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
- Giovanni Musso, MD1,
- Roberto Gambino, MD2,
- Simona Bo, MD2,
- Barbara Uberti, MD2,
- Giampaolo Biroli, MD2,
- Gianfranco Pagano, MD2 and
- Maurizio Cassader, MD2
- 1Gradenigo Hospital, Turin, Italy
- 2Department of Internal Medicine, University of Turin, Turin, Italy
- Address correspondence and reprint requests to Giovanni Musso, Gradenigo Hospital, Corso R. Margherita 8, 10132 Turin, Italy. E-mail: giovanni_musso{at}yahoo.it
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) >2, oxidative stress (nitrotyrosine), soluble adhesion molecules (intracellular adhesion molecule-1, vascular cell adhesion molecule-1, and E-selectin), and circulating adipokines (tumor necrosis factor-α, 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 = 0.0001); positive predictive value: 81 vs. 62% (P = 0.035); negative predictive value 87 vs. 74% (P = 0.012); positive likelihood ratio 4.39 vs. 1.64 (P = 0.0001); and negative likelihood ratio 0.14 vs. 0.35 (P = 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 insulin-resistant 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.
- ALT, alanine aminotransferase
- ATP III, Adult Treatment Panel III
- HOMA-IR, homeostasis model assessment of insulin resistance
- ICAM-1, intercellular adhesion molecule-1
- NAFLD, nonalcoholic fatty liver disease
- OGTT, oral glucose tolerance test
- TNF-α, tumor necrosis factor-α
- VCAM-1, vascular cell adhesion molecule-1
Footnotes
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Published ahead of print at http://care.diabetesjournals.org on 4 December 2007. DOI: 10.2337/dc07-1526.
Additional information for this article can be found in an online appendix at http://dx.doi.org/10.2337/dc07-1526.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C Section 1734 solely to indicate this fact.
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- Accepted November 19, 2007.
- Received August 3, 2007.
- DIABETES CARE
