Levels of the oxidative stress marker γ-glutamyltranspeptidase at different stages of nonalcoholic fatty liver disease.

OBJECTIVES: This study investigated oxidative stress in the liver, by determining hepatic expression and serum levels of γ-glutamyltranspeptidase (GGT) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in different stages of nonalcoholic fatty liver disease (NAFLD), and assessed whether GGT can differentiate between the various stages of NAFLD. METHODS: Expression of GGT and 8-OHdG was examined in biopsy specimens by immunohistochemistry, and serum GGT and 8-OHdG levels were measured by enzyme-linked immuno sorbent assays in patients with simple fatty liver (n = 10), nonalcoholic steatohepatitis (NASH; n = 10) and, as a control, in alcoholic liver disease (ALD; n = 10). RESULTS: Hepatic tissue expression of GGT and 8-OHdG was seen in ALD, NASH and fatty liver patients. The percentage of hepatocytes positive for 8-OHdG expression and serum 8-OHdG levels was significantly higher in patients with NASH than simple fatty liver. Serum GGT levels were increased in all cases with ALD, NASH and fatty liver, and correlated significantly with serum levels of 8-OHdG in ALD and NASH, but not in simple fatty liver. CONCLUSIONS: Levels of GGT in fatty liver patients may compensate for mild oxidative stress by repressing 8-OHdG levels and preventing progression to NASH; however further oxidative stress leads to increased levels of 8-OHdG and the development of NASH.

Role of postprandial hyperglycaemia in cardiovascular disease in diabetes.

Diabetes is associated with a marked increase in the risk of atherosclerotic vascular disorders, including coronary, cerebrovascular and peripheral artery disease. Cardiovascular disease (CVD) could account for disabilities and high mortality rates in patients with diabetes. Conventional risk factors, including hyperlipidaemia, hypertension, smoking, obesity, lack of exercise and a positive family history, contribute similarly to macrovascular complications in type 2 diabetic patients and non-diabetic subjects. The levels of these factors in diabetic patients are certainly increased, but not enough to explain the exaggerated risk for macrovascular complications in diabetic population. Therefore, specific diabetes-related risk factors should be involved in the excess risk in diabetic patients. In this paper, we review the molecular mechanisms for accelerated atherosclerosis in diabetes, especially focusing on postprandial hyperglycaemia. We also discuss here the potential therapeutic strategy that specifically targets CVD in patients with diabetes.