Volume 8, Number 10 October 2005 - National Diabetes Education ...

THOMSON HEALTHCARERelease Date: January 2005Valid Until: June 2006This educational activity is a component ofthe National Diabetes Education Initiative ®(NDEI ® ), sponsored by Thomson ProfessionalPostgraduate Services ® (PPS), Secaucus, NJ.Issue No. 10, October 2005, is part of a 12-partCME activity (January–December 2005).Physicians who wish to receive CME credit forthis educational activity should do the following:(1) read each of the 12 monthly issues inthe series and retain them for future reference;(2) review the original articles discussed in theirentirety; and (3) after completing the last issueof the year (December 2005), obtain the posttestto complete the CME activity. The post-testmay be obtained from www.ndei.org or bycalling 1 (800) 606-6106 and requesting thepost-test. You will receive the post-test, registration,and evaluation forms by fax. To receiveCME credit, the participant must complete the12-part series and post-test and return thecompleted registration and evaluation forms to:Thomson Professional Postgraduate Services,Attn: CME Dept. T150, PO Box 1505, Secaucus,NJ 07096-1505 (Fax: 1 [201] 430-1441).Applicants will receive a certificate of participationfrom PPS by return mail within6 to 8 weeks of the date of receipt of thecompleted evaluation/registration form.Learning ObjectivesAfter studying the literature presented inthis Clinical Insights in Diabetes series,participants will be able to:• Identify patients with type 2 diabetesand the metabolic syndrome• Select an appropriate therapeutic regimenfor patients with type 2 diabetesand the metabolic syndrome• Summarize risk factors for cardiovasculardisease in patients with type 2 diabetesand the metabolic syndromeThomson Professional Postgraduate Services ®is accredited by the Accreditation Council forContinuing Medical Education to providecontinuing medical education for physicians.Thomson Professional Postgraduate Services ®designates this educational activity for amaximum of 4 category 1 credits toward theAMA Physician’s Recognition Award. Eachphysician should claim only those credits thathe/she actually spent in the activity.This CME activity is supported by anunrestricted educational grant fromTakeda Pharmaceuticals North America, Inc.National Diabetes Education Initiative,NDEI, and Clinical Insights in Diabetes aretrademarks used herein under license.Copyright © 2005 ThomsonProfessional Postgraduate Services ® .All rights reserved.CLINICAL INSIGHTS INDiabetesMAYER B. DAVIDSON, MD,* CO-EDITOR-IN-CHIEF; BURTON E. SOBEL, MD, †REVIEWER; TERRENCE F. FAGAN, ‡ MANAGING EDITOR; MARK PALANGIO, § WRITERPrevention of Macrovascular Events inType 2 Diabetes: PROactive StudyType 2 diabetes is associated with anincreased risk of fatal and nonfatalmacrovascular events such as myocardialinfarction (MI) and stroke. Peroxisomeproliferator-activated receptor γ (PPARγ)agonists are used to treat type 2 diabetes,and indirect evidence suggests that theseagents might reduce the occurrence ofmacrovascular complications.In the PROactive study (PROspectivepioglitAzone Clinical Trial In macroVascularEvents), Dormandy and colleagues examinedwhether pioglitazone, a PPARγ agonist,reduces morbidity and mortality in patientswith type 2 diabetes and evidence of macrovasculardisease. A total of 5,238 patientswere randomly assigned to either oralpioglitazone titrated from 15 mg to 45 mg(n=2,605) or matching placebo (n=2,633),administered concomitantlywith theirglucose-lowering orother medications.The primary endpointwas the compositeof all-cause mortality,nonfatal MI (includingsilent MI), stroke,acute coronary syndrome, endovascular orsurgical intervention in the coronary or legarteries, and amputation above the ankle. Asecondary endpoint was a composite of allcausemortality, nonfatal MI (excluding silentMI), and stroke.Over an average observation time of 34.5months, the proportion of patients having atVOLUME 8, NUMBER 10 • OCTOBER 2005Pioglitazone conferred benefitsbeyond those of standardmedical care.least one event within the primary compositeendpoint was lower in the pioglitazone group(20%) than in the placebo group (22%),although this difference was not statisticallysignificant (hazard ratio [HR], 0.90; 95% confidenceinterval [CI], 0.80-1.02; P=0.095). Moreover,the proportion of patients having at leastone event within the secondary compositeendpoint was significantly lower in the pioglitazonegroup (12%) than in the placebo group(14%) (HR, 0.84; 95% CI, 0.72-0.98; P=0.027).Compared with placebo, pioglitazone therapyalso significantly prolonged the time to initiationof permanent insulin therapy (HR, 0.47;95% CI, 0.39-0.56; P

CLINICAL INSIGHTS IN DIABETESPrevention of Macrovascular Events inType 2 Diabetes: PROactive StudyContinuedto mortality (1% vs 1%; P=0.634).The outcomes in this study are relevantbecause pioglitazone conferred benefitsbeyond those of standard medical care (ie,glucose-lowering, antiplatelet, antihypertensive,and lipid-altering therapies). The strengthof these results is underscored by the selectionof high-risk patients with a history of macrovasculardisease. Based on these findings, theinvestigators concluded that adding pioglitazoneto standard care in patients with type 2diabetes improves cardiovascular outcomewhile reducing the need to add insulin toglucose-lowering regimens.Dormandy JA et al. Secondary prevention ofmacrovascular events in patients with type 2diabetes in the PROactive study (PROspectivepioglitAzone Clinical Trial In macroVascularEvents): a randomised controlled trial. Lancet.2005;366:1279-1289.COMMENTARYBurton E. Sobel, MD, E.L. Amidon Professor of Medicine and Director, Cardiovascular ResearchInstitute, University of Vermont College of Medicine, Burlington, Vermont.Results in PROactive show a delay in the time of occurrence of death, non-silent myocardial infarction, orstroke in patients given pioglitazone as add-on therapy to “optimal” treatment of diabetes and the needfor conversion to “permanent treatment” with insulin in many fewer patients. What is less clear is whythese differences occurred. A simplistic view of the hypothesis underlying PROactive is that an insulin sensitizerwould exert beneficial, direct, PPARγ-mediated effects on coronary and cerebral vessel walls. However,this hypothesis was not actually tested. Pioglitazone led to statistically significant better glycemic control,increases in HDL, and significantly lower median systolic blood pressure, triglycerides, and LDL/HDL ratios.These differences are sufficient to explain the better outcomes. Thus, we don’t know whether the benefitwas dependent upon or perhaps entirely independent of direct effects of insulin sensitization on thecoronary and cerebral vessel walls. If benefit was attributable to the better control, we don’t know whetherachieving it through other means would have led to the same improvement. Regardless, the investigatorsin PROactive are to be congratulated. They demonstrated that the inclusion of pioglitazone in an antidiabeticregimen improved cardiovascular outcomes, whether through direct effects on vessel walls, improvedmetabolic and arterial blood pressure control, or both.Treatment withACEIs or ARBsresulted in areduction rangingfrom 4% to 87%in the incidenceof new-onsetdiabetes.Prevention of Type 2 Diabetes With ACEIs or ARBsRecently, several large prospective trialsdemonstrated an unexpected reduction inthe risk of developing type 2 diabetes amongpatients treated with ACE inhibitors (ACEIs) orangiotensin receptor blockers (ARBs). To betterunderstand this relationship, Abuissa andcolleagues performed a meta-analysis of sizeabletrials of ACEIs and ARBs that reportedthe incidence of new-onset type 2 diabetes.Twelve randomized, controlled clinical trialsof ACEIs or ARBs were identified through aMEDLINE search and a review of reports fromscientific meetings. The trials were ALLHAT,ALPINE, ANBP2, CAPPP, CHARM, HOPE, LIFE,PEACE, SCOPE, SOLVD, STOP-2, and VALUE,and involved a total of 72,333 patients withoutdiabetes at baseline. Seven of these trialsused ACEIs and 5 used ARBs.In this analysis, reduction in the incidenceof new-onset diabetes ranged from 4% to87%, reaching statistical significance in 10 ofthe 12 trials. Risk reductions for ACEIs, ARBs,and for either an ACEI or an ARB (pooleddata) were 27%, 23%, and 25%, respectively,and were statistically significant. Overall, suchresults translate into a decrease from 17.4 to14.3 new cases of type 2 diabetes per 1,000patient-years. Possible confounding factors inthis analysis included differing definitions fordiabetes, an open-label design in 2 trials, inclusionof new-onset diabetes as a post-hocendpoint in 10 trials, varying duration of thetrials, and the use of adjunctive medications.The findings of this meta-analysis haveclinical relevance because many common cardiovascularconditions (eg, coronary heartdisease, congestive heart failure, hypertension)are associated with an increased risk for type 2diabetes. The mechanisms by which ACEIs andARBs reduce the risk of type 2 diabetes are notContinued2

CLINICAL INSIGHTS IN DIABETESNDEI MISSIONSTATEMENTThe National Diabetes EducationInitiative ® (NDEI ® ) is amulticomponent educationalprogram on type 2 diabetesdesigned for endocrinologists,diabetologists, cardiologists,primary care physicians, andother healthcare professionalsinvolved in the care andmanagement of patients withtype 2 diabetes and insulinresistance. NDEI programsaddress issues concerninginsulin resistance and type 2diabetes, from the epidemiologyand pathophysiology ofthe disease and its associatedcomplications to the therapeuticoptions for treatment andprevention.NDEI ® upcoming CME events• CME/CE Regional Fall Dinner Meeting Series, “State of the Heart Management ofType 2 Diabetes and CVD: Latest Evidence From Clinical Trials,” (through December 8,2005). Registration by phone: 1 (877) 251-0943 or online at www.ndei.org.• CME Audioconference Series, “New Understandings in Treating Type 2 Diabetes andCardiovascular Disease.” To register for this activity, please visit us online atwww.ndei.org or call 1 (877) 251-0943.• CME Managed Care Dinner Meeting Series, “Getting to the Heart of Type 2Diabetes and Cardiovascular Disease.” To find out if there are programs in your area,please visit us online at www.ndei.org or call 1 (877) 251-0943.• Two case studies for on-demand CME at www.ndei.org:o “A 48-Year-Old Executive With Newly Diagnosed Diabetes Presents With ED,”authored by Bernard Zinman, MDCM. Earn 1 category 1 credit–Free.o “A 58-Year-Old African-American Man With a Recently Treated UncomplicatedMI Presenting With Elevated BG,” authored by Frank Lavernia, MD.Earn 1 category 1 credit–Free.• NEW On-demand CME Activity, Earn free 2.25 category 1 credits. Participate in theon-demand CME program: “Clinical Challenges in Type 2 Diabetes and CVD: A Case-Based Discussion Among Experts.” Explore the intricacies of a typical diagnosis fromthe unique perspectives of an endocrinologist, cardiologist, hospitalist, family physician,and nurse.• On-demand CME program, “PPARs as Therapeutic Targets in Type 2 Diabetes andAtherosclerosis.” Explore the current thinking on PPARs and PPAR agonists and earnfree CME online at www.ndei.org. Earn 2.25 category 1 credits–Free.For more information about upcoming NDEI CME and CE activities,visit us at www.ndei.org or call 1 (800) 606-6106. Visit www.ppscme.org forinformation on other CME or CE activities.Clinical Insights in Diabetes is co-edited by NDEI faculty members Mayer B. Davidson, MD,and Silvio E. Inzucchi, MD.If you have any friends or colleagues who would like to receive this newsletter via email,please fill in their information on the line below and fax this page to us at1 (800) 471-7716 so they can be added to our subscriber list.Name:________________________________________________________________________________Specialty:_____________________________________________________________________________Email Address: ________________________________________________________________________You have received this email because we believe it may be of interest to you. If you wouldlike your name to be removed from our mailing list, please choose from the following:1) Reply to this email and place REMOVE in the subject line.2) Call 1 (800) 873-1362 and leave a message with your name and email address indicatingthat you would like to be removed.Copyright © 2005 Thomson Professional Postgraduate Services ® . All rights reserved.EM-T150-PHYCMEem-1005-17.7K4

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