Liver Disease from Diabetes The Feb '99 issue of Clinical Diabetes has an article reviewing the association between liver diseases and diabetes. Studies have noted excess prevalence of chronic liver disease among Type 2 diabetics. The authors discuss some common liver conditions caused by diabetes, including: * Glycogen Deposition: The authors explain that 80% of diabetics have excess accumulation of glycogen in our livers and review some possible reasons for this. This excessive accumulation may cause liver enlargement (hepatomegaly), abnormal liver enzyme test results, nausea, vomiting, abdominal pain and, rarely, accumulation of fluids in the abdomen (ascites). The authors note that these conditions may improve with improved BG management and that there seems no correlation between fasting BG levels and the amount of glycogen stored in the liver. * Fatty Liver: The authors report that 40-70% of diabetics have accumulations of fat, stored as triglyceride, in our livers. They note that fatty liver is not associated with well-managed Type 1 diabetes, but may be found in as many 70% of Type 2 diabetics, regardless of how well- managed their BG levels may be. Fatty liver is usually observed as an enlarged liver and diabetics with fatty liver may have normal or mildly elevated liver enzyme test results, as well as normal bilirubin levels. Fatty liver can progress to fibrosis and cirrhosis. [A recent report published elsewhere about Type 2 diabetics in Italy noted a high rate of cirrhosis among causes of death.] The authors report that fatty liver can be observed by CT scans and ultrasound testing, but that a negative ultrasound finding cannot exclude the possibility of microscopic fatty infiltration. They note that it is not yet clear that all cases should be investigated by liver biopsy, but that some researchers suggest it should always be done to confirm the diagnosis and determine the degree of fibrosis. The authors note that fatty liver is seen with many other conditions other than diabetes, including: alcoholic liver disease, obesity, protein malnutrition, intestinal bypass surgery, colitis, chronic pancreatitis, and prolonged IV feeding. It can also be caused by toxic damage to the liver from carbon tetrachloride and is often seen with abetalipoproteinemia, HIV infection, and other diseases, as well as with the use of some drugs, including estrogens, gluco- corticoids, tamoxifen, perhixilene, and amiodarone. The authors discuss a type of fatty liver that is not associated with alcoholism nor hepatitis C, called non-alcoholic steatohepatitis (NASH), which involves lobular inflammation and steatonecrosis. This may sometimes appear similar to alcoholic liver disease in diabetics with fatty liver and is most commonly found In obese women with Type 2 diabetes and more commonly found in Type 2 diabetics using insulin. Some people with NASH can progress to liver failure, requiring a liver transplant. The authors urge that diabetic patients with chronically elevated liver enzymes should be evaluated for NASH, particularly if they are obese or have hyperlipidemia. They report that "in type 2 diabetic patients with or without obesity, up to 30% have fat with inflammation, 25% have associated fibrosis, and 1-8% have cirrhosis." They report that gradual weight loss and good BG management are recommended treatment. They specifically caution that the weight loss should be gradual because "rapid weight loss may actually worsen NASH." They note that a weight loss of more than 10% is usually necessary to normalize liver enzymes in people who are significantly overweight and that the use ursodeoxycholic acid may help normalize liver enzymes, without impacting fibrosis. * Cirrhosis The authors note that there is increased incidence of cirrhosis among diabetics and discuss some of the problems of developing accurate statistics about the topic. * Biliary Disease, Cholelithiasis, Cholecystitis Many studies report a higher rate of gallstones among diabetics, but the authors note that obesity and hyperlipidemia may confound the statistics. The authors state that abnormalities in gallbladder emptying have been observed in diabetics, but that many of the predisposing factors for gallstones are associated with obesity and it's just not easy to determine what is directly due to diabetes. * Complications of Diabetes Treatments The authors note that some diabetes treatments can increase the risk of liver disease: - Needles used for insulin therapy may increase the risk of acquiring viral hepatitis; good infection control habits can reduce this risk. - Spring-loaded lancet holders may increase the risk of acquiring hepatitis, as observed in 1996 in a NY hospital and an Ohio nursing home, where hepatitis B may have been spread by lancet holders used for fingerstick BG testing. - Pills to treat diabetes vary in the extent to which they are metabolized by the liver. Metformin (Glucophage) and chlor- propamide (Diabinese) are excreted unchanged in the urine. Glyburide (Diabeta, Glynase, and Micronase) is excreted in bile and urine in a 50/50 ratio. Glipizide (Glucatrol, Glucatrol XL) is mainly metabolized by the liver and levels of glipizide may theoretically be increased in diabetics with liver disease. - Among sulfonylurea class drugs, chlorpropamide (Diabinese) appears to be the most hepatotoxic of these drugs, with cholestatic hepatitis occurring in 0.5% of people using the drug. "Jaundice develops over 2-5 weeks and resolves in virtually all patients when the drug is stopped. Hepatic disease is very rare with tolbutamide (Orinase and generics), and tolazamide (Tolinase and generics). Although very uncommon, acetohexamide and glyburide can cause acute hepatocellular necrosis, and fatalities have been reported. At least two cases of granulomatous hepatitis thought secondary to glyburide have been reported in the literature." - Metformin (Glucophage) has not been associated with injury to the liver, but should not be used by people with existing liver disease, since this may increase the risk of developing lactic acidosis. - Troglitazone (Rezulin) has been associated with damage to the liver and prescribing guidelines discuss the importance of liver enzyme testing before beginning Rezulin, at regular intervals after beginning Rezulin, and whenever any symptoms suggest possible liver problems. - Paula === [People interested in this topic should read the entire article and see: Levinthal GN and Tavil AS, "Liver Disease and Diabetes Mellitus." Clinical Diabetes 1999 Feb;17(2).]