Slow-Twitch Fiber Proportion in Skeletal Muscle Correlates With Insulin Responsiveness

CONTEXT: The metabolic syndrome, characterized by central obesity with dyslipidemia, hypertension, and hyperglycemia, identifies people at high risk for type 2 diabetes. OBJECTIVE: Our objective was to determine how the insulin resistance of the metabolic syndrome is related to muscle fiber composition. DESIGN: Thirty-nine sedentary men and women (including 22 with the metabolic syndrome) had insulin responsiveness quantified using euglycemic clamps and underwent biopsies of the vastus lateralis muscle. Expression of insulin receptors, insulin receptor substrate-1, glucose transporter 4, and ATP synthase were quantified with immunoblots and immunohistochemistry. PARTICIPANTS AND SETTING: Participants were nondiabetic, metabolic syndrome volunteers and sedentary control subjects studied at an outpatient clinic. MAIN OUTCOME MEASURES: Insulin responsiveness during an insulin clamp and the fiber composition of a muscle biopsy specimen were evaluated. RESULTS: There were fewer type I fibers and more mixed (type IIa) fibers in metabolic syndrome subjects. Insulin responsiveness and maximal oxygen uptake correlated with the proportion of type I fibers. Insulin receptor, insulin receptor substrate-1, and glucose transporter 4 expression were not different in whole muscle but all were significantly less in the type I fibers of metabolic syndrome subjects when adjusted for fiber proportion and fiber size. Fat oxidation and muscle mitochondrial expression were not different in the metabolic syndrome subjects. CONCLUSION: Lower proportion of type I fibers in metabolic syndrome muscle correlated with the severity of insulin resistance. Even though whole muscle content was normal, key elements of insulin action were consistently less in type I muscle fibers, suggesting their distribution was important in mediating insulin effects.