THOMSON HEALTHCARERelease Date: August 2006Valid Until: October 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:• Identify patients with type 2 diabetes andthe metabolic syndrome• 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.CLINICAL INSIGHTS ®INDiabetesMAYER A. DAVIDSON, MD,* CO-EDITOR-IN-CHIEF; SILVIO E. INZUCCHI, MD, † REVIEWER;TERRENCE F. FAGAN, ‡ MANAGING EDITOR and WRITERManagement of Hyperglycemia in Type 2 Diabetes:A Consensus Statement From the ADA and EASDNumerous studies have been published onthe management of hyperglycemia inpatients with type 2 diabetes, yet thebest pathway to successful therapy remainsunclear. To address this, the American DiabetesAssociation (ADA) and the European Associationfor the Study of Diabetes (EASD) have developeda consensus approach to assist healthcareproviders in choosing the most appropriatetreatments.Effective weight loss through increasedphysical activity and dietary control is the mostcost-effective means of controlling diabetes, butthe high rate of weight regain in patients limitsthe role of lifestyle intervention in long-termglycemic control. Nevertheless, lifestyle therapyshould be included, with rare exception, as a partof any diabetes management program. Weightlossmedications cannot be recommended as aprimary diabetes treatmentbecause of the high dropoutrates, side effects, andlow sustainability shown instudies of these agents.The algorithm on page 2is based on goals of achievingand maintaining glucoselevels as close to the nondiabeticrange as possible, initiating or changingtherapy when the patient’s A1C level is ≥7%, andchanging interventions, if necessary, as rapidly astitration of medications allows. Selection ofantihyperglycemic agents is primarily based ontheir glucose-lowering efficacy. Tolerability,safety, expense, and extraglycemic effects thatmay help reduce diabetic complications are alsoconsidered. Exenatide, glinides, pramlintide, andα-glucosidase inhibitors are not included in thisalgorithm because of their lower overall efficacyin glycemic control, limited clinical data, and/orrelative expense.As the first step in treatment of new-onsettype 2 diabetes, lifestyle intervention should beimplemented by registered dietitians or otherhealthcare professionals. However, due to thefrequent failure of lifestyle intervention toVOLUME 9, NUMBER 8 • AUGUST 2006Metformin therapyshould be initiatedat diagnosis withlifestyle therapy.achieve or maintain glycemic goals, concurrentmetformin therapy should be initiated at diagnosis.Metformin is recommended because ofits efficacy in glycemic control (~1.5% expecteddecrease in A1C), low level of long-term sideeffects (short-term gastrointestinal side effectsare common), absence of hypoglycemia orweight gain, relatively low cost, and highlevel of acceptance. It should be titrated over1 to 2 months to its maximally effective dose,as tolerated.If glycemic goals are not achieved or sustainedwith metformin within 2 to 3 monthsof its initiation, a second medication should beadded. Either insulin, a sulfonylurea, or a thiazolidinedione(TZD) is recommended, but there isno consensus as to which of the three should beused. The synergy of drug combinations shouldbe considered, as antihyperglycemic medicationswith different mechanisms ofaction will have the greatestsynergy. Metformin plus insulinand insulin plus a TZD are particularlyeffective in loweringglycemia, although the lattercombination has a greater riskof fluid retention that shouldbe monitored. Adding a TZD tometformin has been shown to have modest additiveeffects in lowering A1C.Advantages of insulin include greaterexpected A1C decrease (~1.5% to 2.5%), relativelylow cost, and an improved lipid profile;disadvantages include injections, monitoring,hypoglycemia, and weight gain. Sulfonylureaadvantages include ~1.5% expected A1C decreaseand relatively low cost; disadvantagesinclude weight gain and hypoglycemia, althoughusually not severe. Thiazolidinedione advantagesinclude expected A1C decrease of ~0.5% to 1.4%and an improved lipid profile; disadvantagesinclude fluid retention, weight gain, and relativelyhigher cost. For patients with A1C >8.5%or with symptoms secondary to hyperglycemia,basal insulin should be considered for its greaterglycemia-lowering effect.Continued* Dr Davidson is Director, Clinical Center of Research Excellence at Charles R. Drew University, Los Angeles, California. He hasindicated no relevant financial relationships.† Dr Inzucchi is a Professor of Medicine at Yale University School of Medicine, New Haven, Connecticut. He has indicated thefollowing relevant financial relationships: retained consultant, Takeda Pharmaceuticals North America, Inc.; speakers bureau,GlaxoSmithKline, Merck and Co., Inc., and Takeda Pharmaceuticals North America, Inc.‡ Mr Fagan is a managing editor for Thomson PPS. He has indicated no relevant financial relationships.
CLINICAL INSIGHTS ®IN DIABETESManagement of Hyperglycemia in Type 2 Diabetes:A Consensus Statement From the ADA and EASDContinued®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.If the addition of a secondary medicationdoes not achieve or sustain goal A1C, insulintherapy should be initiated or intensified. If A1Cis close to goal (10%,fasting plasma glucose levels >250 mg/dL, randomglucose levels consistently >300 mg/dL, orthe presence of ketonuria) or diabetes withpolydipsia, polyuria, and weight loss should betreated at the outset with insulin therapy andlifestyle intervention.The authors concluded that interventionsthat achieve glucose levels close to nondiabeticrange can substantially reduce the morbidityassociated with long-term complications in patientswith type 2 diabetes, and that current-daymanagement has failed to achieve and maintainthose levels.Nathan DM et al. Management of hyperglycemia in type2 diabetes: a consensus algorithm for the initiation andadjustment of therapy. A consensus statement from theAmerican Diabetes Association and the European Associationfor the Study of Diabetes. Diabetes Care.2006;29:1963-1972.CME Abstract Podcast SeriesVol 1 now available onwww.ndei.org.Two abstracts from the 2006ADA Scientific Sessions withexpert commentary byVivian Fonseca, MDAlgorithm for the Metabolic Management of Type 2 DiabetesDiagnosisLifestyle Intervention + MetforminNoA1C≥7%Yes*Add Basal Insulin(Most effective)Add Sulfonylurea(Least expensive)Add Glitazone(No hypoglycemia)NoA1C ≥7% Yes* No A1C ≥7% Yes* No A1C≥7% Yes*Intensify Insulin Add Glitazone † Add Basal Insulin Add Sulfonylurea †No A1C≥7% Yes*No A1C ≥7% Yes*Add Basal or Intensify InsulinIntensive Insulin + Metformin +/- Glitazone*Check A1C every 3 months until
CLINICAL INSIGHTS ®IN DIABETESCOMMENTARYSILVIO E. INZUCCHI, MD. Professor of Medicine at Yale University School of Medicine, New Haven,Connecticut.This consensus statement by some of the leading experts in the field presents a logical framework upon whichpractitioners can build rational antihyperglycemic strategies in patients with type 2 diabetes. There are severalimportant “take-home” messages herein. First, the authors underscore the importance of metformin as the initialagent when diet and exercise alone have failed to adequately control blood glucose. Second, combination therapy,when necessary, should be introduced early on in the course of the disease. Third, the addition of insulin isthe most effective intervention in those patients requiring more than 1-2 antihyperglycemic drugs. Finally, oraltherapies should generally be continued when basal insulin is initiated, but secretagogues have little role oncemealtime insulin therapy is begun. As clinicians, we can apply these recommendations in our practice, adaptingthem to our patients’ individual characteristics, predispositions, and tolerances.New interactive case studyfor on-demand CME atwww.ndei.org:“A 30-Year-Old Hispanic-American Female With aHistory of GD DevelopsType 2 Diabetes” authoredby Mark W. Stolar, MD.Earn 1.5 AMA PRA Category 1Credits FreeCOMING SOONAn interactive case studyfor on-demand CME atwww.ndei.org:“A 22-Year-Old African-AmericanWoman Presents With Diabetesand Multiple Risk Factors”authored by Anne Peters, MD.Metabolic Syndrome No More Predictive of CVMortality Than Its Individual ComponentsThe presence of the metabolic syndrome identifiespatients with risk factors for cardiovascular(CV) disease, but the question of whetherthe syndrome predicts risk above and beyond itsindividual components has not been answered.Sundström and colleagues addressed this questionusing a cohort of men examined at age 50years and then at age 70 years, with a maximumof 32.7 years of follow-up (median 29.8 years)and an outcome of CV mortality.The cohort was split into four baselinesamples: two at 50 years of age (the entire cohort[n=2,322] and a primary preventive sample[n=2,198], excluding people with diabetes,stroke, or a myocardial infarction at or beforebaseline) and two at 70 years of age (the entirecohort [n=1,221] and a primary preventive sample[n=872]). All subjects at age 50 baselinewere tested for fasting cholesterol, triglycerides(TG), HDL cholesterol, smoking, hypertension,and homeostasis model assessment—insulinresistance; at age 70 baseline they were tested asabove with the addition of an insulin sensitivitytest using the euglycemic insulin clamp technique.The National Cholesterol Education Programdefinition of metabolic syndrome wasused: fasting glucose ≥110 mg/dL, blood pressure≥130/85 mm Hg or treatment for hypertension,TG ≥150 mg/dL, HDL-C 29.4 kg/m 2 (substituted for waistcircumference measurement).Two measures were used to test the hypothesisthat the metabolic syndrome predictsCV mortality better than the sum of its parts:likelihood ratio tests and areas under receiveroperatingcharacteristics curves (C-statistics).Likelihood ratio tests compared Cox proportionalmodels including only the individual metabolicsyndrome components with models also includingthe metabolic syndrome as a variable.C-statistics were calculated for all metabolicsyndrome components, and then the researcherscompared C-statistics with and without the metabolicsyndrome variable.The metabolic syndrome was present in17.8% of the cohort at 50 years of age (15.9%of the primary preventive sample) and 23.2% ofthe cohort at 70 years of age (15.8% of theprimary preventive sample). During the followupto the baseline examination at age 50, 502persons in the total cohort died from CV disease(8.3 per 1,000 person-years at risk [PYAR]), andan additional 133 died during follow-up afterthe baseline examination at 70 years of age(12.7/1,000 PYAR).Using likelihood ratio tests and comparisonsof C-statistics, the metabolic syndrome did notpredict CV mortality independently of its componentsat any age or in any sample. The authorsconcluded that if these results are confirmed inother samples, the metabolic syndrome might beconsidered not as a strong biological entity butas a clinically handy summary measure of nontraditionalCV risk factors.Sundström J et al. Risk associated with the metabolicsyndrome versus the sum of its individual components.Diabetes Care. 2006;29:1673-1674.Sibutramine Treatment Added to Behavioral TherapyImproves Metabolic Risk Factors in Obese AdolescentsApproximately 15.5% of US adolescents aged12 to 19 years are defined as overweight(>95th percentile for age- and gender-specificmeasures for body mass index [BMI]) and theincidence of type 2 diabetes is increasing inthis population. Cardiovascular risk factors arealso more prevalent compared with adolescentswith BMI
CLINICAL INSIGHTS ®IN DIABETESSibutramine Treatment Added to Behavioral TherapyImproves Metabolic Risk Factors in Obese AdolescentsContinuedSibutramine, a norepinephrine and serotoninreuptake inhibitor, has been shown toassist in weight loss and weight maintenance andto improve metabolic variables in obese adults.In a 12-month, double-blind, randomized studyat 33 US outpatient clinics, Berkowitz and colleaguesevaluated the effects of sibutraminetreatment combined with behavioral therapy onweight loss in adolescents 12 to 16 years of agewith a BMI at least 2 units more than the USweighted mean of the 95th percentile based onage and sex, but not more than 44 kg/m 2 .In addition to behavioral therapy (flexiblelifestyle management therapy tailored to individualneeds), the sibutramine group (n=368)received 10 mg of sibutramine daily, while thecontrol group (n=130) received placebo. The twogroups were well balanced with no clinicallysignificant differences at baseline. At 6 months,participants who did not lose a minimum of 10%of baseline BMI were uptitrated to 15 mg ofsibutramine or placebo.Primary outcome was absolute change inBMI from baseline; secondary end points includedpercentage change in BMI, absolutechange in waist circumference, and percentageand absolute changes in body weight and glycemicand lipid variables. Overall completion ratewas 76% in the sibutramine group vs 62% inthe placebo group (P=0.001), with 6% of thetotal sibutramine group (n=22) and 5% of thetotal placebo group (n=7) withdrawing due toadverse events. Other causes for withdrawalfrom the study included lost to follow-up, withdrawalof consent, administrative reasons, andprotocol deviation.At 12 months, the absolute change in BMIfrom baseline with sibutramine plus behaviortherapy was -3.1 kg/m 2 vs -0.3 kg/m 2 for placeboplus behavior therapy, a mean between-groupdifference of -2.9 kg/m 2 (95% confidence interval[CI], -3.5 to -2.2; P
CLINICAL INSIGHTS ®IN DIABETESClinical Insights ® in Diabetes Post-Test August 20061) Which one of the following is not an ADA recommended treatment fortype 2 diabetes?a. Metformin plus a sulfonylurea agentb. Metformin as initial treatmentc. Metformin plus a sulfonylurea agent plus a glitazoned. Diet and exercise alone as initial treatmente. Insulin plus metformin2) Which one of the following statements is true?a. The metabolic syndrome predicts CVD risk over and beyond the sum of its componentparts.b. The metabolic syndrome may serve as a summary measure of CVD risk.c. The results of this study suggest that the metabolic syndrome is a strongbiological entity.d. The prevalence of the metabolic syndrome is similar in men 50 years of age and those70 years of age.e. Subsequent CVD death rates are similar in men studied at 50 years of age and thosere-studied at 70 years of age.3) Which one of the following is not true? Compared to the group receiving placebo:a. There was a progressive decrease in BMI throughout the 12-month period in adolescentsreceiving sibutramine.b. Fasting triglycerides, HDL-C, insulin levels, and HOMA scores all improved in thesibutramine group.c. Systolic and diastolic blood pressures and pulse rates all significantly increased in thesibutramine group.d. Tachycardia occurred significantly more often in the sibutramine group.e. Rates of growth and Tanner scores were no different between the sibutramineand placebo groups.NDEI MISSION STATEMENTThe National Diabetes Education Initiative ®(NDEI ® ) is a multicomponent educationalprogram on type 2 diabetes designed forendocrinologists, diabetologists, cardiologists,primary care physicians, and otherhealthcare professionals involved in the careand management of patients with type 2diabetes and insulin resistance. NDEI programsaddress issues concerning insulinresistance and type 2 diabetes, from theepidemiology and pathophysiology of thedisease and its associated complicationsto the therapeutic options for treatmentand prevention.ANSWER KEY3) a. There was a progressive decrease in BMI throughout the 12-month period in adolescents receivingsibutramine. Although there was a significant total decrease in BMI in the sibutramine groupcompared with the placebo group, that decrease plateaued at 8 months.2) b. The metabolic syndrome may serve as a summary measure of CVD risk. Sundström and colleaguesconcluded that the metabolic syndrome did not predict cardiovascular mortality independently of itscomponents at any age or in any sample, and that it might be considered not as a strong biologicalentity, but as a clinically handy summary measure of nontraditional cardiovascular risk factors.1) d. Diet and exercise alone as initial treatment. With rare exception, lifestyle therapy should be a partof any diabetes management program. However, due to the high failure rate of lifestyle therapy forlong-term glycemic control, metformin is recommended as a concurrent part of initial therapy.For more information about upcoming NDEI CME and CE activities, visit us at www.ndei.org orcall 1 (800) 606-6106, ext. 6019.Visit www.ppscme.org for information on other CME or CE activities.Clinical Insights ® in Diabetes is co-edited by NDEI faculty members Mayer A. Davidson, MD, and Silvio E. Inzucchi, MD.Clinical Insights ® in Diabetes CME e-newsletter is available to you via email at no cost. To subscribeto receive future issues via email, please visit us online at www.ndei.org or insert your name andemail address below and fax this page back to 1 (800) 471-7716.Name: (Please print) ________________________________ Specialty: _______________________________Email Address: _____________________________________________________________________________You have received this fax because we believe it may be of interest to you. If you would likeyour name to be removed from our fax list, please follow these instructions: Call toll-free1 (800) 311-0217, enter PIN 9633, followed by the # key, and fax number.National Diabetes Education Initiative, NDEI, and Clinical Insights are trademarks used herein under license.Copyright © 2006 Thomson Professional Postgraduate Services ® . All rights reserved.F-T177-08-PHYCME-08065
CLINICAL INSIGHTS ®IN DIABETESCME Activity Evaluation/Registration FormActivity Code: T177-08Issue Date: August 2006CME Credit Availability: October 2006Participants 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:a. Identify patients with type 2 diabetes and the metabolic syndromeStronglyDisagree Disagree AgreeStronglyAgree1 2 3 4 5 6b. Select an appropriate therapeutic regimen for patients with type 2 diabetes andthe metabolic syndrome 1 2 3 4 5 6c. 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.6