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Volume 8, Number 11 November 2005 - NDEI.org

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. 11, November 2005, is part of a12-part CME activity (January–December2005). Physicians who wish to receive CMEcredit for this educational activity should do thefollowing: (1) read each of the 12 monthlyissues in the series and retain them for futurereference; (2) review the original articles discussedin their entirety; and (3) after completingthe last issue of the year (December 2005),obtain the post-test to complete the CMEactivity. The post-test may be obtained fromwww.ndei.org or by calling 1 (800) 606-6106and requesting the post-test. You will receivethe post-test, registration, and evaluation formsby fax. To receive CME credit, the participantmust complete the 12-part series and post-testand return the completed registration andevaluation forms to: Thomson ProfessionalPostgraduate 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 ®INDiabetesSILVIO E. INZUCCHI, MD*, CO-EDITOR-IN-CHIEF; VIVIAN A. FONSECA, MD † , REVIEWER;TERRENCE F. FAGAN ‡ , MANAGING EDITOR; MARK PALANGIO § , WRITER.High-Normal Plasma Glucose Levels PredictType 2 DiabetesGiven that type 2 diabetes is becomingincreasingly more prevalent in individualsin their third to fifth decades of life, earliermeans of identifying young adults at risk areneeded. Normal fasting plasma glucoseis currently defined by the American DiabetesAssociation as

CLINICAL INSIGHTS ®IN DIABETESHigh-Normal Plasma Glucose Levels Predict Type 2 DiabetesContinuedThe investigators concluded that an elevatednormal fasting plasma glucose level isan independent risk factor for type 2 diabetesamong apparently healthy young men. Limitationsof this study include use of a uniquestudy group (ie, Israeli military men), as wellas the lack of glucose-tolerance testing andmeasurement of circulating insulin, C-peptide,and glycosylated hemoglobin levels. Nevertheless,these results suggest that fastingplasma glucose levels combined with BMIand triglyceride levels may be valuable inidentifying young men at increased risk fortype 2 diabetes.Tirosh A et al. Normal fasting plasma glucose levelsand type 2 diabetes in young men. N Engl JMed. 2005;353:1454-1462.COMMENTARYVivian A. Fonseca, MD, Professor of Medicine and Pharmacy, Tullis-Tulane Alumni Chair in Diabetes,Chief, Section of Endocrinology, Tulane University Health Sciences Center, New Orleans, Louisiana.In the face of the epidemic of obesity, it is useful to have simple markers of which individuals are more likelythan others to progress to diabetes. Clearly, impaired fasting glucose (IFG), defined as a fasting blood glucose,helps in such identification. However, it is important to realize that glucose is a continuous variable inthe population, and that although a value of

CLINICAL INSIGHTS ®IN DIABETESThe Metabolic Syndrome and Insulin ResistanceIndependently Predict Cardiovascular RiskContinuedConversely, insulin resistance remained significantlypredictive of vascular events afteradjustment for the metabolic syndrome (standardizedadjusted HR, 1.41; 95% CI, 1.14-1.75;P=0.002). This finding suggests that insulinresistance confers an additional vascular riskthat extends beyond current ATP III metabolicsyndrome criteria. Additional adjustment fortype 2 diabetes demonstrated that both themetabolic syndrome (adjusted HR, 2.57; 95%CI, 1.47-4.51; P=0.001) and HOMA insulin resistance(standardized adjusted HR, 1.37; 95% CI,1.09-1.73; P=0.007) significantly predictedvascular events independent of diabetes status.Based on these data, the authors concludedthat the metabolic syndrome andinsulin resistance are strong and mutuallyindependent predictors of vascular risk amongpatients having undergone angiography.The major limitation of this study is theenrollment of a select group of patients (ie,those undergoing coronary angiography forthe evaluation of CAD), which precludes theapplicability of these results to the generalpopulation. However, these findings underscorethe prognostic importance of the metabolicsyndrome and insulin resistance inestimating cardiovascular risk.Saely CH et al. The metabolic syndrome, insulinresistance, and cardiovascular risk in diabetic andnondiabetic patients. J Clin Endocrinol Metab.2005;90:5698-5703.Patients with heartfailure and type 2diabetes treatedwith metformin hadlower morbidityand mortality thanpatients treated withsulfonylureas alone.Contraindicated Metformin May ImproveOutcomes With Diabetes and Heart FailureAlthough the oral antidiabetic agent metforminis contraindicated in patients withheart failure because of the potential for lacticacidosis, there is little clinical evidence linkingthis medication with it. Indeed, new findingssuggest that metformin might actually bebeneficial for patients with type 2 diabetes andheart failure.Eurich and associates examined clinicaloutcomes associated with metformin administrationin patients with heart failure andtype 2 diabetes using computerized databasesof Saskatchewan Health, the universal healthcaresystem of Saskatchewan, Canada. Among12,272 new users of oral antidiabetic agentsidentified between the years 1991 and 1996(mean age, 72 years; 57% male), subjects withincident heart failure (n=1,833) were groupedaccording to antidiabetic therapy: metforminmonotherapy (n=208), sulfonylurea monotherapy(n=773), or combination therapy (n=852).Differences in all-cause mortality, all-causehospitalization, and the combination ofall-cause hospitalization or mortality werecompared.At the end of the follow-up period (mean,2.5 years), all-cause mortality was considerablyless in the metformin monotherapy group(33%; unadjusted hazard ratio [HR], 0.63;95% confidence interval [CI], 0.49-0.82) andthe metformin-sulfonylurea combinationtherapy group (31%; unadjusted HR, 0.50;95% CI, 0.43-0.58) than in the sulfonylurea monotherapygroup (52%). In a multivariate regressionanalysis adjusting for age, sex, chronic diseasescore, drug therapies, and total physician visits,all-cause mortality was greatly reduced witheither metformin alone (adjusted HR, 0.70; 95%CI, 0.54-0.91) or in combination with other agents(adjusted HR, 0.61; 95% CI, 0.52-0.72) comparedwith sulfonylurea monotherapy. Multivariableanalyses did not reveal any significant differencesbetween the treatment groups with regard tohospitalizations.At study endpoint, the composite outcomeof all-cause hospitalizations or all-cause mortalitywas also less with metformin monotherapy (77%;adjusted HR, 0.83; 95% CI, 0.70-0.99) and combinationtherapy (80%; adjusted HR, 0.86; 95% CI,0.77-0.96) compared with sulfonylurea monotherapy(85%) after adjusting for covariates.Furthermore, no hospitalizations or deaths wereattributed to metabolic acidosis in any treatmentgroup.The conclusions that can be drawn fromthis study are limited by its observational nature.However, the study results are strengthened bythe large unselected patient sample, the longtermfollow-up, and control of confoundingfactors. From these results, the investigatorsinferred that, at the very least, metformin is notassociated with an increased risk of adverseoutcomes in heart failure patients compared withsulfonylureas, the most commonly prescribed oralContinued3

CLINICAL INSIGHTS ®IN DIABETESContraindicated Metformin May ImproveOutcomes With Diabetes and Heart FailureContinuedantidiabetic agents. In this analysis, patientswith heart failure and type 2 diabetes treatedwith metformin, alone or in combination,had lower morbidity and mortality thanpatients treated with sulfonylureas alone,even after adjusting for multiple confoundingvariables. It remains to be determinedwhether prescribing guidelines for metforminin heart failure patients need to be changed.Eurich DT et al. Improved clinical outcomes associatedwith metformin in patients with diabetes andheart failure. Diabetes Care. 2005;28:2345-2351.NDEI 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 at www.ndei.orgor call 1 (877) 251-0943.• CME Managed Care Dinner Meeting Series, “Getting to the Heart of Type 2 Diabetes andCardiovascular Disease.” To find out if there are meetings in your area, please visit us onlineat 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 Uncomplicated MIPresenting With Elevated BG,” authored by Frank Lavernia, MD. Earn 1 category 1credit–Free.• NEW On-demand CME Activity, Earn free 2.25 category 1 credits. Participate in theon-demand CME activity: “Clinical Challenges in Type 2 Diabetes and CVD: A Case-BasedDiscussion Among Experts.” Explore the intricacies of a typical diagnosis from the uniqueperspectives of an endocrinologist, cardiologist, hospitalist, family physician, and nurse.• On-demand CME Activity, “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, andSilvio E. Inzucchi, MD.If you have any friends or colleagues who would like to receive this newsletter via email, please fill intheir information on the line below and fax this page to us at 1 (800) 471-7716 so they can be added toour subscriber list.Name: ___________________________________________________________________________________________Specialty: ________________________________________________________________________________________Email Address: ___________________________________________________________________________________You have received this email because we believe it may be of interest to you. If you would like yourname 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 indicating that youwould like to be removed.Copyright © 2005 Thomson Professional Postgraduate Services ® . All rights reserved.EM-T150-PHYCMEem-1105-74.4K4

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