Contribution of Gluconeogenesis to Overall Glucose Output in Diabetic and Nondiabetic Men

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Abstract
Increased hepatic glucose output is the main cause of fasting hyperglycemia in non-insulin dependent diabetes mellitus. Due to difficulties in obtaining a quantitative estimate of gluconeogenesis in vivo, the relative contribution of gluconeogenesis and glycogenolysis to this increased hepatic glucose output was unknown. The application in vivo of a new isotopic approach based on a mathematical model of the Krebs cycle enabled us to obtain a quantitative estimate of gluconeogenesis in vivo Using this approach, gluconeogenesis was found to account for 28% and 97% of overall hepatic glucose output in healthy volunteers in the postabsorptive and in the fasted state respectively. When this technique was used to compare gluconeogenesis rates in non-insulin dependent diabetes mellitus and nondiabetic patients, gluconeogenesis was found to be increased threefold in the patients with non-insulin dependent diabetes mellitus (12.7 ± 1.6 μ vs 3.6 ± 0.6 μmol/Kg/min) and to be significantly correlated with fasting plasma glucose. Furthermore, the increase in gluconeogenesis could explain more than 80% of the increase in overall hepatic glucose output in patients with non-insulin dependent diabetes mellitus. In conclusion, in non-insulin dependent diabetes mellitus, gluconeogenesis, as measured by a new isotopic technique, is increased and this increase represents the main cause for increased overall hepatic glucose output and fasting hyperglycemia.