Information de reference pour ce titreAccession Number: | 00002591-199307170-00006.
|
Author: | Tuomilehto-Wolf, Eva; Tuomilehto, Jaakko; Hitman, Graham A; Nissinen, Aulikki; Stengard, Jari; Pekkanen, Juha; Kivinen, Paula; Kaarsalo, Esko; Karvonen, Martti J.
|
Institution: | Department of Epidemiology, National Public Health Institute, Helsinki, Finland; Medical Unit, The Royal London Hospital, London E1 1BB; Department of Community Health and General Practice, University of Kuopio, Kuopio, Finland; Loimaa District Hospital, Loimaa, Finland; Pioppi, Italy. Correspondence to: Eva Tuomilehto-Wolf, National Public Health Institute, Department of Epidemiology and Health Promotion, Elimaenkatu 25 A 6th Floor, FIN-00510 Helsinki, Finland.
|
Title: | Genetic Susceptibility to Non-insulin Dependent Diabetes Mellitus and Glucose Intolerance are Located in HLA Region.[Article]
|
Source: | BMJ. 307(6897):155-159, July 17, 1993.
|
Abstract: | Objectives -To test the hypothesis that the genetic susceptibility to non-insulin dependent diabetes mellitus is the same as that to insulin dependent disease and to see whether glucose intolerance is associated with specific HLA haplotypes.
Design -Population based study of men in 1989 first tested for glucose tolerance in 1984. HLA haplotypes, including HLA-A, C, B, DR, and DQ, were defined serologically. HLA haplotype data from a population based Finnish study of childhood diabetes were used for predicting non-insulin dependent diabetes and impaired glucose tolerance.
Setting -Two communities in Finland.
Subjects -Representative cohort of Finnish men aged 70-89, comprising 98 men with non-insulin dependent diabetes mellitus and a randomly selected group of 74 men, who served as controls, who were tested for glucose tolerance twice within five years.
Main outcome measures -Non-insulin dependent diabetes, impaired glucose tolerance, blood glucose concentration.
Results -Diabetes associated HLA haplotypes were present in 94% (85/90) of diabetic subjects, 79% (27/34) of subjects with impaired glucose tolerance, and only 13% (3/23) of non-diabetic subjects. In this group of elderly men sensitivity of the diabetes associated HLA haplotypes for non-insulin dependent diabetes and impaired glucose tolerance was 90%, specificity 87%, and predictive power 97%. Mean fasting blood glucose concentration was only just significantly higher in men with diabetes associated haplotypes than in men with no such haplotypes, but there was a substantial difference in blood glucose values two hours after glucose loading (10.4 and 6.4 mmol/l in men with diabetes associated HLA haplotypes and men with no such haplotypes, respectively (p<0.0001)).
Conclusions -These findings support the hypothesis that specific HLA haplotypes exhibit a common genetic determinant for insulin dependent and non-insulin dependent diabetes. Furthermore, HLA is a major genetic determinant of glucose intolerance in elderly Finnish men. The belief that the HLA predisposition to diabetes is specific for insulin dependent diabetes mellitus is largely incorrect.
(C) British Medical Journal 1993.
|
References: | 1. Neel JV. Diabetes mellitus: a geneticist's nightmare. In: Creutzfeldt W, Kobberling J, Neel JV, eds. The genetics of diabetes. Berling: Springer, 1976:1-11.
2. Pyke DA. Genetics of diabetes. In: Tattersall R, ed. Clinics in endocrinology and metabolism. Vol 6. London: W B Saunders, 1977:285-303.
3. Barnett AH, Eff C, Leslie RDG, Pyke DA. Diabetes in identical twins: a study of 200 pairs. Diabetologia 1981; 20:87-93.
4. Bennett PH, Bogardus C, Tuomilehto J, Zimmet P. Epidemiology and natural history of non-insulin dependent diabetes mellitus: non-obese and obese. In: Albert KGMM, De Fronzo RA, Keen H, Zimmet P, eds. International textbook of diabetes mellitus. Chichester: John Wiley, 1992:147-76.
5. Singal DP, Blajchman MA. Histocompatibility (HL-A) antigens, lymphocytotoxic antibodies and tissue antibodies in patients with diabetes mellitus. Diabetes 1973; 22:429-32.
6. Nerup J, Platz P, Andersson OO, Christy M, Lyngsoe J, Poulsen JE, et al. HLA antigens and diabetes mellitus. Lancet 1974; ii:864-6.
7. Cudworth AG, Woodrow JC. Evidence for HL-A linked genes in juvenile diabetes mellitus. BMJ 1975; iii:133-5.
8. Arnaiz Vellena A, De Cordoba SR, Dujorne IL, Regueiro JR, Bootello A, Serrano-Rios M. HLA factors in non-insulin-dependent diabetes mellitus. N Engl J Med 1980; 303:1065.
9. Tiwari JL, Terasaki PI. Endocrinology. In: HLA disease associations. New York: Springer, 1985:210-2.
10. World Health Organisation Study Group. Diabetes mellitus. WHO Tech Rep Ser 1985; No 727.
11. Harris H. The familial distribution of diabetes mellitus: a study of the relatives of 1,241 diabetic propositi. Annals of Eugenics 1950; 15:95-119.
12. Dahlqvist G, Blom L, Tuvemo T, Nystrom L, Sandstrom A, Wall S. The Swedish childhood diabetes study. Results from a nine year case register and a one year case-referent study indicating that type 1 (insulin- dependent) diabetes mellitus is associated with both type 2 (non-insulin- dependent) diabetes mellitus and autoimmune disorders. Diabetologia 1989; 32:2-6.
13. Tuomilehto J, Lounamaa R, Tuomilehto-Wolf E, Reunanen A, Virtala E, Kaprio EA, et al. Epidemiology of childhood diabetes in Finland. Background of a nationwide study of type 1 (insulin-dependent) diabetes mellitus. Diabetologia 1992; 35:70-6.
14. Diabetes Epidemiology Research International Group. Geographic patterns of childhood insulin-dependent diabetes mellitus. Diabetes 1988; 37:1113-9.
15. Rewers M, LaPorte RE, King HOM, Tuomilehto J. Insulin-dependent diabetes mellitus in childhood: international patterns and trends. World Health Stat Q 1988; 41:179-89.
16. Tuomilehto-Wolf E, Tuomilehto J, Cepatis Z, Lounamaa R, DIME Study Group. New susceptibility haplotype for type 1 diabetes. Lancet 1989; ii:299-302.
17. Tuomilehto J, Nissinen A, Kivela S-L, Pekkanen J, Kaarsalo E, Wolf E, et al. Prevalence of diabetes mellitus in elderly men aged 60 to 84 years in eastern and western Finland. Diabetologia 1986; 29:611-5.
18. Tuomilehto J, Korhonen H, Kartovaara L, Salomaa V, Stengard JH, Pitkanen M, et al. Prevalence of diabetes mellitus and impaired glucose tolerance in the middle-aged population of three areas in Finland. Int J Epidemiol 1991; 20:1010-7.
19. Tienari PJ, Tuomilehto-Wolf E, Tuomilehto J, Peltonen L, Childhood Diabetes in Finland Study Group. HLA haplotypes in type 1 (insulin- dependent) diabetes mellitus: molecular analysis of the HLA-DQ locus. Diabetologia 1992; 35:254-60.
20. Keys A, ed. Coronary heart disease in seven countries. Circulation 1970; 41 (suppl 1):1-211.
21. Nissinen A, Kivela S-L, Pekkanen J, Tuomilehto J, Kostiainen E, Piippo H, et al Levels of some biological risk indicators among elderly men in Finland. Age Ageing 1986; 15:203-11.
22. Pekkanen J, Nissinen A, Puska P, Punsar S, Karvonen MJ. Risk factors and 25 year risk of coronary heart disease in a male population with a high incidence of the disease: the Finnish cohorts of the seven countries study. BMJ 1989; 299:81-5.
23. Tuomilehto-Wolf E, Tuomilehto J, Hitman G, Childhood Diabetes in Finland Study Group. DQA1 and DQB1 heterodimers in insulin-dependent diabetes mellitus: a genetic-epidemiological study in Finland. Ann Med 1992; 24:533-8.
24. Baur MP, Neugebauer M, Albert ED. Reference tables of three-locus haplotype frequencies and delta values in Caucasians, orientals and negroids. In: Albert ED, Baur MP, Mayr WR, eds. Histocompatibility testing. Berlin: Springer, 1984.
25. Briggs BR, Botha MC, Jackson WPU, DuToit ED. The histocompatibility (HLA) antigen distribution in South African blacks (Xhosa). Diabetes 1980; 29:68-70.
26. Williams C, Knowler WC, Butler WJ, Pettitt DJ, Lisse JR, Bennett PH, et al. HLA-A2 and type 2 (insulin-dependent) diabetes mellitus in Pima Indians: an association of allele frequency with age. Diabetologia 1981; 21:460-3.
27. Serjeantson SW, Ryan DP, Ram P, Zimmet P. HLA and non-insulin- dependent diabetes mellitus in Fiji Indians. Med J Aust 1981; i:462-3.
28. Asmal AC, Dayal B, Jialal I, Leary WP, Omar MAK, Pillay NL, et al. Non-insulin-dependent diabetes mellitus with early onset in blacks and Indians. S Afr Med J 1981; 60:93-6.
29. Omar MAK, Hammond MG, Motala AA, Seedat MA. HLA class I and II antigens in South African Indians with non-insulin dependent diabetes mellitus. Diabetes 1988; 37:796-9.
30. Wolf E, Drummond V, Savage M, Dean B, Bottazzo GF, Davidson JC, et al. HLA and islet cell antibodies in diabetics from the West Indies, Qatar and Brazil. Diabetologia 1981; 21:A80.
31. Groop L, Koskimies S, Pelkonen R, Tolppanen E-M. Increased frequency of HLA-Cw4 in type 2 diabetes. Acta Endocrinol 1983; 104:475-8.
32. Zhao T, Chi Z, Wang H, Shen M, Zhou Z, Bu K, et al. HLA and diabetes mellitus in China. Chin Med J 1982; 95:609-12.
33. Serjeantson SW, Owerbach D, Zimmet P, Nerup J, Thoma K. Genetics of diabetes in Nauru: effects of foreign admixture, HLA antigens and the insulin-gene-linked polymorphism. Diabetologia 1983; 25:13-5.
34. Bhatia K, Patel M, Gorogo M. Type 2 (non-insulin dependent) diabetes mellitus and HLA antigens in Papua, New Guinea. Diabetologia (1984; 27:370-3.
35. Spees EK, Kostyu DD, Elston RC, Amos DB. HL-A profiles of the Pima Indians of Arizona. In: Dausset J. Colombani J, eds. Histocompatibility testing. Copenhagen: Munksgaard, 1973:345-9.
|
Language: | English.
|
Document Type: | Papers.
|
Journal Subset: | Clinical Medicine.
|
ISSN: | 0959-8138
|
NLM Journal Code: | 8900488, bmj, 101090866
|
Annotation(s) | |
|
|