MECHANISMS OF HEPATIC AND PERIPHERAL INSULIN RESISTANCE DURING ACUTE INFECTIONS IN HUMANS

To examine mechanisms of insulin resistance, nine patients (age 33 +/- 4 yr, body mass index 22 +/- 1 kg/m2) with acute bacterial or viral infections and in six matched normal subjects were studied. Endogenous glucose appearance (R(a)), glucose disappearance (R(d)), and recycling, the percentage of plasma lactate originating from plasma glucose, total glucose oxidation, and whole body and forearm muscle R(d) were measured after an overnight fast in the basal state and during physiological hyperinsulinemia (serum insulin almost-equal-to 215 pmol/L). Basally R(a), R(d), glucose recycling, and oxidation were similar in both groups. During hyperinsulinemia, insulin stimulated plasma R(d) almost-equal-to 35% less (17.6 +/- 1.3 vs. 26.8 +/- 3.6-mu-mol/kg.min, P < 0.01, patients us. normal subjects), and inhibited endogenous R(a) less in the patients (from 13.3 +/- 0.8 to 5.3 +/- 0.8-mu-mol/kg.min) than in the normal subjects (from 12.8 +/- 1.0 to 2.1 +/- 1.2-mu-mol/kg.min, P < 0.01). The decrease in whole body R(d) was largely explained by a almost-equal-to 75% reduction in muscle R(d) (5.6 +/- 1.5 vs. 20.8 +/- 3.3-mu-mol/kg muscle.min, P < 0.01, patients vs. normal subjects). The defect in R(d) was confined to nonoxidative (4.8 +/- 1.1 vs. 11.0 +/- 3.0-mu-mol/kg. min, P < 0.01, patients vs. normal subjects) but not to oxidative glucose metabolism. The percentage of plasma lactate derived from plasma glucose during hyperinsulinemia averaged 63 +/- 6% in the patients and 79 +/- 5% in the normal subjects, indicating that glycogenolysis did not excessively; dilute glycolytic carbons in the patients. We conclude that during natural infections in humans, abnormal glucose metabolism is confined to the insulin-stimulated state and involves a marked defect in muscle glucose uptake and glycogen synthesis, as well as a less marked hepatic defect.