Aims/hypothesis:  

The pathogenesis of fasting hyperglycaemia in Type II (non-insulin-dependent) diabetes mellitus has yet to be clarified. Rates of glucose production (R _a), 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 μmol/(min-m²) (p < 0.05) in diabetes from 419 ± 20 to 347 ± 32 μmol/(min-m²) in control subjects. Initial R _a 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, R _a 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 R _a. The 25 % increase in glucose concentrations which persisted as stabilized R _a, resulted from about a 20 % lower metabolic clearance rate. [Diabetologia (2001) 44: 983–991]