Differences between metabolic responses to fasting in obese diabetic and obese nondiabetic subjects.

Abstract

The metabolic response to two weeks' fasting and the influence of starvation on glucose tolerance have been studied in obese diabetic and obese nondiabetic subjects. After an overnight fast, mean concentrations of both blood glucose and plasma triglyceride were significantly greater in the diabetics than in the nondiabetics. In neither group, however, were correlations found in any combination between circulating levels of triglyceride, glucose, insulin, free fatty acids, or the degree of obesity. During the fast, concentrations of plasma triglyceride and blood glucose fell slightly in the nondiabetics, but strikingly in the diabetics, and in the latter these reductions were highly correlated. Glucose tolerance was impaired by starvation in the nondiabetics but considerably improved in the diabetics. In the former, the rise in both serum insulin and plasma lactate concentrations was delayed following starvation. In the latter, the most striking change was a reduction in the basal glucose concentration after fasting; a rise in lactate levels was observed prior to starvation but no elevation was detected during the post-fast glucose tolerance test, while serum insulin responses remained unchanged. It is suggested that in some obese diabetics the development of endogenous hypertriglyceridemia is dependent on increased hepatic gluconeogenesis, and that a reduction in gluconeogenesis is the principal mechanism by which both plasma triglyceride levels are decreased, and glucose tolerance improved, in such patients following starvation. It is further suggested that both diminished β-cell responsiveness and decreased muscle glycolysis contribute to the genesis of starvation diabetes.