Possible roles of insulin, glucagon, growth hormone and free fatty acids in the pathogenesis of insulin resistance of subjects with chronic liver diseases

In the present investigation, insulin sensitivity and fasting levels of insulin, C-peptide, glucagon, growth hormone and free fatty acids were estimated and correlated in a population of individuals suffering from liver cirrhosis or chronic hepatitis. Insulin sensitivity, assessed by glucose disappearance rate after intravenous bolus injection of insulin, was reduced but not significantly different from controls in subjects with chronic persistent hepatitis, while it was significantly reduced in individuals suffering from chronic active hepatitis or liver cirrhosis. Insulin, glucagon, growth hormone, and free fatty acid fasting levels were higher than in healthy subjects in individuals with liver cirrhosis or chronic active hepatitis but not in subjects with chronic persistent hepatitis. C-peptide concentrations did not differ from controls in subjects with liver disease. Significant negative correlations occurred between coefficients of insulin sensitivity and fasting concentrations of insulin, glucagon, growth hormone and free fatty acids, but not with fasting levels of C-peptide. Positive relationships were present between fasting levels of free fatty acids and both glucagon and growth hormone concentrations. These results show that, unlike subjects with liver cirrhosis and chronic active hepatitis, individuals suffering from chronic persistent hepatitis do not differ from healthy subjects in insulin sensitivity and fasting levels of insulin, glucagon, growth hormone, and free fatty acids. Moreover, they suggest that both hyperinsulinemia and high concentrations of counterregulatory substances might play a role in the pathogenesis of insulin resistance in subjects suffering from chronic liver disease.