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A Randomized Trial

Katherine Esposito, MD; Alessandro Pontillo, MD; Carmen Di Palo; Giovanni Giugliano, MD; Mariangela Masella, MD; Raffaele Marfella, MD, PhD; Dario Giugliano, MD, PhD

JAMA. 2003;289:1799-1804.

Context  Obesity is an independent risk factor for cardiovascular disease, which may be mediated by increased secretion of proinflammatory cytokines by adipose tissue.

Objective  To determine the effect of a program of changes in lifestyle designed to obtain a sustained reduction of body weight on markers of systemic vascular inflammation and insulin resistance.

Design and Setting  Randomized single-blind trial conducted from February 1999 to February 2002 at a university hospital in Italy.

Patients  One hundred twenty premenopausal obese women (body mass index 30) aged 20 to 46 years without diabetes, hypertension, or hyperlipidemia.

Interventions  The 60 women randomly assigned to the intervention group received detailed advice about how to achieve a reduction of weight of 10% or more through a low-energy Mediterranean-style diet and increased physical activity. The control group (n = 60) was given general information about healthy food choices and exercise.

Main Outcome Measures  Lipid and glucose intake; blood pressure; homeostatic model assessment of insulin sensitivity; and circulating levels of interleukin 6 (IL-6), interleukin 18 (IL-18), C-reactive protein (CRP), and adiponectin.

Results  After 2 years, women in the intervention group consumed more foods rich in complex carbohydrates (9% corrected difference; P<.001), monounsaturated fat (2%; P = .009), and fiber (7 g/d; P<.001); had a lower ratio of omega-6 to omega-3 fatty acids (-5; P<.001); and had lower energy (-310 kcal/d; P<.001), saturated fat (-3.5%; P = .007), and cholesterol intake (-92 mg/d; P<.001) than controls. Body mass index decreased more in the intervention group than in controls (-4.2; P<.001), as did serum concentrations of IL-6 (-1.1 pg/mL; P = .009), IL-18 (-57 pg/mL; P = .02), and CRP (-1.6 mg/L; P = .008), while adiponectin levels increased significantly (2.2 µg/mL; P = .01). In multivariate analyses, changes in free fatty acids (P = .008), IL-6 (P = .02), and adiponectin (P = .007) levels were independently associated with changes in insulin sensitivity.

Conclusion  In this study, a multidisciplinary program aimed to reduce body weight in obese women through lifestyle changes was associated with a reduction in markers of vascular inflammation and insulin resistance.

Author Affiliations: Center for Obesity Management, Department of Geriatrics and Metabolic Diseases (Drs Esposito and Pontillo and Ms Di Palo), Chair of Plastic and Reconstructive Surgery (Dr G. Giugliano), Department of Psychiatry (Dr Masella), and Cardiovascular Research Center (Drs Marfella and D. Giugliano), Second University of Naples, Naples, Italy.

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ABSTRACT | FULL TEXT  

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ABSTRACT | FULL TEXT  

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ABSTRACT | FULL TEXT  

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ABSTRACT | FULL TEXT  

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ABSTRACT | FULL TEXT  

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ABSTRACT | FULL TEXT  

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ABSTRACT | FULL TEXT  

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ABSTRACT | FULL TEXT  

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ABSTRACT | FULL TEXT  

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ABSTRACT | FULL TEXT  

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ABSTRACT | FULL TEXT  

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FULL TEXT  

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ABSTRACT | FULL TEXT  

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ABSTRACT | FULL TEXT  

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ABSTRACT | FULL TEXT  

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FULL TEXT  

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ABSTRACT | FULL TEXT  

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FULL TEXT  

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ABSTRACT | FULL TEXT  

Production and Release of Macrophage Migration Inhibitory Factor from Human Adipocytes
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ABSTRACT | FULL TEXT