To determine if the abnormal A-cell function of human diabetes can be corrected by insulin therapy, 10 patients with juvenile-type and 10 with adult-onset types of diabetes were aggressively treated with insulin for up to 10 days. Glucose, immunoreactive glucagon (IRG), and, where possible, insulin were measured in plasma specimens obtained at two-hour intervals for periods of up to 10 days. These patients were compared with nine nondiabetics who were studied similarly.

During a two-day “uncontrolled” period, marked hyperglycemie, glycosurie, and elevated IRG concentrations were present in both groups of diabetic patients. “Improved control” was achieved in the juvenile-type diabetic group with an average insulin dose of 115 ± 24 U. per day. Such therapy significantly reduced the mean plasma glucose (p < 0.001) and IRG (p < 0.05) concentrations when compared with the “uncontrolled” period, but both remained above (p < 0.05) the values seen in the nondiabetk subjects.

“Improved control” was achieved in the maturity-onset group of patients with an average insulin dose of 160 ± 24 U. per day. This dose was associated with a mean plasma-insulin value of 106 ± 26 μU. per milliliter, significantly greater (p < 0.05) than that of the nondiabetk: group. Mean plasma glucose (p < 0.001) and IRG (p < 0.02) concentrations were reduced significantly as compared with the “uncontrolled” period; the mean IRG level was the same as that of the nondiabetics, but the mean plasma glucose levels remained significantly greater (p < 0.001) than in the nondiabetics.

The results indicate that aggressive administration of insulin by conventional means does significantly reduce the average IRG level in juvenile-type and adult-type diabetics. However, despite the large doses of insulin and unphysiologically high concentrations of circulating insulin in the juvenile-diabetic group, IRG remained significantly above that of the nondiabetics. In the adult-onset group, although it was reduced to normal, the IRG level can be viewed as above normal relative to the persistent hyperglycemie and hyperinsulinemia.