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Volume 9, Number 7 July 2006 - National Diabetes Education Initiative

T H O M S O N H E A L T H C A R ERelease Date: July 2006Valid Until: September 2006SponsorThis educational activity is a component of theNational Diabetes Education Initiative ® (NDEI ® ),sponsored by Thomson Professional PostgraduateServices ® (PPS), Secaucus, NJ.Clinicians who wish to receive CME credit forthis educational activity should do the following:(1) read the current issue; and (2) complete thepost-test and evaluation form included to concludethis CME activity. You may also complete thepost-test and evaluation form on our website,www.ndei.org. To apply for CME credit, returnthe completed post-test and evaluation form to:Thomson Professional Postgraduate Services ®CME Dept. T1775 Paragon DriveMontvale, NJ 07645-1725You may also fax the completed materials to1 (888) 251-5650. If you have any questions,please call 1 (800) 606-6106 Ext. 6019.Applicants will receive a certificate of participationfrom PPS by return mail within 6 to 8 weeks of thedate of receipt of the completed evaluation formand post-test. Online applicants will automaticallyreceive their CME credit certificate upon completionof the online post-test and evaluation form.Target AudienceThis educational activity is designed for primarycare physicians, internal medicine specialists,endocrinologists, diabetologists, cardiologists,and other healthcare professionals involved inthe care and management of patients with type2 diabetes, insulin resistance, and cardiovasculardisease.Learning ObjectivesAfter studying the literature presented in thisClinical Insights ® in Diabetes, participants shouldbe better able to:• Select an appropriate therapeutic regimenfor patients with type 2 diabetes and themetabolic syndrome• Summarize risk factors for cardiovasculardisease in patients with type 2 diabetes andthe metabolic syndromeAccreditationThomson Professional Postgraduate Services ® isaccredited by the Accreditation Council forContinuing Medical Education to providecontinuing medical education for physicians.Thomson Professional Postgraduate Services ®designates this educational activity for a maximumof .75 AMA PRA Category 1 Credit. Physiciansshould only claim credit commensurate with theextent of their participation in the activity.Clinical Insights ® in Diabetes (2006-2007) hasbeen reviewed and is acceptable for up to 6Prescribed credits by the American Academy ofFamily Physicians. AAFP accreditation begins04/01/06. Term of approval is for one year fromthis date. This issue is approved for .5 Prescribedcredit. Credit may be claimed for one year fromthe date of this issue.GrantorThis CME activity is supported by an educationalgrant from Takeda Pharmaceuticals NorthAmerica, Inc.C L I N I C A L I N S I G H T S ®I NDiabetesV O L U M E 9 , N U M B E R 7 • J U L Y 2 0 0 6SILVIO E. INZUCCHI, MD,* CO-EDITOR-IN-CHIEF; HENRY N. GINSBERG, MD, † REVIEWER;TERRENCE F. FAGAN, ‡ MANAGING EDITOR; MARK PALANGIO, CO-WRITER §Greater 24-Hour Glucose Decrease After AMI Predicts LowerMortality in Patients Without DiabetesAmong patients hospitalized with acutemyocardial infarction (AMI), baseline hyperglycemiahas been linked to pooreroutcomes, both in the presence and absence ofdiabetes. However, it was not clear whetherglucose levels after hospital admission haveprognostic value.Goyal and colleagues evaluated the prognosticsignificance of baseline glucose and thechange in glucose in the first 24 hours followingAMI. This analysis included 1,469 AMI patients(250 of whom had diagnosed diabetes) withbaseline and 24-hour glucose data from theComplement And ReDuction of INfarct size afterAngioplasty or Lytics (CARDINAL) trial database.The CARDINAL trials examined the effect of inhospitaladministration of pexelizumab, a complementinhibitor, in patients with ST-elevationAMI who were treated with primary percutaneouscoronary intervention or fibrinolysis. Multivariablemodels for 30- and 180-day mortalityconsidered baseline glucose and the 24-hourchange in glucose.There were 45 deaths in the total cohort at30 days and 74 deaths at 180 days. As baselineglucose values increased, there were significantincreases in 30-day (P=0.008) and 180-day(P=0.020) mortality. Cox model analyses revealedthat 30-day mortality was predicted by bothbaseline glucose (hazard ratio [HR], 1.08; 95%confidence interval [CI], 1.05-1.12, per 10 mg/dLincrease; P

C L I N I C A L I N S I G H T S ®I N D I A B E T E SCOMMENTARYHenry N. Ginsberg, MD. Irving Professor of Medicine at the College of Physicians and Surgeons atColumbia University and Director, Irving Center for Clinical Research at the Columbia University MedicalCenter, New York, New York.By demonstrating that the change in the blood glucose over the first 24 hrs after admission predicts 30- and180-day mortality in patients with acute myocardial infarctions, the paper by Goyal et al, extends prior studiesthat found similar associations between baseline blood glucose levels and mortality. In a fully adjusted modelthere was an interaction between both glucose levels and the presence of diabetes such that the baseline glucoselevel and the 24-hr change in glucose predicted 30- or 180-day mortality only in the nondiabetics. The authorssuggest that better treatment of hyperglycemia may be beneficial for nondiabetic patients with acute myocardialinfarctions. However, questions remain that confound the interpretation of these results. For example, was thelack of a fall in blood glucose over 24 hrs a reflection of poorer overall care, or a marker of insulin resistance andincreased numbers of risk factors in that group? Conversely, did the 24-hr fall in blood glucose fail to predictoutcome in the diabetic group because they were all treated more aggressively, or because they all had thecluster of risk factors associated with diabetes? The importance of these issues is clear when one considers thesparse and inconsistent data in the literature regarding the efficacy of aggressive glucose-lowering therapiesin this population. Epidemiologic studies identify questions of interest; clinical trials are needed to obtain clearanswers to such questions.Clinical Insights®in Diabetesis now available througha new channel ofdistribution via Podcast.To participate in thisCME activity via Podcast,please visit us online atwww.ndei.org.Elevated Retinol-Binding Protein 4 Linked toIncreased Insulin Resistance and Cardiovascular RiskIn insulin-resistant states, serum levels ofretinol-binding protein 4 (RBP4), a proteinsecreted by adipocytes, are increased, whereasthe expression of glucose-transporter 4 (GLUT4),the principle insulin-stimulated glucose transporter,is down-regulated in adipocytes. Studiessuggest that elevated levels of RBP4 are associatedwith insulin resistance. Furthermore, elevatedRBP4 levels have been detected in patientswith type 2 diabetes.Graham and associates examined the relationshipbetween serum RBP4 levels and insulinresistance, and whetherelevated serum RBP4 levelsare associated with reducedexpression of GLUT4 in adipocytes.Serum RBP4 levels,insulin resistance, and componentsof the metabolicsyndrome were assessed in3 groups of subjects. Group1 (n=21 men) compared 5 lean control subjectswith 7 obese subjects without diabetes and 9obese subjects with diabetes. Group 2 (n=60)compared 20 normal control subjects (9 men, 11women) with 20 subjects with impaired glucosetolerance (9 men, 11 women) and 20 subjectswith type 2 diabetes (9 women, 11 men). Studyparameters in Group 2 were assessed at baselineand after 1 month of exercise training. Group 3comprised 26 nonobese normoglycemic menwith at least one first-degree relative withtype 2 diabetes. GLUT4 protein was measuredElevated RBP4 levelsmay be a marker forinsulin resistance andcardiovascular risk.in isolated adipocytes in Group 3.In Group 1, mean serum RBP4 levels wereelevated in obese subjects with and withoutdiabetes compared with lean control subjects.Serum RBP4 levels correlated positively withbody mass index (R=0.64; P=0.001) and fastinginsulin levels (R=0.72; P

C L I N I C A L I N S I G H T S ®I N D I A B E T E SElevated Retinol-Binding Protein 4 Linked toIncreased Insulin Resistance and Cardiovascular RiskContinuedIn Group 3, among nonobese normoglycemicmen with relatives with type 2 diabetes,serum RBP4 levels correlated inversely withglucose disposal rate (R=-0.59; P=0.002) andcorrelated positively with fasting insulin level(R=0.71; P

C L I N I C A L I N S I G H T S ®I N D I A B E T E SOn-demand CME/CE activity atwww.ndei.org,Earn 2.5 AMA PRA Category 1Credits-Free. Participate in theon-demand CME activity,“The Cardiologist’s Imperatives inTreating Patients With Diabetes.”This activity brings together thebest of emerging science andexamines the clinical implicationof anti-diabetic agents and theirrole in the management of CVD.Clinical Insights ® in Diabetes Post-Test July 20061) Choose the correct statement from the following choices, based on the Goyal study:a. Admission plasma glucose in nondiabetic AMI patients predicts higher mortalityb. A greater decrease in plasma glucose in nondiabetic AMI patients during the first24 hours of admission predicts higher mortalityc. Admission plasma glucose in diabetic AMI patients predicts higher mortalityd. A greater decrease in plasma glucose in diabetic AMI patients during the first24 hours of admission predicts lower mortality2) True or False?In the study by Graham et al, retinol-binding protein 4 (RBP4) was found to be a newmarker of insulin resistance in obese but not in nonobese individuals.a. Trueb. False3) According to the study by Phillips et al, patients with impaired fasting glucose (IFG)at the level of 110 mg/dL or higher had a greater degree of which characteristic, ascompared to those with IFG of between 100 to 109 mg/dL?a. Metabolic syndrome (by NCEP-ATP III criteria)b. LDL-C >130 mg/dLc. Albuminuriad. Post-challenge hyperglycemiae. All of the aboveANSWER KEY1. a) Admission plasma glucose in nondiabetic AMI patients predicts higher mortality. Plasma glucose levels ofpatients admitted with an AMI but without diabetes predicted 30-day and 180-day mortality.2. b) False. RBP4 was also found to be a marker in nonobese persons with a strong family history of diabetes.3. e) All of the above. Patients at an IFG level ≥110 mg/dL were at greater risk of metabolic syndrome, high LDL-C,albuminuria, and post-challenge hyperglycemia than those with IFG levels

C L I N I C A L I N S I G H T S ®I N D I A B E T E SActivity Code: T177-07Issue Date: July 2006CME Credit Availability: September 2006CME Activity Evaluation/Registration FormParticipants who wish to obtain CME credit for this activity, please complete the contact informationbelow, sign this form, and fax it with the completed post-test to 1 (888) 251-5650 or mail to: ThomsonProfessional Postgraduate Services ® , CME Dept. T177, 5 Paragon Drive, Montvale, NJ 07645-1725. Youmay download previous issues of Clinical Insights ® in Diabetes e-newsletters by visiting us online atwww.ndei.org.I completed this activity as designed: ____________________________________________________________________________________(Signature)PLEASE PRINT CLEARLY:Name:Address:City:Phone:Email Address: State: ZIP Code: - - Fax: - - Professional Classification: MD DO PharmD RN NPOther___________________________________________________________________Specialty: Endocrinology Cardiology Internal medicine Primary careOther________________________________________________________________________________________Overall Program1. The activity met the stated objectives in such a way that I am better able to:StronglyDisagree Disagree AgreeStronglyAgreea. Select an appropriate therapeutic regimen for patients with type 2 diabetes andthe metabolic syndrome 1 2 3 4 5 6b. Summarize risk factors for cardiovascular disease in patients with type 2 diabetesand the metabolic syndrome 1 2 3 4 5 62. Overall, the activity was presented in a fair-balanced manner. Yes No** If you checked “No,” please explain.3. In reflecting on your practice, what type of impact will this educational activity have?This program has validated my practice in the treatment of type 2 diabetes and its cardiovascular complications.Need more information before making a change.(Please specify what information you would require.)I will:Identify patients with type 2 diabetes and the metabolic syndromeSelect an appropriate therapeutic regimen for patients with type 2 diabetes and the metabolic syndromeOther (Please specify.)4. What topics should be dealt with in more detail? (List topics)Thank you for your participation.5

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