Increase in gamma-glutamyltransferase level and development of established cardiovascular risk factors and diabetes in Japanese adults.

BACKGROUND: We investigated the predictive value of changes in serum gamma-glutamyltransferase (GGT) for the development of cardiovascular disease (CVD) risk factors in Japanese. METHODS: A total of 1514 adult participants in a general health examination program were followed for 3 years until January, 2006. The subjects were divided into two groups according to whether their serum GGT level had decreased (< or =0 U/L) or increased (> or =1 U/L) from the baseline level of GGT during the study period. The logistic regression model was used to analyze the relationship between increases in GGT levels and the incidence of diabetes (DM), impaired fasting glucose (IFG), dyslipidemia, and hypertension (HT). RESULTS: The mean value of GGT level was significantly higher at baseline than the 3-year follow-up point (47 +/- 41 versus 41 +/- 51, P < 0.0001), and the average 3-year GGT change was -5.7 +/- 32.3 U/L. The subjects with an increased GGT over the 3 years had an increased risk of developing DM, IFG, high triglyceride (TG) levels, and HT, in comparison with that of the subjects with a decreased GGT level, with an odds ratios (OR) of 6.13 (95% confidence interval [CI], 2.83-13.25), 2.70 (1.68-4.34), 2.65 (1.76-3.99), and 1.54 (1.12-2.13), respectively, after adjusting for age, sex, and alcohol habits. Further adjustments for baseline GGT, alanine aminotransferase (ALT), body mass index (BMI), and 3-year changes in BMI did not alter these associations. CONCLUSIONS: The increased change in GGT over 3 years was a significant and an independent risk factor for the development of high TG, HT, IFG, and DM in Japanese.

Hepatic steatosis rather than visceral adiposity is more closely associated with insulin resistance in the early stage of obesity.

The aim of the present study was to investigate the specific relationship between hepatic steatosis and insulin resistance in the early stage of obesity. Among general health examinees who received an ultrasound scanning, 131 subjects without fatty liver (non-FL group) and 142 subjects with fatty liver (FL group) were selected so that both groups were matched for age, sex, body mass index, and % body fat. The FL group was then subdivided into 2 groups according to the severity of steatosis by ultrasound. Insulin resistance was assessed by homeostasis model assessment for insulin resistance, serum high-molecular-weight (HMW) adiponectin, and insulin-like growth factor binding protein 1 concentrations. Unexpectedly, the non-FL group showed higher waist circumference than the FL group. Nevertheless, homeostasis model assessment for insulin resistance as well as conventional insulin resistance indexes such as serum insulin, free fatty acid, and triglyceride levels demonstrated a stepwise increase, and HMW adiponectin and insulin-like growth factor binding protein 1 demonstrated a stepwise decrease with increasing degree of hepatic steatosis. Overall, insulin resistance markers correlated with obesity indexes, but only HMW adiponectin no longer showed any meaningful correlation in the presence of fatty liver. The prevalence of BP, fasting serum glucose, and high-density lipoprotein cholesterol above or below cutoff points and subjects having 2 or more metabolic syndrome components were higher in the moderate to severe FL group compared to the non-FL group. In conclusion, these results in nondiabetic and relatively normal-body mass index subjects suggest that hepatic steatosis is independently associated with insulin resistance regardless of extrahepatic adiposity and might be the earliest event in pathogenesis of the metabolic syndrome.