The assessment of hepatic and peripheral insulin sensitivity in hypertriglyceridemia

Abstract

Peripheral insulin resistance is a common finding in hypertriglyceridemia. However, hepatic insulin sensitivity has rarely been investigated. We measured hepatic and peripheral insulin sensitivity in eight nondiabetic, nonobese hypertriglyceridemic subjects (HT) with raised triglyceride concentrations (4.3 ± 0.6 mmol · L −1, mean ± SEM) and eight age-, sex-, and weight-matched control subjects (C) with normal triglyceride concentrations (1.2 ± 0.2 mmol · L −1). Insulin secretion was assessed during a 75-g oral glucose tolerance test (OGTT). Glucose turnover was determined using 3 3H glucose in the postabsorptive state and during euglycemic glucose clamps at insulin infusion rates of 0.25 and 1.0 mU · kg −1 · min −1. At identical fasting glucose concentrations (HT, 5.2 ± 0.2; C, 5.2 ± 0.2 mmol · L −1), the glucose responses to OGTT were similar in both groups. Fasting plasma insulin (HT, 8.3 ± 1.2; C, 4.6 ± 0.4 mU · L −1; P = .02), and C-peptide (HT, 1.7 ± 0.2; C, 1.1 ± 0.1 μg · L −1; P = .006) concentrations were higher in hypertriglyceridemic subjects. The insulin and C-peptide responses to OGTT were greater in hypertriglyceridemic subjects (insulin, P = .005; C-peptide; P = .01). Hepatic glucose appearance in the postabsorptive state was similar (HT, 11.4 ± 0.3; C, 10.9 ± 0.7 μmol · kg −1 · min −1; NS). At low insulin concentrations (HT, 20.7 ± 1.4; C, 20.5 ± 1.4 mU · L −1), hepatic glucose appearance was equally suppressed (HT, 9.6 ± 0.9; C, 10.5 ± 1.3 μmol · kg −1 · min −1; NS). At high insulin concentrations (HT, 60.4 ± 2.6; C, 67.3 ± 5.0 mU · L −1), glucose utilization was lower in HT (HT, 32.8 ± 2.2; C, 43.3 ± 1.2 μmol · kg −1 · min −1; P = .02). Endogenous insulin secretion was suppressed to a similar degree during insulin infusion (HT, 63.4% ± 7.0%; C, 63.4% ± 9.9% of base values; NS). We conclude that hypertriglyceridemic subjects have peripheral insulin resistance, but hepatic insulin sensitivity is largely preserved.