Diabetes and Chronic Liver Disease: Etiology and Pitfalls in Monitoring

Abstract

T he liver is one of the major targets for insulin and its counterregulatory hormones, such as glucagon. Chronic liver disease (CLD) is often associated with glucose intolerance and diabetes. CLD is very prevalent in the general U.S. population and includes 2% of adult Americans (5.3 million) infected with hepatitis B or C1 and an estimated 31% or more with non-alcoholic fatty liver disease (NAFLD).2 The population of Americans with CLD continues to expand because of the epidemics of obesity and diabetes. In some subpopulations such as the morbidly obese, the prevalence of NAFLD is as high as 88%.3 The association of NAFLD with concurrent diabetes increases general mortality.4 Liver cirrhosis from alcohol abuse is another important cause of CLD.5,6 Genetic conditions such as hemochromatosis (HC), cystic fibrosis, and sclerosing cholangitis are less frequent causes of CLD. Their prevalence is population-based; for HC, the homozygous state prevalence is 0.6–1% in whites.7 Individuals with HC have an odds ratio for diabetes as high as 5.4 compared to control subjects.8 Assessing glucose control using A1C or fructosamine (FA) testing in CLD has significant limitations. These limitations must be clearly understood to avoid misinterpretation of the results. Ordering these tests should sometimes be avoided altogether in patients with a high likelihood of falsely low results. The presence of CLD is associated with significant impairment in glucose homeostasis. Glucose intolerance is seen in up to 80% of patients with CLD, and frank diabetes is present in 30–60%.9,10 Depending on its etiology, CLD has a significant impact on hepatic glucose metabolism. One of the common causes of CLD is chronic hepatitis C. Chronic hepatitis C is accompanied by insulin resistance, which causes impaired glucose tolerance. Multiple mechanisms have been implicated, including fat accumulation …