Figure 1.

Common chronic diseases of metabolic dysfunction. Prediabetes-Diabetes and NAFLD-NASH-Cirrhosis are subsets of interconnected metabolic disease with significant global prevalence. These disease states are broadly impacted by environmental factors interacting with genetic predisposition. The primary precipitating factor is metabolic dysfunction/selective insulin resistance. Loss of glycemic control is precipitated by decompensation of pancreatic islet function resulting in the diagnosis of diabetes based on elevated plasma glucose. In a subset of individuals, progressive structural changes and loss of hepatic function results from ineffective repair/regenerative mechanisms. The definition NASH is based on pathology as read from liver biopsies. NAFLD/NASH and type 2 diabetes, whether diagnosed separately or as concomitant conditions, have common adverse cardiovascular outcomes. Liver-related events accelerate with increasing fibrosis (tissue damage) and loss of liver acinar structure (cirrhosis). In a subset of patients, portal pressure will continue to rise, resulting in clinical decompensation characterized by varices, hepatic encephalopathy, and liver failure.