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

The liver is one of the principal organs involved in glucose metabolismtogether with skeletal muscle and adipose tissue. A link between diabetesand chronic liver disease (CLD) was first observed in the early half of thelast century, but to date several questions remain unsolved. Altered glucosetolerance has been well described in alcoholic CLD, non-alcoholic fattyliver disease, chronic hepatitis C and portal hypertension. Moreover, insulinresistance is assuming an ever-growing importance in CLD; chronic hepatitisC has recently been proposed as a metabolic disease and insulin sensitivity asa 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 isdetermined by several factors, including malnutrition, impaired liver functionand reduced expression of hepatic GH receptors. We recently described thepossible role of tumour necrosis factor-alpha (TNF-α) in blunting the hepaticresponse to GH in patients with chronic hepatitis C. The role of GH in impairedglucose metabolism is well known, and recent evidence suggests a receptorand/or post-receptor modulation of insulin signalling. Moreover, as in otherchronic inflammatory conditions, pro-inflammatory cytokines may directlymodulate the signal cascade that follows insulin binding to its receptor in thecourse of CLD.In this review, the proposed links between impaired glucose toleranceand CLD are analysed, special emphasis being focussed on the most recentfindings concerning the interplay of chronic inflammation, GH resistance and insulin resistance.