In vivo insulin action in hepatocellular and cholestatic liver cirrhosis

The in vivo dose response curve to insulin were studied, using an euglycemic insulin clamp technique, in 13 cirrhotic patients [8 with “hepatocellular” (HC) (nonalcoholics) and 5 with “cholestatic” (CHOL) cirrhosis] and 12 healthy controls (N). Subjects were studied in the basal state and during infusion of insulin at 3 different rates — 1, 3, 10 mU kg⁻¹ min⁻¹. Insulin responsiveness was similar in N and in HC, but it was 23% greater in CHOL (p < 0.001). Insulin sensitivity was decreased in cirrhotics as compared with N but this difference was only significant (p < 0.001) in HC. (ED50:62 + 5, 88 + 13 and 136 + 16 µu ml⁻¹ in N, CHOL and HC respectively). Insulin clearance rate (ICR) was significantly (p < 0.005) decreased in HC (1060 ± 80, 996 ± 95 and 776 ± 128 ml sq m⁻¹ ml⁻¹ in N, CHOL and HC respectively. Basal hepatic glucose production (BHGP) was 39% lower in HC (p < 0.005) and 24% lower in CHOL (p < 0.05) than in N. Erythrocyte cholesterol phospholipid ratio was significantly elevated (p < 0.001) in both groups of cirrhotic patients but was not correlated to specific metabolic changes described. In summary: i) intervariations in insulin dependent glucose metabolism were described in different cirrhotic groups; ii) basal hepatic glucose production and insulin clearance rate impaired in the different groups of cirrhotics; iii) the role of decreased cholesterol/phospholipid ratio on tissues glucose metabolism in cirrhotic patients should be further studied.