Genetic susceptibility to the development of retinopathy in insulin-dependent diabetics.

HLA types and blood glucose control were investigated in 127 insulin-dependent diabetics with different grades of severity of retinopathy. The means of all afternoon clinic blood glucose levels from the diagnosis of diabetes were 9.9 +/- 2.1 mmol/L for patients with no retinopathy, 11.8 +/- 2.1 mmol/L for patients with background retinopathy, and 12.4 +/- 2.1 mmol/L for patients with proliferative retinopathy (P less than 0.0001). HLA-DR4 was present in 61 of 87 patients (70%) with background or proliferative retinopathy and 21 of 39 (54%) with no retinopathy. The frequency of HLA-DR4 was lowest in patients with no retinopathy despite "poor control" (mean blood glucose greater than or equal to 11.5 mmol/L) and highest in those who had developed retinopathy despite "good control;" the frequencies of HLA-DR2 showed the reverse pattern. Mantel-Haenszel tests were used to calculate the odds ratios for the presence of retinopathy associated with "poor control" and with HLA-DR4, since each modified the effect of the other. The odds ratio for retinopathy associated with "poor control" was 6.7 (P less than 0.0001). The odds ratio with HLA-DR4 was 3.7 (P less than 0.005). When both risk factors were present, the odds ratio increased to 33.3 (P less than 0.0001). Genetically determined factors appear to influence susceptibility to retinopathy in insulin-dependent diabetics.