRANG J M, McCLUCGACE, HB, and BROWALEE, M A Afetabolism in undernutrition Its change during treatment with high caloric diet, Arch Int Gred 55 958, 1935 110 STRANO, J M MCCLUGCACE HB, and EVANS FA The nitrogen balance during dietary correction of obesity, Am I M Sc 181 336, 1931 111 STRANC, J M, MCCLLCCACE, H B and Evans F A Further studies in the dietary correction of obesity, Am I 1 Sc 179 678, 1930 112 STROUSE, S, and Dye M Studies on the metabolism of obesity I The relation between food intake and body weight in some obese persons, Arch Int Ned 34 267, 1924 113 STHOUSE, S, WANC, CC, and DYE M Studies on the me tabolism of obesity II Basal metabolism, Arch Int Afcd 34 275, 1924 114 TAINTEN, ML Actions of Benzedrine and Propadrine in the control of obesity. / Nutrition 27 69, 1944 115 TALBOT, N B Obesity in children, M Clin North America 29 1217, 1945 118 THOUPSON, K J Some observations on the development and tourse of hypertensne vascular diseisc, Proc 3rd Annual Meet- Praca Kied Sert & Tuin Contentinn 1950 ·138 OBESITY ITS CAUSE CLASSIFICATION AND CARE 82 NEWBURCH LH Control of hyperglycemia of obese diabetics by weight reduction Ann Int Med 17 935 1942 83 NEWBURCK LH and CONV I V A new interpretation of hyperglycemia in obese middle aged persons J ASI A 1127 1939 84 NEWBURGII LH and JOHASTON MW The nature of obesity / Clin Investigation 8 197 1929 85 NEWBURGH L H and JOHNSTON M W Endogenous obesity a misconception Ann Int Med 3 815 1930 86 ODELL L D and MENCERT W F The overweight obstetric patient JAMA 128 87 1945 87 PAYNE R W Stud es on the fat mobilizing factor of the an terior pituitary gland Endocrinology 45 305 1949 88 PENNINGTON A W Practical reducing regime In "Olcreat ing Overweight and Obesit/" Nutrition Symposium Series No 6 New York The National Vitamin Foundation Inc Jan 1953 89 PENNINCTON A W A reorientation on obesity New England J Med 248 959 1953 90 PLOTZ CM KNOWLTO AI and AGAN C The natural history of Cushing's syndrome Am J Med 13 597 1952 91 PLUVVIER WA Body weight in spontaneous myxedema Tr Am A Stud, Go ter pp 88-98 1910 92 POPJAK G and BEEKMAN M L Extrahepatic lipid synthesis B ochem / 47 233 1950 93 PRICE WH CORI C F and COLOWICE, S P The effect of anterior pituitary ertract and of insulin on the hero kinase reaction J Biol Chem 160 633 1915 94 RAAB V The role of the posterior pituitary hormone in fat metabolism Endocrinology 14 6 1930 95 RABSON S M The fatty tissues Normal anatomy and changes 1 on 5 96 iger 1940 97 State J Med 54 6 1954 98 RONY HR Obes ty and Leanness Philadelph a Lea and Feb 99 RYNEARSON EH and GASTINEAU CW Obes ty Spring field ill Clas C Thomas Publisher 1949 100 SEWAND B P A clinical study of mild grades of hypothyro d ism Ann Int Med 9 178 1935 101 SIIAPIRO B and WERTHEIMER E The synthesis of fatty acids 10 adipose tissue in vitro I Biol Chem 173 725 1948 102 SCHOENHELMER R and RITTENBERG D Deuterium as an ind ·Inder Arne from cortisone 112 Activity effects on body weight 56-57, 72 73-74 Addiction to amphetamine 105 Adenosine triphosphate activity 18 Adipose tissue 12-15 blood supply, 14 cell origin 12-13 innervation, 13-14 nature of stored fat 15 source of stored fat 15 Adolescent obesity 29 Adrenal factors in obesity 29-30 63 Adrenalectomy and fat mobiliza tion 24 Adrenocorbcal factor in fat mobiliza tion 24 Adrenotropie hormone and fat mobilization 24 Agranulocytosis from dinitrophenol 74 Ammonium chloride d uretics 110 d' Amphetamine 100 weight loss from tables 98 99 Amphetamine preparations 98-105 addition to 105 d amphetamine 100 methamphetamine 105 side effects of 103 Antirond type of obes ty 27 Anorexia nervosa 89 Anorevigenic agents 98-108 125 d amphetamine 100 amphetanine preparations 96-103 cinscal data talle 102 comparative loss froni table 101 Anorerigenic agents (conid ) methamphetanute 105-107 side effects of table 103 Anxiety overeating in 42 Appetste 33 Arthritis in obesity 131 Ascorbic acid 114 Atherosclerosis in obesity 8 ATP (adenosine Inphosphate) 18 Basal metabolistn 52-53 Belladonna preparations 115 Biedl Laurence Moon syndrome 31 68 Blood cholesterol levels of 68 gli cose levels of and food intake 36 press ire mereasca in obesity 8 lowered after weight loss 130 Supply to adipose tissue 14 Body components of 5 hcat production 34 35 Buffalo obesity 03 Bulk in slet 113 Calunic allowances in dset 50 Calunes excess intake of and Height gain 54 Carbohydrates adequate amount of 19 jotenebry metabolism 18-21 tolerance decrensed 64 Cardios ascular abnormalities in obesity 8 Custration and obesity GI Cataracts fruin durstrophenol 74 ·140 OBESITY. ITS CAUSE, CLASSIFICATION, AND CARE 119 VANLIENE, EJ, and SLEETH, C K The effect of Benzedrmne Sulfate on the emptying time of the human stomach, Pharmacol & Exp Therap 6 111, 1938 120 WALKER W J. LOWRY, EY, LOVE, DE, MANN, GV, LEVINE, S A, and STARR, FJ Effect of weight reduction and calore balance on serum lipoproteins and cholesterol level, Am J Med 14 654, 1953 121 WELL, R and Ross, S Growth hormone and fat metabolism, Endocrinology 45 207, 1949 122 WELHAM, WC, and BEHNKE, A R The specific gravity of healthy men-Body weight, volume and other physical char acteristics of exceptional athletes and naval personnel, JAMA 118 499, 1942 123 WELLS HG Adipose tissue, a neglected subject, JAM A. 114 2177, 2284 1940 124 WERTHEIMER E and SHAPIRO, B The physiology of adipose tissue Physiol Rev 28 451, 1948 125 WILDER RM The regulation of the weight of the body, Internat Clin (Series 42) 1 31 1932 126 WILDER RM, and WILBUN, DL Progress in internal medicine diseases of metabolism, Arch Int Med 61 297, 1938 127 WILENS SL Bearing of general nutritional state on atherosclerosis Arch Int Med 79 129 1947 128 WILFIELMIJ CA The specific dynamic action of food, Physiol Red 15 202 1935 129 130 131 ZELNIAN, S The liver in obesity, Arch Int Med yu 141, 1934 ·Index Acne from cortisone 112 Anorexigenic agents (contd) Activity effects on body weight methamphetan ine 105-107 50-57 72 73-74 side effects of table 103 Addiction to amphetamine 105 Anxety overeating in 42 Adenosine triphosphate activity 18 Appetite 33 Adipose tissue 12-15 Arthntis in obesity 131 blood supply 14 Ascorbic acid 114 cell origin 12-13 Athery clerosis in obesity 8 innervation 13-14 ATP (adenosine tripl osphate) 18 nature of stored fat 15 source of stored fat 15 Basal metabolism 52-53 Adolescent obesity 29 Bellados na preparations 115 Adrenal factors in obesity 29-30 Bied! Laurence Moon syndrome 31 63 69 Adrenalectomy and fat mobiliza Blood cholesterol levels of 68 tion 24 glucose levels of and food intake Adrenocortical factor in fat mobilizi 36 tion 24 Adrenotropic hormone and fat pressure increased in obesity 8 lowered after weight loss 130 mobilization 24 Agranulocytosis from dinitropheno! supply to adipose tissue 14 Body components of 5 74 Ammonium chloride du retics 116 I eat production 34 35 dAmphetamine 100 Buffalo obesity 63 weigl loss from tables 98 99 Bulk in diet 113 Amphetamine preparations 96-105 add ction to 10 Caloric allowances an diet 90 d amphetamine 100 Calories excess intake of and methamphetamine 105 weight gan 54 side effects of 103 Carbohydrates adequate amount of 79 Android type of obesity 27 Anurea nervosa 69 u termediary metabolisz 18-21 Anorexigenic agents 90-108 125 tolerance decreased 64 d amphetamine 100 Cardios ascular abnormalities in amphetamise preparation 96–105 obesity 8 clinical data table 102 Castration and obesity 61 comparative loss from table 101 Citaracts from dinatrophenol 74 11 AF ·142 INDEX Cell ongin of adipose tissue, 12-13 Dilution test for fat measurements, Cellulose in diet, 113 6 Childhood obesity, 67-68 Deutrophenol, and metabolic rate, diet in, 93 74 results of therapy, 126 Diuretics, 29, 115 Cholesterol levels, 68 Drugs, 74-77 Classification of obesity, 26–32 combinations of, 116 Climacteriwn and obesity, 61 Dynamic action of food, 53-55 Colitis, from purges, 116 Dysmenorrhea, and obesity, 131 Constipation from protein powder, 83 Eating, mechanism of, 33 Contractions, stomach, 33 Overeating, 38, 42, 69, 122 Cortisone, and fat metabolism, 24 Edema 112 in obesity, 112 Electrocardiography in obesity, 8 Course of weight reduction, 119-132 Emotional factors in overeating, 42, Cushing's syndrome, 30, 62, 63 69 Endocrine, factors in obesity, 28, Death rate in obesity, 11, 131 59-66 Definition of obesity, 1 adrenals, 63 Dehydration, 115-116 fat mobilization, 24 Densitometry and fat measurement, gonads, 60-61 pancreas, 6485 Dercum's disease, 31 pituitary, 61-63 Dermatitis, 118 thyroid, 59-60 Desorycorticosterone, and fat mobitherapeutic preparations, 109-112 lization, 24 cortisone acetate, 112 Desoryephedrine, 105-107 estrogen, 111 Diabetes, glycolysis in, 23 11 orycorticoids, 111-112 pituitary, 109, 110 and obesity, 9, 64, 131 prednisone, 112 Diet, 78-95 sex bormones, 111 basic menus, 86-89 testosterone, 111 bulk, 113 thyroid, 109 caloric allowances, 90 Endogenous obesity, 26 causing obesity, 47 Energy, derivation of, 56 for children, 93 expenditure, increased, 73-77 food factors in basic 1000 calorie intake, decreasing, 78-95 diet, 91 Environmental factors, 41 functions of, 78 Estimation of body fat, 5 high fat, 84-90 Estrogen therapy, 111 high protein, 80-81 Etology of obesity, 38-68 instructions to patients, 93-95 basal metabolic rate, 52–53 Pennington, 84 dietary factors, 47 planning, 78–80 digestion and absorption, 50 prescription for, 90-93 dynamic action of foods, 53-55 protein powders, 82-84 endochine factors, 28, 59-66 regulation of food intake, 33-37 environmental factors, 41 unnatural, 81 glandular dyscrasia, 26 vitamins, 114 gonads, 60-61 ·INDEX 143 Enology of obesity (contd) hereditary factors 28 39-42 111 hypothalamus 43-47 ketosis 55-56 Lipophila 57-58 luxury consumption 55 metabouc factors 48-58 nervous factors 43 nitrogen exchange 50 pancreas 61-65 physical activity 56-57 pituitary 61-63 psychological factors 42 69 rebound of metabolism 55 respiratory quotient 50-52 thyroid 59-60 Exercise 73-74 effects on weight 56-57 72 Exogenous obesity 26 Familial lipodystrophy 31 111 obesity 28 39-43 Fasting, glycolysis in 23 Fat diet high' 84-90 embolism front surgery 117 estimation of 5-7 chemical analysis 5 clinical valuation 7 densitometry 5-6 dilution tests 6 skínfold measurements 5 intermediary metabolism 16-17 mobilization 425 relocation, 112 Fluld and salt intake 94 115 Follicle stimulating hormones and fat mobilization 24 Follow up of obesity 119-133 Food intake regulation 33-37 glucostatic mechanison theory 35,37 hunger and appetite 33 mechanisins 31 theriostatic mechanism theory 3435 Freudian concept, 42 Frohlich s syndrome 29 31 61 treatment, 110 Frustration overeating in 42 Gallbladder disease in obesity 9 Castric inntation from protein powder 83 Gastrointestinal disorders from d amphetamine 102 Glandular dyscrasia causing obesty 28 Glucagon 64 Clucose blood levels of and food intake 36 metabolism 18 and servous system activity 36 shunt 21 tolerance increased after weight loss 131 Glucostatic mechanism theory 35 37 Glycolysis acceleration 23 Glycosura 48 65 Gold thioglucose obes ty 27 Gonads 60-61 Growth of fat tissue 13 hormones and fat mobilization 24 Cynold obesity 27 Habit obes y 28 32 69 Hazards of obesity 8-11 131 morbidity 8-11 mortality 11 131 Heat body product on of in obesity 34 in thin persons 35 cabinets 116 Height weight tables 123 Mereditary upodystrophy 31 111 obesity 27' 39-42 Hlesokinase activity rate 24 Flerosemonophosphate shunt 20-21 Ilormones See Endocrines Ilunger 33 122 ITurtley hypothesis of fahy acid metabolism 16 Hyperglycem c syndrome of mice 40 57 64 Hyperhidrosis in obesity 131 Ilyperinsulinist 65 Hyperphagia 43 46 ·INDEX Hypertension in obesity 8 Management of obesity (contd) Hypoinsulinism 65 anorexigenic agents 96-108 Hypothalamic obesity 27 28 29 belladonna preparations 115 bulk 113 Hypothalamus temperature sensitive in childhood 93 126 cells in 35 decreasing energy intake 78-95 Hypothyroidisin and obesity 30 59 dehydration 115-116 74 diet 78-95 See also Diet Inactivity and food intake 57 dimitrophenol 74 Incidence of obesity 7 drugs 74-77 Innervation of adipose tissue 13-14 endocrine preparations 109-112 Insomnia from d amphetamine 102 exercise 73-74 Insulin 64 general considerations 69 effects on herokinase activity 24 hormones 109 elimination of after weight loss increasing energy expenditure 131 73-77 hyperinsulinism 65 massage 117 hypoinsulinısı 65 methamphetamine 105-107 requirements for fat storage 45 11-oxycorticoids 111 Intertrigo in obesity 131 physician s role 70-72 physiotherapy 117 Kaolin in diet 113 pitwtary therapy 109 110 Ketone bodies 16 protein powders 82 Letonemia and fat mobalization 84 psychological factors in 69-70 Ketosis 18 55-56 results 126-132 knoop Boxdation theory 16 See also Results of therapy ser hormones 111 Laboratory examinations 124 succrssful results 130-132 Lactogenic hormones and fat surgery 117 mobilization 24 termination of therapy 120 Laurence Moon Biedl syndrome thyroid therapy 109 31 68 vitamin preparations 114 Lipid and carbohydrate metabolism Massage 117 18 Mayer's glucostatic mechanism the- Lipodystrophy familial 31 111 Lipogenesis 16 22-24 Measurement of obesity 1-5 Lipophilia 57-58 fat content percentage 5 Loss of weiglt See Weight loss frame distinction 2 Luteinizing hormones and fat height weight tables 1-5 mobilization 24 Men height weight table 3 Luxury consumption 55 Menarche in obese girls 89 Menopause weight changes in 31 Machay theory of fatty acid metab- 61 111 olism 17 Menstrual disorders and obesity Management of obesity 69–118 61 68 131 123-126 Miental retardation and obesity 68 amphetamme preparations 98- Menus basic 88-89 105 See also Diet cry 35 ·145 LINDEX Mercurial diuretics 116 Mesencephalıc-pituitary system disturbances 63 Metabolism 48-58 basal 52-53 carbohydrate 18-21 digestion and absorption 50 dynamic action of foods 53-55 ts 16-17 etosis 55-58 pophulla 57-58 ultury consumption 55 astrogen exchange 50 pathways table 19 physical activity 58-57 Tebound of 55 respiratory quotient 50-52 lethamphetamine 105-107 side effects 106 107 Methyl cellulose in diet 113 114 Middle age spread 31 Minerals adequate amount of 79 Moon Biedi Laurence syndrome 31 68 Aforbidity with obesty 8-11 131 Morgagni Morel syndrome 31 Mortality in obesity 11 131 tables 9 10 Mouth dryness from belladonna 115 Mydriasis from belladonna 115 Mysedema and obesity 30 60 74 Nausea from proten powder 83 Nerves in fat tissue 13-14 Nervous obesity 28 29 Nervous system glucose activity in 36 Mervousness from d amphetamine 102 Neuritis from ditutropi enol 74 Nitrogen exchange 50 Nutrition See Det Obstetrical complications in obesity 10 teoarthritis in obesity 10 131 Ovarian obesity 30 lil Overeating, 38 42 69 Overeating (contd ) dunng therapy 122 Otaloacetate formation 18 Ondation mechanism in fat metabolism 16 Oddat on theory of knoop 16 Oxycorticoids 111-112 11 'Otycorticoids 111-112 Pancreas activity 64 Pennington diet 8+ Physical activity 56-57 73 examination 124 Physician s role 70-72 Pituitary factors in obesity 31 61- 63 hormones and fat mobilization 24 ul erapy with 109 110 and mesencephal c system dos turbances 63 Patuitrin 63 Potas tum 112 Prednisone therapy 112 Pregnancy 10 bi Prescription of diet 90-93 Protamine zinc insul n 64 Protein adequate amount of 79 diet hagh 80-81 powders 82-81 Pseudoobesity 63 Psychiatric therapy 70 Psychological factors 42 69-70 Puberty weight changes in 61 Purges 115 Pyruvate activity in metabolism 18 Pyruvic acid inhibitory effect of 84 Reduction of weight. See Weight loss Relocation of fat 112 Respiratory quotient, 50-52 in animals 44 Results of therapy 126-132 average patients 127-130 children 126 patients with strong incentive 126 successful weight reduction 130 ·146 Results of therapy (contd ) tables 128 130 Return visits 71 121 ANDET Salt and fud intale 94 115 Ser hormones 111 Simmonds disease 62 treatment 109 Skin rashes from dinitrophenol 74 temperature after eating 34 Skinfold measurement of fat 5 Source of excess fat 38 Specific dynam c action 34 53 Stadıe theory 17 Sterility and obesity 61 Stewart Morel Vorgangi syndrome 31 Stomach contractions of 33 imitation from protein powder 83 Stored fat nature and source of 15 Surgery 117 Synthesis of fat 15 Temperature environmental and weight gain 35 skin after eating 34 Termination of treatment 120 Testosterone therapy 111 Thermostatic mechanism theory 31-35 Thiouracil and fat metabolism 24 and food intake decrease 35 Thyroid gland factors in obesity 59-60 hormone therapy 74 109 calorigenic effect 75 Thyroid hormone therapy (contd) tolerance to 76 toucity 75 Thyroidectomy and fat mobiliza tion 24 and food intake decrease 32 Thyrotropic hormone and fat mobilization 24 Thyroune and fat mobilization 24 and food intake increase 35 Treatment See Management of obesity Turkish baths 115 Types of obesity 28 of patients 126 Vagotomy food intake after 115 Vitamins adequate amount of 79 defic encies 124 125 preparations 114 Water restrictions 115 retention 29 Weight average 1 desirable for adults 3 and height tables 1-5 loss 93 119 average weekly rate 129 calonc diet us protein powder 82 det and vitamin C, 115 methamphetamine us placebo 106 unsatisfactory 122 optimum 1 Women height we ght table for 3

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