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...

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.

These results show that decreased plasma adiponectin concentrations are closely correlated with nonalcoholic HS in healthy obese individuals.

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, HOMA-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.

BackgroundIt has been demonstrated that IL-17A is able to induce GC insensitivity. Although several studies have reported the role of IL-17 in GC insensitivity the mechanism underlying remains still largely unclear.ObjectivesTo understand the effects of interleukin-17 (IL-17) on the enzyme 11β-hydroxysteroid dehydrogenases (11β-HSDs) in the two main classes of monocytes, CD14 and CD16.MethodsPeripheral Blood Mononuclear Cells (PBMCs) were isolated from 5 healthy donors and were sorted into CD14 and CD16 subpopulations using cell sorting. Effect of IL-17 on 11β-HSD1 enzyme activity was measured in terms of conversion of cortisone to cortisol in sorted and unsorted monocytes using Homogeneous Time-Resolved Fluorescence (HTRF). The direct involvement of 11β-HSD1 in the conversion of cortisone to cortisol was confirmed using carbenoxolone, an inhibitor of 11β-HSD1.ResultsMonocytes showed a concentration-dependent decrease in the 11β-HSD1 enzyme activity when incubated with increasing concentrations of IL-17. CD14 and CD16 cells stimulated similarly with IL-17 showed a significant difference in the enzyme activity between the untreated and stimulated cells in all treatment groups. However, a dose dependent decrease was observed only in case of CD14 cells. Both unsorted monocytes and monocyte sub-populations showed a significant decrease in the concentration of cortisol measured when co-incubated with carbenoxolone, indicative of the direct involvement of 11β-HSD1 enzyme in the conversion of cortisone to cortisol.ConclusionsThe results of this study showed that IL-17 induced GC insensitivity might be dependent on the reduced 11β-HSD1 enzyme activity in inflammatory conditions. We showed that the pro-inflammatory cytokine IL-17 causes a significant decrease in the 11β-HSD1 enzyme activity.Disclosure of InterestNone declared