ABNORMAL TRANSIENT RISE IN HEPATIC GLUCOSE-PRODUCTION AFTER ORAL GLUCOSE IN NON-INSULIN-DEPENDENT DIABETIC SUBJECTS

A transient rise in hepatic glucose production (HGP) after an oral glu cose load has been reported in some insulin-resistant states such as i n obese fa/fa Zucker rats. The aim of this study was to determine whet her this rise in HGP also occurs in subjects with established non-insu lin-dependent diabetes mellitus (NIDDM). Glucose kinetics were measure d basally and during a double-label oral glucose tolerance test (OGTT) in 12 NIDDM subjects and 12 non-diabetic 'control' subjects. Twenty m inutes after the glucose load, HGP had increased 73% above basal in th e NIDDM subjects (7.29 +/- 0.52 to 12.58 +/- 1.86 mu molkg/min, P < 0. 02). A transient rise in glucagon (12 pg/ml above basal, P < 0.004) oc curred at a similar time. In contrast, the control subjects showed no rise in HGP or plasma glucagon. HGP began to suppress 40-50 min after the OGTT in both the NIDDM and control subjects. A 27% increase in the rate of gut-derived glucose absorption was also observed in the NIDDM group, which could be the result of increased gut glucose absorption or decreased first pass extraction of glucose by the liver. Therefore, in agreement with data in animal models of NIDDM, a transient rise in HGP partly contributes to the hyperglycemia observed after an oral gl ucose load in NIDDM subjects.