Nonalcoholic Fatty Liver Disease Is Independently Associated With an Increased Incidence of Cardiovascular Events in Type 2 Diabetic Patients

Targher, Giovanni; Bertolini, Lorenzo; Rodella, Stefano; Tessari, Roberto; Zenari, Luciano; Lippi, Giuseppe; Arcaro, Guido

doi:10.2337/dc07-0349

Cited by 488 publications

(387 citation statements)

References 18 publications

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“…In the Valpolicella Heart Diabetes Study, the presence of ultrasound-diagnosed NAFLD in a large cohort of type 2 diabetic individuals was associated with an increased incidence of CVD events, independently of a broad number of confounding factors [37,42]. Almost identical results were reported in a community-based cohort of 1,637 nondiabetic individuals [43].…”

Section: Nafld and Increased Incidence Of Cvdmentioning

confidence: 59%

“…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].…”

Section: Evidence Linking Nafld With Cvdmentioning

confidence: 99%

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

2008

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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.

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Section: Nafld and Increased Incidence Of Cvdmentioning

confidence: 59%

Section: Evidence Linking Nafld With Cvdmentioning

confidence: 99%

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

2008

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“…The association between the amount of fat in these sites and insulin resistance or metabolic diseases has been reported. [19][20][21] However, whether ectopic fat deposition in these sites, except the visceral cavity, is a causal factor or a consequence of cardiometabolic disease remains a matter of debate. This cross-sectional study offered the finding that altered partitioning of fat in muscle (greater low-density muscle area or lower muscle attenuation) and the liver (lower liver attenuation) was observed relatively early in the development of type 2 diabetes, along with an increased visceral fat mass.…”

Section: Discussionmentioning

confidence: 99%

High fat stores in ectopic compartments in men with newly diagnosed type 2 diabetes: an anthropometric determinant of carotid atherosclerosis and insulin resistance

et al. 2009

Int J Obes

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Objective: The objective of this study was to analyze how fat partitioning in the liver, muscle and visceral compartments is altered by diabetes and age, and whether altered fat distribution is associated with a higher carotid artery intima-media thickness (C-IMT) and insulin resistance. Methods: This was an observational study performed on 21 young healthy men (mean age±s.d., 28.6±3.8 years) and 73 men with newly developed type 2 diabetes (38 young (29.2 ± 4.1 years) and 35 middle-aged (47.1 ± 6.0 years) subjects). Abdominal visceral and subcutaneous fat areas, mid-thigh muscle attenuation and liver attenuation characteristics were determined; the mid-thigh muscle was divided into low-and normal-density muscle areas. Results: The young and middle-aged diabetic subjects had higher visceral fat areas, higher liver attenuation and higher lipid-rich muscle (greater low-density muscle area and decreased muscle attenuation) when compared with healthy individuals; however, no differences were observed between the two diabetic groups. In contrast, the C-IMT increased with both age and diabetes. On the basis of multiple regression analyses, mid-thigh low-density muscle area and muscle attenuation were independently associated with the C-IMT, and the mid-thigh normal-density muscle area and muscle attenuation were independent factors of insulin resistance. Conclusions: High fat stores within ectopic compartments were observed at an early stage in the development of diabetes. Furthermore, altered lipid partitioning within muscle was independently associated with carotid atherosclerosis and insulin resistance.

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“…Although there has been some conflicting work (112) , a systematic review has found that carotid plaques are two to three times more likely to be observed in patients with NAFLD and intima-media thickness is strongly associated with NAFLD (113) . Furthermore, multiple population studies have observed increased CVD events in patients with NAFLD diagnosed by ultrasonography and have demonstrated that the increased risk for CVD in NAFLD is independent of conventional risk factors and components of the metabolic syndrome (114)(115)(116) . These data add to population data that have shown that elevated liver enzymes are also associated with increased risk for CVD (67,117) .…”

Section: Genetic and Environmental Factors Associated With Non-alcohomentioning

confidence: 99%

Non-alcoholic fatty liver disease: the hepatic consequence of obesity and the metabolic syndrome

2010

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Non-alcoholic fatty liver disease (NAFLD) is now the most common liver disease in both adults and children worldwide. As a disease spectrum, NAFLD may progress from simple steatosis to steatohepatitis, advanced fibrosis and cirrhosis. An estimated 20-35% of the general population has steatosis, 10 % of whom will develop the more progressive non-alcoholic steatohepatitis associated with markedly increased risk of cardiovascular-and liver-related mortality. Development of NAFLD is strongly linked to components of the metabolic syndrome including obesity, insulin resistance, dyslipidaemia and type 2 diabetes. The recognition that NAFLD is an independent risk factor for CVD is a major public health concern. There is a great need for a sensitive non-invasive test for the early detection and assessment of the stage of NAFLD that could also be used to monitor response to treatment. The cellular and molecular aetiology of NAFLD is multi-factorial; genetic polymorphisms influencing NAFLD have been identified and nutrition is a modifiable environmental factor influencing NAFLD progression. Weight loss through diet and exercise is the primary recommendation in the clinical management of NAFLD. The application of systems biology to the identification of NAFLD biomarkers and factors involved in NAFLD progression is an area of promising research.

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Nonalcoholic Fatty Liver Disease Is Independently Associated With an Increased Incidence of Cardiovascular Events in Type 2 Diabetic Patients

Cited by 488 publications

References 18 publications

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

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

High fat stores in ectopic compartments in men with newly diagnosed type 2 diabetes: an anthropometric determinant of carotid atherosclerosis and insulin resistance

Non-alcoholic fatty liver disease: the hepatic consequence of obesity and the metabolic syndrome

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