Insulin secretion improves following dietary control of plasma glucose in severely hyperglycemic obese patients

Severely hyperglycemic obese patients show deficient insulin secretion as well as insulin resistance. To determine whether the secretory defect is reversible, we placed 7 hospitalized patients on severe caloric restriction for 4--12 wk. Insulin secretory responses to oral glucose and intravenous tolbutamide were assessed before and after the diet. On entry, mean fasting plasma glucose (FPG) was 326 +/- 23 mg/dl. The insulin response to oral glucose was completely flat, although modest secretion was evoked by tolbutamide. After initiating caloric restriction, FPG rapidly fell, reaching 150 +/- 21 mg/dl by 2 wk, and remained low throughout the duration of the diet period. At restudy, improved oral glucose tolerance was accompanied by significant increases in the insulin secretory responses to both glucose and tolbutamide. These results support the concept that control of plasma glucose concentration allows recovery of insulin secretion. The degree of weight loss necessary to achieve this effect was modest. Since blood glucose was effectively controlled by caloric restriction alone, exogenous insulin is probably not required in the initial management of most obese patients with severe hyperglycemia.