Management of the Metabolic Syndrome

The current management of MetS reflects two major considerations: (1) promotion of healthy lifestyle changes to ameliorate the root environmental causes; and (2) the therapeutic approaches to manage the individual components of MetS.

Healthy lifestyle promotion includes: (1) dietary changes in terms of moderating calorie intake to achieve a 5-10% loss of body weight in the first year and changing dietary composition; (2) increasing physical activity; and (3) changes in dietary composition to lower intake of saturated fats, trans fats and cholesterol, and include carbohydrates with a low glycemic index and high content of soluble fiber.

Finally, because of the heightened risk of vascular disease, MetS patients should receive other broad-spectrum preventive treatments such as aspirin. The targets for lipids and blood pressure should follow guidelines and recommendations for higher-risk patients. The treatment of the atherogenic dyslipidemia in MetS is aimed at correcting the fundamental disturbances - namely reducing plasma triglycerides and raising plasma HDL cholesterol. Among currently available agents, the fibrates, which are PPAR-g agonists, are best at normalizing MetS dyslipidemia. In contrast, statins target LDL cholesterol, but their role in vascular disease prevention is supported by a much wider evidence base. Many clinicians will first choose a statin as dyslipidemia therapy for MetS patients, especially when triglycerides are only mildly elevated. Other treatment alternatives include the judicious use of niacin preparations and also combinations of a fibrate, statin, and/or cholesterol absorption inhibitor, such as ezetimibe.

The management of associated hypertension follows conventional guidelines for therapy (with a preference toward angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in patients who progress to type 2 diabetes).45 The role of specific therapy for the insulin resistance associated with MetS (in the absence of frank diabetes mellitus) remains problematic. Specifically, the use of biguanides, thiazolidinediones, acarbose, and orlistat has been proposed to delay the onset of frank diabetes.46 Their long-term effectiveness in reducing the atherosclerotic complications of MetS has yet to be established. There is an urgent need for prospective randomized studies for treatment strategies in patients with MetS.


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Ross D Feldman, MD, FACP, FRCPC, is the RW Gunton Professor of Therapeutics, Departments of Medicine (and of Pharmacology and Physiology) at the University of Western Ontario. Since 2001, he has been the deputy scientific director of the Robarts Research Institute. He received his medical degree from Queen's University in Kingston, Ontario in 1977 and training in Internal Medicine (University of Toronto) and Clinical Pharmacology (Vanderbilt University). Following his postgraduate training, he has held teaching positions at the University of Iowa College of Medicine in Iowa City and then at the University of Western Ontario (since 1989). Among a number of awards and scholarships, he was the recipient of a Career Investigator Award (Heart and Stroke Foundation of Ontario), the George Morris Piersol Teaching and Research Scholarship (American College of Physicians), and the Burroughs-Wellcome Clinical Pharmacology Award. He is a member of editorial boards for several journals, including American Journal of Physiology- (Cellular and Endocrine sections), Clinical Pharmacology and Therapeutics, and Pharmacological Reviews. He has been vice president of the American Society of Clinical Pharmacology and Therapeutics, Chair of the Clinical Pharmacology Division of the American Society of Pharmacology and Experimental Therapeutics, as well as President of the Canadian Hypertension Society. He just completed a 3-year term as Chair of the Steering Committee of the Canadian Hypertension Education Program which, since 1999 has produced and disseminated yearly updates of the Canadian Recommendations for the Management of Hypertension.

Robert A Hegele, MD, FACP, FRCPC, is the Jacob J Wolfe Chair in Functional Genomics and the Edith Schulich Vinet Canada Research Chair in Human Genetics in the Faculty of Medicine and Dentistry at the University of Western Ontario. He received his MD (Honours) from the University of Toronto in 1981, followed by an Internal Medicine residency and an Endocrinology fellowship at the University of Toronto. His postdoctoral fellowships in metabolism and human genetics were at the Rockefeller University in New York and the Howard Hughes Medical Institute in Salt Lake City. In 1989, he joined the University of Toronto faculty and was staff endocrinologist at St Michael's Hospital. In 1997, he joined the Robarts Research Institute and the University of Western Ontario, both in London, Ontario, and is currently Professor of Medicine and Biochemistry. He is the director of the Blackburn Cardiovascular Genetics Laboratory and the London Regional Genomics Centre. He directs a tertiary referral clinic for lipoprotein and metabolic disorders at the London Health Sciences Centre. He is a consulting editor for Arteriosclerosis, Thrombosis and Vascular Biology and is a member of the editorial boards of the Journal of Lipid Research and the Journal of Human Genetics. He previously served on the Advisory Board for the Institute for Aboriginal Peoples' Health of the Canadian Institutes for Health Research.

© 2007 Elsevier Ltd. All Rights Reserved Comprehensive Medicinal Chemistry II

No part of this publication may be reproduced, stored in any retrieval system or transmitted ISBN (set): 0-08-044513-6 in any form by any means electronic, electrostatic, magnetic tape, mechanical, photocopying, recording or otherwise, without permission in writing from the publishers ISBN (Volume 6) 0-08-044519-5; pp. 381-387

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