Nonalcoholic fatty liver disease and the metabolic syndrome

Marchesini, Giulio; Marzocchi, Rebecca; Agostini, F.; Bugianesi, Elisabetta

doi:10.1097/01.mol.0000174153.53683.f2

Cited by 434 publications

(385 citation statements)

References 43 publications

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“…This finding provides further evidence that ALT and other serum liver enzymes appear to be insensitive markers for NAFLD, especially in the type 2 diabetic population. Indeed, it is well known that the full histological spectrum of NAFLD may be present among patients with 'normal' serum liver enzymes, which therefore cannot be reliably used to exclude the presence of advanced NAFLD [1][2][3][4]. Our finding further supports the notion that the 'normal' reference values for serum liver enzymes currently used to exclude NAFLD need to be revised [2,21,22].…”

Section: Discussionsupporting

confidence: 68%

“…Non-alcoholic fatty liver disease (NAFLD), in its whole spectrum of disease ranging from simple steatosis to steatohepatitis and cirrhosis, is the most common cause of abnormal liver function tests among adults in Western countries [1][2][3][4]. The prevalence of NAFLD has been reported to be in the 15 to 30% range in the general population in various countries [5][6][7] and is almost certainly increasing.…”

Section: Introductionmentioning

confidence: 99%

“…Compared with non-diabetic individuals, people with type 2 diabetes appear to be at increased risk of developing NAFLD and certainly have a higher risk of developing fibrosis and cirrhosis [1][2][3][4]. It has been reported that ∼70 to 75% of type 2 diabetic patients have some form of NAFLD [8,9].…”

Section: Introductionmentioning

confidence: 99%

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Non-alcoholic fatty liver disease is independently associated with an increased prevalence of chronic kidney disease and proliferative/laser-treated retinopathy in type 2 diabetic patients

et al. 2007

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Aims/hypothesis Non-alcoholic fatty liver disease (NAFLD) is associated with an increased risk of cardiovascular disease in type 2 diabetes. Currently, there is a lack of information on associations between NAFLD and microvascular complications of diabetes. We assessed the associations between NAFLD and both chronic kidney disease (CKD) and retinopathy in a large cohort of type 2 diabetic individuals using a cross-sectional design.Methods Prevalence rates of retinopathy (by ophthalmoscopy) and CKD (defined as overt proteinuria and/or estimated GFR ≤60 ml min) were assessed in 2,103 type 2 diabetic individuals who were free of diagnosed cardiovascular disease and viral hepatitis. NAFLD was ascertained by patient history, blood sampling and liver ultrasound. Results NAFLD patients had higher (p<0.001) age-and sex-adjusted prevalence rates of both non-proliferative (39 vs 34%) and proliferative/laser-treated retinopathy (11 vs 5%), and CKD (15 vs 9%) than counterparts without NAFLD. In logistic regression analysis, NAFLD was associated with increased rates of CKD (odds ratio 1.87; 95% CI 1.3-4.1, p=0.020) and proliferative/laser-treated retinopathy (odds ratio 1.75; 1.1-3.7, p=0.031) independently of age, sex, BMI, waist circumference, hypertension, diabetes duration, HbA 1c , lipids, smoking status and medications use. Conclusions/interpretation Our findings suggest that NAFLD is associated with an increased prevalence of CKD and proliferative/laser-treated retinopathy in type 2 diabetic individuals independently of numerous baseline confounding factors. Further studies are required to confirm the reproducibility of these results and to evaluate whether NAFLD contributes to the development or progression of CKD and retinopathy.

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Section: Discussionsupporting

confidence: 68%

Section: Introductionmentioning

confidence: 99%

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Non-alcoholic fatty liver disease is independently associated with an increased prevalence of chronic kidney disease and proliferative/laser-treated retinopathy in type 2 diabetic patients

et al. 2007

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“…Physical activity can reduce muscle insulin resistance [20,21]; however, studies have also shown that physical activity is associated with a lower intrahepatic fat content [22], and that intrahepatic fat content is associated with hepatic insulin sensitivity [23,24]. Consequently, a differential effect of physical activity on progression to diabetes in individuals with i-IFG and i-IGT could be expected.…”

Section: Introductionmentioning

confidence: 99%

Differential relationship between physical activity and progression to diabetes by glucose tolerance status: the Inter99 Study

Engberg

Glümer²,

Witte

et al. 2009

Diabetologia

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Aims/hypothesis The aim of the study was to analyse how strongly commuting and leisure-time physical activity affect progression to diabetes and to study whether this relationship is different in individuals with isolated impaired fasting glucose (i-IFG) and isolated impaired glucose tolerance (i-IGT). Methods We studied the incidence of diabetes in 4,031 individuals without diabetes at baseline who participated in the baseline and 5 year follow-up examinations of a population-based primary prevention study, the Inter99 Study. Glucose tolerance status at baseline and at followup were based on OGTTs. Commuting and leisure-time physical activity at baseline were assessed by questionnaire. We present rate ratios from Poisson regression analyses adjusted for relevant confounders. Results The progression rate to diabetes was lower among physically active individuals in the total study population and particularly among those with i-IGT. The associations were attenuated and lost statistical significance after further adjustment for BMI. We observed no impact of physical activity on the progression to diabetes in individuals with i-IFG. Conclusions/interpretation Physical activity was associated with a lower progression to diabetes in the total study population and in individuals with i-IGT, a condition primarily characterised by muscle insulin resistance. Physical activity did not predict progression to diabetes in individuals with i-IFG, a condition primarily characterised by hepatic insulin resistance. Our results suggest that there is a differential relationship between physical activity and progression to diabetes among those with i-IFG and i-IGT. Therefore, clinical trials testing the effect of physical activity on progression from i-IFG to diabetes are needed.

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“…NAFLD predicts development of the metabolic syndrome and is involved in the pathophysiology of atherosclerosis, insulin resistance and type 2 diabetes [1][2][3][4][5][6][7]. While these data emphasise the critical role of fatty liver in human metabolism, the mechanisms involved in the process of hepatic fat accumulation in humans are not fully understood.…”

Section: Introductionmentioning

confidence: 99%

Low hepatic stearoyl-CoA desaturase 1 activity is associated with fatty liver and insulin resistance in obese humans

et al. 2008

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Aims/hypothesis Stearoyl-CoA desaturase 1 (SCD1) is the rate-limiting enzyme in monounsaturated fatty acid synthesis. It is imperative for the assembly of VLDL particles, which transport triacylglycerol (TG) from liver to adipose tissue and other sites. We aimed to determine the role of hepatic SCD1 activity in human glucose and lipid metabolism. Methods We studied 54 people participating in a lifestyle intervention programme with diet modification and increased physical activity. Insulin sensitivity was determined during a euglycaemic-hyperinsulinaemic clamp and estimated from an OGTT. Liver fat was quantified by 1 H-magnetic resonance spectroscopy at baseline and after 9 months of intervention. The pattern of fatty acids in serum VLDL-TGs was determined by ultracentrifugation followed by thin layer and gas chromatography, with the 18:1 n-9: 18:0 ratio providing an index of hepatic SCD1 activity. Results The hepatic SCD1 activity index correlated negatively with liver fat (r=−0.29, p=0.04) and positively with insulin sensitivity, both p=0.003) and clamp-derived (r=0.27, p=0.07). These correlations depended on overall adiposity. They were absent in leaner participants (n=27, liver fat: p=0.34, insulin sensitivity [OGTT]: p=0.75, insulin sensitivity [clamp]: p=0.24), but were strong in obese individuals (n=27, p=0.004, p=0.0002 and p=0.006, respectively). Furthermore, during intervention a high SCD1 activity index at baseline predicted a decrease in liver fat only in obese participants (r=−0.46, p=0.02). Conclusions/interpretation Our data suggest that high hepatic SCD1 activity may regulate fat accumulation in the liver and possibly protects from insulin resistance in obesity.

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Nonalcoholic fatty liver disease and the metabolic syndrome

Cited by 434 publications

References 43 publications

Non-alcoholic fatty liver disease is independently associated with an increased prevalence of chronic kidney disease and proliferative/laser-treated retinopathy in type 2 diabetic patients

Non-alcoholic fatty liver disease is independently associated with an increased prevalence of chronic kidney disease and proliferative/laser-treated retinopathy in type 2 diabetic patients

Differential relationship between physical activity and progression to diabetes by glucose tolerance status: the Inter99 Study

Low hepatic stearoyl-CoA desaturase 1 activity is associated with fatty liver and insulin resistance in obese humans

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