Insulin resistance in advanced liver cirrhosis : the role of liver dysfunction and the “dissociated” effect on glucose versus lipid and amino acid metabolism

Background: Chronic liver failure is characterized by the progression of multiple important metabolic derangements, simultaneously interesting all main metabolic pathways. In liver cirrhosis, an impaired glucose tolerance with insulin resistance is frequently observed (20% of these patients may develop overt diabetes mellitus during the disease progression). Aim: to evaluate (1) the role of liver dysfunction in inducing the alteration of insulin sensitivity in patients with advanced stage of liver cirrhosis and (2) the effect of this metabolic derangement on amino acid and lipid metabolism in patients with liver cirrhosis with respect to healthy controls and to patients with type II diabetes mellitus.Materials and methods: To this purpose 23 subjects with documented advanced liver cirrhosis (LC), 14 age and sex-matched healthy subjects (controls) and 10 patients with type II diabetes mellitus without liver disease (DM) were studied. A FSIVGTT test (Frequently Sample Intravenous Glucose Tolerance Test) with simultaneous evaluation of glucose, lipid and amino acid metabolism parameters was performed and the results for glucose, Insulin and C-peptide were analyzed by the MINMOD program, able to adapt data to three different mathematical models, generating predictions of kinetic of glucose disappearance and insulin and C-peptide production; FSIVGTT lipid metabolism parameters (NEFA levels) were measured by colorimetric kit and FSIVGTT amino acid metabolism parameters [Branched Chain Amino Acid, (BCAA) and Aromatic Amino Acid, (AAA) profile], by Amino Acid Analyzer. Results: The MINMOD integration of data concerning secretion and kinetics of C-peptide with those of insulin, confirm that advanced-stage liver cirrhosis is characterised by significant insulin-resistance with hyperinsulinemia and suggest the main role of reduction of insulin liver extraction (h) in insulin-resistance syndrome of liver cirrhosis. The effects of this liver-failure inducted insulin-resistance seem to have some peculiarities concerning lipid and amino acid metabolism, consisting in a relative conservation (greater effect than that observed in DM subjects) of insulin effect in peripheral tissues: in LC patients insulin seems to maintain a relative greater capacity to promote both BCAA and NEFA utilization by muscle and fat tissue (“dissociated effect”) with respect to patients with type II diabetes mellitus. Conclusion: The relative preservation of insulin sensibility by peripheral tissues represents an important and a positive fact, as rationalizes the use, for example, of BCAA solutions for nutritional purposes in presence of starvation or negative azoth balance, all conditions known to negatively influencing some neuropsychological complications of liver cirrhosis.