Carbohydrate intolerance associated with reduced hepatic glucose phosphorylating and releasing enzyme activities and peripheral insulin resistance in alcoholics with liver cirrhosis.

Carbohydrate intolerance was investigated in 8 alcoholics with liver cirrhosis and in controls. Indices of carbohydrate metabolism, glucose and insulin levels after glucose loading, were compared with glucose phosphorylating (glucokinase, hexokinase) and releasing (glucose-6-phosphatase) enzymes. Comparison was also made with pericellular collagen in liver biopsies and with insulin sensitivity assessed by the euglycemic clamp technique and with conventional liver function tests including oral antipyrine test. Glucokinase activity was low or absent, hexokinase activity increased and the GK/HK ratio reduced. Glucose-6-phosphatase activity was lowered and insulin sensitivity decreased. Pericellular collagen was increased (P less than 0.001) and related to the fasting glucose (r0.593) and insulin levels (r0.526). Blood glucose was related to antipyrine metabolism (r-0.727) but not to the other liver tests. Glucose intolerance in cirrhosis seems to be associated with reduced glucose phosphorylating and liberating enzyme activities. Hyperinsulinaemia, developing secondarily, may then lead to insulin resistance.