Aims/hypothesis: The pathogenesis of fasting hyperglycaemia in Type II (non-insulin-dependent) diabetes mellitus has yet to be clarified. Rates of glucose production (Ra), utilization and metabolic clearance rate were therefore measured during an extended fast, in control subjects and in Type II diabetic patients.
Methods: Nine subjects with newly-diagnosed or diet-treated diabetes and seven control subjects matched for age and weight (BMI 36.0 +/- 2.4 and 35.3 +/- 3.1 kg/m2 respectively) underwent an overnight fast followed by a 10-h unprimed infusion of [6-3H]glucose. Plasma tracer concentrations were fitted by a single-compartment model.
Results: The metabolic clearance rate was near-constant [61.7 + 2.4 ml/(min-m2)] in diabetic patients and [75.5 +/- 3.3 ml/(min-m2)] in control subjects (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 calculated volume of distribution was 17.3 +/- 1.4 l (18.2 % weight, diabetes), 19.6 +/- 2.4 l (18.4 % weight, control). Glycaemia fell from 10.7 +/- 0.8 mmol/l to 6.5 +/- 0.3 mmol/l by 10 h (p < 0.05) in diabetes and from 5.6 +/- 0.6 to 4.8 +/- 0.1 mmol/l in control subjects (p < 0.05). The rate of glucose production decreased in parallel, from 563 +/- 33 to 363 +/- 23 micromol/(min-m2) (p < 0.05) in diabetes from 419 +/- 20 to 347 +/- 32 micromol/(min-m2) in control subjects. Initial Ra was higher in diabetic patients than in control subjects (p < 0.05) and was highly correlated to glycaemia (r = 0.836, p = 0.0001). By 10 h, Ra had converged in diabetic patients and control subjects and all correlation with glycaemia was lost (r = 0.0017, p = 0.95).
Conclusions/interpretation: In relatively early diabetes, the more "labile" portion of fasting hyperglycaemia, which subsequently decreased, was closely related to the simultaneously decreasing Ra. The 25 % increase in glucose concentrations which persisted as stabilized Ra, resulted from about a 20 % lower metabolic clearance rate.