Krikler, Dennis M.

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26 July 1969 E Die L JOUR AL 931TABLE XVlll. KIDNEY TUMOURS (I 0): \ ILM' AND HYPER EPHROM BY GE AND EXMale FemaleHypernephroma Hypernephroma Wilm's HypernephromaTotal o. adenocarcinoma adenocarcinoma average age average ageYear ofcases Wilm's + sarcoma Wilm's + sarcoma peranllllm per annum194 3 I I 1 2 year -9 year1949 3 1 1 4 month -9 year1950 3 I 4 months 50 year1951 I I 35 years1952 2 2 36 years1953 5 2 I 2 2t years 37 year1954 3 I 2 ~ months 43 year1955 5 2 2 1 3 -year 44 year1956 5 2 I 1 5t year 34 year1957 3 1 I I 4 year 60 year195 6 2 1 I 2 7 year 65 year1959 6 2 I 3 2 year 41 year1960 4 2 2 9 month 66 year1961 11 4 3 3 4 years 4 year1962 6 2 2 2 It year 57 year1963 9 4 2 3 ~ years 41 years1964 9 3 3 I 2 year 45 yearTotal 88 13 32 20 23Other clinical observations are made on the increasing num-ber of cases at certain age, suggesting altering ho t resi lance.This i followed on release of control by a relatively uniformrapid growth, suggesting that host-tumour relationship habeen modified allowing a presumed dormant cell to developuncontrollably.The inference is that the host-tumour relationship is partiallycontrolled by hormone imbalance.I wi h to thank Or W. H. F. Kenny, Medical Superintendentof Baragwanath Hospital, for permission to undertake thissurvey, and Or A. Schmaman for access to the pathologyrecord. I am also indebted to the late Or A. G. Oettle whosuggested this survey but unfortunately died in the earlystages before having an opportunity to assemble the data-his analysis would indeed have been very valuable.J should al 0 like to thank Mr Haywood, of the regi try atBaragwanath Hospital, for hi help and adequate recordkeeping; Mr C. Maba 0 for hi a i tance with extraction ofthe bed letter; and Me dames O. 'yickery, . Woolford andJ. Doody for their untiring assistance in tran cribing andrecording detail from numerou ources.REFERENCESJ. Higgin on, J. and Oettlt!, A. G. (1960): J. Nat. Cancer Inst., 24. 5 9.2. Oenlt!, A. G. (1964): Ibid., 33, 3 3.3. World Health Organiz.ation (1951): Mallual of the IlItematiollal Statis·tical Classification of Diseases, Injuries and Causes 01 Death, 7th re-vision, vo!. I, p. 15. Geneva: WHO.4. De Moor. N. G. (196 ): S. Afr. Med. J., 43, 92.DIABETES IN RHODESIAN SEPHARDIC JEWS*DENNlS M. KRIXLER,t M.B. (CAPE To ), M.R.C.P., M.R.C.P. (Em .), Consultant Physician, Prince of Wales'sHospital, London, UKThere are well-defined genetic difference betweenAshkenazi (Central and Eastern European) and Sephardi(Mediterranean and ear Eastern) Jews, and this is re-presented in differing liabilities to ome di ea es.'" TheJewi h population of outhern Rhode ia (5,500) is largelyof A hkenazi origin, but in Salisbury (total Jewish popu-lation 2,500) there is a Sephardi community numberingabout 550. Apart from a few recent arrivals, the Sephardisor their immediate ancestors came from the Dodecaneseislands of Rhodes and Cos and the adjacent Turkish main-land town of Budrum (Hallicarna sus). When Rhodesiawa colonized at the end of the 19th century, the originalimmigrants included Sephardi Jew and Greek Cbri tianfrom these areas, a well a A hkenazi Jews, mainlyfrom Lithuania:Because of the presence of these distinct Jewish com-munities, which largely remained unmixed until recent• Date received: 26 September 196 .Formerly Phy ician, Central Hospital, Salisbury, Rhodesia.year, but which have very imilar economic and ocialbackground, it wa decided to make a retro pective sur-vey of illnes es in over 5,000 un elected patients of variousethnic group een between 1958 and 1966. This revealeda pre iously unsuspected high incidence of diabete melli-tu in the ephardic community.THE SURVEYThe patient were all seen in a con ultant practice thathad no pecial bias towards diabete ; 30% of tho e eenhad cardiova cular di ea e. Most were drawn from ali-bury and the re t of Mashonaland, but ome camefrom other parts of Rhode: ia and from neighbouringterritorie. African patient were only occa ionallyencountered. The patient of all group were referred bythe same practitioners. While the number of Jewi h patientwa di proportionately (approximately 3 times) higher thanin the general population, the A hkenazi- ephardi patientratio wa comparable with that in the community, and932 .A. TYD KRIF VIR GE EE KU DE 26 J ulie 1969TABLE I. I ClUE CE OF DIABETES IN MAIN ETHNIC GROUPSDiabeticsTABLE H. INCfDE CE OF DIABETES I JEWISH SUBGROUPS A D GREEKSDiabeticsthere were no factor likely to cause pecial election ofeither of the e group .Diabete wa diagno ed according to the criteria of theBritish Diabetic A ociation.' In all patients the urine wate ted for glucose, and the great majority had postpran-dial blood-glucose estimation, which, in doubtful case ,were upplemented by gluco e-tolerance curve.Of 5,162 patient of all group, 188 (3·6%) were dia-betic; the incidence in the main ethnic group is hown inTable I. The Jewish groups were more precisely cia ified,and data for Greek Chri tians were extracted for com-parison (Table Il). The difference in the incidence ofdiabetes in the A hkenazi and Sephardi populations ihighly ignificant (X = 7·6, p<O·O I) but the figures forA hkenazi and Greek are comparable, and the differencebetween A hkenazis and White gentiles is not significant(p = 0·20). Among the Indians (Table Ill) the few Goanesehad an exce of diabetes, but the actual numbers are toosmall to warrant firm conclusions.Juvenile diabetics were found in all ection exceptSephardis (Table IV), but the difference between Ash-kenazi and Sephardi i not significant (p = 0·35, 2-tailedte t). The clinical presentation and age tructure ofTABLE IV. MAT RE AND JUVE lLE DIABETICSGroup Pancreatic Latent / DoubtfulpotentialA hkenazi 0 2 2Sephardi 0 I 0[ndian 2 I 1White genlile 6 2 2mature diabetics were imilar in all group, but there waan excess of males in the mature Indian and White gentileca es, and of female in White gentile juvenile diabetics.Pancreatic and 'potential' or latent diabetic were alsofound in the survey and, with doubtful ca es, are li ted inTable V.TABLE v. SECO DARY OR DOUBTFUL DIABETESDlSCUSSIOThis is not a study of the prevalence of diabete but ofits occurrence in patients referred for all causes. A pro-pective survey of the whole community was not practical,but a retro pective study can be of some epidemiologicalvalue.' While observer bias cannot be excluded, the oppo-site outcome had actually been expected, i.e. more dia-betes in the Ashkenazis than in the Sephardis.As a general rule, Rhodesian Whites and Indians areprosperous, and almost all receive private medical care.Living conditions among the Whites are comparable, withno major differences between the 2 Jewish sections savethat the traditional Sephardi diet resembles the Greek;this is only important among the older members. BothJewish groups may make greater use of medical facilitiesthan other groups, and this may lead to the detection ofmore diabetics because they present for examinationregularly instead of only in the case of illness. However,the difference between Ashkenazis and gentiles in thissurvey was not significant, and this would not explainthe higher numbers among the Sephardis. Greeks andSephardis are similar in temperament; both groups arelargely occupied in trade. Caffeine inge tion, which doesnot appear to be as important a factor in the pathogenesisof diabetes as previously thought: is probably greater inGreeks and Sephardis than in the other groups. Thehigher incidence of diabetes in Sephardis than Ashkenazior Greeks suggests that they possess a trait, possiblygenetic, not present in the others.Diabetes may be inherited a a simple Mendelian-recessive trait,' but others believe that multifactorialinheritance is more likely: The impression that diabetesis more common in Jews than gentiles has been contra-dicted;" but if Jews do have a greater tendency to diabetesit may reflect the effects of repeated inbreeding." Becauseit is usually difficult to obtain details of consanguinity incommunities prone to diabetes,ll the findings in theSephardis of Rhodesia are important.The impression that this community is highly inbred isconfirmed by study of !he marriage records of the Salis-bury Jewish congregations, which were checked withsenior members of the communities as well as the familiesof those concerned (Table VI). There are no known casesof consanguineous marriages in the Ashkenazi com-munity. Until 1935, marriages between Asbkenazisand Sephardis were rare, but they have steadily becomemore frequent; and there are now sign that the division%8·98·728·625I I12 3148 110All casesumber %29 6·415 14·41 10o 05 5·6umber %45 7·931 11·3110 2·62 2·1umber101182o 02 1919 6245610410I89112127288TotaloI135712754,22195TotalJuvenileoI6I2991I1135Matureo1856Male Female Total Male Female Total Male Female Total13 12 25 3 I 4 16 13 297 8 15 0 0 0 7 8 15TABLE Ill. I ClUE CE OF DIABETES IN INDIA SUBGROUPSDiabeticsTotalGroupJewsIndians ..GentilesMiscellaneousGroupAshkenaziSephardi (from Rhodes)Sephardi (not from Rhodes) ..Mixed (Ashk.-Seph.)Greek ChristiansGroupMoslemHindu ..GoaneseOtherGroupAshkenaziSephardi (Rhodes)Sephardi (nolRhodes)IndianWhite gentile26 July 1969 MEDICAL JOUR AL 933TABLE VI. JEWISH 1ARRI GES I ALL B RY (1910-1954)between the communitie are breaking down. The rela-tion hip between the partners in Sephardi con anguineousmarriage i often c10 e (fable VII). The e figure191()-34 1935-54 Total 19I()-34 1935-54 TOlolTo members of the samegroup (non<onsan-guineous) 22 49 71 48 143 191Consanguineous 8 13 21 . 0 ?OTo members ofother groups 4 27 31 0 12 12To gentile proselytes I 3 4 I 0 ITotal 35 92 127 49 155 2·Information not available.TABLE VII. SEPHARDI CO SA GUI EOUS 1ARRIAGEScently been recognized among the avajo Indian ofArizona; maturity-on et diabete i common, yet theju enile form unknown. 1l Unfortunately it eem impo -ible to make accurate tudie of the marriage patternamong the a ajo because of the matrilineal tru tureand the con tant changing of name ." The a ajo do notappear unduly prone to a cular complication which do.however, occur in many of the Rhode ian ephardicdiabetics.Migration from Rhode re ulted from economic de-cline and lack of opportunity for the young. Undercondition of poverty, the diabetic trait may have beenadvantageous-a 'thrifty genotype"S which became detri-mental under the pro perous condition in Rhodesia.Another genetic a ociation with diabete of po ibleimportance in a community from the ea tern Mediter-ranean is gluco e-6-pho phate dehydrogena e (G-6-PD)deficiency. Not only is the association between thi con-dition and impaired gluco e tolerance unclear," butG-6-PD deficiency is extremely rare in Jews from Rhode;there were no in tance in a random ample of 35 ubjectexamined in Salisbury," and only one family among tho eliving in I rael i known to be affected."umberI5232Ashk~na:; congr~atio"S~phardi congrqationRelationshipUncle-nieceFirst cousinFirst cousin, once removedSecond cousin ..Second cousin, once removedMore distantprobably understate the frequency of such marriages, ait was customary for single men to migrate to Rhodesiaand, once established, temporarily to return to the i landfor an arranged marriage, often to a relative. This has notbeen possible since the outbreak of the war in 1939 andthe virtual annihilation of the community in Auschwitzin 1944.1'Consanguineous marriage are generally more frequentin small communities·· and are favoured by religioustradition in the Middle East.' They are often contractedby Moslems," among whom the Jews of Rhodes had livedsince the island fell to the Turk~ in 1522. But there isanother factor favouring consanguineous marriages in thisparticular community. Because girls who had marriedmen from elsewhere and left the island with them lackedthe protection of their men-folk and were ometimes ill-treated, this practice wa banned by rabbinical decree in1767.15 Men were allowed to bring wives from abroad tothe island, but unless a foreigner who wished to marry agirl from Rhode was prepared to ettle on the island, thewomen were often forced by circumstances to marry closerelatives. This tradition persisted, so that when men whohad migrated from the island returned to fetch bride, itwould be natural for them to marry relatives. Althoughthe average frequency of cousin marriages in an Ash-kenazi sample in Israel was higher than is usual inwestern countries, it was much less than that found inmany non-Ashkenazi communities;" and experience inRhodesia showed that consanguineous marriages were notfavoured by Ashkenazis (fable VI). Cousin marriages arenot a feature among the Greeks in Salisbury, but appearto be common among the few Goanese, who also had ahigh incidence of diabetes (fable Ill).The lack of juvenile diabetics among the Sephardis isstriking, but may not be statistically significant and isdifficult to under tand. It argues against the contentionthat late-onset cases of diabetes are heterozygote, andjuvenile cases homozygotes.'" A imilar situation ha re-SUMMARYDiabetes mellitus is more common in Sephardi Jew than inother European or Asian ethnic groups in Rhodesia. MostRhodesian Sephardi Jew are Ihe original immigrants fromthe island of Rhodes, or their immediate descendants. Con-sanguineous marriages have been favoured by them for manygenerations; the great frequency of diabetes is probably dueto this, and not to their Jewish descent, or environmentalfactor alone.I wish to thank Mesdames P. Meltzer and H. Woolfson forextracting the marriage records, and Dr M. J. S. Langman forhelp with the statistical analysis.REFERENCEI. Groen, J. J. (1964): Arch. Intern. Med., 113, 543.2. Sheba, C., Suinberg. A., Ramot, B.. dam. A. and Ashkenazi, I.(1962): Amer. J. Publ. Hlth, 52. 1101.3. Krikler, D. M. (196): Wiener Library Bulletin, 22. 19.4. Fittgerald, M. G. and Keen, H. (1964): Brit. Med. J., I, 156 .5. Mulcahy, R., Hickey, . and Maurer, B. I. (1967): Ibid., 2, 312.6. Jankelson, O. M., Beaser. S. B., Howard. F. M. and Mayer, J. (1967):Lancet, I. 527.7. Steinberg, A. G. (1961): Diabetes, 10, 269.Simpson, . E. (1965): Ibid., 13, 462.9. Cohen, A. M. (1961): Metaboli m, 10, 50.10. Renold, A. E. and Cahill. G. F. inr in Stanbury, J. B.• Wyngaarden.J. B. and Fredrickson, D. S .. eds. (1967): The Melabolic Basis 0/Inheriled Disorder. 2nd ed., p. 72. ew York: McGraw-Hill.11. White. P. (1965): Med. Clin. . Amer., 49, 57.12. Galante. A. (194 ): Appendice a I'Hislorie des Jui/s de Rhodes, Chio,Cos. elC., p. 65. Istanbul: Kagit ve Basum lsleri A.S.13. Dunn, L. C. (1959): HeredilY and Evolulion in Human Populaliolls. p.112. Cambridge, Mass.: Harvard University Prcs_s.14. Ronen, A., Ronen, I. and Goldschmidt. E. in Goldschmidt, E.. ed.(1963): The Genelics 0/ Migranr and Isolale Populruions, p. 340. Balti·mOre: Williams & Wilkins.15. Galante, A. (1935): Hisloire des Jui/s de Rhodes, p. 71. Istanbul: .A.de Papeterie et d']mprimerie Fratelli Haim.16. Harris, H. (1950): Ann. Eugen. (Lond.). IS, 95.17. Saiki, J. H. and Rimoin, D. L. (196 ): Arch. Intern. Med .• 122, I.18. 'eel, J. V. (1962): Amer. J. Hum. Genet., 14, 353.19. Eppes, R. B.• Brewer, G. J., DeGowin. R. L., Mc amara, J. V..Flanagan. C. L., Schrier, S. L .• Tarlov, A. R., Powell. R. D. andCarson, P. E. (1966): ew Engl. J. Med., 275. 55.20. Kinnear, A. A. (1966): Personal communication.21. heba, C. (1967): Personal communication.

Diabetes in Rhodesian sephardic Jews

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Diabetes in Rhodesian sephardic Jews

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