Nonalcoholic fatty liver disease (NAFLD) is closely correlated to several metabolic syndrome features. We assessed prospectively whether NAFLD predicts future cardiovascular disease (CVD) events among type 2 diabetic individuals, independent of metabolic syndrome features and other classical risk factors. We carried out a prospective nested case-control study in 2,103 type 2 diabetic patients who were free of diagnosed CVD at baseline. During 5 years of follow-up, 248 participants (case subjects) subsequently developed nonfatal coronary heart disease (myocardial infarction and coronary revascularization procedures), ischemic stroke, or cardiovascular death. Using risk-set sampling, 496 patients (control subjects) among those who remained free of diagnosed CVD during follow-up were randomly selected in a 2:1 ratio, matched for age and sex to the case subjects. After adjustment for age, sex, smoking history, diabetes duration, HbA 1c , LDL cholesterol, liver enzymes, and use of medications, the presence of NAFLD was significantly associated with an increased CVD risk (odds ratio 1.84, 95% CI 1.4 -2.1, P < 0.001). Additional adjustment for the metabolic syndrome (as defined by National Cholesterol Education Program Adult Treatment Panel III criteria) appreciably attenuated, but did not abolish, this association (1.53, 1.1-1.7, P ‫؍‬ 0.02). In conclusion, NAFLD is significantly associated with a moderately increased CVD risk among type 2 diabetic individuals. This relationship is independent of classical risk factors and is only partly explained by occurrence of metabolic syndrome. Diabetes 54: [3541][3542][3543][3544][3545][3546] 2005 N onalcoholic fatty liver disease (NAFLD) is currently the most common abnormality observed in hepatology practice. NAFLD is a clinicopathologic syndrome that is closely correlated to visceral obesity, dyslipidemia, insulin resistance, and type 2 diabetes, thus suggesting that NAFLD is another feature of the metabolic syndrome (1-4).A great deal of evidence suggests that the metabolic syndrome predicts incident cardiovascular disease (CVD) (5-8), so it is possible to hypothesize that NAFLD patients might portend a greater CVD risk and that NAFLD itself might confer a CVD risk above that associated with individual metabolic syndrome risk factors. Recent crosssectional studies have clearly documented that patients with NAFLD have, other than several features resembling the metabolic syndrome, a markedly greater carotid artery wall thickness than those without NAFLD (9,10). This finding was also validated by the results of a large population-based study (11). However, carotid artery wall thickness is only a marker of early generalized atherosclerosis (12), so currently it is uncertain whether NAFLD is significantly associated with increased risk of future CVD events. Clarification of this aspect may help to explain the underlying mechanisms and may be of clinical importance for undertaking preventive and therapeutic strategies. We have, therefore, assessed prospectively in a large sam...

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OBJECTIVE -Nonalcoholic fatty liver disease (NAFLD) is closely associated with several metabolic syndrome features. We assessed whether NAFLD is associated with carotid artery intima-media thickness (IMT) as a marker of subclinical atherosclerosis and whether such an association is independent of classical risk factors, insulin resistance, and metabolic syndrome features. RESEARCH DESIGN AND METHODS-We compared carotid IMT, as assessed by ultrasonography, in 85 consecutive patients with biopsy-proven NAFLD and 160 age-, sex-, and BMI-matched healthy control subjects.RESULTS -NAFLD patients had a markedly greater carotid IMT (1.14 Ϯ 0.20 vs. 0.82 Ϯ 0.12 mm; P Ͻ 0.001) than control subjects. The metabolic syndrome (according to Adult Treatment Panel III criteria) and its individual components were more frequent in those with NAFLD (P Ͻ 0.001). The marked differences in carotid IMT observed between the groups were only slightly weakened after adjustment for age, sex, BMI, smoking history, LDL cholesterol, insulin resistance (by homeostasis model assessment), and metabolic syndrome components. Notably, carotid IMT was strongly associated with degree of hepatic steatosis, necroinflammation, and fibrosis among NAFLD patients (P Ͻ 0.001 for all). Similarly, by logistic regression analysis, the severity of histological features of NAFLD independently predicted carotid IMT (P Ͻ 0.001) after adjustment for all potential confounders.CONCLUSIONS -These results suggest that the severity of liver histopathology among NAFLD patients is strongly associated with early carotid atherosclerosis, independent of classical risk factors, insulin resistance, and the presence of metabolic syndrome. Diabetes Care 29:1325-1330, 2006N onalcoholic fatty liver disease (NAFLD), the most common cause of abnormal liver function tests in hepatology practice, is frequently associated with visceral obesity, dyslipidemia, insulin resistance, and type 2 diabetes and may represent another component of the metabolic syndrome (1-3).Recent cross-sectional studies (4 -6) have shown that NAFLD is associated with increased carotid artery intimamedia thickness (IMT), a marker of early generalized atherosclerosis (7). However, in these studies the NAFLD diagnosis was exclusively based on ultrasound imaging but was not confirmed by liver biopsy, which is the best diagnostic tool for confirming NAFLD (1-3).Thus, currently it is uncertain whether there is a significant association between early carotid atherosclerosis and the severity of liver histology among NAFLD patients. Clarification of this aspect may help to explain the underlying mechanisms and may be of clinical importance in planning preventive and therapeutic strategies.We have, therefore, assessed whether patients with biopsy-proven NAFLD have a greater carotid IMT than control subjects and whether there is a significant association between liver histology and carotid IMT among NAFLD patients. RESEARCH DESIGN ANDMETHODS -A total of 85 consecutive outpatients with NAFLD were recruited from clinics, 50...

These results indicate that, in non-smoking, non-diabetic men, the significant increase of plasma biomarkers of inflammation and endothelial dysfunction in the presence of non-alcoholic HS is largely mediated by abdominal visceral fat accumulation.

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