[Hepatogenic diabetes: pathophysiology, therapeutic options and prognosis]

About 80% of patients with chronic liver diseases such as cirrhosis are glucose intolerant and some 20-30% eventually develop frank diabetes mellitus. In a given individual it seems impossible to determine whether or not acquired liver diabetes or inherited non-insulin-dependent diabetes mellitus is present. The high prevalence, however, of impaired glucose tolerance and the finding that insulin sensitivity is reduced in nearly all cirrhotic patients before any impairment in glucose tolerance becomes manifest, make it likely that in the majority of patients the hepatic disease is the cause of the development of the hepatogenous diabetes. The insulin resistance resides in muscle and largely results from a defect in glycogen synthesis. Glucose intolerance ensues as a result of two abnormalities that occur simultaneously: insulin resistance of muscle and an inadequate response of the B-cell to appropriately secrete insulin to overcome the defect in insulin action. Diabetes mellitus in insulin-resistant cirrhotic patients develops as a result of a progressive impairment in insulin secretion together with the development of hepatic insulin resistance, leading to fasting hyperglycemia. Until recently, only little was known about the etiology of insulin resistance and impaired insulin secretion. However, most recent studies have shown that prolonged reduction of hyperinsulinemia in cirrhosis normalize insulin-mediated glucose uptake and glycogen synthesis in muscle. These results indicate that chronic hyperinsulinemia causes insulin resistance in cirrhosis and therefore plays a central role in the etiology of the hepatogenous diabetes.