Objectives (a) To study whether there was an increased prevalence of glucose intolerance in the parents of probands with Type 1 diabetes and (b) to look for any possible link between the glucose intolerance in the parents with HLA-DQB1 alleles transmitted in excess to the Type 1 diabetes offspring.
Study Design and Methods
From 215 families of South Indian Type 1 diabetes probands, 336 parents (170 fathers, age 30ยฑ70 years; 166 mothers, age 23ยฑ72 years) were studied by oral glucose tolerance test (GTT). Glucose intolerance in the parents was compared with the population data available. HLA-DQB1 alleles in 170 of the families were studied by the Olerup method (based on sequence speciยฎc primers) and the transmission disequilibrium test (TDT) was used to determine the Type 1 diabetes-associated DQB1 alleles.
Results Among the parents 11.2% had Type 2 diabetes which was similar to the population data of 11.6%. However there was a male predominence among the diabetic parents (x 2 =7.0, p=0.008), while in the population there was a female predominence. Prevalence of IGT was signiยฎcantly more among the parents (13.6%) compared with the population data (9.1%) (x 2 =6.43, p=0.011). Both HLA-DQB1*0201 ( p<0.0001) and DQB1*0302 ( p=0.0001) were positively associated with Type 1 diabetes in the probands although 21% of the probands possessed neither DQB1*0201 or DQB1*0302. The distribution of glucose tolerance categories in the parents of the probands differed according to the presence of DQB1*0302 (p= 0.035) whilst no such differences existed for DQB1*0201.
Conclusions In summary, the presence of Type 1 diabetes in the South Indian offspring does not predict a higher occurrence of Type 2 diabetes in the parents. However, there is an increased occurrence of impaired glucose tolerance (IGT) among the parents. Family based studies demonstrate increased transmission of HLA-DQB1*0201 and HLA-DQB1*0302 with Type 1 diabetes similar to North American and European Caucasian subjects. Furthermore, HLA-DQB1*0302 may be a minor determinant of glucose tolerance in parents of offspring with Type 1 diabetes.