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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2006;26:e30.)
© 2006 American Heart Association, Inc.

Letter to the Editor

Optimal Treatments for the Metabolic Syndrome

Dario Giugliano; Katherine Esposito

Division of Metabolic Diseases,, University of Naples SUN, Naples, Italy

To the Editor:

We read with interest the review of Blaschke et al¹ dealing with obesity and the interrelated disorders of the metabolic syndrome as forerunners of diabetes and cardiovascular disease. To date, chronic diseases represent a huge proportion of human illness, as cardiovascular diseases, various forms of cancer, and diabetes combine to make up nearly 70% of all deaths in the U.S.² Obesity is supposed to be one main risk factor underlying these conditions. Lifestyle changes, such as unhealthy diets and a lack of physical activity, have contributed to a worldwide increase in the prevalence of obesity and the metabolic syndrome.³ Accordingly, low consumption of fruit and vegetables, together with physical inactivity, are now among the top 10 causes of mortality in developed countries.⁴ Abdominal obesity is the body fat parameter most closely associated with the metabolic syndrome and cardiovascular risk.^5,6

Lifestyle interventions are the initial therapies recommended for treatment of visceral obesity and the metabolic syndrome.⁷ This recommendation, however, seems to have been built up exclusively on the assumption that, being key elements in the treatment of all components of the syndrome when they occur in isolation, lifestyle interventions hold the premise to be also an effective treatment for the metabolic syndrome as a whole. The first goal of whatever therapy is the resolution of the disease, where possible. In particular, this may be accomplished by reducing the amount of visceral fat or disconnecting obesity from the metabolic syndrome: in theory, both strategies would lead to a reduced burden of diabetes and cardiovascular disease.

There are some recent studies dealing specifically with the effect of interventions on the resolution of the metabolic syndrome. These studies^8–13 were randomized controlled trials with a placebo/control group, a follow-up longer than 6 months, and absence of frank diabetes in participants. Three studies^8–10 were based on lifestyle interventions and 4 studies^9,11–13 on drugs, with a total of 3369 subjects, 1399 on lifestyle changes and 1970 on drugs. The Diabetes Prevention Program (DPP) addressed the effect of both lifestyle changes and metformin, and therefore the placebo group was counted twice. The follow-up ranged from 6 to 38 months. The results are shown in the Table. The first study was published in 2004⁸: in180 overweight subjects with the metabolic syndrome after a 2-year lifestyle program focusing mainly on a Mediterranean-style diet there was a 48% net reduction in the prevalence of the syndrome. In the participants in the DPP⁹ who had impaired glucose tolerance at baseline, 18% of the placebo group and 38% of the lifestyle group no longer had the syndrome at 3 years. The Dietary Approach to Stop Hypertension (DASH) diet used in the Iranian study¹⁰ is quite similar to a Mediterranean-style diet. Rimonabant is a cannabinoid-1 receptor blocker which has been shown promising in reducing body weight in obesity.^11,12 Besides reducing insulin resistance, rosiglitazone improves inflammation and endothelial dysfunction.¹ The weighed mean resolution of the syndrome was 24.4% for lifestyle changes and 14.25% for drugs. Excluding the negative results obtained with metformin, the weighed mean resolution for drugs rose to 26.9%, not different from that obtained with lifestyle changes. In most studies, resolution of the syndrome was dependent on reduction in waist circumference and weight loss,^9–12 in others it was independent of weight changes.^8,13

View this table: [in this window] [in a new window]   Resolution of the Metabolic Syndrome Through Therapeutic Lifestyle Intervention or Drug Treatment

To date, both intensive lifestyle interventions and some drugs (rimonabant and rosiglitazone) may reduce the prevalence of the metabolic syndrome in about one fourth of patients. However, we agree with Blaschke et al¹ that achieving modifications in lifestyle has proven to be difficult, and weight reduction drugs have not been particularly effective for treatment of obesity. The search for more effective and better-tolerated drugs for the control of obesity and the metabolic syndrome will continue. In the meantime, lifestyle modifications may be a good companion of drugs for reducing the metabolic and cardiovascular burden of visceral obesity and the metabolic syndrome.

References

1. Blaschke F, Takata Y, Caglayan E, Law RE, Hsueh WA. Obesity, peroxisome proliferator–activated receptor, and atherosclerosis in type 2 diabetes. Arterioscler Thromb Vasc Biol. 2006; 26: 28–40.[Abstract/Free Full Text]
2. Arias E, Anderson RN, Kung HC, Murphy SL, Kochanek KD. Deaths: final data for 2001. Natl Vital Stat Rep. 2003; 52: 1–115.[Medline] [Order article via Infotrieve]
3. Esposito K, Giugliano D. Diet and inflammation: a link to metabolic and cardiovascular diseases. Eur Heart J. 2006; 27: 15–20.[Abstract/Free Full Text]
4. The World Health Report 2004. Global strategy on diet, physical activity, and health. Geneva, World Health Organization, 2004.
5. Carr DB, Utzschneider KM, Hull RL, Kodama K, Retzlaff BM, Brunzell JD, Shofer JB, Fish BE, Knopp RH, Kahn SE. Intra-abdominal fat is a major determinant of the National Education Program Adult Treatment Panel III criteria for the metabolic syndrome. Diabetes. 2004; 53: 2087–2094.[Abstract/Free Full Text]
6. Yusuf S, Hawken S, Ôunpuu S, on behalf of the INTERHEART Study Investigators. Obesity and the risk of myocardial infarction in 27000 participants from 52 countries: a case-control study. Lancet. 2005; 366: 1640–1649.[CrossRef][Medline] [Order article via Infotrieve]
7. Grundy SM, Cleeman JI, Daniels RD, Donato KA, Eckel RH, Franklin BA, Gordon DJ, Krauss RM, Savage PJ, Smith SC, Jr., Spertus JA, Costa F. Diagnosis and management of the metabolic syndrome. An American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement. Circulation. 2005; 112: 2735–2752.[Free Full Text]
8. Esposito K, Marfella R, Ciotola M, Di Palo C, Giugliano F, Giugliano G, D’Armiento M, D’Andrea F, Giugliano D. Effect of a Mediterranean-style diet on endothelial dysfunction and markers of vascular inflammation in the metabolic syndrome: a randomized trial. J Am Med Assoc. 2004; 292: 1440–1446.[Abstract/Free Full Text]
9. Orchard TJ, Tempros M, Goldberg R, Haffner S, Ratner R, Marcovina S, Fowler S; Diabetes Prevention Program Research Group. The effect of metformin and intensive lifestyle intervention on the metabolic syndrome: the Diabetes Prevention Program randomized trial. Ann Intern Med. 2005; 142: 611–619.[Abstract/Free Full Text]
10. Azadbakht L, Mirmiran P, Esmaillzadeh A, Azizi T, Azizi F. Beneficial effects of a dietary approaches to stop hypertension eating plan on features of the metabolic syndrome. Diabetes Care. 2005; 28: 2823–2831.[Abstract/Free Full Text]
11. Van Gaal LF, Rissanen AM, Scheen AJ, Ziegler O, Rossner S, for the RIO-Europe Study Group. Effects of the cannabinoid-1 receptor blocker rimonabant on weight reduction and cardiovascular risk factors in overweight patients: 1-year experience from the RIO-Europe study. Lancet. 2005; 365: 1389–1397.[CrossRef][Medline] [Order article via Infotrieve]
12. Després J-P, Golay A, Sjöström L, for the Rimonabant in Obesity–Lipids Study Group. Effects of rimonabant on metabolic risk factors in overweight patients with dyslipidemia. N Engl J Med. 2005; 353: 2121–2134.[Abstract/Free Full Text]
13. Esposito K, Ciotola M, Carleo D, Schisano B, Saccomanno F, Sasso FC, Cozzolino D, Assaloni R, Merante D, Ceriello A, Giugliano D. Effect of rosiglitazone on endothelial function and inflammatory markers in patients with the metabolic syndrome. Diabetes Care. 2006; In press.

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				K. Esposito, M. Ciotola, and D. Giugliano Pioglitazone reduces endothelial microparticles in the metabolic syndrome. Arterioscler. Thromb. Vasc. Biol., August 1, 2006; 26(8): 1926 - 1926. [Full Text] [PDF]

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