INSULIN RESISTANCE IN LIVER-CIRRHOSIS - POSITRON-EMISSION TOMOGRAPHY SCAN ANALYSIS OF SKELETAL-MUSCLE GLUCOSE-METABOLISM

Background. Insulin resistance and glucose intolerance are a major fea ture of patients with liver cirrhosis. However, site and mechanism of insulin resistance in cirrhosis are unknown. We investigated insulin-i nduced glucose metabolism of skeletal muscle by positron-emission tomo graphy to identify possible defects of muscle glucose metabolism in th ese patients. Methods. Whole body glucose disposal and oxidation were determined by the combined use of the euglycemic-hyperinsulinemic clam p technique (insulin infusion rate: 1 mU/kg body wt per min) and indir ect calorimetry in seven patients with biopsy-proven liver cirrhosis ( Child: 1A, 5B, and 1C) and five healthy volunteers. Muscle glucose upt ake of the thighs was measured simultaneously by dynamic [F-18]fluorod esoxyglucose positron-emission tomography scan. Results. Both whole bo dy and nonoxidative glucose disposal were significantly reduced in pat ients with liver cirrhosis (by 48%, P < 0.001, and 79%, P < 0.0001, re spectively), whereas glucose oxidation and the increase in plasma lact ate were normal. Concomitantly, skeletal muscle glucose uptake was red uced by 69% in liver cirrhosis (P < 0.003) and explained 55 or 92% of whole body glucose disposal in cirrhotics and controls, respectively. Analysis of kinetic constants using a three-compartment model further indicated reduced glucose transport (P < 0.05) but unchanged phosphory lation of glucose in patients with liver cirrhosis. Conclusions. Patie nts with liver cirrhosis show significant insulin resistance that is c haracterized by both decreased glucose transport and decreased nonoxid ative glucose metabolism in skeletal muscle.