Diabetes in chronic liver disease: from old concepts to new evidence

Abstract

SummaryThe liver is one of the principal organs involved in glucose metabolism together with skeletal muscle and adipose tissue. A link between diabetes and chronic liver disease (CLD) was first observed in the early half of the last century, but to date several questions remain unsolved. Altered glucose tolerance has been well described in alcoholic CLD, non-alcoholic fatty liver disease, chronic hepatitis C and portal hypertension. Moreover, insulin resistance is assuming an ever-growing importance in CLD; chronic hepatitis C has recently been proposed as a metabolic disease and insulin sensitivity as a predictive factor for liver fibrosis.CLD is also complicated by acquired growth hormone (GH) resistance, characterized by low concentrations of insulin-like growth factor-1 (IGF-1) with respect to normal or elevated GH levels. GH resistance in CLD is determined by several factors, including malnutrition, impaired liver function and reduced expression of hepatic GH receptors. We recently described the possible role of tumour necrosis factor-alpha (TNF-α) in blunting the hepatic response to GH in patients with chronic hepatitis C. The role of GH in impaired glucose metabolism is well known, and recent evidence suggests a receptor and/or post-receptor modulation of insulin signalling. Moreover, as in other chronic inflammatory conditions, pro-inflammatory cytokines may directly modulate the signal cascade that follows insulin binding to its receptor in the course of CLD.In this review, the proposed links between impaired glucose tolerance and CLD are analysed, special emphasis being focussed on the most recent findings concerning the interplay of chronic inflammation, GH resistance and insulin resistance.

Pharmacokinetics in Patients with Chronic Liver Disease and Hepatic Safety of Incretin-Based Therapies for the Management of Type 2 Diabetes Mellitus

“…The complex bi-directional relationship linking liver and diabetes mellitus has recently gained great interest [1,2] . Type 2 diabetes mellitus (T2DM) favours non-alcoholic fatty liver disease (NAFLD), progressing from steatosis to non-alcoholic steatohepatitis, (NASH) and possibly cirrhosis [3] , while alcoholic cirrhosis and chronic hepatitis C virus are frequently associated with glucose metabolism disturbances [4] .…”

Prevalence of Type 2 Diabetes Mellitus in patients with Chronic Liver Disease

“…1, 2 Patients acquiring diabetes as a result of cirrhosis of liver differ from typical type 2 diabetes mellitus patients by having a lower prevalence of family history of diabetes and a lower risk of macro and micro angiopathic complication. 1 In a point prevalence study, the prevalence of micro and peripheral macro angiopathy and coronary heart disease in cirrhosis with diabetes mellitus was comparable to that of controls, and was significantly lower than that observed in randomly selected patients with T2DM.…”

Pharmacokinetic and toxicological considerations for the treatment of diabetes in patients with liver disease

“…A link between diabetes and chronic liver disease (CLD) was first observed in the early half of the last century, and the complex and bi-directional relationship linking the liver and diabetes has recently gained intense new interest ( Figure 1) [1,2]. Type 2 diabetes mellitus (T2DM) favors non-alcoholic fatty liver disease (NAFLD), both steatosis and non-alcoholic steatohepatitis (NASH) [3] while alcoholic cirrhosis, chronic hepatitis C virus and hemochromatosis are frequently associated with diabetes [4].…”