Non-alcoholic fatty liver disease and type 2 diabetes mellitus. I. Pathogenesis

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease, affecting 25% of world population. NAFLD and its progressive subphenotype, non-alcoholic steatohepatitis (NASH) are prevalent in obese individuals, and also frequently coexist with type 2 diabetes mellitus (DM). NAFLD is associated with a 2- to 3-fold increased risk of developing DM, that parallels with the severity of liver disease. NAFLD and diabetes act synergistically increasing the risk of adverse clinical outcomes. Patients with diabetes frequently have fatty liver, and diabetes is a strong predictor of the progression of NAFLD to NASH or to fibrosis and cirrhosis. Genetic factors, and increased caloric intake, dysfunctional adipose tissue, insulin resistance, free fatty acids, proinflammatory cytokines, lipotoxicity and glucotoxicity play a pivotal role in the development of NAFLD and diabetes. In this review we describe the pathogenetic mechanisms that mirror the complex causal link between these two metabolic diseases.