GENETIC SUSCEPTIBILITY TO NON-INSULIN-DEPENDENT DIABETES-MELLITUS ANDGLUCOSE-INTOLERANCE ARE LOCATED IN HLA REGION

Objectives-To test the hypothesis that the genetic susceptibility to n on-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, incl uding HLA-A, C, B, DR, and DQ, were defined serologically. HLA haploty pe data from a population based Finnish study of childhood diabetes we re used for predicting non-insulin dependent diabetes and impaired glu cose tolerance. Setting-Two communities in Finland. Subjects-Represent ative cohort of Finnish men aged 70-89, comprising 98 men with non-ins ulin dependent diabetes mellitus and a randomly selected group of 74 m en, who served as controls, who were tested for glucose tolerance twic e within five years. Main outcome measures-Non-insulin dependent diabe tes, impaired glucose tolerance, blood glucose concentration. Results- Diabetes associated HLA haplotypes were present in 94% (85/90) of diab etic subjects, 79% (27/34) of subjects with impaired glucose tolerance , and only 13% (3/23) of non-diabetic subjects. In this group of elder ly men sensitivity of the diabetes associated HLA haplotypes for non-i nsulin dependent diabetes and impaired glucose tolerance was 90%, spec ificity 87%, and predictive power 97%. Mean fasting blood glucose conc entration was only just significantly higher in men with diabetes asso ciated haplotypes than in men with no such haplotypes, but there was a substantial difference in blood glucose values two hours after glucos e loading (10.4 and 6.4 mmol/l in men with diabetes associated HLA hap lotypes and men with no such haplotypes, respectively (p<0.0001)). Con clusions-These findings support the hypothesis that specific HLA haplo types exhibit a common genetic determinant for insulin dependent and n on-insulin dependent diabetes. Furthermore, HLA is a major genetic det erminant of glucose intolerance in elderly Finnish men. The belief tha t the HLA predisposition to diabetes is specific for insulin dependent diabetes mellitus is largely incorrect.