Insulin resistance in human liver cirrhosis is not modified by porto-systemic surgical shunt

Cirrhosis of the liver is characterized by glucose intolerance and hyperinsulinaemia. It is considered an insulin resistant state with both a receptor and a post-receptor defect of insulin activity. It would appear that reduced hepatic degradation rather than increased B-cell production is responsible for hyperinsulinaemia. The effect of surgical portosystemic shunt on insulin resistance was studied in 18 cirrhotics with impaired glucose tolerance (12 males, 6 females; mean age 46.9 ± 0.7 years) by measuring: glucose production (³H-glucose infusion), glucose utilisation (euglycaemic clamp at ~ 100, ~ 1000 and ~ 10000 μU/l), plasma insulin and C-peptide levels, and liver function indices (serum bilirubin, albumin, ALT, GGT) before and 2 months after surgery. Liver sorbitol clearance was also employed to measure variations in the functional liver plasma flow induced by the shunt. No significant changes were noted in: glucose production (1.94 ± 0.17 SEM vs 1.96 ± 0.17 mg/kg/min), glucose utilisation (metabolic clearance rate: 3.32 ± 0.48 vs 3.42 ± 0.43 at ~ 100 μU/ml; 9.70 ± 1.0 vs 9.16 ± 0.9 at ~ 1000 μU/ml; 10.92 ± 1.1 vs 11.07 ± 0.8 ml/kg/min at ~ 10000 μU/ml), fasting plasma insulin, C-peptide and C-peptide/insulin molar ratio (4.66 ± 0.47 vs 5.50 ± 0.54), and the liver function indices. By contrast, there was a significant decrease in functional liver plasma flow (813 ± 34 vs 604 ± 34 ml/min, P < 0.001). These results suggest that surgical shunt does not modify the mechanisms and the degree of insulin resistance in human liver cirrhosis and that hyperinsulinaemia can not be primarily referred to change of liver perfusion, but is most probably related to liver cell damage.