Obesity, Fat Metabolism and Diabetes David Adlersberg, M.D..* New York City The frequent association of obesity and diabeses has been known for many years I led co the view that this combination represents a special form of diabetes ("“lipo- genic diaberes") caused by impaired glycogen storage in the liver."* According to this concept, obesity is the pi- mary abnormnality and hyperglycemia and glycosuria are secondary phenomena, This concepe is based chiefly on the observation that adequate weight seduction restores carbohydrate tolerance to normal* This concept is not shared by many.** Persistence of abnormal ghucose col- france ests after adequate weight reduction has been often observed in originally obese diabetics and afc subsidence of all clinical symptoms (figures 1a & b). ‘The duration of diabetes, the frequeney of complications, the incidence of diabetes in parents and siblings and che proportion of licavy babies ae very similar among obese and nonobese diabetics (table 1) whereas one would ‘expect consicrable differences between the two types if they weve etiologically distinct conditions® Thus, subsi- dence of symproms of diabetes does not mean disap. earance of diabetes in the originally obese diabetic. There is no proof that obesity causes disbeces. Among 170 million Americans there ace fifty to sixty million overweight persons, Of these only exo million have di betes, an incidence of 3 t0 4 per cent. The incidence in he general population is approximately 2 per cent Both abnormalities may be manifestaions of the sane ‘cause or causes, Some are of the opinion that an obese person after weight loss still has the anomaly that caused the obesity and may be considered. “poten- tially obese” despite normal body weight and normal caloric balance for the-very same reason thae @ symptom- fice diabetic remains 2 diabetic ‘OBESITY AND DIABETES—CORRELATIONS ‘The prevalence of obesity among diabetics today ap- pears t0 be higher than at the turn of the cennury. Fretichs observed 15 per cent obesity among, his patients ‘with diabetes, Segen 30 per cent, Bouchard 45 pee cent Presented at sponsored by e Diabetes As Inew on Oct. 12, 1957. From the Departments of Medicine and Chemisty, Movae Sinai Hospital, 236 and von Noorden 22 per cent? Von Norden consid red the posbility that many of these data are t00 lov because of weight loss prior to the discovery of diabetes, ‘Acer correction, his ratio of obese diabetics rose 10 35 per cent. The early figures of Joslin and Umber were 40 per cent and 34 per cent, respectively. In contrast, at least 80 per cent of the diabetic, persons living at present in the United States ate of have been over- weighe™ Te would be of great interest 10 compare the preva- lence of overweight with that of diabetes of with dia- 300; 250) 200) 150) 100} 50) 44454647 a a WEIGHT —= INSULIN 500 400. 300 1941 1948 200 FASTING 1 Marked waight reduction of an obese diabetes in groduel subsidence of symptoms and signs af igo was reduced from 180 units {hb}. Despite absence of symptoms and signs the gle fois faanee til honed’ Tied eke, vases DIABEIES, VOL. 7, NO. 3 1458TABLE 1 Duration of diabetes, frequency of complications (poly cataract) ad ineidence of dabete Mild diabetes ‘with obesity er cent 1 15 a o COMPLICATIONS OF DIABETES Poly. noortis Retinitis Cataract No.of Pee Pee Per patiomts No, Diabetes eared wihiasiin” 277 72 26 +21 8 2% 95 Mild diabetes withotesty 107 21 196 8 7S 6 56 MEREDITY No.of Diabetes in parest Type of diaketes patients or sii Diabetes requir isin” tstment a 22 Mil isbetes ‘wih esi _107 2 Wabi ci bial co dd prowal By GO Rich MBs Ncvete upon yas Eoganh an ae eel He Ose Diba Hh appt in bisniits 9545 TARLE 2 Diabetes mortality Covmtey 1938 United States 264 Canada 203 Finland 539 Swedes os France 33 Switzeriand 13 Enaland=—Wales 15 Alstealia 188 20 New’ Zealand heres moctalicy in various countries since sch & com: parison might perhaps explain the geographic variations in dieberes mortality (rable 2)." Unfortunately, chere are no collected dasa on overweight, There is some indi cation thar after correction for difference ia beight, Amer- jean men are about 10 tb. heavier and women 4 0 6 Jb, hesviee than cheie English counterparts." Hundley” antempeed t0 cortelare the percentage gain in average body weight heeween ages twenty-five to sixcy with diaberes mortality sates after age forey-five in four popu: MAY JUNE, 1958 TABLE 3 Therese ia average body weight betwen twenty aod : . Diabetes mortality? tween ages 25 Over 45 years Countiy® and GOyears Faye All ages Mea Women Men Women Japan. 2420 England 33 ot ida 12 23's 207340 Japanese wen, ORT ins in heighi—women, 59.5 in (helt national average in” 1949); English-and’ Canadian mca, 6f fin. in height women, (Gvithout shoes); US" men, 67 10, tall--women. 63 fa, (with shoes) PMortaity rates: per” 100,000. poptiation in 1948, Intions in the year 1948 (table 3). In ehece popalasions wich marked weight increases higher diabeses morealicy rates were observed (England, Canada, Unived States of Ainerica, in comparison with Japan). Nevertheless, dia bees mortality varied considerably among, the fst chree counties probably due to some additional factors, To «x plain che bigh mortality sues feom diabeces inthe U ced Seats, dive possible factors have been consiered generous dice consumed by many in exeess, incressing use of labor-saving devices and die prevalence of ove weight in adules. Ie is of interest chat a downward trend in diabetes moray in the United Seaces has been observed since the te 19408 Diabetes mortality in 1954 wis 9 por vent less chan in 1949 despite the increasing proportion of oll people in the population’* The possibitcy thae this decrease in moctlity may be due, at least in past, c0 the growing awareness of the importance of weight conteol muse be considered” ‘Many objections can be raised against the correlations mentioned shove, Such factors as Improved diagnosis of Giabetes, regional vasitions in statistical procedures, prolongition of life in general, and especially in person with disbetes, by ever teatmeat, and perhaps differ fences in many envieonmental influences (socio-econom~ 4 occupational, verison, climatic) may explain many of these observations. Compacative epidemiologic studigs in diabetes a3 well as in other diseases (athero- sclecsis) are exposed to this criticism, CARBOHYDRATE TOLERANCE IN OBESE PERSONS ‘WITHOUT DIABETES ‘The impaired carbohydace eolerance appears t0 be related chiefly to the duzacion of obesiy. ln the Nutri tion Clinie of The Moune Sinai Hospital, Drs. Weil and Williams studied the glucose tolerance in fifty-four ebese persons, predominantly women (unpoblished observa: tions). Only persons who had no glyeosuri and nosinal ar 4 : : q x ee nee aritnfasting blood sugars were inchided. They were divided in to two groups. Nineteen persons had obesity for several years only they were in the “dynamic” active") phase ‘of weight gaining during the study. The ocher group of thirgy-five were in the “static” phase with a history of steady overweight for ten co twenty-five yews, The aver age age of the “dynamic” group was 3355 yeas, that of the “static” 4644. The average ideal weight was 127 Ib. in the “dynamic” group and 129 in the “static.” The average actual weight was 188 and 205 Ib, sespectively, and the average overweight expressed in’ per ceot of ideal weight was 27 and 57 pee cent, respectively. Thus, Ithe “serie” group consisted of olde, heavier and longer ‘obese persons chan the “dynamic” group. Persons of cor- responding ages and normal body weigh served as con trols. The data are summarized in figure 2 GLUCOSE TOLERANCE TEST 16 0 -F7!00ars DEXTROSE, ORALLY TS yoRaa “sTaTiC" OBESITY 1-7) NM i ‘DYNAMIC"OBESITY| —\ BLOOD SUGAR, mgs./100 mi. FIG. 2. Glucose tolerance tents in. “static” and “dynamic” ‘Sbesity end’ in normal contol, ‘Note Tower Sverage Carve in Mdynamie" obesity. For detail, see fox A ttcnd without stacstical significance is indicaeed in that persons. in the “static” phase of obesity exhibit hhigher blood sugar curves than those in the “dy- namic” phase in agreement with the observations of Beaudoin ec al” These findings might be explained by differences in actual weight, age and duration of overweight between the ovo groups. Age may be al faceor per se in that the probability of decreased carbohydrate tolerance increases with age” The as- sumprion of basic differences between the two groups, such as decreased oxidation of fae and proporcionstely ast increase oxidation of glucose is speculative and ux proved GENETIC asrcrs ‘There are only fimiced obseevations on che hereditary aspects of the Common varity of obesity. Separation of genetic from environmcnsal faccors in the ctislogy of obesity i dificule. Among, parents of obese patients, the incidence of overweight and of diabetes was wo to ten times normal When both parents were obese 75, per cent of the offspring showed this abnormaliys if ‘nly one parene was obese, 44 pee cent of the childven were found 0 be obese; if both parents had noemal weight, only 9 per cent of the childeen were obese.” hae Body build is inherited is well known, Hereditary factors seem to play a role in the genesis of obesity, the imporcance of which is dficule ro evaluace, The dictum of Newburgh,” "Body build is inhereed obesity is no,” is perhaps 100 dogmatic, A modified version is suggested "Body build is inherited, obesicy perbyps inherived Family stdies in obese diabecics reveal a5 per cene incidence of diabetes and Go pee cent incilence of cobesi:® The ein study method has been applied ex tensively to investigations concerning, the eantribucion of heredity © pachological states, A pair of mono zygotic wins sudied by Warkany ec al” is of in terest in this sespect, The two brodhers vere concord- ant in all blood factors studied. They became discordane in the cighth year of life when one ewin be came diabetic and romaine! lean and small despite ade- quate second tio be came obese. He remained frce from diabeces up 0 the end of the follow-up period at age ewenryrcight. Ic is well known thae concordance in diabetes #8 much moze frequent ia monouygotie than in diaygoric twins. lathe shove-mentioned family diabetes occurred in the morh- e's family and obesity in the families of both parents The observation by Warkany et al, again suggests close etiologic relationship between obesity and diabetes mellitus. One mighe assume chat a single gene oF per- Japs eo closely-rclated genes might be respoasible for the 19 metabolic abnormalities Among nonglycosurie obese a5 well nonobese fam ily members of obese adule diabetics, in our experienc, abnormal ghicose tolerance tests ate no infrequently seen, The frequent combination of obesity and diabetes, in aduls supports the concepr that human obesity may’ represent a hereditary trait accompanying diabetes. This would be in accord with Mayers observations in obese lyperslyeemic mice. To paraphrase Joslin, diabetes is a punishmene of obesity bue probably only in_ che pre- disposed person, treatment whereas theThe teatment of the obese diabetic must be pri marily directed againse obesity. Ie is well esablished fhae weight reduction achieves ia many instances full conszol of sympcoms of diabetes. The easy way of trea. ing this form of diabetes with insulin or tolbutamide is inadvisable and should be used only as an exception co the rule. Some consider insulin “conteaindicated” in the ‘obese diabetic excepe for complications? SERUM LIPIDS IN DIABETES ‘The relationships between lipid and. carbobydeace setabolism have been extensively studied. Very impore- a observations have been presented in the papers of Doctors Stale, Dole, Albrink and Man, Olson andl others carlier in this Symposium, The possible implications of these studies for the pathogenesis and perhaps therapy of diabetes mellitus, obesity and atherosclerosis remain (0 be investigated. Que own studies were concerned with the serum lipid partition i diabetes. Extremely high serum lipid levels have been observed occasionally in patients with diabetes mellitus” The highest seporced figure of total lipids is 48 gm/tco mi” However, this figure obtained hy the contrfuge method for buccer fat is oper co criti= ism, Ocher high figures for serum total lipids range from 13 c0 20 gm/ro0 ml:* The highest value of our observation was 16 gm./t0o mil, Ie was seen in absence ‘of keiomucia in one of oue five patients with boch dae beccs mellius and idiopathic hypeslipemia” Since then, we have observed rheee additional cases of this rather rare syndrome. ‘These patients present alkerations of lip merabolisn characteristic of idiopathic hypeclipemia often in asso: iasion with skin santhoma. The appearance of the serain is milky or creamy in the fasting state. ‘There is tacked elevation of serum criglycerides and of otal Jipids with a moderace to marked increase of serum cholesterol and phospholipid. The average level of total lipids in this groap was 8282 mg/100 mil. and the highest cholesterol level was 1,480 mg /100 ml. The dia. betes encountered in this group is usually mild; only two pients among the eight eequived sinall quantcies of insulin, In che other cases, good contral of the diabetes could be achieved on lowered intake of calories and fat, Patients with his syndrome reveal a remarkable ta bility of secum lipids in connection with ehe hypergly- emia and glycosuria even in absence of ketomuria To illustrace this, the above-mentioned patient pre- seated on admission marked turbidity of the serum, serum total lipids of 16,000 mg/roo ml, and total cholesterol of 669 mg./t00 ml. The fasting blood siigar was 300 mg/109 ml. There. were eruptive SAKIENE, 1958 anchona of the skin and lipemia retinal, A. low Calorie segimnen without insulin resulted in a loss of 12 Ib, in weight (ftom 187 «© 175 Ib). The curbicity of the serum was reduced t0 1-4, total lipids declined t0 2500 mg./100 ml. and serum cholesterol 19 329, This observation was made in 1948. A similar sequence of events was observed five years later in connection wich overeating. The weight of che patient increased, hyper- slycemia and gheosuria reappeared with recarcence of ruptive sanchona, marked hyperlipeinia and hyper. holesteremia, A tow calorie dice again resect in Joss of weight, disappearance of glycosuria and dectease in blood sugar, serum total lipids and serum cholesterol (able 4). The patient presented similar episodes of hyperglycemia and enhanved hyperlipemia and hyper cholesteemia in 1954 and again in 1956, Milder instances of a similar nacure may bave been observed by Hirsch ec al*and Appel and Hansen" whose pitients exhibited marked elevation of esterified faty acids of the blood in the presence of hyperglycemia, In this connection, recene observations by Dole and Gordon ton che relationship between nonesterified fry acids of she plasma (NEA), lipid teansport and glucose metabo- Tiso deserve emphasis. Complications of human diabetes may be associated with welldetined changes in serum lipids and scrum polysucharides in che absence of ketosis ot acidosis Pacients with severe retinopathy, hypertension, edema and proteinuria (Kimmelstiel:Wilson syndcome) show Aecided elevation of all serum lipid fractions and of complex carbohydares. It is of interest thae = gcoup of diabetics with ently retinopathy but without any dlence of renal involvement, presene signifcane differences in comparison with patients having uncompliciced dia- betes and with nondiabetics, consisting of increase in serum ighcerides and total lipids, in serum ghueost mine and coral serum polysuecharides while serum cto: lesterol and phospholipid remain normal (cable 5). One must consider, cherefore, dae those blood changes per- haps precede the degenerative alteration of the tissue and the deposition of certain proceinsipid and protcin- ‘corbolydrate compounds in the setina and in the renal alomezatus, LOW PAT DIE IN DIABETES ‘The possible relation between diet, and especially ictary fat, and atherosclerosis has bec the topic of many studies. Regardless of all arguments, a nutitional regimen preventing obsity, which ceetainly is a health Juzard in general and especially in the manifest oF poten tial diabetic, appears to be justified. Such a dice should be nutritionally adequate and should provide only 25ODISIIY, FAT METAROLISM AND DIANETES TABLE 4 Summary of data of patent with mild dinbcts mellitus and idiopathic hypertipemia during three observation pete in 1988,"1953 and 19sa2 PP * a ae z - He g hs ap 3 2 ears Frise sapiens 304k 16000 ra ay Egeiis ater . eee lr e300 3 ins U8 Enptse sgptona MS ba 6700 790 FEBS ABRoy _ sao se _ MO 4S 4th 4am aa sours get ne i 27 2k 44 2a 220 senaed GRE fraik Took eat aw 10 a LUrr,T——~—t——— EE _ 340 4967270 Dl Serum chotesirol was dstermined_ by the Sporty Schoophcimer method: phospholipid by Sperry’s modification of the an sow method and total lipids by the iloor method. Serum neutral fat was Calculated’ By wohuscting the feos al cholesterol plus phospholipid from that oF the twa) Tipe Fis TABLE $ Serum constituents in nondiabetic controls and in diabeties with and without complications" 1 u ut Diabetes. & Kimmel Normat Uncomplicated Diabetes. & Wilson Controls diaetes retinopathy syndrome wot . ) D) (Da) (Daw) Cholesterol, me. Toit Dass Sisn6e reviled Phospholipis, mg. % ‘Total lipids, me Neutral fats me. Glucosamine, me. Polysaccharie, me. % Das. De Das Dosw Cholesterol, total 033 iy Phospholipis, 8.035 Not significant by inspection ‘Total tia ois ‘ues Ghocosamine o.0001 002s Polysaccharide Buoois 0013 “Those are calculated figures; no standard deviation given, ‘er cent of the calories from fat intend of the customary studies that excessive amounts of fae resul in impaied 45, er cent, Thus, a 2,000-crlorie. diabetic diet should. carbohydrate tolerance ia animals and man: ‘These ead include only 500 calories from fat per day (approxi- ies also wete performed in patients with disheves in mately 60 ym). It was shown long ago in extensive shore and long periods of isocalorie nuurition in whichthe content of curbolyteate, protein and fit varied from limited 0 excessive amounts.” Low-fat diets have been recommended for patients with anild diabeces. ceated without insulin as well as for chose wich the severer variety requiting insulin, Because of the importane role of obesity in clinbetes and becuuse of the possible scl tionship beween high-alorie and highfat diets and atherogenesis, che use of low-fat regimens in che cherapy of diabetes deserves se-cmnphasis SUMMARY Over 80 per cent of adule diabetics are of were obese, Jn the predisposed person, diabetes is “punishment of obesity.” Obesity is probably an hesoditary trai accom- praying diabetes. The treatment of the obese diabetic ‘aust be primarily dicected agiinse obesity. Obese persons without manifest disbetes tend to cexhibie after ingestion of glucose higher blood sugar ‘curves doring the “static” phase than dusing the "dy- namie” phase, Inthe sumple obseeved, the findings could be explained by differences between the two groups in actual weight, age and duration of obesity. Extremely high seram lipid levels may be occasionally observed in patients with diabetes mellitus, even in ab- sence of Keronuria, The highest values of our observa- tion were encountered in patients presenting the associa- tion of idiopathic bypedlipemia and diabetes melas, A remarkable bility of serum lipids in connection with hyperglycemia and glycosuria, even in absence of keto- nara, i a characteristic feacuze of this syndrome abctes complicated by retinopachy, hypertension, Jdema an proteinuria (Kimmelstiel-Wilson syndrome) may be associated with elevation ofall secura lipid frac- tions as well as of complex carbohydestes}in eacly dia- betic retinopathy without evidences of renal involve- ‘ment, increases in serum exiglycerdes and total lipids were observed while serum cholesterol and phospho- Jipid remained normal. Simultaneous elevation of serum slucosamine and cocal serum polysaccharides was seen, i ‘The use of otherwise adequate low-fue diers is sug: gested in order to combat an important associated dis turbance of diabetes, obesity, and perhaps atherogenesis. SUMMARIO IN INTERLINGUA Obesitate, Metabolismo De Grassia, E Diabete Plus que 80% del diabeticos adulte es 0 esseva obese, In fe subjecto predisponite, diabete es un “puni- tion pro obesicate:" Il es probabile que obesicace es un tcxcto hereditabile que accompanin diabete, In le caso det diabecicas obese, Je cractumento debe occupar se primarimente del obesicare Subjectos obese sin diabete de forma a a reager al ingestion de glucosa per plus alte curvas de nifeste tende MAY-JUNE, 1958 suero sanguince durance fe phase “setic” que durante le phase “dynamic.” In le exemplos studiate, le datos esseva explicable per diferencias inter le duo grupos quanto al peso actu, al erate ¢ al duration del obesieace Abissime nivellos de lipido seral se observa a vices in patientes con diabere mellite, mesmo ia le absentia de eetonuria, Le plus alte valores in nostce experientia esseva incontrate in pacientes in qui hyperlipemia ioe pathic esseva associate con diabere mellite. Un aspects characteristic de ice syndrome es le remarcabile labli- «ate del lipidos seeat in connexion con hyperglycemia alycosuria, mnesmo in Je absentia de cetonucia. Diabete complicate per retinopathia, hypertension, edema, © proteinuria. (syndcome de Kimmelstiel: Wil. son) pote esser associate con tin elevation de omne Je fractiones de lipido seral como etiam de carbohydrstos ‘complexe, In cisos de retinopathia diabetic precoce sin evidensia de un affection del senes, augmentos del rivellos secal de criglyceridos © de lipidos esseva ob- seevate, durante que le valores de cholesterol ¢ de phospholipide det sero semaneva normal, Esseva.ob- servate elevationes simultanee de glacosimina del polysaccharidos rotal del sero, Es proponite Je uso de dictas a basse contento de ‘geass sed alteremente adequace pro combattee obesitate —que es un importante disordine associate con diabete =e forsin etiam atherogenese., ACKNOWLEDGMENT ‘This study was supported in pare by research grants H-364 and H-9$2, Nacional Insticutes of Heal, Unie ed States Public Health Service, Acknowledgment is made of permission co reproduce figures 1(a) and (b), which appeared in An. nt. Med. 4031024, 1954; tables 2 and 3, in J. Amer, Diet. Assoc. 32:418-19, 1956; table 1, in DIABETES 2:454, 19533 table 4, in DIABETES 4:210, 1955; and table 5, in DIABETES, 33436, 1936, [REFERENCES "Newburgh 1. H,, aed Coan, J. Wor A new interpretation of hyperplycemin in obese middleaged pessons. JAMA, 1222 7 1939. "Newburgh, L. H.: Contzol of the hyperalycemia of obese “disbetes” by weight reduction. Ana. Int. Med. 17:935, 1942. *Olmstal, W. IL: Obesiey: Key to the prevention of di betes. J. Michigan Mel. Soe. 52:1057, 1933. “Marphy, Ruz Obesity and diabetes ‘mellitus. J. Michigan Mail. Soc. $5:1209, 1956, *Shackey, T. P= Diabetes mellias and obesity. Ohio Med J. 492986, 1935. *Rictuadson, G. O.: The obese diabetic, Diabetes 2:454 Kinney, J. R2 Weight reduction in an obete diabetic, nn Mei. voto, 1934 "Rony. AM. R.: Obesity and feanness, Philadelphia, Lea and Febigec, 1940. 47.“Von Nooren, Cand Isaac, S.: Die Zuckerkeankhelt vad ihre Behandhang. Betlin, Jul. Speingee, Sth Tal, 1927, p. 8. “Hundley, J. Ms Diabeusoverseight: US. problems, J Anier. Diet. Assos, 32:418419, 1936 Kemstey, W. FE: Weight and heigl in 1943. Ann, Eugenics 15:161, 1930. Marks, H. His Recent statics on diabetes. Diabetes 42 227, 1955 "Beaudoin, K, Van Ile, 7. B, and Mayer, J. Catbohy: tate metabolism’ in “active” and “atic” human obesigy J, Clin, Nuwe 191, 1953, * Ogilvie, R. Ri Sugte tolerance in obese subjects; « review of sintysive cases. Qua. J. Mod. 285345, 1935. Fellows, H. Hu: Studie of relatively notmal obese in viduals during and aftee dietary resttations. Am. J. Med. Se 181:301, 1931 "Gumey, Ramsdell: The hereditary factor in obesity, Arch Jat. Med. 55:557, 1936. "Newburgh, LH: Textbook of Endocrinology, eh R. HL Williams, Philadelphia, W. B. Sounders Co, 1930, "Obesity, Chap. 21, p. 66. "Warkany, J, Guest, GM. aad Cochrane, W. A Dis ‘onlane monozyyoric twins, diabetes mellites and obesity. Am. J Dis. Child. 89:685, 19. Aillesberg, D. Hasmonal influences on serum lips. Am. J. Med. 23:763, 1997 “Chase, 1. A: Diabecic lipemia retinals; case Moh Asoc. J. 17:197, 1927 “Herbert, F. K.: Observations on blood fats in diabetic Tipaemia. Biochem. J. 2921887, 2935. * Aulenberg, D., and Wang, C1 Syastome of iliopathic Fnyperipemia, mild diabetes mellins aad sevece vascular dar ane. Diabetes 4:210, 1955 * (2). Hirsh, FF, amd Curbouaro, L: Serum esterified fatty acids with far tolerance tess ia siahetes mellitus, Arch, Tat Med. 86:519, 1930. (b). Hirsh, EF, Plibbs, BP. and Car bonsro, L: Parallel relation of hypersycemnis and hypetipera (sterited fry acids) in diabetes. AMA. Atch. Int. Med g1s106, 1993 Appel, W., and Haasea, K. J: Ocber den Abfall der vers terten Fausturen und der Amindsiuten des Blutes nach Lasulin ‘Baschr. Physiolon. Cherm. 297349, 1934 * Gonlon, RS, J: Unesterifed fay acids ia human boot plasma, J. Clin, Invest. 332206, 196, (a). Dole, V.P.: A relation beoween nonesterified fy acs in plasina and the mecabolism of glucose. J. Clin, Fovest 353150, 1936. (b)- Dole, V. P,, Bierman, F. Ly and Rober Nu: Plasma Nera as an index of cathobydrace utilization (Abseeace). J, Clin, Haves 36:88, 1957 Aalershag, Det a: Serum lipids aul polyssccharies i iabetes mellitus, Diabetes 33126, 1936 (a). Auletsberg, D.: The use of high protein diets in the treatment of diabetes mellitus. Proc. Am. Disheter Assoc. 6 409, 1946. (bh). Le traitement du diabete sucee par un resime pauvre en prsises, La paste Med. #20 (Marth t1), 195% of & population Canad DISCUSSION Howarp Root, MD. Dr. Adlersberg has given us food for thought in this very interesting paper, which evaluates the importance of several factors related to bit ‘man diabetes and places special emphasis on lipid mex ‘abolisen and obesity. He has pointed out besic clinical factors that conccibute 10 mortality rates. 1 should like to stress again the fact of the increasing duration of life of diabetic pacients, The cases with on. set of diabetes before fifteen years of age, who have died in recene years, ly lived ten 10 ewenty times as long as those children who had similar onset and lived in the period before insulin, The average uration of diabetes has doubled in middle life, That factor itself must influence vital statistics which deal ‘with such complications as coronary actetiosclerosis, ret nitis, ec cetera. The actual expectation of life of those children has now reached a length of forty-four years Tam very much interested in his emphasis on hered ny, We recognize in our diabetic patients « multiple- ‘ype of heredity, Ie carties with it some special features that we cannoc as yer define very well, The inheritance of food habies is one thing. The heredity of she bosly build is another. Recently we have had wo patients in whom necrobiosis lipoidica diabeticurum wis present for a long period of time before any clinical or chemi- cal evidence of diabetes occurred, One was 2 child of ten years, the second, a woman of thirgy-five years who gor necrobiosis long before blood ‘suget tests disclosed dliaberes. Other features, possibly illustrating heredity, interest us. For example, the children of diaberie moth. fers gain weight and become quite rotund by che time they are five, sis, or seven years, even though the pat cents have made efforts to prevent such gains in weight ‘The mild diabetes of the obese middle-aged. the so called mild diabeces thae we hear discussed, nevertheless produces in thet man’s son or daughter, or his grandson for granddaughter, che sime kind of severe stable diaberes as is found is Heredity, then, is a major feature which gives a ma Tignane chacacter 20 ehe diabetic problem of today. The face thac one our of four people is estimated <0 carry the diabetic heredity factor and that he may ot it to his sons of daughters, bur may pass i¢ on co more distance relarives, is worth remembering The incidence of heredity becomes higher the longer you observe patients. I have just studied 247 of our pacients who have Ind diabeces for over thirgy-five years, and already over Go pee cent of those now know fof diabetes in their families, So, 1 appreciate what Dr, ‘Adlersberg has said about heredity 1 hink the lipoprotein analyses in our diabetics have also emphasized the fact thar clevation of seruin lipo: proteins occurs at che time when diabetic parients are under poor control, when they begia ta ten the corner,when severe forms of retinitis are beginning, There is something about char elevation in the lipids, particu: hhely the lipoproteins, which marks a milestone in the development of che Kimmelstiel-Wilson disease, when those values are highest. T would ike to corroborate all that he has said about diet. I am sure thae we are all going co be more and more interested in emphasizing the necessity of diet in che control of diabetes rulay. Henoent Pottack, MDs Dr, Adlersberg has eeally presented a kaleidoscopic summary of a very vast probe fem. We do noc know coo much aboue diabetes, we do ‘nor Know coo much about atherosclerosis, we donot know coo much about lipoproteins, but we surely know a lor abour obesiry. So we can calk a toe about dobesicy and ies cure, Lets take the energy balance story of the obese peo- ple, and lees give just one possible explanation as to why they might develop diabeces. By the rule of chumb, which works oue faisly wel, you know thac the basal calorie requirements of an individual are approximacely cen. calories per pound. IF we take the 150-Jb. normal-weight individeat, we can assume that his basic requirements are in the ordee of 1,500 calories. Nest we cake a moderately obese person of 200 tb, and we can assume that the basie caloric sequirements are in the ordet of 2,000. Thac is a ditference of 309 calories a day hae the obese person snwst supply in order co maincain his basal metabolic processes. We know from the R.Q. studies that approxi imately owo fifehs of this is in che form of earbobydeate —these extra calories—which means that che obese per- son is burning approximately 209 calories of catbo- hydrate, o¢ approximately 50 gm, of carbohydrate, a day ‘more than the nonobese, This means that he requires ‘more insulin—aboue 15 unies of inst quired by a normal-weight individual If we have a pancreas and we burden ie with this exera load day in and day our, then we can readily ap- eeciate the possiblicy of decompensation, One of the manifestations, as Dr. Adlershery showed, is thar when weight ceduction is accomplished you fre: quently can restore, at least temporarily, the glacose tolerance. Because of che reduced metabolic fosd, che pancreas is able to handle it, This is probably one of che explanations, o a¢ least i is an explanation, of this pheaomenoa which we obserce between weight loss and insu and weight gsin and precipitation of diabetes, Just one word about diet; thar is, I jast want co. make a plea that when we focus our atrention on, the in more than is re- requirements, MAP JUNE, 1958 diabetic and his diet, tee us noc forget thae his: nui tional requirements are still those of a normal person, and thar the diabetic dice should not be perverted in aay sense whatsoever, We ate limited in the amount of carbohydrate thac we can prescribe for a diabetic pa- tiene if we are using insulin and if our aim, in therapy, is control of glycosuria and hyperglycemia, When the corbohydrate gets much above 200 of 250 go. a day, complete contzol of glycosurix is virtually impossible with che types of insulin we have coday, because the postprandial plehort of carbohydrate will inevitably result in postprandial glycosuri With a limitation of 2 maximum of 250 gm. of car- bohydrace, and with a coral caloric intake of 1,500, and with the limiracions of protein in the way af economic and satiety requirements, then, obviously, the rest of the caloric intake muse be supplied by fat. We have no choice. And to state categorically that you cannot give ‘more than 100 gin. of fae a day is a mistake. The diet muse be milored to ehe iadividwal, Ie must be tailored to his coxil caloric requisement. The limita 1s of the diet are such with respect #0 exbohydrate and protein thar the difference must be supplied by fat in order to give him char amouac of calories to maintain his optimum weight, Ia a 1,000-calorie diet one usually inclutes co gin. of prorcin, This amoune of protein supplied by the common foods will include aboue 40 gi Of fat of, expressed in terms of calories, 360. Thus the low calorie diets have as high as 36 pec cent of che calories from fat sources, Ie would be mose difieule to keep the far contene co 2-5 per cent of the calories, Da. ApLuRswerc: L wish 10 thank che discussers for theie remarks, Lam glad thac Dr. Root stressed the importance of heredity. ‘This is really one leading fresor, frequently neglected, bue imporcane for our understanding of smany clinical observations in patients with diabeces. Ie is interesting that in ewo of Dr, Roor's patients, nectobiosis was the initial symptom of diabetes. The same may be seen in ocher complications. We have ob- served a number of cases in whom retinopathy of che type seen in diaberes o¢ neuropathy was presene before glycosuria and hyperglycemia became apparent, 1 would like co emphasize thae the classical high fat diets originated in che pre-insulin era when they were @ Today che fat content of the diabecie diet may be similar ro thae of nondiabetics amounting to Go t0 $0 um. per day. The rese of the calories is covered by cat- Dohydrates and somewhae lasger quantities of protei ‘The use of the old-fashioned high fae diets in the treat: mene of diabetes is noc justified in 1957.Diabetes in Central America Kelly M. West, M.D., and John M. Kalbfleisch, M.D., Oklahoma City SUMMARY prevalence of di Eomewhat gecater than i + in Central America ae it Pakistan and Malaya, Teee tially ese than, tates, Differencee sone instouces, In all I Ametiean 00s tes a8 erence was probally attributable women, Agenmtched pope countries of three continents w heen tested using standardived methods, Presa: tes vatied greatly, sed differeners were more Berween 1965 and 1967 a large-scale nutrition susvey was conducted in Centeal America as a cooperative vndertaking of the Institute of Nutrition of Centeal Amctica and Panama, the governments of the six re publics of Centzal America, and the Office oF Inserne tional Research of the National Institutes of Health of the United Staves This survey provided an unusual ‘opportunity 0 ces a representative sample of the popst= lations of exch of the countries, and t0 compare che Blucose tolerance of these subjects with many other variables, ‘These circumstances also permite us 10 compare our data with sesults in other populations tested previously by the same methods, Prevalence r21es for diabetes had nor been determined before in any of these couatties, ‘The six contiguous sepublics (Guatemala, El Sal: vador, Honduras, Casta Rica, Nicaragua, and Panama) forin a land mass of approximately 181,090. square miles, stighily lurger than the stace of California and about twice the size of the United Kingdom. The com: bined population of the six countries is approximately From the Depargment of Medicine, “sity of Oklahoma School of Medicine, Oklahoma City, Okldhomi 75104. 656 fiftcen million, Most of the people ‘live in small villages; there is, however, at. least one large center in exch OF the countries Levels of social economic development in this region are highs | jn Southeast Asia and substantially lower than-in Tu for the United States; income levels pet capita ave about $300 (US.) per year. The economy is ‘mainly om agricuteure, Most of the people are of m blood ("mestizos"). The predominate mixture is 01 Inclian and European (usually Spanish). Smaller tions of the total population are of pte Indian Bl ‘or of “pure” Caveasian (European) descent, Neg make up a still smaller portion of the population, T are some racist differences among the countries example, there are more Indians of pure blood in tain parts of Guatemala, and there are Fewer Ini and fewer of mixed blood in Costa Rica where of the population is of Spanish descent. METHODS Selection of subjects In each country a highly systematic program developed ro identify and selece 2 representative san of the general population. Details of the methods ployed have been described elsewhere."* Reyes: locations were selected by means of a systematic ran procedure. do exch country the number “of lecatl selected in each of the several administrative divisi fr regions was proportional to che population of region. AC each location cwency dwelling. sites selected at random from recent census data, In counery the ratio of rural dwellings eo urban dwell in the sample reflected the nural-urban. distribution the population (predominandy cural), In spite of ef to abraia represensative samples, several sources of tential bias developed. At most of the 209 locati the rate of participation-was high, often exceeding per cons of the families and of family members selec On the other hand, at some sites the rare of recruitin for the diaberes-related studies was lower, s0 that about «wo thirds of those i the total, simple, w tested. Specific data ate given in table 1 by cova DIABETES, VoL, 19. 4 7o880 JOHN st Katmeuascen, sem TABLE 1 Diahetestefated studies in Central America Sites of Country (esting Suijeots ested Standitd wight Males Females Mates Femates Costa Rica 39 46 ign 266 oT 109 % of sample* ee 11% El Salvador » 265 7 168, o 96 at samp 61% 5895 Gustemala 48 9s od 24 » %» % of sample® are 67% Honduras 26 saan tis 208 1 of sumiple® ca 74% Nicaragua 35 3930. 259 os tor “eoksimple® S406 18% Panama 32 MS tas 200 9310s FF otsample® 360% 6966 ~ - “THs represents the percentage of the subjects in the representative sample ad sex with regard to the portion of the sample who ee ee ee adely representative of the universe from which they ere drawn. Even so, the county-wide samples are uch beter than are usually ‘available for estimating valence rates. As shown in nible 1 the number of ‘ring locations zanged from wemty-six to forty-cight country, The nutrition survey included al! age ups: Although some younger subjects were tested dlabetes, the resvlts reported here include only ‘sons _more than thirty-four years of age, Glucose ding tests were performed and certain selated data jected on 2,285 subjects, The frequency ages was the sume for males and females. Frequency ribotion of age by country and for all Central ericans is given in cable 5, Jistribution ‘he aumber of subjects cested in cach ecunty for » sex is given in table 1, The size of che sample h country was not large, ranging frem 265 in El dor to 498 in Guatemala, bu these numbers were entrared in one age group (over thicty-four). Even I Selvator che number tested in this age group four times greater in relation ta its population than vortion tested in the National Health Survey of the ed Stares?” An effort was made 10 avoid either a ive or oegarive bias for diabetes in the selection and recruitment of subjects. The subjects did not know that they were « be tested for diaberes The glucose loading test AU subjects received an oral glucose load of 1 ge/kg, of body weight, administered in an approximate concentration of 25 per cent. Venous blood was drawn a€ (v0 hours. Glucose levels were determined on plasma, using the AuroAnalyzer method. The plasma values were later converted to whole blood values to facilitate comparison with results of other scudies. This was done by assuming thac plasma levels were 14 per cene higher than whole blood levels: ‘The consistency of the rela: tionship between plasma and whole blood levels has been welt documented.” With few exceptions the cests were performed ia the latter pare of che morning, as in ocker countries? Usually che lead was administered three to four hours after breakfase but the duracion of the fasting ranged from one to fourrcen hours. Except for a very few instances the subject had fasted for more than «wo hours prior tw che administation of ghicose. We are aware that in certain circumstances variacions in time of day oF duration of fasting may produce small bue significant effects on glucose tolerance. However, sys- tematic studies in other councties had indicated that these factors had lice effect on our results under # TABLE 2 Frequency disteibution af two-hour slucose values in Central America 0 a. 209 130.209 130-479 019 90419 6.89 <0 at 1s os 24 78 20 S06 79 ative % 1s 23 46 14 a4 oa 100.0 sta, 1979 srTABLE 3 Frequency, distribution of two-hour glucose values by country in Central America Glucose in mg. per 100 mh >is Costa Rica ‘Males 3 Females Ts oth sexes? sa ‘Cumulative sa EI Salvador ‘Males 2a Fenyales 42 Bolh sexes? 32 ‘Cumulative 32 Guatemala Mates 29 Females 5a Both sexe a2 ‘Cuntuative 42 Honduras Mates 1s Females 67 Both sexes? a ‘Cumulative an Nicaragua Males 23 Females Tr Both sexes” $0 ‘Comulative 50 Pans ‘Mates 09 Femates 50 Both sexes 2 ‘Cumulative 2s Per cont of values 120.149 100-19 < 56 122 32 165 a4 14.6 S148 208 1 62 165 107 20 85 193 ua 5t0 1 2 a 43 102 3 95 & 76 67 25 96 ny 46 108 17 7 28 80 34 39 particular conditions? In order w confirm these previ ‘ous observations we also analyzed the results of 1,013 tests in Central American subjects in which ehe dura- tion of fasting was recorded. No significant effect of duration of fasting was foond. There was no significant correlation between doration of fasting and age, RESULTS Prevalence of diabetes The frequency distribution of the ewo-hour blood glucose levels for all subjects tested in Central America is shown in table 2. The results for each country are given in table 3. We have arbitrarily classified as "aia etic’ those subjects whose rwo-hour venous whole blood glucose values exceeded 149 mg/100 ml. How- ever, examinacion of tables 2 and 3 permits decermina tions of prevalence rates using diagnostic eriterix which are either more “conservative” or moze “liberal” than ours. For example, 46 per cent of all subjects had ‘diabetes” by our criteria, but only 2.3 per cent had values above 179 mg./100 ml, while 12.4 per cent had values greater than 119 mg,/109 ml, Although ‘vo: oss “Rate based on projected resulls if an equal number of males and females had beon texed hhour values as low as 129 mg.’160 ml. have b considered abnosinal by some workers, recente suggests thar in subjects in ehis age group values wy about 156 mg./1G0 ml. ate probably aoemal.” O'S: yan and Maban have measured the degice to wl prevalence rates are aftected by changes in dingne criteria” Because comparable frequency distrib data ate available for exch population, the prevalene diabetes for these and other countries" can be comp: with the use of any one of several diagnostic ext We recognize the limitations of a single ewo-howe ¥: a 4 definitive diagnostic instrument in specific i vidlals: Bor ie seems quite likely that the prevale of elevated owoshour values ins group would be porcional © the prevalence of impairment of role by more elaborace resting. Moreover, even if all jects had “complete” tolerance tess with ghicose de rinacions at five different intervals, the problems clasifiacion and interpretation would remain with gard both 0 the group of tests and certain indivi Jn incerpreting this rate of prevalence for CenSULY M. WES, any a America (46 per cene) (ewo-hour glucose over nd, twenty-four were known beri: Thus in this age group the observed preva. ‘ce of known (and confirmed) diabetes was ir pet 6 amd the rate for occole “diabetes” was 3.5. per nt. Our results show that in every country of Central ‘metica most of the people with diabetes didnot vow they had it We have adjusted slighely nce for all of Central Am sich takes inte accoune the observed rate of preva- erica by projecting a rate he relative populations of * si countries; and another adjustment was applied conreet for the face thae the number of ferales ‘ed was somewhat greater than the number of males ¢ two adjustments result in a small change from observed prevalence rte of 46 per cent to a pron ved rite of 4.2 per cent, “able 3 gives the prevalence rates for each of the Onries, Diflrences among counties were modes, 3ing from 2.5 per cent for Panama to 5.4 per cene osta Rica, Small differences among countriés in ved prevalence rates, such as 42. pet cent for temala and 5.0 per cene for Nicaragua, may not be fieane. We believe that le differences, such as Der cent for Cosca Rica and 3.2 per cent for El dor, are sigiticane, sue x compares the prevalence of diabetes in 0 JOHN St KALOPLEISCH, M60, and those to be presented below for otter groups, several considerations should be Kepe in mind, First, these rates apply only to the Be group tested (over thiny-four years of age). Rates for che entre geners! populaion including all age groups would probably be less than half a8 great (see below). Second, prevalence rates based! on testing all subjects with glucose loads can be expected to yield anweh higher rates than rates based on the methods that have been more commonly employed. Mose preva. fence rates have been based on screening with less sensitive methods such as urine glicose determinations da testing subjects in Uruguay, Venezuela, Malaya, and Pakistan we had an opporcanity to compace the sensi- tivity of several standard screening procedhites in sub. ects who had glucose loading tests. Ie was found that » this ae Broup prevalence rates based’ on loading all Eabjects were from ewo to five times higher than those Pasa on cereain traditional procedures in which only positive screenees received ghicose loads. Finally, the prevalence cates given in this report include known dia, tics as well as those in whom the presence of dishetes iad not been idenciied previously. OF the r06 persone whom “abnormal” tolerance 49 mg/r00 ml.) was foun [] 2% est eaistans 3.3% Matava 4.0% CENTRAL aetica 6.9% utuouay 7.0% VeNEDUSLA —_ cc aml = FIG. 1, Preralonce of diabetes in the ol thietrfour years} of seven popul "Based on extapclations ned oo ments (over loee test. Central America with rates in ocher age-matched popue Iitions tested by these methods” The prevalence rate in Central America was lower than in Venezuela and Uruguay and somewhat higher than sates for East Pakistan and Malaya, The prevalence of diabetes is subs stantially lower in Central America than in age-matched groups of certain affluent nations. Studies have not been eported for representative samples ofthe general popu Iitions of fluent countries using these methods. It is bossible, however to make crude comparisons by make ing certain extrapolations, Results of st et al" by Gordon e¢ al," and by Unger" suggest that in the United States the rate of “abnormal” tolerance by criteria equivalent t0 ours is roughly 15 per cent fer this age gronp. Our own studies in Bangor, Penn- Sslvania yielded a rate of x7 per cen in this age group using these methods and these criteria? Extrapolation, from glucose loading results for general populations in Norway! and Britain! suggese tha a simile oF slightly lower portion (about 10 t0 15 per cent) of those in {his age group have “impairment” of tolerance by iaeds equivalene co those employed heee, We also fhe Cherokee Indians of North Carolina by these meth- ods. They are very obese. The population sample tested was not adequate t0 establish a prevalence rite with precision, bur the data suggesiod a prevalence rate of roughly 25 per cent in this o> group. Association of prevalence wit other factors As indicated in table 3 the prevalence of diabetes 8s higher in females than in males in every country. For all subjects in Central America the observed rate in males was 2.1 per ceat while the observed prevalence in females was 62 per cent. The higher rate in females cannot be seributed 10 paricy was demonsteable between lence (see betow. ies by Mayner stan- tested because no association parity and diabetes. preva- ). On the other hand, overweight was 659.biaairees 18 CHSTRAL, AMERICA TABLE [Relationship of age and giucose tolerance in Central America <190 100-129 “Young” (35-44 yrs) 71% 7% Middle-aged” (5-64 yrs) ne 20% Ola" (more than 64 yes) Ge 2086 mach more common in females than in males, and this could accoune for the difference in prevalence between the sexes, Detailed information will be reported else where concerning the association between adiposity and diabetes in these and other populations. Suffice it to soy hhece thac in Central America the mean per cent of standard weight for women was 103 per cent and for men 95 per cent. These subjects were considerably thinner than age-matched subjects in the United Seaccs and decidedly fatter thas the Asian populations studied “The data in table 1 show che mean per cent of standard weight for each country by sex. Although the differ: ‘ences among countries were relatively small with respect to both diabetes. prevalence end mean per cent of standard weight, there was a good correlation between the cwo, For example, weights were lowest and preva fence rates lowest in Panama and EI Salvador, while och prevalence rates and weights were greatest in Costa Rica and Nicaragua There were small variations in the dict among the couneries and in various parts of individual nasions™* However, the diet for the entire region can be charac terized in a general way, Ja comparison co the typical diet in the United States, che diet in Central America is lower in calories, protein, and aniumal fat. In Central “Tworhour glicose in mg./100 130163 > 4 oa" a 20 54% 5.0% ‘America a greater portion of the sotal caloric intake derived from carbohydrates, But in comparison 0 mo Asian diets the Central American diet is low i. carb Iydrate and high in fat. “The number of full-term pregnancies (sever or mo months) was recorded for each of the women teste Mean parity was seven, anda subscantisl portion | these women had had from nine to wenty-two pre nancies. No sigaificanc selstionship was found becwe: parity and prevalence of diaberes. In Venezuela at Uruguay we had found an impressive association tween parity and diabetes, but pare or all of this as ciation could have been attributable co a posit relationship beeween parity and adiposity? “Table 4 shows the negative relacionship between and glucose tolerance in Central America, This sa inverse sclationship was observed in each of the s counties, as shown in table 5. These data demonstr the crucial importance of matching for age bef _making comparisons of prevalence. “The associations between prevalence and cerssin of actors such as socigecoriomic status, eectrocardiograp findings, and nvsritional status will be reporced decail in other presentations. Suffice it © say h that there was a strong association between the pre TAULE 5 nition of ages and prevatence of iahetes by age group for each country Countey Att subjects asa Costa Ria %, 109 314 revalence 38 42 EI Salvador 300 362. Prevatence 34 10 Gustemals % 100 365 fevukence % 44 16 Honduras 100 ss Provatenee 47 46 Nicaragis 9 100 321 Prevalence % 3 16 Pa 10 m8 29 oo Ati counties 109 346 Prevalence % 46 2 6 ‘Age in years 4584 206 33. 283 27 323 37 263 204 4KELLY Mt wust, sD, AND lence of diabetes and socioeconomic satus. In an in: ‘pendent survey these families were cased a having {hish?” “medium,” or “low” socioeconomic status, Dist ‘betes was more thin twice as common in those with high” starus as in hose with “low” status We have now studied by a common method popula. tows amade up of many races and genetic groups. cluding Chinese Cin Malaya), Malays, Indians (in Malaya and Pakistan), American Indians, Negroes (in Central Amevica), and Cavcasians in Cones, South, aod Nosth America, Differences in prevalence were quite small when races or populations were matched for furness, For example, diabetes was twice as common in Venezuela as in Guatemala, but the rate of diabetes as the same in weight-marched groups from the twa countries. In Central America diabetes was more than three times as frequent in subjects whose weights ex. ceeded r09 per cent of standard than in leaner persoes in the same population, Dur methods were not designed t0 evaluate dizedy eid thoroughly the effects of race and heredity on the evalence and character of diabetes. No evident differ. Ences were noted in the chatacier of diabetes in those of differant races. The prevalence of diabetes was some. wist higher in Costa Rica (mainly persons of Spins Kescene) dsm in Guatemala (Indians and persoos of nised blood), but hese small diferences inay. be feriborable to other factors such as the greater adi “sity of subjects from Costa Rica where income levels “ea little higher Ibaracter of siabeses These studies were not designed co evaluate certain ‘te clinical characteristics of diabetes, and the group 206 persons who had impaiemene of glucose toler se determinations will be reported ‘lsewhee Te was sistribue DIScUssiON View of the other pressing health problems Jn FOUN M. KALAPLESCH, 340, Central America, diabetes-related progeams would not sccm to warrant highest priority. Nevertheless, diabetes is 4 very signifcane health problem in the region. No ‘ysematic studies were made in children oF younger adults, but on the basis of glucose tolerance teste in a small nuinber of military and civilian personnel, clinical Experiences of local conditions, and mote than 1000 family histories, we concluded that diabetes way much ‘ess common in the younger segment of the population than in those over thiny-four years of age. Askiming this the prevalence of diabetes is very small in young adults and that approximately cwo thitds ofthe popule tion ace less than chiety-five years of age, about 225,000 People in Central America have “diabetes” (15 per cent of fifteen million). Our dats show that a majority of these “diabetics” have very mild abnormalities, of slucose tolerance. Therefore, the total number of People in the six countries with “clinical” dishetes is roughly fifty co one hundred thousand, ‘McDonald has recenily reviewed the literature on the Prevalence of diabetes in the Americas” It has been evident for a tong time that environmental faciors influence the prevalence of diabetes. But, is Knowles ‘nas pointed out, ic has been diffcule to collec dara which would cleatly demonstrate the extent and. chars ‘acter of these effecs, Our resules show that prevalence fates sometimes differ markedly even when standardined ‘Pechods and criteria ate used, and the data sugges fat the differences. observed ‘were related more to eavironment than to race. Diabetes is very common in the Todians of East Aftica.® certain Yemenites of Israel urban Uruguayans? and rich Céfiral” Ameri ‘ans, while itis earé in heir racial and genetic counter, pects who have lived in diffrent circumstances. Ap. parently diabetes is_als0 many times more comeen in those Polynesians#) and. Hiitiat9 who have need in relative affluence than in theit poor relatives, All of ‘these comparisons, including our studies, leave something to be desited with respecc to the experimental conditions. On the other hand, in making compatisons, we did have the adwonages. of standardized methods, age- ‘matched groups, and population samples which were a least crudely representative, Considered in the aggregate ‘he epidemiologic evidence suggess that genetic suscep. ‘ibility to diabetes is common in mose-o¢ all of the major races, and that under certain environmental con dicions s lage portion of genetically susceprible persons dlo not develop diabetes. The data do not argue apainee the hypothesis thar diabetes is an hereditary disorder, 664DDIANETES 180 CENTRAL AMERICA but they suggest shar the penezrance may be very low in some circumstances. Our dita donor exclude the possibility chat there are significant differences among the races in the frequency of diaberesrelird genetic traits, Buc diferences in prevalence among the popular tio: and subpopulations we tested were modest when subjects were matched for adiposity. Jackson and his associates" have reported an exception 10 the general correlation between adiposity and prevalence of dix betes. A group of fat Afvican women had less diabores than other leaner groups tester under similar condi- tions. Other sioalt and relatively isolwed populations have rates of diabetes thar suggest rates of genetic susceptibility which are higher (Maltese;* and Pima" and Cherokee” Indians) of lower (cerisin Eskimos") than those prevailing in the major races, bur environ smencal factozs may be at lease party responsible for these unwsual prevalence rates, For example, the Chere kees and Pinas are quite fat. The preponderance of ecent evidence suggests that byperinsulinism is the effect and not the cause of obssity. Rimoin” has recently shown some interesting differences between the Amish and the Navajo Indians with respect to the pathologic physiology and characterisies of diabetes If glomervlosclerosis and retinopathy are genetic manifestations unrelated to hyperglycemia or selative insulin insuliciency, shey wood occur commonly in populations protected from hyperglycemia by their en- onments, We know of no repores of typical glomern- losclerosis oF retinopathy in normogljcemics of Pukis- tan, Malaya, Israel, India, Central America o rural Uruguay. While not conclusive, these circumstances suggest that those who ave protected from hypergly- ceinia by envizonmenial conditions such as relative un- dernucttion ace also protected from certain (or pechaps all) clinical manitestacions of diabetes. Therefore, these epidemiologic observations fie best the hypotheses thie the vascular lesions of diabetes are not independent and inevitable manifesations in genetically susceptible per sons, and that these Tesions canbe prevented! by avoiding insulin insufficiency (absolute or relative) ACKNOWLEDGMENT, ‘The list of contributors to these studies is extremly Jong and cannot be given completely here. More comn- plete lists of participants have beet given elsewhere." Many members of the staff of dhe Institute of Nucticion fof Central Amezien and Panama made contributions «0 four studies, Wemer Ascoli, M.D, and Guillermo At- royave, Ph.D, of INCAP served as coordinators of the 662 nutrition surveys which made these diabeses-elated sta ies possible Edwin Bridgforth, Associate Profesor of Statistic University of Mississippi Medical Center, supervise certain aspects of the colletion and analyses of the da relating to diabetes, Walter Unglub, MD, of Tol University and W. J. MeGanity, MID, of the Univers of Tesas (Galveston) also assisted and advised Arnold Schaefer, Ph.D, director of the Nutrition Po ‘eam of the US. Public Health Service, provided adv and support wing and conducting these sti “The major responsibility for the testing activities i the field was borne by thied and fourth year medic sudenss from the United Stes and che survey tea embers inthe different These_ medic students included Rod Tripplet from Vandesbile wh worked in El Salvadoe, and Philipp Borastein fro Washington University ae Se Louis who worked Honduras. The following students from the of Texas Medical Center at Galveston. pasicipats Michiel Cabuzos (Honduras), FE. G. Vega (Nicatagea Ron Smotherman (capitol cites), Rudotfo Villar (Panama), and Orlando Garza. (Costa Rica). The fe Towing stents from the Universiy of Oklahoma pe ticipated: R. 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