AIMS:To estimate the prevalence of cardiovascular disease (CVD) in Type 2 diabetic patients with and without non-alcoholic fatty liver disease (NAFLD), and to assess whether NAFLD is independently related to prevalent CVD.METHODS:We studied 400 Type 2 diabetic patients with NAFLD and 400 diabetic patients without NAFLD who were matched for age and sex. Main outcome measures were prevalent CVD (as ascertained by medical history, physical examination, electrocardiogram and echo-Doppler scanning of carotid and lower limb arteries), NAFLD (by ultrasonography) and presence of the metabolic syndrome (MetS) as defined by the World Health Organization or Adult Treatment Panel III criteria.RESULTS:The prevalences of coronary (23.0 vs. 15.5%), cerebrovascular (17.2 vs. 10.2%) and peripheral (12.8 vs. 7.0%) vascular disease were significantly increased in those with NAFLD as compared with those without NAFLD (P < 0.001), with no differences between sexes. The MetS (by any criteria) and all its individual components were more frequent in NAFLD patients (P < 0.001). In logistic regression analysis, male sex, age, smoking history and MetS were independently related to prevalent CVD, whereas NAFLD was not.CONCLUSIONS:The prevalence of CVD is increased in patients with Type 2 diabetes and NAFLD in association with an increased prevalence of MetS as compared with diabetic patients without NAFLD. Follow-up studies are necessary to determine whether this higher prevalence of CVD among diabetic patients with NAFLD affects long-term mortality.

Non-alcoholic fatty liver disease (NAFLD) is closely associated with several metabolic syndrome (MetS) features. We assessed whether NAFLD is significantly associated with carotid artery intima-media thickness (IMT), as a marker of subclinical atherosclerosis, and whether such association is independent of classical cardiovascular risk factors and MetS features. We studied 100 diet-controlled Type 2 diabetic patients with ultrasonographically diagnosed NAFLD and 100 diabetic patients without NAFLD who were comparable for age and sex. Main outcome measures were carotid IMT (by ultrasonography), classical risk factors, insulin resistance [as estimated by homeostasis model assessment (HOMA)-IR] and MetS (as defined by the Adult Treatment Panel III criteria). NAFLD patients had a markedly greater carotid IMT (1.24±0.13 vs 0.95±0.11 mm; p<0.001) than those without the condition. The MetS and all its clinical traits were more highly prevalent in those with NAFLD (p<0.001). Adjustment for age, sex, smoking history, diabetes duration, glycosylated hemoglobin, LDL cholesterol, liver enzymes and microalbuminuria did not really affect the significant differences in carotid IMT that were observed between the groups. Further adjustment for the MetS also had little impact, but additional adjustment for HOMA-IR score consistently attenuated any statistical significance (p=0.28). In multivariate regression analysis, HO-MA-IR score along with age and MetS (principally raised blood pressure values) were independently related to carotid IMT, whereas NAFLD was not. In conclusion, these results suggest that among diet-controlled Type 2 diabetic individuals the significant increase of carotid IMT in the presence of NAFLD is largely explained by HOMA-estimated insulin resistance.

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, HbA1c, 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.

OBJECTIVES To evaluate whether subjects with nonalcoholic hepatic steatosis (HS) differed in their circulating adiponectin levels compared with those in subjects without HS and, if so, to examine to what extent such differences are mediated by the adverse pattern of the metabolic syndrome variables, typically observed in these subjects.DESIGN AND PATIENTS In a cross-sectional study, we analysed 68 healthy, mildly obese individuals with a negative or negligible daily alcohol consumption.MEASUREMENTS HS (by ultrasonography), glucose tolerance status (by oral glucose load), insulin resistance [by homeostasis model assessment (HOMA)], and plasma adiponectin concentration [by enzyme-linked immunosorbent assay (ELISA)] were measured.RESULTS Subjects with nonalcoholic HS (n = 43) had markedly lower plasma adiponectin concentrations than those without HS (n = 25) (5.6 +/- 3 vs. 10.8 +/- 4 mug/ml; P < 0.001). In addition, the former had significantly higher values for body mass index (BMI), waist/hip ratio (WHR), HOMA-insulin resistance score,plasma insulin (at fasting and after glucose load), plasma triglyceride and liver enzyme concentrations [such as alanine aminotransferase (ALT) and gamma-glutamyltranspeptidase (GGT)], and tended to have lower high density lipoprotein (HDL) cholesterol concentration. The significant differences in plasma adiponectin levels that were observed between the groups were little affected by adjustment for potential confounding variables, such as age, sex, BMI, WHR, lipids and HOMA-insulin resistance score. Similarly, in multivariate regression analyses, hypoadiponectinaemia significantly predicted the presence of HS (P < 0.001) and the increased levels of GGT and ALT (P < 0.05), independently of potential confounders.CONCLUSIONS These results show that decreased plasma adiponectin concentrations are closely correlated with nonalcoholic HS in healthy obese individuals.