Abstract
Hepatogenous diabetes (HD) is a distinct clinical entity that arises as a direct consequence of chronic liver disease, particularly cirrhosis. The complex interplay between hepatic dysfunction and glucose metabolism gives rise to unique pathophysiological mechanisms, including severe hepatic insulin resistance, pancreatic β-cell dysfunction, chronic inflammation, oxidative stress, and alterations in gut microbiota. HD is frequently underdiagnosed due to the limitations of traditional diagnostic criteria, as patients often exhibit normal fasting glucose and HbA1c levels despite significant postprandial hyperglycemia. The oral glucose tolerance test is more sensitive for detecting HD in this population. HD differs from type 2 diabetes mellitus in its temporal relationship with liver disease, absence of classic metabolic risk factors, greater glycemic variability, and a lower prevalence of microvascular complications. The prevalence of HD increases with the severity of liver dysfunction and varies according to the underlying etiology, with the highest rates observed in metabolic-associated fatty liver disease and hemochromatosis. HD is associated with accelerated liver fibrosis, increased risk of hepatocellular carcinoma, higher rates of hepatic decompensation, and increased mortality. Management strategies require careful consideration of the altered pharmacokinetics and increased risk of hypoglycemia in advanced liver disease. Individualized management strategies, including risk stratification and targeted therapies, hold promise for improving outcomes. This review synthesizes current knowledge on the epidemiology, pathophysiology, clinical implications, diagnosis, and management of HD, and highlights areas for future research to enhance recognition and treatment of this important but often overlooked complication of chronic liver disease.