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


Advances in the Management of Dyslipidemia in Diabetic Patients


GOAL
To provide physicians with current information on new advances in the management of dyslipidemia in diabetic patients.

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

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

  • Discuss the risk patients with type 2 diabetes have of developing coronary heart disease, experiencing cardiovascular events, and dying from cardiovascular causes.
  • Describe the interrelationship between atherosclerosis and insulin resistance.
  • Provide a rationale for aggressive lipid modification in type 2 diabetic patients.

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 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 continuing medical education activity for a maximum of 2 hours in Category 1 credit toward the American Medical Association Physicians’ Recognition Award. Each physician should claim only those hours of credit that are actually spent on the educational activity. Credits are available until the expiration date of November 30, 2003.

This continuing education activity was produced under the supervision of Christopher D. Saudek, MD, Professor of Medicine, Department of Endocrinology, 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.

FACULTY ADVISORS

    Christopher D. Saudek, MD
    Professor of Medicine
    Department of Endocrinology
    Johns Hopkins University School of Medicine
    Baltimore, Maryland
    • Dr Saudek reports receiving research support from Parke-Davis and serving on the advisory boards for MiniMed, Aradigm, and Diabetex.

PARTICIPATING FACULTY

    Christie M. Ballantyne, MD
    Professor of Medicine
    Clinical Director, Section of Atherosclerosis
    Baylor College of Medicine
    Houston, Texas
    • Dr Ballantyne reports receiving grant/research support from Reliant, Novartis, Pfizer, Schering-Plough, AstraZeneca, and Merck; serving as a consultant to Reliant, Novartis, Pfizer, and Merck; receiving honoraria from Reliant, Novartis, Pfizer, Merck, and AstraZeneca; and serving on the speakers' bureaus for Reliant, Novartis, Pfizer, and Merck.

    Henry N. Ginsberg, MD
    Director, Irving Center for Clinical Research
    Columbia University College of Physicians and Surgeons
    New York, New York
    • Dr Ginsberg reports receiving grant/research support from Takeda-Lilly; and serving as a consultant to Takeda Lilly, GlaxoSmithKline, Pfizer, Merck, Ross Labs, and TAP.

    Steven M. Haffner, MD
    Professor of Internal Medicine
    Division of Clinical Epidemiology
    University of Texas Health Science Center at San Antonio
    San Antonio, Texas
    • Dr Haffner reports no financial or advisory relationships with any pharmaceutical company.

    Jorge Plutzky, MD
    Director, Vascular Disease Prevention Program
    Brigham and Women's Hospital
    Boston, Massachusetts
    • Dr Plutzky reports receiving grant/research support from Pfizer; and receiving honoraria from and serving as a consultant to Pfizer, Merck, Takeda, and Lilly.

Advanced Studies in Medicine provides disclosure information from contributing authors, participating faculty, and presenters only. 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.

This issue of Advanced Studies in Medicine focuses on selected presentations at the 61st Scientific Sessions of the American Diabetes Association (ADA) that address the link between diabetes and cardiovascular disease. Focusing on the link between these diseases is particularly germane because it coincides with the ADA's Diabetic Cardiovascular Disease Initiative announced at the Scientific Sessions held in Philadelphia, Pennsylvania in June 2001. The 3-year initiative is being launched in conjunction with a similar effort by the National Diabetes Education Program.

Featured in this issue are highlights of a symposium, "Advances in the Management of Dyslipidemia in the Patient with Diabetes," held during the ADA meeting, as well as selected poster presentations addressing the need for better control of hypercholesterolemia and hypertension in diabetic patients, the use of statin therapy in these patients, and barriers to managing elevated cholesterol levels more aggressively.

Symposium Highlights

The 4 speakers participating in the symposium examine various aspects of diabetes and dyslipidemia, a major contributor to atherosclerosis, and explain why the intersection of these 2 diseases is such a dangerous one.

Dr Steven M. Haffner, of the University of Texas Health Science Center at San Antonio, discusses the scope of diabetic vascular disease and the need to base treatment strategies on modification of cardiovascular risk factors as well as on glycemic control. A key point is that patients with diabetes and patients with established heart disease are at equivalent risk for coronary events and warrant equivalent treatment.

Dr Henry N. Ginsberg, of the Irving Center for Clinical Research at Columbia University College of Physicians and Surgeons in New York City, describes the clinical challenges of syndrome X, also known as the insulin resistance syndrome, and its interrelationship with atherosclerosis. He explains how the characteristic dyslipidemia seen in almost all patients with syndrome X develops and reviews the approaches to treatment. He discusses the coagulation abnormalities seen in most patients with this syndrome, and notes the need for better control of hypertension, which is seen in at least half of the patients with syndrome X.

Characterizing atherosclerosis as an exceedingly complex disease, Dr Jorge Plutzky, of Harvard Medical School and the Brigham and Women's Hospital in Boston, notes that in no other setting is atherosclerosis more complex than in the patient with diabetes. Drawing from recent research findings, particularly those that shed additional light on the inflammatory nature of atherosclerosis, he explains why the disease is more pervasive in patients with diabetes.

In another presentation, Dr Christie M. Ballantyne of Baylor College of Medicine in Houston emphasizes that early and aggressive lipid-modifying therapy is warranted in patients with type 2 diabetes because cardiovascular disease has a more profound impact on these patients. He points out that pharmacologic therapy of dyslipidemia is effective in reducing the risk of cardiovascular events and mortality from cardiovascular causes, both in diabetic and nondiabetic patients. He also notes that such therapy would reduce cardiovascular risk in prediabetic individuals, a group in which coronary heart disease often develops before the onset of clinical diabetes.

Poster Presentations

The poster presentations selected for this issue underscore the need for more aggressive management of lipid disorders in patients with diabetes and confirm the efficacy of statin therapy in diabetic and nondiabetic subjects.

One poster presentation looks at the effects of rosuvastatin on neurovascular function as well as its effects on cholesterol and triglycerides. Dr Norman E. Cameron of the Institute of Medical Sciences at the University of Aberdeen in Aberdeen, Scotland, and his associates describe the findings of a series of experiments in diabetic rats. On a dose-dependent basis, rosuvastatin corrected deficits in motor and sensory nerve conduction velocity and produced beneficial effects on the small nerve fiber systems involved in thermal pain and erectile function. Rosuvastatin also corrected deficits in peripheral nerve and ganglion blood flow and reduced triglyceride levels. The investigators conclude that this new statin could prove useful in the treatment of diabetic neuropathy and vasculopathy.

Dr Donald B. Hunninghake, of the Heart Disease Prevention Clinic at the University of Minnesota in Minneapolis, along with his co-investigators, report the results of a study evaluating the efficacy of 5 varying dosages of rosuvastatin versus placebo in lowering triglyceride levels and modifying other lipid parameters in 156 patients with Frederickson Type IIb or Type IV hypertriglyceridemia. Of these patients, 10% had type 2 diabetes. Rosuvastatin produced statistically significant reductions in total triglyceride levels and LDL levels relative to placebo at all doses studied and also produced a significant increase in high-density lipoprotein (HDL) levels compared with placebo at all doses except the lowest (5 mg). The investigators conclude that rosuvastatin favorably modifies atherogenic and atheroprotective lipid fractions and is an effective treatment option for patients with hypertriglyceridemia, including those with type 2 diabetes.

The Atorvastatin versus Simvastatin Safety and Efficacy Trial (ASSET) compared the efficacy of these statins in patients with or without coronary heart disease and diabetes over 54 weeks. On behalf of the ASSET Investigators, Dr William Insull, Jr., of Baylor College of Medicine and The Methodist Hospital in Houston, Texas, reports the findings of a subgroup analysis of ASSET patients with mixed dyslipidemia and concurrent type 2 diabetes. Atorvastatin produced significantly greater reductions in LDL than simvastatin, and also produced greater reductions in triglyceride levels regardless of baseline triglyceride levels. Both the larger study and the subgroup analysis showed that statin therapy is at least as effective in patients with type 2 diabetes as it is in nondiabetics.

In a poster on the use of statins in patients with diabetes who were hospitalized for acute coronary syndromes, Dr Charles L. Lucore, of the Prairie Heart Institute in Springfield, Illinois, and his co-investigators report that patients receiving statins before admission and at hospital discharge or at discharge only had fewer deaths or myocardial infarctions than patients receiving no statin therapy. They also note that the odds of receiving statin therapy at discharge in the patients they studied increased with prior catheterization, prior hypercholesterolemia, and prior aspirin use.

Dr. Cristian E. Sciutto and his team of investigators at Emory University School of Medicine and Grady Health System in Atlanta, Georgia, shed some light on why treatment of hypercholesterolemia in patients with type 2 diabetes is often suboptimal. In a 3-month study, they asked health care providers at a diabetes clinic to complete a simple questionnaire at the end of each patient visit: ie, was the patient's low-density lipoprotein (LDL) level at goal (less than 100 mg/dL) and if not, was therapy initiated or intensified? They found that LDL levels were not at goal and therapy was not intensified in a significant proportion of patients, most often because therapy had already been intensified recently, because of expectations that LDL levels would normalize without treatment or were already improving, or because the patients desired to try dietary changes first.

Drs Janice C. Zgibor and Trevor J. Orchard, both of the University of Pittsburgh in Pittsburgh, Pennsylvania, note that control of hyperlipidemia and hypertension in patients with type 1 diabetes has not improved over time. In a representative cohort of patients with type 1 diabetes who were followed with 6 biennial examinations for a period of up to 10 years, the prevalence of both hypertension and hypercholesterolemia increased over time; additionally, an increase was also seen in the lack of awareness on the patients' part regarding increasingly elevated blood pressure and cholesterol levels and inadequacy of their current therapy. The treatment gap was especially wide for hypercholesterolemia. Clearly, educational efforts and more aggressive approaches to treatment are needed.

Guidelines and Initiatives

The role of dyslipidemia in the development of atherosclerosis and the more profound impact of atherosclerosis and other cardiovascular diseases in persons with diabetes prompted the ADA, the American Heart Association and, most recently, the National Cholesterol Education Program to revise their guidelines regarding the treatment of hypercholesterolemia and dyslipidemia. Highlights of the revised guidelines include:

  • Reclassifying type 2 diabetes as a coronary heart disease risk equivalent, rather than a risk factor;
  • Calling for lower treatment goal levels of LDL cholesterol on the basis of an individual patient's overall risk for a coronary event;
  • Underscoring the need to lower elevated triglyceride levels and raise reduced levels of HDL cholesterol levels, especially in patients with type 2 diabetes; and
  • Calling for earlier and more aggressive therapy with a lipid-modifying agent, usually a statin, to accomplish these treatment goals.

While the revised guidelines are directed toward physicians and other health care professionals to promote proper diagnosis and more adequate therapy in all at-risk patients, the ADA's Diabetic Cardiovascular Disease Initiative is targeting the public as well as physicians to increase awareness of the link between diabetes and cardiovascular disease, provide patient and professional education, and reduce the morbidity and mortality associated with these diseases.

Together, the revised guidelines, the 3-year ADA initiative, and the National Diabetes Education Program are expected to have a favorable impact on the treatment and prevention of cardiovascular disease and death in patients with diabetes.

*Professor of Endocrinology, Johns Hopkins University School of Medicine; Director, Johns Hopkins Diabetes Center, Baltimore, Maryland; President, American Diabetes Association, 2001-2002.





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.