Solutions of 15 per cent glucose were administered by continuous intravenous infusion for five to seven days to six normal subjects, seven tolbutamide-responsive adult diabetics, and six tolbutamide-nonresponsive adult diabetics. Blood glucose concentration, plasma insulin activity, and net assimilation of carbohydrate were determined daily. An “insulogenic index,” relating level of circulating insulin activity to magnitude of glycemic stimulus, enabled comparison of the insulin-secreting capacity of respective groups.

In nondiabetic subjects, mean daily blood glucose levels remained normal, and carbohydrate loads averaging 717 gm. per day were wholly retained. In both diabetic groups, increasing blood glucose and glycosuria permitted net glucose uptakes of only 88 per cent in tolbutamide-responders and 56 per cent in tolbutamide-nonresponders.

Plasma insulin activity increased significantly in all groups. In both normal subjects and tolbutamide-responsive diabetics, enhanced levels appeared on the first day, were sustained at high titers each day thereafter, and exhibited mean maximal value on the last day of infusion. Conversely, in tolbutamide-nonresponsive diabetics, average maximal insulin activity was achieved on the second day, whereafter it declined progressively and sometimes disappeared completely.

Compared to an insulogenic index of 100 per cent to represent the greatest secretory response of normal subjects, the corresponding maximal index was 49 per cent for tolbutamide-responders and 17 per cent for tolbutamide-nonresponders. On the last day of infusion, capacity for sustained insulin release was reflected by insulogenic indexes of 55 per cent, 32 per cent and 0.1 per cent in the respective groups.

The data indicate that unremitting hyperglycemia tends to exhaust insulogenic reserve in adult-onset diabetics, and that betacytotropic collapse occurs most rapidly in patients with severest clinical intolerance to carbohydrate. This demonstration strengthens the view that maturity-onset diabetes and growth-onset diabetes represent different stages of the same disease. The findings suggest that the fundamental lesion in hereditary human diabetes is either primary beta cell deficiency or impaired responsiveness of peripheral tissues to the action of insulin—or, quite possibly, a combination of both.

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