Non-alcoholic fatty liver disease and increased risk of cardiovascular disease

Non-alcoholic fatty liver disease (NAFLD) is present in up to one-third of the general population and in the majority of patients with cardio-metabolic risk factors such as abdominal obesity, type 2 diabetes and other components of the metabolic syndrome (MetS). Currently, the importance of NAFLD and its relationship to the MetS is increasingly recognized, and this has stimulated an interest in the possible role of NAFLD in the development of cardiovascular disease (CVD). Indeed, the impact of NAFLD on CVD risk deserves particular attention in view of the implications for screening/surveillance strategies in this growing number of patients. Recent evidence suggests that the severity of liver histology in NAFLD patients is closely associated with markers of early atherosclerosis such as greater carotid artery wall thickness and lower endothelial flow-mediated vasodilation independently of classical risk factors and components of the MetS. Moreover, NAFLD is associated with greater overall mortality and independently predicts the risk of future CVD events. Overall, the current body of evidence strongly suggests that NAFLD is likely to be associated with increased CVD risk, and raises the possibility that NAFLD may be not only a marker but also an early mediator of atherosclerosis.     

Non-alcoholic fatty liver disease, the metabolic syndrome and the risk of cardiovascular disease: the plot thickens.

Non-alcoholic fatty liver disease (NAFLD) affects a substantial proportion of the general population and is frequently associated with many features of the metabolic syndrome (MetS). Currently, the importance of NAFLD and its relationship with the MetS is being increasingly recognized, and this has stimulated an interest in the possible role of NAFLD in the development of atherosclerosis. Recent studies have reported the association of NAFLD with multiple classical and non-classical risk factors for cardiovascular disease (CVD). Moreover, there is a strong association between the severity of liver histopathology in NAFLD patients and greater carotid artery intima-media thickness and plaque, and lower endothelial flow-mediated vasodilation (as markers of subclinical atherosclerosis) independent of obesity and other MetS components. Finally, it has recently been demonstrated that NAFLD is associated with an increased risk of all-cause death and predicts future CVD events independently of other prognostic factors, including MetS components. Overall, therefore, the evidence from these recent studies strongly emphasizes the importance of assessing the global CVD risk in patients with NAFLD. Moreover, these novel findings suggest a more complex picture and raise the possibility that NAFLD, as a component of the MetS, might not only be a marker but also an early mediator of CVD.     

NAFLD,and cardiovascular and cardiac diseases: Factors influencing risk,prediction and treatment

Background and aimNon-alcoholic fatty liver disease (NAFLD), affecting up to around 30% of the world’s adult population, causes considerable liver-related and extrahepatic morbidity and mortality. Strong evidence indicates that NAFLD (especially its more severe forms) is associated with a greater risk of all-cause mortality, and the predominant cause of mortality in this patient population is cardiovascular disease (CVD). This narrative review aims to discuss the strong association between NAFLD and increased risk of cardiovascular, cardiac and arrhythmic complications. Also discussed are the putative mechanisms linking NAFLD to CVD and other cardiac/arrhythmic complications, with a brief summary of CVD risk prediction/stratification and management of the increased CVD risk observed in patients with NAFLD.ResultsNAFLD is associated with an increased risk of CVD events and other cardiac complications (left ventricular hypertrophy, valvular calcification, certain arrhythmias) independently of traditional CVD risk factors. The magnitude of risk of CVD and other cardiac/arrhythmic complications parallels the severity of NAFLD (especially liver fibrosis severity). There are most likely multiple underlying mechanisms through which NAFLD may increase risk of CVD and cardiac/arrhythmic complications. Indeed, NAFLD exacerbates hepatic and systemic insulin resistance, promotes atherogenic dyslipidaemia, induces hypertension, and triggers synthesis of proatherogenic, procoagulant and proinflammatory mediators that may contribute to the development of CVD and other cardiac/arrhythmic complications.ConclusionCareful assessment of CVD risk is mandatory in patients with NAFLD for primary prevention of CVD, together with pharmacological treatment for coexisting CVD risk factors.     

Cardiovascular risk across the histological spectrum and the clinical manifestations of non-alcoholic fatty liver disease:an update

Non-alcoholic fatty liver disease(NAFLD) is considered to be an independent cardiovascular disease(CVD)risk factor. However, simple steatosis has a benign clinical course without excess mortality. In contrast, the advanced form of NAFLD, non-alcoholic steatohepatitis(NASH) with liver fibrosis increases mortality by approximately 70%, due to an increase in CVD mortality by approximately 300%. Chronic kidney disease(CKD) may be caused by NAFLD/NASH and it substantially increases CVD risk, especially in the presence of type 2 diabetes mellitus. Moreover, CKD may trigger NAFLD/NASH deterioration in a vicious cycle. NAFLD/NASH is also related to increased arterial stiffness(AS), an independent CVD risk factor that further raises CVD risk. Diagnosis of advanced liver fibrosis(mainly by simple non-invasive tests), CKD,and increased AS should be made early in the course of NAFLD and treated appropriately. Lifestyle measures and statin treatment may help resolve NAFLD/NASH and beneficially affect the CVD risk factors mentioned above.     

Role of ezetimibe in non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) encompasses a histological spectrum ranging from simple steatosis to steatohepatitis,advanced fibrosis and inflammatory changes.Ezetimibe inhibits cholesterol absorption from the intestinal lumen into enterocytes.The molecular target of ezetimibe is the sterol transporter Niemann-Pick C1-like 1 protein (NPC1L1).Human NPC1L1 is abundantly expressed in the liver and may facilitate the hepatic accumulation of cholesterol.Ezetimibe ex-erts beneficial effects on several metabolic variables.Ezetimibe treatment attenuates hepatic steatosis and is beneficial in terms of NAFLD biochemical markers.The combination of ezetimibe with other interventions may also be beneficial in NAFLD patients.Our group inves-tigated the ezetimibe-orlistat combination treatment in overweight and obese patients with hypercholeste-rolemia,with beneficial effects on NAFLD biochemical markers.These results are promising for patients with NAFLD,who usually have increased cardiovascular disease risk and need a multifactorial treatment.How-ever,it should be mentioned that most results are from animal studies and,although modest elevation of liver function tests may raise the suspicion of NAFLD,none of these tests are sensitive to establish the diagnosis of NAFLD with great accuracy.     

Increased prevalence of cardiovascular disease in Type 2 diabetic patients with non-alcoholic fatty liver disease.

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.     

Nonalcoholic fatty liver disease - A multisystem disease?

Non-alcoholic fatty liver disease(NAFLD) is one of the most common comorbidities associated with overweight and metabolic syndrome(Met S). Importantly, NAFLD is one of its most dangerous complications because it can lead to severe liver pathologies, including fibrosis, cirrhosis and hepatic cellular carcinoma. Given the increasing worldwide prevalence of obesity, NAFLD has become the most common cause of chronic liver disease and therefore is a major global health problem. Currently, NAFLD is predominantly regarded as a hepatic manifestation of Met S. However, accumulating evidence indicates that the effects of NAFLD extend beyond the liver and are negatively associated with a range of chronic diseases, most notably cardiovascular disease(CVD), diabetes mellitus type 2(T2DM) and chronic kidney disease(CKD). It is becoming increasingly clear that these diseases are the result of the same underlying pathophysiological processes associated with Met S, such as insulin resistance, chronic systemic inflammation and dyslipidemia. As a result, they have been shown to be independent reciprocal risk factors. In addition, recent data have shown that NAFLD actively contributes to aggravation of the pathophysiology of CVD, T2 DM, and CKD, as well as several other pathologies. Thus, NAFLD is a direct cause of many chronic diseases associated with MetS, and better detection and treatment of fatty liver disease is therefore urgently needed. As non-invasive screening methods for liver disease become increasingly available, detection and treatment of NAFLD in patients with MetS should therefore be considered by both(sub-) specialists and primary care physicians.     

Oxidative stress: New insights on the association of non-alcoholic fatty liver disease and atherosclerosis

Non-alcoholic fatty liver disease (NAFLD) represents the most common and emerging chronic liver disease worldwide. It includes a wide spectrum of liver diseases ranging from simple fatty liver to non-alcoholic steatohepatitis (NASH), which may progress to fibrosis and more severe liver complications such as cirrhosis, hepatocellular carcinoma and liver mortality. NAFLD is strongly associated with obesity, insulin resistance, hypertension, and dyslipidaemia, and is now regarded as the liver manifestation of the metabolic syndrome. The increased mortality of patients with NAFLD is primarily a result of cardiovascular disease and, to a lesser extent, to liver related diseases. Increased oxidative stress has been reported in both patients with NAFLD and patient with cardiovascular risk factors. Thus, oxidative stress represents a shared pathophysiological disorder between the two conditions. Several therapeutic strategies targeting oxidative stress reduction in patients with NAFLD have been proposed, with conflicting results. In particular, vitamin E supplementation has been suggested for the treatment of non-diabetic, non-cirrhotic adults with active NASH, although this recommendation is based only on the results of a single randomized controlled trial. Other antioxidant treatments suggested are resveratrol, silybin, L-carnitine and pentoxiphylline. No trial so far, has evaluated the cardiovascular effects of antioxidant treatment in patients with NAFLD. New, large-scale studies including as end-point also the assessment of the atherosclerosis markers are needed.     

Increased risk of cardiovascular disease and chronic kidney disease in NAFLD

NAFLD is very common in the general population and its prevalence is increasing worldwide in parallel with the increasing incidences of obesity and metabolic diseases, mainly type 2 diabetes. In some cases, however, the diagnosis of NAFLD remains uncertain because other causes of liver disease are not easy to exclude in patients who are diagnosed with NAFLD after a biochemical or ultrasonographic analysis. Several studies have documented a strong association between NAFLD and traditional and nontraditional risk factors for cardiovascular disease (CVD) and chronic kidney disease (CKD). Accordingly, patients with NAFLD have an increased prevalence and incidence of both CVD and CKD. It is reasonable to believe that NAFLD, CVD and CKD share common risk factors (such as visceral obesity, insulin resistance, dysglycaemia, dyslipidaemia and hypertension) and therefore that NAFLD might simply be a marker rather than a causal risk factor of CVD and CKD. In this context, the identification of NAFLD might be an additional clinical feature to improve the stratification of patients for their risk of CVD and CKD. Growing evidence suggests that in patients with NAFLD, especially if NASH is present, several molecules released from the steatotic and inflamed liver might have pathogenic roles in the development of atherosclerosis and kidney damage. If these findings are confirmed by further studies, NAFLD could become a target for the prevention and treatment of CVD and CKD. NAFLD, whatever its role (marker or causal risk factor), is therefore a clinical condition that deserves greater attention from gastroenterologists, endocrinologists, cardiologists and nephrologists, as well as internists and general practitioners.     

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

Non-alcoholic fatty liver disease (NAFLD), comprising a spectrum of conditions ranging from pure steatosis to steatohepatitis and cirrhosis, has reached epidemic proportions and represents the most common cause of chronic liver disease in the community. The prevalence of NAFLD has been estimated to be between 20% and 30% in the general population, but this value is much higher (∼70–80%) in type 2 diabetic patients, who are also at higher risk of developing advanced fibrosis and cirrhosis. Increasing recognition of the importance of NAFLD and its strong relationship with the metabolic syndrome has stimulated an interest in the possible role of NAFLD in the development of cardiovascular disease (CVD). Several epidemiological studies indicate that NAFLD, especially in its more severe forms, is linked to an increased risk of CVD, independently of underlying cardiometabolic risk factors. This suggests that NAFLD is not merely a marker of CVD, but may also be actively involved in its pathogenesis. The possible molecular mediators linking NAFLD and CVD include the release of pro-atherogenic factors from the liver (C-reactive protein, fibrinogen, plasminogen activator inhibitor-1 and other inflammatory cytokines) as well as the contribution of NAFLD per se to whole-body insulin resistance and atherogenic dyslipidemia, in turn favouring CVD progression. The clinical impact of NAFLD on CVD risk deserves particular attention in view of the implications for screening and surveillance strategies in the growing number of patients with NAFLD. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorised users.     

Experimental models of metabolic and alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) is a multi-systemic disease that is considered the hepatic manifestation of metabolic syndrome (MetS). Because alcohol consumption in NAFLD patients is common, there is a significant overlap in the pathogenesis of NAFLD and alcoholic liver disease (ALD). Indeed, MetS also significantly contributes to liver injury in ALD patients. This “syndrome of metabolic and alcoholic steatohepatitis” (SMASH) is thus expected to be a more prevalent presentation in liver patients, as the obesity epidemic continues. Several pre-clinical experimental models that couple alcohol consumption with NAFLD-inducing diet or genetic obesity have been developed to better understand the pathogenic mechanisms of SMASH. These models indicate that concomitant MetS and alcohol contribute to lipid dysregulation, oxidative stress, and the induction of innate immune response. There are significant limitations in the applicability of these models to human disease, such as the ability to induce advanced liver injury or replicate patterns in human food/alcohol consumption. Thus, there remains a need to develop models that accurately replicate patterns of obesogenic diet and alcohol consumption in SMASH patients.     

Nonalcoholic Fatty Liver Disease: Dyslipidemia,Risk for Cardiovascular Complications,and Treatment Strategy

Studies have shown that nonalcoholic fatty liver disease (NAFLD) is strongly associated with several metabolic disorders and diseases, such as obesity, type 2 diabetes mellitus, and dyslipidemia. In NAFLD, dyslipidemia is manifested as increased serum triglyceride and low-density lipoprotein cholesterol levels and decreased high-density lipoprotein cholesterol levels, all of which are key risk factors for cardiovascular disease (CVD). CVD is a leading cause of mortality in NAFLD patients. Thus, implementation of an aggressive therapeutic strategy for dyslipidemia with hypolipidemic agents may mitigate the risk for CVD among NAFLD patients. Here, we provide a current review of literature regarding NAFLD, with particular emphasis on dyslipidemia and available treatment options.     

Modern approach to the clinical management of non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) is the most common and emerging form of chronic liver disease worldwide. It includes a wide spectrum of liver diseases ranging from simple fatty liver to steatohepatitis, which may progress to cirrhosis, liver cancer, and liver mortality. Common metabolic diseases, which are well established cardiovascular risk factors, have been associated to NAFLD and cardiovascular disease is the single most important cause of morbidity and mortality in this patient population. The pathogenesis of NAFLD appears multifactorial and many mechanisms have been proposed as possible causes of fatty liver infiltration. Management of fatty liver has become a major challenge to healthcare systems as the consequence of the increasing rates of obesity worldwide. First-line management focuses on lifestyle modifications. Moderate weight reduction either by dietary restriction or by increased habitual physical activity is safe and highly recommended. Several therapeutic interventions have been proposed. These include insulin sensitizer agents, lipid lowering drugs, antioxidants such as vitamin E and supplementation of vitamin D₃. However, therapeutic strategies have been largely empirical so far, and experimental trials have mostly been carried out in uncontrolled settings with small sample sizes. Metabolic conditions such as diabetes mellitus, obesity, hypertension and hyperlipidemia, should be strongly considered and a multidisciplinary approach should be personalized for individual patients. Treatment of co-morbidities should be regarded as of paramount importance in the management of these patients. The purpose of this review is to examine different approaches for the clinical management of non-alcoholic fatty liver disease.     

MicroRNAs as controlled systems and controllers in non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) is a multi-faceted condition including simple steatosis alone or associated with inflammation and ballooning (non-alcoholic steatohepatitis) and eventually fibrosis. The NAFLD incidence has increased over the last twenty years becoming the most frequent chronic liver disease in industrialized countries. Obesity, visceral adiposity, insulin resistance, and many other disorders that characterize metabolic syndrome are the major predisposing risk factors for NAFLD. Furthermore, different factors, including genetic background, epigenetic mechanisms and environmental factors, such as diet and physical exercise, contribute to NAFLD development and progression. Several lines of evidence demonstrate that specific microRNAs expression profiles are strongly associated with several pathological conditions including NAFLD. In NAFLD, microRNA deregulation in response to intrinsic genetic or epigenetic factors or environmental factors contributes to metabolic dysfunction. In this review we focused on microRNAs role both as controlled and controllers molecules in NAFLD development and/or their eventual value as non-invasive biomarkers of disease.     

Impact of non-alcoholic fatty liver disease on accelerated metabolic complications

Insulin resistance is the basis of both non-alcoholic fatty liver disease (NAFLD) and metabolic syndrome (MetS), the two conditions are often found in the same individual. The mortality of patients with NAFLD is significantly higher than that among the general population and cardiovascular risk may compete with liver-related risk in dictating the final outcome. Recent prospective studies have reported that NAFLD is associated with an increased incidence of MetS and type 2 diabetes mellitus, independent of obesity and other components of MetS. Thus, NAFLD may not only be a liver disease but also an early mediator of type 2 diabetes mellitus and MetS. The biological mechanisms by which NAFLD contributes to a higher risk of developing metabolic disorders are not fully understood. However, the fatty liver could contribute in the same way as visceral adipose tissue to insulin resistance, systemic inflammation and oxidative stress, while the decreased serum adiponectin concentrations might also be part of the mechanism. In contemporary clinical practice, it has become mandatory to evaluate the metabolic risk factors in NAFLD patients and to consider careful surveillance and aggressive treatment, not only of the resultant liver disease, but also of the possible underlying metabolic and vascular complications. Future studies might address the question whether earlier adjustment to a more efficient lifestyle or a pharmacological treatment that mobilizes fat out of the liver could reduce these risks.     

Metabolic complications in liver transplant recipients

The metabolic syndrome(MS), which includes obesity,dyslipidaemia, hypertension and hyperglycaemia according to the most widely accepted definitions now used, is one of the most common post-transplant complications, with a prevalence of 44%-58%. The MS, together with the immunosuppression, is considered the main risk factor for the development of cardiovascular disease(CVD) in transplant recipients, which in turn accounts for 19%-42% of all deaths unrelated to the graft. The presence of MS represents a relative risk for the development of CVD and death of 1.78. On the other hand, non-alcoholic fatty liver disease(NAFLD), considered as the manifestation of the MS in the liver, is now the second leading reason for liver transplantation in the United States after hepatitis C and alcohol. NAFLD has a high rate of recurrence in the liver graft and a direct relation with the worsening of other metabolic disorders, such as insulin resistance or diabetes mellitus. Consequently, it is vitally important to identify and treat as soon as possible such modifiable factors as hypertension, overweight, hyperlipidaemia or diabetes in transplanted patients to thus minimise the impact on patient survival. Additionally, steroid-free regimens are favoured, with minimal immunosuppression to limit the possible effects on the development of the MS.     

非酒精性脂肪性肝病在心血管疾病发生发展中的作用

随着经济水平的提高、饮食结构和生活方式的改变,非酒精性脂肪性肝病(non-alcoholic fatty liver disease,NAFLD)的发病率不断上升,逐渐成为全球慢性肝病的主要病因.心血管疾病(cardiovascular disease,CVD)作为NAFLD患者的主要死亡原因,越来越多的研究发现两者之间存在相关性;NAFLD患者CVD发生发展的风险更大,其机制可能与血管和内皮细胞功能障碍、胆汁酸代谢、氧化应激、全身炎症反应和肾素-血管紧张素系统的激活等相关.其中,代谢综合征在两者联系中发挥了重要的作用.因此,早期识别NAFLD患者心血管疾病相关危险因素,进而减少心血管相关并发症,对于改善该类患者的预后至关重要.     

非酒精性脂肪性肝病与心血管疾病相关性研究进展与现状

随着非酒精性脂肪性肝病(non-alcoholic fatty liver disease,NAFLD)的深入研究,近几年来发现与心血管疾病(cardiovascular disease,CVD)密切相关.现已证明,NAFLD是CVD发生的重要危险因素,也是年青人动脉硬化、冠心病、高血压发病的重要机制.本文就NAFLD对动脉粥样硬化和CVD的影响、发病机制进行综述,以提高肝病和CVD医师的认识水平,为做好防治提供资源.     

Nonalcoholic fatty liver disease in patients with inflammatory bowel disease: Beyond the natural history

BACKGROUND Nonalcoholic fatty liver disease(NAFLD) is a frequently reported condition in patients with inflammatory bowel disease(IBD). Both intestinal inflammation and metabolic factors are believed to contribute to the pathogenesis of IBDassociated NAFLD.AIM To evaluate the prevalence of steatosis and liver fibrosis(LF) in a cohort of IBD patients and the identification of metabolic-and IBD-related risk factors for NAFLD and LF.METHODS IBD patients were consecutively enrolled from December 2016 to January 2018.Demographic, anthropometric and biochemical data were collected so as eating habits. Abdominal ultrasound and transient elastography were performed to evaluate the presence of NAFLD and LF respectively.RESULTS A total of 178 consecutive patients were enrolled and included in the analysis(95 Ulcerative colitis, 83 Crohn's disease). NAFLD was detected by imaging in 72(40.4%) patients. Comparison between patients with and without NAFLD showed no significant differences in terms of IBD severity, disease duration,location/extension, use of IBD-related medications(i.e., steroids, anti-TNFs, and immunomodulators) and surgery. NAFLD was significantly associated with thepresence of metabolic syndrome [MetS; odds ratio(OR): 4.13, P = 0.001] and obesity defined by body mass index(OR: 9.21, P = 0.0002). IBD patients with NAFLD showed higher caloric intake and lipid consumption than those without NAFLD, regardless disease activity. At the multivariate analysis, male sex,advanced age and high lipid consumption were independent risk factors for the development of NAFLD. An increased liver stiffness was detected in 21 patients(16%) and the presence of MetS was the only relevant factor associated to LF(OR:3.40, P = 0.01).CONCLUSION In this study, we demonstrate that risk factors for NAFLD and LF in the IBD population do not differ from those in the general population.     

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

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.