Reduced insulin binding in a large kindred with severe diabetic retinopathy

Specific insulin binding to erythrocyte receptors (IRB) has previously been reported to be unaltered in children and adolescents with insulin dependent diabetes mellitus (Ped. 66:385, 1980). However, we report here that five insulin dependent, ketosis-resistant juvenile diabetics from the same kinship have a significant reduction in the percent IRB (normal 8.32±2.71 vs 4.72±0.84 for the diabetic children). Three non-diabetic juveniles in the family have an intermediate value of 5.77±1.08. The youngest child shows normal binding. Scatchard analysis of the high and low affinity insulin binding sites indicates that the reduced IRB is due to a decrease in the number of receptor sites per cell. There is no correlation with circulating plasma insulin values nor with the severity of diabetes. However, the insulin dependent diabetics have an inordinate degree of ocular and vascular complications for the severity of their diabetes. Human lymphocyte antigens A, B, C, and D as well as islet cell antibodies are being determined in all family members to correlate with IRB data. Since diabetes mellitus is a heterogeneous disorder, we postulate that abnormal IRB in these patients may be genetically determined and related etiologically to their severe microangiopathy (retinopathy).