Influence of genetic factors (HLA class II genes, insulin-gene region polymorphisms) and metabolic control on the development of diabetic nephropathy.

Both metabolic and genetic factors may contribute to the etiology of diabetic nephropathy. We selected 2 different groups of Type I diabetic patients in an attempt to evaluate both factors. HbA1c values and urinary albumin excretion were examined in 114 selected Type I diabetes patients with disease duration of more than 15 yr. We found signs of late renal complications in 28% of these patients. A clear difference in blood glucose control appeared between the 2 groups; the mean HbA1c value during the last 3 yr was 9.5% in the group with microalbuminuria or nephropathy, compared to 8.5% in the normoalbuminuric group (p < 0.0001). With the aim of studying genetic markers alone, we selected a group of 30 Type I diabetes patients with microalbuminuria and a control group of patients without microalbuminuria, but with very similar blood glucose control (e.g. similar mean 1 yr HbA1c values), age and disease duration. All individuals in both patient groups were genomically typed for HLA-DR, -DQ genes and insulin-gene region (INS) polymorphisms. We found no association between HLA class II alleles and microalbuminuria. Neither did we find any association with particular INS polymorphisms. This data indicates that neither genes in the HLA nor in the insulin region are of importance for development of diabetic microalbuminuria. However, all 11 patients with overt nephropathy carried a given INS polymorphism, suggesting an influence of this region for progression to overt nephropathy.