Leptin as a key player in insulin resistance of liver cirrhosis? A cross-sectional study in liver transplant candidates

Abstract

Insulin resistance is associated with increased risk of death and liver transplantation in the cirrhotic population, independent of disease aetiology. However, factors accounting for insulin resistance in the context of cirrhosis are incompletely understood. This study aimed to investigate the association between adiponectin and leptin with insulin resistance in cirrhotic patients and to assess the influence of disease severity on insulin resistance and metabolic status. This cross-sectional study included 126 non-diabetic cirrhotic transplant candidates. The homeostasis model assessment 2 model was used to determine the insulin resistance index, and fasting adiponectin, leptin, insulin, c-peptide, glucose, HbA1c, and lipid profiles were analysed. Insulin resistance was detected in 83% of subjects and associated with increased leptin, fasting plasma glucose and body mass index, and lower triglyceride levels. Logistic regression analysis identified leptin and triglycerides as independent predictors of insulin resistance (OR 1.247, 95% CI 1.076–1.447, p = 0.003; OR 0.357, 95% CI 0.137–0.917, p = 0.032). Leptin levels remained unchanged, whereas adiponectin levels increased (p < 0.001) with disease progression, and inversely correlated with HbA1c (ρ = −0.349, p < 0.001). Our results indicate that leptin resistance, as indicated by elevated leptin levels, can be regarded as a contributing factor to insulin resistance in cirrhotic patients, whereas triglycerides elicited a weak protective effect. Progressively increasing adiponectin levels elicited a positive effect on glucose homeostasis, but not insulin sensitivity across disease stages.