The effects of total starvation upon response to glucose and tolbutamide were studied in obese nondiabetic and in obese diabetic individuals. Response was determined by serial measurement of plasma insulin, glucose, NEFA, and beta-hydroxybutyrate levels. In confirmation of other reports, obese diabetics had significantly greater plasma insulin responses to glucose and tolbutamide prefasting. Following a prolonged fast, obese nondiabetics developed increased insulin resistance manifested by impaired glucose tolerance without significant change in plasma insulin response. In contrast, obese diabetics had little further deterioration in glucose tolerance or increase in insulin resistance. In both groups studied, the response of blood glucose and plasma insulin levels to tolbutamide was unaltered by caloric deprivation. Carbohydrate intolerance of fasting appeared best explained by increased contra-insulin factors and decreased islet cell responsiveness to glucose. Fasting, for at least seven days, failed to reproduce in the nondiabetic obese individuals the patterns of response to glucose and tolbutamide seen in obese diabetic subjects.

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