Dimitriadis, George

To assess the normality of islet A- and B-cell responses to a nonglucose secretogogue as well as the modulating effect of glucose in NIDDM, we examined plasma C-peptide and glucagonresponses to arginine in eight patients with NIDDM and in six age- and weight-matched nondiabeticvolunteers under conditions of identical hypoglycemia (∼70 mg/dl), euglycemia (94 mg/dl), and hyperglycemia (∼190 mg/dl). Plasma C-peptide responses to glucose and to arginine in the diabetic subjects were both significantly reduced at all glucose concentrations studied (P < 0.01–0.005). The modulating effect of glucose on both islet A- and B-cell responses (slope of relation between plasma Cpeptide or glucagon response versus plasma glucose concentration) was reduced 80% in the diabetic subjects (P < 0.01). We conclude that islet A- and B-cell responses to nonglucose secretogogues are abnormal in patients with NIDDM and that this may result from a functional defect in the modulating effect of glucose on insulin and glucagon secretion, which in some patients may be compensated for by hyperglycemia.

Since little is known regarding the appropriate time for preprandial insulin administration, we compared the effects of 30-min subcutaneous insulin infusions started 60 min, 30 min, and immediately before meal ingestion on postprandial plasma glucose and insulin profiles in eight subjects with insulin-dependent diabetes mellitus. Of these three regimens, administration of insulin 60 min before meal ingestion provided plasma glucose and insulin profiles closest to normal and permitted less insulin to be used. Our results suggest that adjustments in the timing as well as in the amount of insulin administered preprandially may be used in the management of diabetes and that prolonging the interval between administration of insulin and meal ingestion may reduce insulin requirements and thus decrease the hyperinsulinemia usually associated with insulin therapy.