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© 2003 by the American Diabetes Association, Inc.
Letters: Comments and Responses |
The Effect of Weight Loss on Endothelial Functions in Obesity
Response to Sciacqua et al.
Department of Geriatrics and Metabolic Diseases, Center for Obesity Management, Second University of Naples, Naples, Italy
Address correspondence to Katherine Esposito, MD, Center for Obesity Management, Policlinico della Seconda Università di Napoli, Piazza Miraglia, 80138 Napoli, Italy. E-mail: katherine.esposito{at}unina2.it
We read with interest the article by Sciacqua et al. (1) showing improvement of endothelial function in healthy obese subjects (no sex specified) after short-term (12–16 weeks) weight loss. By adopting a low-calorie diet associated with exercise, only two-thirds of the subjects enrolled in the study were able to achieve a reduction of at least 10% of initial weight (due to a high drop-out rate). In these subjects, maximal vasodilator response to the highest dose of acetylcholine increased from 211 to 358% of baseline, indicating improved endothelium-dependent vasodilation. The choice of obese subjects without known additional risk factors was the right one to make, thus avoiding the many possible confounders affecting endothelial function.
However, we disagree with the conclusions of the authors that "this is the first study to prospectively evaluate the effects of weight loss and physical activity on endothelium-dependent vasodilation of obese normotensive subjects," as our study of a multidisciplinary program, including low-calorie Mediterranean-type diet, exercise, and behavioral and nutritional counseling in obese women, was published earlier (2). In that study, we performed the first long-term prospective evaluation of the effect of weight loss on endothelial functions and circulating markers of vascular inflammation in 56 obese but otherwise healthy women (2). After 12 months, the women lost at least 10% of their initial weight (-9.8 ± 1.5 kg [range 7.5–13]) and increased their physical activity from 46 ± 12 to 131 ± 29 min/week. All of this was associated with improved endothelial functions as assessed by the hemodynamic (blood pressure decrease) and rheologic (platelet aggregation response to ADP) responses to L-arginine (3 g i.v.), the natural precursor of nitric oxide (3). Moreover, the raised circulating concentrations of proinflammatory cytokines (interleukin-6 and tumor necrosis factor-
) and intracellular and vascular cell adhesion molecules (ICAM-1 and VCAM-1, respectively) that the obese women had at baseline were significantly reduced after weight loss.
The pathogenesis of endothelial dysfunction in obesity remains uncertain; the relative roles of insulin resistance, circulating nonesterified fatty acids, or adipocyte-associated cytokines are being delineated. For example, both nonesterified fatty acids (4) and interleukin-6 or tumor necrosis factor- (5) can induce vascular dysfunction and insulin resistance. In obese individuals, circulating nonesterified fatty acids and proinflammatory cytokines are increased, which may explain, at least in part, their increased cardiovascular risk. We have also shown that a long-term (2 years) multidisciplinary program aimed to reduce body weight through lifestyle changes in obese women was associated with reduction of insulin resistance and increased adiponectin concentrations (6). Because adiponectin possesses anti-inflammatory properties and improves glucose tolerance (7), hypoadiponectinemia may contribute to the low-grade inflammation and the insulin resistance that characterize human obesity. Thus, the increased cardiovascular risk of obese people may be seen as the result, at least in part, of increased inflammatory stimuli and decreased anti-inflammatory mechanisms.
References
- Sciacqua A, Candigliota M, Ceravolo R, Scozzafava A, Sinopoli F, Corsonello A, Sesti G, Perticone F: Weight loss in combination with physical activity improves endothelial dysfuction in human obesity. Diabetes Care 26:1673–1678, 2003
[Abstract/Free Full Text]
- Ziccardi P, Nappo F, Giugliano G, Esposito K, Marfella R, Cioffi M, D’Andrea F, Molinari AM, Giugliano D: Reduction of inflammatory cytokine concentrations and improvement of endothelial functions in obese women after weight loss over one year. Circulation 105:804–809, 2002
[Abstract/Free Full Text]
- Giugliano D, Marfella R, Terrazzo G, Acampora R, Nappo F, Ziccardi P, Coppola L, D’Onofrio F: L-arginine for testing endothelium-dependent vascular functions in health and disease. Am J Physiol 273:E606–E612, 1997
- Mather KJ, Steinberg HO, Baron AD: Weight loss and endothelial function in obesity (Editorial). Diabetes Care 26:1927–1928, 2003
[Free Full Text]
- Bhagat K, Balance P: Inflammatory cytokines impair endothelium-dependent dilatation in human veins in vivo. Circulation 96:3042–3047, 1997
[Abstract/Free Full Text]
- Esposito K, Pontillo A, Di Palo C, Giugliano G, Masella M, Marfella R, Giugliano D: Effect of weight loss on vascular inflammatory markers in obese women: a randomized trial. JAMA 289:1799–1804, 2003
[Abstract/Free Full Text]
- Stefan N, Stumvoll M: Adiponectin: its role in metabolism and beyond. Horm Metab Res 34:469–474, 2001
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