Non-alcoholic fatty liver disease is associated with carotid artery wall thickness in diet-controlled Type 2 diabetic patients

Abstract

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.

Increased risk of cardiovascular disease in non-alcoholic fatty liver disease: causal effect or epiphenomenon?

“…The main cross-sectional [16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31] and prospective [11,[32][33][34][35][36][37][38][39][40][41][42][43] studies on the association between NAFLD and intermediate markers of CVDor clinical outcomes are shown in Tables 1 and 2 of the Electronic supplementary material. NAFLD, endothelial dysfunction, early carotid atherosclerosis and left ventricular dysfunction NAFLD is associated with circulatory endothelial dysfunction [16,17], a marker of early atherosclerosis. Compared with non-steatotic controls, non-diabetic patients with NAFLD show a significant decrease in brachial artery flow-mediated vasodilation, which is related to the severity of NAFLD histology, independently of age, sex, BMI and HOMA-IR [16].…”

“…Carotid artery intima-media thickness (IMT), another marker of early atherosclerosis, is also markedly increased in patients with NAFLD patients compared with that in age-, sex-and BMI-matched healthy controls [20][21][22][23][24][25], and NAFLD histology predicts carotid IMT independently of traditional risk factors, HOMA-IR and features of the metabolic syndrome [24]. Similarly, patients with NAFLD, also in the absence of obesity, hypertension and diabetes, exhibit echocardiographic features of early left ventricular dysfunction [18] and impaired energy metabolism as measured by cardiac 31 P magnetic resonance spectroscopy [19].…”

Nonalcoholic fatty liver disease and cardiovascular disease risk

“…Several cross-sectional studies have demonstrated an increase in carotid artery intima-media thickness (CIMT) in patients with NAFLD [34][35][36]. However, in these studies diagnosis of NAFLD was based on evaluation of liver enzymes or on ultrasound evaluation but not confirmed by liver biopsy, which is regarded as the "gold standard" in the diagnosis of NAFLD [10••].…”

C-reactive protein mediates the association of liver fat and carotid intima–media thickness in healthy men and men with the metabolic syndrome and/or uncomplicated type 2 diabetes

“…NAFLD is highly prevalent in insulin resistant subjects such as individuals with the MetS and T2DM [3][4][5][6], who are additionally characterized by an increased cardiovascular disease (CVD) risk [7]. Indeed, several studies have demonstrated that NAFLD is associated with CVD [8], carotid artery atherosclerosis [9][10][11] and endothelial dysfunction [12], independent of classical risk factors such as insulin resistance and components of the MetS.…”

“…Carotid intima-media thickness (cIMT), assessed by ultrasound, is a validated parameter for subclinical atherosclerosis [17], predictive of both myocardial infarction and stroke [18]. cIMT has been related to the severity of liver damage in NAFLD, as measured by liver biopsy [19] and by ultrasound [11]. However, at present, the inter-relationship of liver fat accumulation, subclinical atherosclerosis and a pro-inflammatory state is still incompletely understood.…”