HYPERINSULINAEMIA AND INSULIN RESISTANCE OF CIRRHOSIS: THE IMPORTANCE OF INSULIN HYPERSECRETION

Publisher Website
Google Scholar
Abstract
The mechanism for the hyperinsulinemia in cirrhosis was investigated using 2 different approaches. In the 1st study, the metabolic clearance rate of insulin [MCRIRI was measured at steady state in 13 cirrhotic and 13 wt-matched control subjects. With comparable insulin infusion rates (1.00 .+-. 0.19 vs. 1.07 .+-. 0.15 mU/kg per min), steady-state plasma insulin concentrations (104 .+-. 25 vs. 87 .+-. 12 .mu.U/ml; P > 0.5) and MCRIRI (13.6 .+-. 1.6 vs. 15.4 2.0 ml/kg per min; P > 0.5) wee similar. In the 2nd study, fasting and oral glucose stimulated C-peptide/insulin ratios were compared in 16 cirrhotic and 18 wt-matched control subjects. Although fasting glucose levels were significantly higher in the cirrhotic groups, all values were in the normal range (5.5 .+-. 0.3 vs. 4.8 .+-. 0.1 mmol/l, P < 0.02). Fasting insulin (0.171 .+-. 0.02 vs. 0.068 .+-. 0.004 nmol/l) and C-peptide (1.02 .+-. 0.13 vs. 0.42 .+-. 0.02 nmol/l were strikingly higher (P < 0.001) in cirrhotic subjects. Fasting C-peptide/insulin ratios were not statistically different in the 2 groups (6.18 .+-. 0.52 vs. 6.77 .+-. 0.46; P > 0.3). Thus, .beta. cell hypersecretion apparently was the principal cause of the fasting hyperinsulinemia, rather than decreased insulin hepatic extraction. Following the glucose load in 13 of the control and 7 of the cirrhotic group, the C-peptide/insulin ratio fell in both groups but was significantly lower in the cirrhotic compared to control subjects at 30, 60 and 120 min, consistent with possible impairment of hepatic insulin extraction. Thus in cirrhosis, fasting hyperinsulinemia apparently is due to .beta. cell hypersecretion, whereas at higher insulin secretion rates following a glucose load, reduced hepatic insulin extraction may also contribute to the hyperinsulinemia.