This chapter focuses on the relationships of three common chronic liver diseases—nonalcoholic fatty liver disease (NAFLD), viral hepatitis, and cirrhosis—and of gallstone disease with diabetes.
NAFLD requires finding fat (steatosis) in the liver in the absence of heavy alcohol consumption and other secondary causes of hepatic steatosis. In a nationally representative sample of the U.S. population, the prevalence of NAFLD assessed by ultrasonography was greater among persons with diagnosed (45.5%) and undiagnosed (43.1%) diabetes and prediabetes (24.9%) compared to those with normal glucose (15.9%). Diabetes and insulin resistance are thought to be closely linked to the development and progression of NAFLD. However, there is also evidence that NAFLD increases the risk of diabetes. The risk of incident diabetes was at least twice as high among persons with NAFLD in several prospective studies that defined NAFLD based on elevated liver enzymes.
Hepatitis C virus (HCV) infection has been associated with an increased risk of diabetes, although results of population-based studies have been inconsistent. In contrast, there is little evidence that hepatitis B virus (HBV) infection increases the risk of diabetes. In a nationally representative sample of the U.S. population, HCV infection (HCV antibody positive) was not associated with diabetes (odds ratio [OR] 0.8) or prediabetes (OR 1.0). Similarly, HBV infection (HBV core antibody positive) was unrelated to diabetes (OR 1.0) and prediabetes (OR 1.1).
Diabetes is found in a high proportion of patients with cirrhosis (35%–71%), regardless of the liver disease etiology. Furthermore, the proportion of diabetes among those with cirrhosis is particularly high (as much as 71%) in studies that have included oral glucose tolerance testing. Among patients listed as candidates for liver transplantation, more than one-quarter carry a diagnosis of diabetes, which is double the proportion 20 years ago. Patients with diabetes awaiting liver transplantation have an increased risk of removal from the waiting list due to dying before transplantation or to deteriorating health resulting in medical contraindications to transplantation (OR 1.2). After liver transplantation, new-onset diabetes has been commonly reported (as high as 54% of HCV positive patients), usually among patients without adequate glucose testing before transplantation.
Finally, a high prevalence of gallstone disease (gallstones or history of cholecystectomy) was documented by ultrasound among persons with diagnosed (33.3%) and undiagnosed (23.3%) diabetes and prediabetes (20.8%) compared to persons with normal glucose (16.7%) in a nationally representative sample of the U.S. population. This relationship was present across demographic subgroups, for both gallstones and cholecystectomy. Review of published epidemiologic studies of ultrasound-detected gallstone disease likewise indicates a fairly consistent association of gallstone disease with diabetes independent of adiposity or other shared risk factors. An association of insulin resistance with gallstone disease has also been shown among those without diabetes. For example, gallstone disease was 60% more common among the highest compared to the lowest fasting serum insulin quintile among U.S. women. Insulin resistance may be a link between diabetes and gallstone disease.