Volume 9, Number 5 May 2006 - National Diabetes Education Initiative

CLINICAL INSIGHTS ®IN DIABETESCOMMENTARYSave the Date—CME BreakfastSymposium at ENDO 2006Monday, June 26, 6:00 AMTargeting β-Cell Dysfunction:Emerging Science and TherapiesYou must be registered forThe Endocrine Society’s 88thAnnual Meeting to attendthis symposium.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.Vivian A. Fonseca, MD. Professor of Medicine, Tullis-Tulane Chair in Diabetes, Chief, Section of Endocrinology,Tulane University Health Sciences Center, New Orleans, Louisiana.Recently there has been considerable interest in homocysteine (tHcy) as a risk factor for vascular disease. Theassociation seems to be particularly strong for stroke. The concept is particularly attractive since tHcy can be loweredby simple and cheap vitamin therapy or perhaps a diet high in folate (which is also associated with a low riskof CVD). Preliminary studies with vitamins showed improvement in a variety of surrogate markers of CVD, includingendothelial function. However, what are needed are outcome studies, and in this respect, treatment withvitamins has proved disappointing. One European study showed less restenosis with folate following coronaryangioplasty, but other studies have been negative. Despite the negative effect of treatment, a high tHcy remainsa predictor of events in these populations. One needs to consider the reasons for the negative studies. It isunlikely that the patients in these studies are folate deficient, and post-load elevations in tHcy are better predictorsof CVD than those measured in the fasting state. It may just be that tHcy is indeed a risk factor and a perpetuatorof the disease process, but the treatment that should be considered is not tHcy lowering, but agentsproven to reduce events, such as statins. In this context, an animal study by Murthy et al demonstrated a reductionin vascular hyperplasia in hyperhomocysteinemic, insulin-resistant rats treated with a thiazolidinedione. Thisconcept has not been tested in humans.Murthy SN et al. Rosiglitazone reduces serum homocysteine levels, smooth muscle proliferation, and intimal hyperplasiain Sprague-Dawley rats fed a high methionine diet. Metabolism. 2005;54:645-652.Acute Glucose Fluctuation Is a Greater Activator ofOxidative Stress Than Sustained Chronic Hyperglycemiain Type 2 DiabetesType 2 diabetes is associated with microvascularand macrovascular complications. Accumulatingevidence suggests that superoxideoverproduction leading to oxidative stress is amajor factor in hyperglycemia-induced vasculardamage. Hyperglycemia in type 2 diabetes ischaracterized by both chronic sustained increasesin glucose levels and acute glucose fluctuationsoccurring over the course of the day. The individualroles of sustained chronic hyperglycemiaand acute glucose fluctuations on oxidative stressactivation have not been fully elucidated.Monnier and colleagues recently comparedthe contributions of sustained chronic hyperglycemiaand acute glucose fluctuations to oxidativestress in a case-control study of 21 patients withtype 2 diabetes versus 21 age- and sex-matchedcontrols. The main outcome measures were oxidativestress, estimated from 24-hour urinaryexcretion rates of free 8-iso prostaglandin F 2α(8-iso PGF 2α ), and glucose fluctuations, whichwere determined from continuous glucose monitoringsystem data by calculating the mean amplitudeof glycemic excursions (MAGE). Additionally,postprandial contribution to hyperglycemiawas measured by determining the postprandialglucose level increment above preprandial values(mean postprandial incremental area under thecurve [AUCpp]). Parameters of long-term glucoseexposure were hemoglobin A1C, fasting glucoselevels, and mean 24-hour glucose concentrations.Mean urinary 8-iso PGF 2α excretion rates(± standard deviation) were significantly higherin the diabetic group (482 ± 206 pg/mg ofcreatinine) than in the control group (275 ±85 pg/mg of creatinine) (P

CLINICAL INSIGHTS ®IN DIABETESAcute Glucose Fluctuation Is a Greater Activator ofOxidative Stress Than Sustained Chronic Hyperglycemiain Type 2 DiabetesContinuedtriggering effect on oxidative stress than didchronic sustained hyperglycemia. No relationshipwas observed with parameters of long-term glucoseexposure. The main limitation of this studywas the cross-sectional, observational design. Theinvestigators suggested that interventional trialsin type 2 diabetes should be directed at flatten-ing acute glucose fluctuations in addition toreducing hemoglobin A1C and mean glucoseconcentrations.Monnier L et al. Activation of oxidative stress by acuteglucose fluctuations compared with sustained chronichyperglycemia in patients with type 2 diabetes. JAMA.2006;295:1681-1687.Two case studies for On-DemandCME at www.ndei.org:“A 53-Year-Old Female WithType 2 Diabetes PresentsWith Dyspnea,” authored byRobert J. Chilton, DO, FACC.Earn 1.5 AMA PRA Category 1Credits—Free.“An 80-Year-Old NoncompliantFemale Patient With Type 2 Diabetesand a Recent AMI,” authored byWilliam M. Simpson, Jr., MD.Earn 1.0 AMA PRA Category 1Credit—Free.Impact of Moderate Alcohol Consumption on CoronaryAtherosclerosisAUsing Coxproportionalhazards analysis,alcohol intake wasthe only negativepredictor of cardiacmortality.therosclerotic cardiovascular disease (CVD) isthe leading cause of death among US adults.Epidemiological studies have found that moderatealcohol consumption is associated with reducedCVD risk. However, the physiologic basisfor alcohol’s protective effect remains unclear.Femia and colleaguesanalyzed theassociation of alcoholconsumption with coronaryatherosclerosis in acohort of 2,141 men(n=1,676) and women(n=465) who underwentcoronary angiographyfrom 1983 to 1992 aspart of a work-up ofsigns or symptoms ofCVD. An index of angiographyresults (ATSscore) was calculated based on the total percentnarrowing of all stenoses in the main coronaryvessels. Alcoholic beverage consumption wasassessed by questionnaire.The study cohort was stratified by sex andpresence (ATS+) or absence (ATS-) of documentedcoronary narrowing. Based on univariateanalysis, ATS score was significantly (P≤0.001)associated with CVD risk factors including age,male sex, smoking, hypertension, diabetes, serumcholesterol levels, and family history of ischemicheart disease. Compared with nondrinkers,alcohol consumption (median 231 g/wk in men,154 g/wk in women) was associated with lowerATS (P=0.02) and lower diabetes rates (P≤0.05)in men and women and less frequent hypertensionand lower blood pressure levels in womenonly. In multivariate analysis, moderate alcoholintake was associated with a lower ATS scoreindependently of other CVD risk factors (P

Clinical Insights ® in Diabetes Post-Test May 2006On-Demand CME/CE activityat www.ndei.org.Earn 2.5 AMA PRA Category 1Credits—Free.Participate in the On-DemandCME activity, The Cardiologist’sImperatives in Treating PatientsWith Diabetes. This activity bringstogether the best of emergingscience and examines the clinicalimplication of antidiabeticagents and their roles in themanagement of CVD.1) Alcohol consumption is associated with all of the following except:a. less coronary artery stenosis in menb. less diabetes in womenc. less hypertension in mend. lower blood pressure in women2) Compared to placebo, a combination of folic acid, vitamin B 6, and vitamin B 12significantlylowered which of the following:a. homocysteine levelsb. risk of mortality from cardiovascular eventsc. death from any caused. hospitalization rates for unstable angina3) Urinary free 8-iso prostaglandin F 2α (8 iso-PGF 2α ), a measure of oxidative stress, is associatedwith all of the following except:a. mean amplitude of glucose excursions (MAGE)b. A1C levelsc. postprandial incremental area under the curve (AUCpp)d. type 2 diabetesNDEI 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 complications tothe therapeutic options for treatment andprevention.You have received this email because webelieve it may be of interest to you. If youwould like your name to be removed from ourmailing list, please choose from the following:1) Reply to this email and place REMOVEin the subject line.2) Call 1 (800) 873-1362 and leave amessage with your name and emailaddress indicating that you would liketo be removed.National Diabetes Education Initiative, NDEI,and Clinical Insights are trademarks usedherein under license.ANSWER KEY1) c. less hypertension in men. Although alcohol consumption was associated with a lower risk of coronaryartery stenosis and type 2 diabetes in men and women, alcohol consumption’s lowering effect onhypertension incidence and blood pressure was only found in women.2) a. homocysteine levels. Although treatment with folic acid, vitamin B6 and vitamin B 12 significantlylowered plasma homocysteine levels, it did not significantly reduce the risk of major CV events in thestudy’s high-risk patient population.3) b. A1C levels. Oxidative stress is higher in patients with type 2 diabetes than in controls, and acuteglucose excursions had a greater triggering effect on oxidative stress than did chronic sustainedhyperglycemia.For more information about upcoming NDEI CME and CE activities, visit us at www.ndei.org orcall 1 (800) 606-6106. Visit www.ppscme.org for information 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 are not receiving this free, CME e-Newsletter via email, pleasefill in their information on the lines below and fax this page back to us at 1 (800) 471-7716 and we willadd them to our subscriber list.Name: (Please print) ______________________________ Specialty: _______________________________Email Address: _____________________________________________________________________________Copyright © 2006 Thomson ProfessionalPostgraduate Services ® . All rights reserved.EM-T177-05-PHYCME-05064

Activity Code: T177-05Issue Date: May 2006CME Credit Availability: July 2006CME Activity Evaluation/Registration FormParticipants who wish to obtain CME credit for this activity, please complete the contactinformation below, sign this form, and fax it with the completed post-test to (201) 430-1441.You may download previous issues of Clinical Insights ® in Diabetes e-newsletters by visiting usonline at www.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 Family medicineOther _________________________________________________________________________________________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 witn 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.EM-T177-PHYCMEem-0506-145K5

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