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SHOULD NONALCOHOLIC FATTY LIVER DISEASE BE INCLUDED IN THE DEFINITION OF METABOLIC SYNDROME? A CROSS-SECTIONAL COMPARISON WITH ATP III CRITERIA IN NONOBESE NONDIABETIC SUBJECTS

¹Gradenigo Hospital, Turin
²Department of Internal Medicine, University of Turin, Italy

giovanni_musso{at}yahoo.it

ABSTRACT

Objective: The ability of ATP III criteria of metabolic syndrome (MS) to identify insulin resistant (IR) 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: Insulin resistance (HOMA-IR >2), oxidative stress (nitrotyrosine), soluble adhesion molecules (ICAM-1, VCAM-1, E-selectin) and circulating adipokines (TNF-symbol 97 \f "Symbol" \s 12a, leptin, adiponectin, resistin) were cross-sectionally correlated to ATP III criteria and to NAFLD in 197 unselected nonobese nondiabetic subjects.

Results: NAFLD more accurately predicted IR than ATP III criteria: sensitivity 73% vs.38% (p=0.0001); positive predictive value (PPV): 81% vs. 62% (p=0.035); NPV: 87% vs. 74% (p=0.012); positive likelihood ratio (LR): 4.39 vs. 1.64 (p=0.0001); negative LR: 0.14 vs. 0.35 (p=0.0001). Adding NAFLD to ATP III criteria significantly improved their diagnostic accuracy for IR. 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, independently of adiposity or any feature of MS in IR subjects.

Conclusions: NAFLD is more tightly associated with IR and with markers of oxidative stress and endothelial dysfunction than ATP III criteria in nonobese nondiabetic subjects and may help identify individuals at increased cardiometabolic risk in this population.

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				G. Musso, R. Gambino, S. Bo, and M. Cassader Should Nonalcoholic Fatty Liver Disease Be Included in the Definition of Metabolic Syndrome? A Cross-Sectional Comparison With Adult Treatment Panel III Criteria in Nonobese Nondiabetic Subjects: Response to Sookoian et al. Diabetes Care, May 1, 2008; 31(5): e43 - e43. [Full Text] [PDF]