BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) and insulin resistance are common in overweight adolescents. OBJECTIVE: The purpose of this study was to determine the relation between NAFLD and insulin sensitivity in liver and skeletal muscle by studying overweight adolescents with a normal or high intrahepatic triglyceride (IHTG) content, who were matched for age, sex, body mass index (BMI; in kg/m(2)), and Tanner stage. DESIGN: Stable-isotope-labeled tracer infusion and the hyperinsulinemic-euglycemic clamp procedure were used to assess skeletal muscle and hepatic insulin sensitivity, and magnetic resonance spectroscopy was used to assess the IHTG content in 10 overweight (BMI = 35.9 +/- 1.3) adolescents with NAFLD (IHTG = 28.4 +/- 3.4%) and 10 overweight (BMI = 36.6 +/- 1.5) adolescents with a normal IHTG content (3.3 +/- 0.5%). RESULTS: The baseline plasma glucose concentration and the rate of appearance of glucose in plasma were the same in subjects with a normal (87.1 +/- 1.2 mg/dL, 16.2 +/- 1.1 micromol . kg fat-free mass(-1) . min(-1)) or high (89.2 +/- 2.5 mg/dL, 16.3 +/- 1.2 micromol . kg fat-free mass(-1) . min(-1)) IHTG content. However, compared with subjects who had a normal IHTG content, subjects with NAFLD had a lower hepatic insulin sensitivity index, based on baseline glucose kinetics and insulin concentrations (4.0 +/- 0.5 compared with 2.4 +/- 0.4; P < 0.05) and an impaired increase in glucose uptake during insulin infusion (169 +/- 28.1% compared with 67 +/- 9.6% above baseline; P < 0.01). In addition, the plasma triglyceride concentration was greater and the plasma HDL-cholesterol concentration was lower in subjects with NAFLD than in those with a normal IHTG content. CONCLUSION: An elevated IHTG content in overweight adolescents is associated with dyslipidemia and with insulin-resistant glucose metabolism in both liver and skeletal muscle.
BACKGROUND:Nonalcoholic fatty liver disease (NAFLD) and insulin resistance are common in overweight adolescents. OBJECTIVE: The purpose of this study was to determine the relation between NAFLD and insulin sensitivity in liver and skeletal muscle by studying overweight adolescents with a normal or high intrahepatic triglyceride (IHTG) content, who were matched for age, sex, body mass index (BMI; in kg/m(2)), and Tanner stage. DESIGN: Stable-isotope-labeled tracer infusion and the hyperinsulinemic-euglycemic clamp procedure were used to assess skeletal muscle and hepatic insulin sensitivity, and magnetic resonance spectroscopy was used to assess the IHTG content in 10 overweight (BMI = 35.9 +/- 1.3) adolescents with NAFLD (IHTG = 28.4 +/- 3.4%) and 10 overweight (BMI = 36.6 +/- 1.5) adolescents with a normal IHTG content (3.3 +/- 0.5%). RESULTS: The baseline plasma glucose concentration and the rate of appearance of glucose in plasma were the same in subjects with a normal (87.1 +/- 1.2 mg/dL, 16.2 +/- 1.1 micromol . kg fat-free mass(-1) . min(-1)) or high (89.2 +/- 2.5 mg/dL, 16.3 +/- 1.2 micromol . kg fat-free mass(-1) . min(-1)) IHTG content. However, compared with subjects who had a normal IHTG content, subjects with NAFLD had a lower hepatic insulin sensitivity index, based on baseline glucose kinetics and insulin concentrations (4.0 +/- 0.5 compared with 2.4 +/- 0.4; P < 0.05) and an impaired increase in glucose uptake during insulin infusion (169 +/- 28.1% compared with 67 +/- 9.6% above baseline; P < 0.01). In addition, the plasma triglyceride concentration was greater and the plasma HDL-cholesterol concentration was lower in subjects with NAFLD than in those with a normal IHTG content. CONCLUSION: An elevated IHTG content in overweight adolescents is associated with dyslipidemia and with insulin-resistant glucose metabolism in both liver and skeletal muscle.
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