Production and metabolic clearance of glucose under basal conditions in Type II (non-insulin-dependent) diabetes mellitus

Aims/hypothesis. The pathogenesis of fasting hyperglycaemia in Type II (non -insulin-dependent) diabetes mellitus has yet to be clarified. Rates of glu cose production (R-a), utilization and metabolic clearance rate were theref ore measured during an extended fast, in control subjects and in Type II di abetic patients. Methods. Nine subjects with newly-diagnosed or diet-treated diabetes and se ven control subjects matched for age and weight (BMI 36.0 +/- 2.4 and 35.3 +/- 3.1 kg/m(2) respectively) underwent an overnight fast followed by a 10- h unprimed infusion of [6-H-3]glucose. Plasma tracer concentrations were fi tted by a single-compartment model. Results. The metabolic clearance rate was near-constant [61.7 + 2.4 ml/(min -m(2))] in diabetic patients and [75.5 +/- 3.3 ml/(min-m(2))] in control su bjects (p < 0.05). It was correlated to the glucose concentrations both at t = 0 (r = -0.752, p = 0.0008) and t = 10 h (r = -0.675, p = 0.004). The ca lculated volume of distribution was 17.3 +/- 1.41 (18.2% weight, diabetes), 19.6 +/- 2.41 (18.4% weight, control). Glycaemia fell from 10.7 +/- 0.8 mm ol/l to 6.5 +/- 0.3 mmol/l by 10 h (p < 0.05) in diabetes and from 5.6 +/- 6.6 to 4.8 +/- 0.1 mmol/l in control subjects (p < 0.05). The rate of gluco se production decreased in parallel, from 563 <plus/minus> 33 to 363 +/- 23 mu mol/(min-m(2)) (p < 0.05) in diabetes from 419 <plus/minus> 20 to 347 /- 32 mu mol/(min-m(2)) in control subjects. Initial R-a was higher in diab etic patients than in control subjects (p < 0.05) and was highly correlated to glycaemia (r = 0.836, p = 0.0001). By 10 h, R-a had converged in diabet ic patients and control subjects and all correlation with glycaemia was los t (r = 0.0017, p = 0.95). Conclusions/interpretation. In relatively early diabetes, the more "labile" portion of fasting hyperglycaemia, which subsequently decreased, was close ly related to the simultaneously decreasing R-a. The 25% increase in glucos e concentrations which persisted as stabilized R-a, resulted from about a 2 0% lower metabolic clearance rate.