[Study of insulin resistance in cirrhosis by the hyperinsulin euglycemia clamp]

To explore the insulin resistance state in liver cirrhosis and to assess the respective role of insulin sensitivity and cellular metabolism alterations, an euglycemic glucose clamp was performed in 12 cirrhotic patients and 6 healthy volunteers with 3 successive hyperinsulinemic periods of 90 mn (infusions of 7, 20 and Iu/h). An artificial beta-cell model allowed to quantify the amount of glucose needed to keep glycemia at 4.70 mmol/l. In 7 cirrhotic patients, insulin secretion was tested by an intravenous glucose tolerance test. The dose-response curves showed a significant (p less than 0.01) decrease of the theoretical maximal metabolic clearance rate of glucose (capacity). The insulin concentration corresponding to the half-maximal response (ED50) did not differ between cirrhotic and control subjects because of a very important dispersion of individual values in cirrhotics. The ED50 value was lower than the values of control subjects in five cirrhotic patients and normal or enhanced in seven other patients; the former showed the most reduced values for capacity, and the latter a more marked hyperinsulinemia during the intravenous glucose tolerance test. The two subgroups of patients did not differ for clinical or biological parameters of cirrhosis, or for glucose tolerance. These results 1) show a constant and marked impairment of glucose metabolism capacity in liver cirrhosis, 2) and suggest that the insulin resistance inconstantly observed in this state is a consequence of chronic hyperinsulinemia.