Should Nonalcoholic Fatty Liver Disease Be Included in the Definition of Metabolic Syndrome?

Abstract

OBJECTIVE -The ability of the Adult Treatment Panel III (ATP III) criteria of metabolic syndrome to identify insulin-resistant subjects at increased cardiovascular risk is suboptimal, especially in the absence of obesity and diabetes. Nonalcoholic fatty liver disease (NAFLD) is associated with insulin resistance and is emerging as an independent cardiovascular risk factor. We compared the strength of the associations of ATP III criteria and of NAFLD to insulin resistance, oxidative stress, and endothelial dysfunction in nonobese nondiabetic subjects. RESEARCH DESIGN AND METHODS-Homeostasis model assessment of insulin resistance (HOMA-IR) Ͼ2, oxidative stress (nitrotyrosine), soluble adhesion molecules (intracellular adhesion molecule-1, vascular cell adhesion molecule-1, and E-selectin), and circulating adipokines (tumor necrosis factor-␣, leptin, adiponectin, and resistin) were cross-sectionally correlated to ATP III criteria and to NAFLD in 197 unselected nonobese nondiabetic subjects.RESULTS -NAFLD more accurately predicted insulin resistance than ATP III criteria: sensitivity 73 vs. 38% (P ϭ 0.0001); positive predictive value: 81 vs. 62% (P ϭ 0.035); negative predictive value 87 vs. 74% (P ϭ 0.012); positive likelihood ratio 4.39 vs. 1.64 (P ϭ 0.0001); and negative likelihood ratio 0.14 vs. 0.35 (P ϭ 0.0001). Adding NAFLD to ATP III criteria significantly improved their diagnostic accuracy for insulin resistance. Furthermore, NAFLD independently predicted HOMA-IR, nitrotyrosine, and soluble adhesion molecules on logistic regression analysis; the presence of NAFLD entailed more severe oxidative stress and endothelial dysfunction, independent of adiposity or any feature of the metabolic syndrome in insulinresistant subjects.CONCLUSIONS -NAFLD is more tightly associated with insulin resistance and with markers of oxidative stress and endothelial dysfunction than with ATP III criteria in nonobese nondiabetic subjects and may help identify individuals with increased cardiometabolic risk in this population. Diabetes Care 31:562-568, 2008M etabolic syndrome is a cluster of metabolic and cardiovascular risk factors that sharing the hallmark of insulin resistance; its prevalence according to Adult Treatment Panel III (ATP III) criteria is 20% among Western adults (1). Insulin resistance is an independent predictor of cardiovascular disease and type 2 diabetes and should be identified and treated early (2-5).Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in Western countries (1). NAFLD predicts incident diabetes independent of classic risk factors and C-reactive protein in large prospective cohort studies and may therefore be an early marker of mechanisms predisposing to future metabolic events (1,6). In a parallel way, NAFLD is emerging as a marker of early atherosclerosis: liver enzymes predicted incident cardiovascular disease independent of traditional risk factors, C-reactive protein and metabolic syndrome, and liver histology correlated with early carotid atherosclerosis in NAF...

Metformin versus dietary treatment in nonalcoholic hepatic steatosis: a randomized study

“…39 Unlike other insulin sensitizers, such as thiazolidinediones, whose side effects may raise concern, the long-term safety of metformin is well established. 12,29,40 Our present findings are in agreement with results of Bugianesi et al, 18 who reported that metformin was more efficacious than dietary treatment on metabolic parameters in NAFLD patients and of Haukeland et al 41 , who found that the use of metformin was associated with weight loss and amelioration in the metabolic profile in NAFLD patients. Other studies have also found a beneficial effect of metformin on metabolic parameters, [15][16][17]41 and on liver enzymes and histology in NAFLD patients.…”

Metabolic syndrome: comparison of diagnosis criteria

“…Alguns autores consideram a presença da esteatose como a manifestação hepática da RI 13,15 . No estudo de Schwimmer et al 29 , as crianças e os adolescentes que apresentavam DGFNA tinham valores absolutos mais altos para marcadores de risco cardiovascular, além de maior frequência da SM.…”

“…Musso et al 13 verificaram associação positiva entre RI e DGFNA e também sugeriram a inclusão da DGFNA nos critérios para o diagnóstico da SM. D'Ádamo et al 14 , em estudo transversal com 100 crianças obesas e pré-púberes, encontraram prevalência de esteatose hepática de 52%.…”

Síndrome metabólica: comparação de critérios diagnósticos

“…11 Chan et al 12 conducted a systematic literature review and propose that non-alcoholic fatty liver disease (NAFLD) be acknowledged as a component of MS given that it is implicated in the context of risk factors for the development of type 2 diabetes mellitus and early-onset CVD. Musso et al 13 observed a positive correlation between IR and NAFLD and also suggested including NAFLD as diagnostic criteria for MS. D'Ádamo et al 14 carried out a cross-sectional study with 100 obese prepubertal children and found a prevalence of 52% for hepatic steatosis. Obese children with steatosis, when compared with the control group of normal-weight children and with obese children without steatosis, had higher HOMA-IR indices, which suggests an association between IR and steatosis.…”