Beta-Cell Dysfunction in Nondiabetic HLA Identical Siblings of Insulin-Dependent Diabetics

B-cell function was tested in siblings of insulin-dependent diabetics (IDD). From previous studies, it is now recognized that the risk of developing IDD is highest in those sharing both haplotypes (S_2H) and lowest in those sharing neither haplotype (S_OH) with the diabetic. Insulin secretion in response to intravenous arginine and glucose was evaluated in S_2H, S_OH, and matched controls. Intravenous arginine and glucose elicited an exaggerated acute phase of insulin secretion in S_2H compared with controls when analyzed as incremental insulin area 0–10′, peak level attained, and mean insulin levels postinjection. Insulin responses to arginine and glucose in S_OH and matched controls were identical. We hypothesize that the increased beta-cell activity found in S_2H predisposes their beta-cells to damage by environmental factors and may be part of the mechanism conferring the increased risk of IDD in S_2H.