Hepatic insulin action in adolescents with insulin-dependent diabetes mellitus: relationship with long-term glycemic control

Abstract

The relationship between hepatic insulin action and long-term glycemic control was assessed in 20 adolescents with insulin-dependent diabetes mellitus (IDDM) and five healthy matched controls using a two-step (0.8 and 1.6 mU/kg/min) hyperinsulinemic-euglycemic clamp and [6,6-2H2]glucose. The night before the study, diabetic patients received variable-rate intravenous insulin in an attempt to normalize fasting plasma glucose concentrations. In the postabsorptive state, hepatic glucose production (HGP) was similar in IDDM patients and controls (593 +/- 40 v 518 +/- 27 mumol/m2/min); however, plasma glucose and free insulin concentrations were higher in IDDM patients than in controls (6.5 +/- 0.4 v 5.4 +/- 0.1 mmol/L [P = .01], and 207 +/- 21 v 104 +/- 10 pmol/L [P < .001], respectively). There was a positive correlation (r = .62 P = .002) between basal HGP and glycohemoglobin level (HbA1). Separation of the patients at the median HbA1 (group no. 1 < and group no. 2. > 11.4% HbA1) revealed two distinct patient populations with regard to hepatic and peripheral insulin action and plasma free fatty acid (FFA) suppression. During hyperinsulinemia, the percent suppression of HGP was lower in group no. 2 compared with group no. 1 (65.7% +/- 9.8% v 94.4% +/- 3.8%; P = .018). Rates of glucose disposal were lower in group no. 2 compared with controls and with group no. 1. Postabsorptive FFA levels were similar between group no. 2 and group no. 1 (0.45 +/- 0.03 and 0.43 +/- 0.04 mmol/L) despite higher free-insulin concentrations in group no. 2 (260 +/- 30 v 171 +/- 25 pmol/L; P = .04).(ABSTRACT TRUNCATED AT 250 WORDS)