Glucoregulatory Response to Insulin-Induced Hypoglycemia in Laennec’s Cirrhosis

Abstract

The glucoregulatory response to hypoglycemia induced by the iv injection of 0.15 U/kg insulin was studied in eight normal subjects and 11 cirrhotic patients after an overnight fast. Glucose release by the liver (Ra) and tissue uptake (Rd) were determined by the primed constant infusion technique using [3–3H]– glucose. Under basal conditions, no significant differences in plasma glucose, Ra, and Rd between the two groups were observed, whereas hyperinsulinemia and hyperglucagonemia were present in cirrhotics. After insulin injection, the pattern of the hypoglycemic response was similar in the two groups. In normal subjects, Ra displayed a prompt fall soon after insulin and then rose to a peak 74% above the baseline at 60 min, whereas in cirrhotics, the initial fall in Ra was significantly greater and the recovery was slower and delayed. The enhancement of glucose uptake by insulin was less marked in cirrhotics than in controls; the reduced responsiveness to insulin effect was also evident if the tissue sensitivity was evaluated as metabolic clearance rate of glucose. The plasma disappearance of exogenous insulin was grossly comparable in the two groups, whereas the glucagon response to hypoglycemia was more pronounced in cirrhotic patients. These findings demonstrate that differences in the glucoregulatory response to insuli-induced hypoglycemia exist between normal subjects and cirrhotic patients despite similar blood glucose responses to insulin. The occurrence of tissue resistance to insulin effect in cirrhotics is clearly demonstrated and the greater suppression of glucose output in these patients can be accounted for by a greater vulnerability of the liver to insulin as well as a reduced sensitivity to glucagon.