Insulin resistance in cirrhosis: prolonged reduction of hyperinsulinemia normalizes insulin sensitivity.

摘要: Insulin resistance is present in nearly all patients with cirrhosis, but its etiology remains unknown. Chronic hyperinsulinemia has been suspected as a potential candidate, and we therefore tested the hypothesis that, prolonged reduction of restores insulin sensitivity. Whole-body sensitivity (euglycemic insulin-clamp technique), glucose turnover (6,6-2H2-glucose isotope dilution), oxidation (indirect calorimetry), non-oxidative disposal, fractional glycogen synthase activity muscle (biopsies) were measured eight clinically stable cirrhosis before at end 4-day continuous subcutaneous infusion somatostatin-analogue octreotide (200 microg/24 h) designed to continuously reduce plasma levels. Baseline data compared results obtained healthy individuals matched for sex, age, weight (n = 8). During baseline (pre-octreotide) study, demonstrated significant decrease insulin-mediated uptake controls (5.75 +/- 0.21 vs. 7.98 0.84 mg/kg/min; P < .03), which was entirely accounted by an impairment disposal (P .04). Four-day cirrhotic patients: 1) reduced postabsorptive meal-stimulated levels approximately 35% 45% without significantly affecting tolerance; 2) did not alter free fatty acids (FFA), growth hormone, glucagon state during meal test; 3) normalized whole-body (7.63 0.72 mg/kg/min post-octreotide; control). Restoration utilization caused normalization disposal; 4) associated considerably more pronounced stimulation pre-octreotide (increment above pre: 0.035 0.010 post: 0.060 0.023 nmol/min/mg protein; Fractional correlated (r .69; .03). Prolonged 96 hours normalizes synthesis muscle. We conclude that chronic causes cirrhosis.