Hepatogenous Diabetes: An Underestimated Problem of Liver Cirrhosis

The prevalence of diabetes mellitus in cirrhotic patients is much higher than that in the general population. Two types of diabetes are usually seen in patients with cirrhosis: type 2 diabetes mellitus and hepatogenous diabetes (HD). The HD is an acquired condition which is believed to be caused by impaired insulin clearance and pancreatic β-cell dysfunction in cirrhotic patients. Increased levels of advanced glycation end products and hypoxia-inducible factors have been implicated in the pathogenesis of HD. Patients with HD typically present with normal fasting glucose, but abnormal response to an oral glucose tolerance test, which is required for the diagnosis. Because the level of glycated hemoglobin is often falsely low in patients with cirrhosis, it does not help in the early diagnosis of HD. HD is associated with an increased rate of complications of cirrhosis, decreased 5-year survival rate, and increased risk of hepatocellular carcinoma. The major complications of cirrhosis associated with HD include hepatic encephalopathy (HE), spontaneous bacterial peritonitis, sepsis, variceal hemorrhage, and renal dysfunction. Treatment of HD may be difficult as many antihyperglycemic therapies are associated with increased risk of complications in cirrhosis, particularly hypoglycemia. Biguanides, alpha-glucosidase inhibitors, and new medications such as dipeptidyl peptidase-4 inhibitors and sodium-glucose co-transporter 2 inhibitors appear to be safe in patients with cirrhosis. Though insulin therapy is currently advocated, requirement of insulin is variable and is difficult to predict. The liver transplantation usually results in reversal of HD. This review article provides an overview of magnitude, patients' characteristics, clinical implications, pathophysiological mechanisms, diagnosis, and management of HD.