Characterization of an early decline in baseline plasma glucose concentration after acute insulin elevation during euglycemic hyperinsulinemic clamp in patients with type 2 diabetes mellitus.

To investigate the contribution of the liver to whole-body insulin resistance in patients with type 2 diabetes mellitus, we analyzed the early decline (slope "a") in the baseline plasma glucose level following acute hyperinsulinemia in the initial phase of a euglycemic hyperinsulinemic clamp study, rather than using an isotope-dilution method. Slope "a" was comparable among groups of diabetic and non-diabetic subjects, and did not correlate well with glucose infusion rate (GIR), an index of peripheral (primarily skeletal muscle) insulin resistance. In contrast, slope "a" was significantly lower in obese (BMI > 25) type 2 diabetic patients compared with their non-obese counterparts, consistent with the general belief that obesity is a condition of insulin resistance in liver as well as in peripheral tissues. A subset of six insulin-resistant (nearly zero GIR) type 2 diabetic patients (pubertal adolescents) demonstrated a markedly blunted slope "a". Their insulin resistance (GIR) substantially recovered concomitant with an increase in slope "a" after pretreatment with somatostatin analogue in two cases studied, suggesting possible suppression of hepatic glucose production through lowering of plasma glucagon concentrations. Furthermore, slope "a" correlated significantly (r = -0.480, p<0.0001) with HOMA index (FPG x FIRI), the latter being recently regarded as an index of hepatic insulin resistance. These data showed that slope "a" obtained from euglycemic hyperinsulinemic clamp may be a clinically useful index of hepatic insulin resistance rather than an index of peripheral insulin resistance.