Does overnight normalization of plasma glucose by insulin infusion affect assessment of glucose metabolism in Type 2 diabetes?

Aims: In order to perform euglycaemic clamp studies in Type 2 diabetic patients, plasma glucose must be reduced to normal levels. This can be done either (i) acutely during the clamp study using high-dose insulin infusion, or (ii) slowly overnight preceding the clamp study using a low-dose insulin infusion. We assessed whether the choice of either of these methods to obtain euglycaemia biases subsequent assessment of glucose metabolism and insulin action.

Methods: We studied seven obese Type 2 diabetic patients twice: once with (+ ON) and once without (- ON) prior overnight insulin infusion. Glucose turnover rates were quantified by adjusted primed-constant 3-3H-glucose infusions, and insulin action was assessed in 4-h euglycaemic, hyperinsulinaemic (40 mU m-2 min-1) clamp studies using labelled glucose infusates (Hot-GINF).

Results: Basal plasma glucose levels (mean +/- sd) were 5.5 +/- 0.5 and 10.7 +/- 2.9 mmol/l in the + ON and - ON studies, respectively, and were clamped at -5.5 mmol/l. Basal rates of glucose production (GP) were similar in the + ON and - ON studies, 83 +/- 13 vs. 85 +/- 14 mg m-2 min-1 (NS), whereas basal rates of glucose disappearance (Rd) were lower in the + ON than in the - ON study, 84 +/- 8 vs. 91 +/- 11 mg m-2 min-1 (P = 0.02). During insulin infusion in the clamp period, rates of GP, 23 +/- 11 vs. 25 +/- 10 mg m-2 min-1, as well as rates of Rd, 133 +/- 32 vs. 139 +/- 37 mg m-2 min-1, were similar in the + ON and - ON studies, respectively (NS).

Conclusions: Apart from basal rates of Rd, assessment of glucose turnover rates in euglycaemic clamp studies of Type 2 diabetic patients is not dependent on the method by which plasma glucose levels are lowered.