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Disclaimer: CME certification for these activities has expired. All information is pertinent to the timeframe in which it was released.


Creating an Optimal Strategy for Lipid Management in Diabetes


GOAL
To provide physicians with current information and recommendations for creating the optimal strategy for lipid management in patients with diabetes.

TARGET AUDIENCE
This activity is designed for cardiologists, endocrinologists, internists, and primary care physicians.

LEARNING OBJECTIVES
After reading this issue, the participant should be able to:

  • Explain the relationship between elevated lipid levels and coronary heart disease (CHD) risk in patients with diabetes.
  • Describe the ramifications of diabetes as a formal CHD risk equivalent by the National Cholesterol Education Program Third Adult Treatment Panel guidelines.
  • Discuss and identify the challenges in getting diabetic patients to their target low-density lipoprotein cholesterol goal.
  • Evaluate safety and efficacy of cholesterol-reducing agents in patients with diabetes and metabolic syndrome.

ACCREDITATION STATEMENT
This activity has been planned and produced in accordance with the Essential Areas and Policies of the Accreditation Council for Continuing Medical Education. The Johns Hopkins University School of Medicine is accredited by the Accreditation Council for Continuing Medical Education to sponsor continuing medical education for physicians. The Johns Hopkins University School of Medicine takes responsibility for the content, quality, and scientific integrity of this CME activity.

CREDIT DESIGNATION STATEMENT
The Johns Hopkins University School of Medicine designates this educational activity for a maximum of 2 hours in Category 1 credit toward the American Medical Association (AMA) Physicians' Recognition Award. Each physician should only claim those hours of credit that he/she actually spends in this educational activity. Credits are available until the expiration date of November 30, 2004.

This continuing education activity was produced under the supervision of Peter O. Kwiterovich, Jr, MD, Director, Lipid Clinic, and Professor of Medicine, Johns Hopkins University School of Medicine.

This program is supported by an unrestricted educational grant from AstraZeneca LP.

Publisher's Note and Disclaimer: The opinions expressed in this issue are those of the authors, presenters, and/or panelists and are not attributable to the publisher, editor, advisory board of Advanced Studies in Medicine, or The Johns Hopkins University School of Medicine or its Office of Continuing Medical Education. Clinical judgment must guide each professional in weighing the benefits of treatment against the risk of toxicity. Dosages, indications, and methods of use for products referred to in this issue are not necessarily the same as indicated in the package insert for the product and may reflect the clinical experience of the authors, presenters, and/or panelists or may be derived from the professional literature or other clinical sources. Consult complete prescribing information before administering.

Advanced Studies in Medicine (ISSN-1530-3004) is published by Galen Publishing, LLC, an HMG Company. P.O. Box 340, Somerville, NJ 08876. (908) 253-9001. Web site: www.galenpublishing.com. Copyright ©2001 by Galen Publishing, LLC. All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, without first obtaining permission from the publisher. Bulk postage paid at Somerville, NJ Post Office and at additional mailing offices. Advanced Studies in Medicine is a registered trademark of The Healthcare Media Group, LLC. Printed on acid-free paper. BPA Membership applied for December 2000.

CHAIR

    Peter O. Kwiterovich, Jr, MD
    Chief, Lipid Research
    Director, Lipid Clinic
    Professor of Medicine
    Johns Hopkins University School of Medicine
    Baltimore, Maryland
    • Dr Kwiterovich reports receiving grants and/or research support from AstraZeneca, Merck/Schering-Plough; serving as a consultant to Atherotech, Merck/Schering-Plough, Sankyo; and receiving honoraria from AstraZeneca, Merck, Merck/Schering-Plough, Pfizer, Kos, and Sankyo.

PARTICIPATING FACULTY

    Steven M. Haffner, MD, MPH
    Professor
    Department of Medicine
    Division of Clinical Epidemiology
    University of Texas Health Science Center at San Antonio
    San Antonio, Texas
    • Dr Haffner reports receiving honoraria from Merck/Schering-Plough, Pfizer, and AstraZeneca.

    Lawrence A. Leiter, MD, FRCPC, FACP
    Professor of Medicine and Nutritional Sciences
    University of Toronto
    Head, Division of Endocrinology & Metabolism
    St. Michael's Hospital
    Toronto, Ontario, Canada
    • Dr Leiter reports receiving grants and/or research support, serving as a consultant to, and being on the speakers bureau for AstraZeneca, Bristol-Myers Squibb, Merck/Schering-Plough, Novartis, Fournier, and Pfizer.

    Jaakko Tuomilehto, MD, PhD, MPolSc
    Academy Professor
    National Public Health Institute
    Diabetes and Genetic Epidemiology Unit
    Department of Epidemiology and Health Promotion
    Mannerheimintie, Helsinki, Finland
    • Dr Tuomilehto reports receiving grants and/or research support from AstraZeneca and Novartis serving as a consultant to Novartis; and receiving honoraria from Novartis and Novo Nordisk.

Advanced Studies in Medicine provides disclosure information from contributing authors, lead presenters, and participating faculty. Advanced Studies in Medicine does not provide disclosure information from authors of abstracts and poster presentations. The reader shall be advised that these contributors may or may not maintain financial relationships with pharmaceutical companies.

Creating an Optimal Strategy for Lipid Management in Diabetes
Peter O. Kwiterovich, Jr, MD*

Guidelines on the management of dyslipidemia in adults were published by the National Cholesterol Education Program's Third Adult Treatment Panel (NCEP ATP III) in 2001. The guidelines called for even more stringent control of low-density lipoprotein cholesterol (LDL-C) levels than previously recommended, especially for those with coronary heart disease (CHD) risk factors. One year later, the medical community strives to incorporate the NCEP ATP III guidelines into practice. One of the biggest surprises of the new guidelines, outside diabetology and endocrinology circles, was the identification of diabetes as a CHD risk factor. Including diabetes in the guidelines has enormous implications in the number of persons requiring treatment and in the way diabetes patients should be managed.

The causal relationship between diabetes and CHD has been known to diabetologists and endocrinologists for some time. Nonetheless, vascular disease is the most common cause of mortality in diabetic patients, indicating that our prevention and treatment strategies for CHD are suboptimal. Hopefully, the NCEP ATP III guidelines will lead to advances in the prevention and treatment of vascular disease in diabetic patients, especially given the numerous complications of diabetes.

A common marker for CHD risk and/or vascular disease is the plasma level of LDL-C. LDL-C, high-density lipoprotein cholesterol (HDL-C), and very-low-density lipoprotein cholesterol (VLDL-C) constitute the total cholesterol measurement, as most of the plasma cholesterol is transported in these 3 lipoproteins. Lipoprotein metabolism is interrelated and complex, also involving lipoprotein (a) [Lp(a)]. Therefore, a true determination of CHD risk should be based on analysis of a lipoprotein profile, rather than the measurement of 1 or 2 lipoprotein types.

Cholesterol Metabolism
To understand the rationale behind the NCEP ATP III guidelines, or any other guidelines on dyslipidemia from recognized authorities, it helps to have an understanding of cholesterol metabolism.

The primary goal of treating dyslipidemia is to reduce LDL-C levels, which promote atherosclerotic lesion formation. LDL-C is oxidized after crossing over the endothelial cell wall from the bloodstream into the vessel wall. Oxidized LDL-C is taken up by macrophages, which are transformed into foam cells, and foam cells secrete growth factors that stimulate proliferation and migration of arterial smooth muscle cells—the beginnings of an atherosclerotic lesion.1

Another goal of treatment is to increase HDL-C levels to benefit from its cardioprotective mechanisms. HDL-C is able to impede the oxidation of LDL-C—and, therefore, its uptake by macrophages/foam cells—and can participate in reverse cholesterol transport, which transfers cholesterol back to the bloodstream. About one half of the cholesterol taken up by HDL-C is delivered to the liver; the other half distributes the cholesterol among VLDL, LDL, and intermediate LDL. HDL-C also acts by reducing levels of vascular endothelial and intracellular adhesion molecules, which contribute to plaque formation. And finally, HDL-C helps to promote fibrinolysis, which can be attenuated by high Lp(a) levels.1

The 2 approved treatments to modify lipid levels in diabetic patients are HMG-CoA reductase inhibitors (statins) and fibrates. Statins lower LDL-C levels; fibrates increase HDL-C levels. Niacin traditionally has not been recommended in diabetic patients, but recent data suggest that it may be safe alone, or in combination with a statin.

This issue of Advanced Studies in Medicine provides a detailed review of a symposium held preceding the 62nd Scientific Sessions of the American Diabetes Association (San Francisco, CA; June 16, 2002). Summaries of related posters and abstracts presented at the conference are also included.

Symposium faculty included 3 leading experts on diabetes and dyslipidemia. Dr Steven M. Haffner introduces the NCEP guidelines and their implications for diabetologists—why the guidelines are important and what diabetologists/endocrinologists can do to ameliorate the high rates of death due to vascular disease in diabetic patients.

Drs Lawrence A. Leiter and Jaakko Tuomilehto review the clinical trial data of statins and fibrates from 2 different perspectives. Dr Leiter analyzes the main efficacy trials of statins with respect to clinical outcomes. The data clearly show that statins offer the same clinical benefits to diabetic and nondiabetic patients. Dr Tuomilehto reviews the major efficacy trials in terms of markers of disease progression (ie, lipid levels) and the benefits to diabetic patients.

Dr Tuomilehto also reviews the efficacy of fibrates and combinations of statin + fibrate in diabetic patients. The promising results suggest that combination therapies may be the strategy of choice for addressing multiple aspects of dyslipidemia, although further study is needed.

Dr Tuomilehto provides insight into the efficacy of lifestyle changes in the prevention of diabetes, which would, of course, be the optimal strategy for CHD prevention. The American Heart Association has recently published their guidelines for the primary prevention of cardiovascular disease and stroke. These guidelines are focused on the "assessment, management, and follow-up of patients who may be at risk for but who have not yet manifested cardiovascular disease." The guidelines discuss the importance of the physician-patient relationship and the development of a plan of preventive action: "The continuing message is that adoption of healthy life habits remains the cornerstone of primary prevention..."2

Managing dyslipidemia is clearly now in the purview of diabetologists and endocrinologists. The choice of effective therapies, along with the lifestyle changes so integral to appropriate management, can greatly deter the public health consequences of CHD.

REFERENCES
1. Kwiterovich PO Jr. The metabolic pathways of high-density lipoprotein, low-density lipoprotein, and triglycerides: a current review. Am J Cardiol. 2000;86(suppl)5L-10L.
2. Pearson TA, Blair SN, Daniels SR, et al. AHA guidelines for the primary prevention of cardiovascular disease and stroke: 2002 update. Circulation. 2002;106:388-391.

*Chief, Lipid Research; Director, Lipid Clinic; Professor of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.





Johns Hopkins Advanced Studies in Medicine (ISSN-1558-0334), is published by Galen Publishing, LLC, d/b/a ASiM, PO Box 340, Somerville, NJ 08876. (908) 253-9001. Copyright ©2012 by Galen Publishing. All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, without first obtaining permission from the publisher. ASiM is a registered trademark of The Healthcare Media Group, LLC.