IMPAIRED NONOXIDATIVE GLUCOSE-METABOLISM IN PATIENTS WITH LIVER-CIRRHOSIS - EFFECTS OF 2 INSULIN DOSES

Glucose intolerance is encountered in the majority of cirrhotic patien ts. This alteration has been attributed to a defective insulin-mediate d glucose uptake in peripheral tissue, where nonoxidative glucose disp osal seems to be chiefly impaired. To further investigate insulin acti on under euglycemic conditions, we studied how physiological (100 mu/m L) and pharmacological (1,000 mu U/mL) plasma insulin concentrations a ffect whole-body insulin-mediated glucose uptake, as well as oxidative and nonoxidative glucose disposal, in cirrhotic patients and controls . To this aim, a sequential two-step insulin euglycemic clamp combined with indirect calorimetry was performed in eight cirrhotic patients a nd six control subjects. During the first step of the clamp, total glu cose uptake was reduced by 40% in cirrhotic patients versus controls ( 4,42 +/- 1.39 v 7,63 +/- 1.60 mg/kg/min P =.002). By increasing insuli n to pharmacological levels, glucose disposal increased in both groups . However, the maximum rate of glucose metabolism achieved in cirrhoti c patients was lower than in controls at all times (10.29 +/- 2.04 v 1 2.82 +/- 0.51 mg/kg/min, P =.012). Glucose oxidation was lower in cirr hotics in the basal state, but similar in both groups during insulin/g lucose infusion. On the other hand, the reduced nonoxidative glucose d isposal observed in cirrhotic patients was not normalized even by incr easing insulin to pharmacological levels. In conclusion, in liver cirr hosis a reduced insulin sensitivity is associated with a reduced insul in responsiveness that is mainly caused by defective nonoxidative gluc ose disposal, Copyright (C) 1997 by W.B. Saunders Company.