2017
Targeting Pioglitazone Hydrochloride Therapy After Stroke or Transient Ischemic Attack According to Pretreatment Risk for Stroke or Myocardial Infarction
Kernan WN, Viscoli CM, Dearborn JL, Kent DM, Conwit R, Fayad P, Furie KL, Gorman M, Guarino PD, Inzucchi SE, Stuart A, Young LH. Targeting Pioglitazone Hydrochloride Therapy After Stroke or Transient Ischemic Attack According to Pretreatment Risk for Stroke or Myocardial Infarction. JAMA Neurology 2017, 74: 1319-1327. PMID: 28975241, PMCID: PMC5710663, DOI: 10.1001/jamaneurol.2017.2136.Peer-Reviewed Original ResearchConceptsTransient ischemic attackIschemic attackMyocardial infarctionIschemic strokeHigh riskPioglitazone groupInsulin resistanceLower riskCox proportional hazards regression modelProportional hazards regression modelsMedian riskEfficacy of pioglitazoneInsulin Resistance InterventionQualifying ischemic strokePlacebo-controlled trialHazards regression modelsLow baseline riskType 2 diabetesGreater absolute benefitDay of entryFuture strokeHydrochloride therapyPlacebo groupHazard ratioSecondary preventionPioglitazone and cardiovascular risk reduction
Perdigoto AL, Young LH, Inzucchi SE. Pioglitazone and cardiovascular risk reduction. Cardiovascular Endocrinology & Metabolism 2017, 6: 55-61. PMID: 31646121, PMCID: PMC6768516, DOI: 10.1097/xce.0000000000000110.Peer-Reviewed Original ResearchInsulin Resistance InterventionCV outcomesInsulin resistanceResistance InterventionImpact of thiazolidinedionesCardiovascular risk reductionGlucose-lowering drugsCardiovascular disease riskInsulin-resistant patientsType 2 diabetesCV complicationsMacrovascular eventsCV riskSecondary preventionResistant patientsStroke patientsStroke trialsPathophysiological abnormalitiesAntihyperglycemic agentsInsulin sensitivityDiabetes managementClinical practiceStroke resultsPatientsDisease risk
2015
Autonomic dysfunction independently predicts poor cardiovascular outcomes in asymptomatic individuals with type 2 diabetes in the DIAD study
Chyun DA, Wackers FJ, Inzucchi SE, Jose P, Weiss C, Davey JA, Heller GV, Iskandrian AE, Young LH, Investigators F. Autonomic dysfunction independently predicts poor cardiovascular outcomes in asymptomatic individuals with type 2 diabetes in the DIAD study. SAGE Open Medicine 2015, 3: 2050312114568476. PMID: 26770763, PMCID: PMC4679226, DOI: 10.1177/2050312114568476.Peer-Reviewed Original ResearchCardiac autonomic neuropathyHeart rate ratioAdverse cardiac outcomesHigher pulse pressureAutonomic neuropathyType 2 diabetesCardiac outcomesNon-Black ethnicityHeart rate variabilityInsulin useAsymptomatic individualsPulse pressureCardiac diseaseHeart rateRate ratioGreater systolic blood pressure decreasePower spectral analysisSystolic blood pressure decreaseRate variabilityAsymptomatic Diabetics (DIAD) studyAsymptomatic type 2Composite clinical outcomeHigher glycated hemoglobinPoor cardiac outcomesPoor cardiovascular outcomes
2012
The heart rate response to adenosine: A simple predictor of adverse cardiac outcomes in asymptomatic patients with type 2 diabetes
Hage FG, Wackers FJ, Bansal S, Chyun DA, Young LH, Inzucchi SE, Iskandrian AE. The heart rate response to adenosine: A simple predictor of adverse cardiac outcomes in asymptomatic patients with type 2 diabetes. International Journal Of Cardiology 2012, 167: 2952-2957. PMID: 22981277, PMCID: PMC3723723, DOI: 10.1016/j.ijcard.2012.08.011.Peer-Reviewed Original ResearchConceptsAbnormal myocardial perfusion imagingMyocardial perfusion imagingHeart rate responseCardiac eventsMPI abnormalitiesAsymptomatic patientsAdenosine myocardial perfusion imagingHard cardiac event rateCardiovascular risk factor managementCox proportional regression modelType 2 diabetes mellitusAsymptomatic Diabetics (DIAD) studyCardiac event rateNonfatal myocardial infarctionCardiac autonomic neuropathyRate responseRisk factor managementYears of followAdverse cardiac outcomesProportional regression modelHigh cardiac riskType 2 diabetesDetection of ischemiaAbnormal HRRAutonomic neuropathyGender-based divergence of cardiovascular outcomes in asymptomatic patients with type 2 diabetes: Results from the DIAD study
Tandon S, Wackers F, Inzucchi SE, Bansal S, Staib LH, Chyun DA, Davey JA, Young LH. Gender-based divergence of cardiovascular outcomes in asymptomatic patients with type 2 diabetes: Results from the DIAD study. Diabetes And Vascular Disease Research 2012, 9: 124-130. PMID: 22228772, DOI: 10.1177/1479164111431470.Peer-Reviewed Original ResearchMeSH KeywordsAgedAsymptomatic DiseasesCanadaCardiovascular DiseasesDiabetes ComplicationsDiabetes Mellitus, Type 2FemaleHumansIncidenceKaplan-Meier EstimateMaleMass ScreeningMiddle AgedMyocardial Perfusion ImagingPredictive Value of TestsPrognosisProspective StudiesRisk AssessmentRisk FactorsSex FactorsTime FactorsUnited StatesConceptsType 2 diabetesMyocardial perfusion imagingCardiovascular outcomesStress myocardial perfusion imagingAsymptomatic Diabetics (DIAD) studyBetter cardiac outcomesHigh-risk womenCoronary artery diseaseHigh-risk menDetection of ischemiaMPI abnormalitiesAsymptomatic patientsAsymptomatic menCardiac eventsCardiac outcomesArtery diseaseAsymptomatic womenAbnormal screeningDiabetic studyPerfusion imagingDIAD studyWomenMenDiabetesOutcomes
2011
SCREENING ASYMPTOMATIC PATIENTS WITH TYPE 2 DIABETES FOR SILENT MYOCARDIAL ISCHEMIA: IMPORTANT GENDER DIFFERENCES FROM THE DETECTION OF ISCHEMIA IN ASYMPTOMATIC DIABETICS (DIAD) STUDY
Tandon S, Bansal S, Inzucchi S, Staib L, Davey J, Chyun D, Young L, Wackers F. SCREENING ASYMPTOMATIC PATIENTS WITH TYPE 2 DIABETES FOR SILENT MYOCARDIAL ISCHEMIA: IMPORTANT GENDER DIFFERENCES FROM THE DETECTION OF ISCHEMIA IN ASYMPTOMATIC DIABETICS (DIAD) STUDY. Journal Of The American College Of Cardiology 2011, 57: e745. DOI: 10.1016/s0735-1097(11)60745-6.Peer-Reviewed Original Research
2009
Cardiac Outcomes After Screening for Asymptomatic Coronary Artery Disease in Patients With Type 2 Diabetes : The DIAD Study: A Randomized Controlled Trial
Young LH, Wackers FJ, Chyun DA, Davey JA, Barrett EJ, Taillefer R, Heller GV, Iskandrian AE, Wittlin SD, Filipchuk N, Ratner RE, Inzucchi SE, Investigators F. Cardiac Outcomes After Screening for Asymptomatic Coronary Artery Disease in Patients With Type 2 Diabetes : The DIAD Study: A Randomized Controlled Trial. JAMA 2009, 301: 1547-1555. PMID: 19366774, PMCID: PMC2895332, DOI: 10.1001/jama.2009.476.Peer-Reviewed Original ResearchConceptsCoronary artery diseaseType 2 diabetesNonfatal myocardial infarctionAsymptomatic coronary artery diseaseMyocardial perfusion imagingCardiac event rateMyocardial infarctionCardiac deathMPI defectsCardiac outcomesEvent ratesScreened groupArtery diseaseSymptoms of CADRadionuclide myocardial perfusion imagingAsymptomatic Diabetics (DIAD) studyHigh cardiac riskLow event ratesPositive predictive valueDetection of ischemiaPrimary medical preventionCoronary revascularizationDiabetes clinicIdentifies patientsControlled TrialsAMP‐activated protein kinase: a core signalling pathway in the heart
Kim AS, Miller EJ, Young LH. AMP‐activated protein kinase: a core signalling pathway in the heart. Acta Physiologica 2009, 196: 37-53. PMID: 19239414, DOI: 10.1111/j.1748-1716.2009.01978.x.BooksConceptsProtein kinaseEssential cellular processesTumor suppressor LKB1Downstream AMPK targetsProduction of ATPProtein phosphataseAMPK targetsActivated AMPKIntracellular glycogen accumulationCellular processesUpstream kinaseFatty acid metabolismCardiac myocyte hypertrophyAMPK activationAMPK activityImportant intracellularMolecular mechanismsMajor regulatorAMPKProtein synthesisKinaseAcid metabolismOral hypoglycaemic drugsGlycogen accumulationType 2 diabetes
2007
Screening for Coronary Artery Disease in Patients With Diabetes
Bax JJ, Young LH, Frye RL, Bonow RO, Steinberg HO, Barrett EJ. Screening for Coronary Artery Disease in Patients With Diabetes. Diabetes Care 2007, 30: 2729-2736. PMID: 17901530, DOI: 10.2337/dc07-9927.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsCoronary artery diseaseArtery diseaseCardiovascular diseaseHigh-risk coronary artery diseaseStable coronary artery diseaseCoronary artery calcium scoringAdditive survival benefitIntensive medical managementRecognition of diabetesCVD risk reductionPercutaneous coronary revascularizationStrong clinical suspicionAmerican Diabetes AssociationType 2 diabetesClinical trial resultsCost of diabetesAsymptomatic patientsAtherosclerotic burdenCoronary revascularizationCardiac eventsClinical suspicionCoronary atherosclerosisDiabetic populationSurvival benefitAsymptomatic atherosclerosisResolution of Asymptomatic Myocardial Ischemia in Patients With Type 2 Diabetes in the Detection of Ischemia in Asymptomatic Diabetics (DIAD) Study
Wackers FJ, Chyun DA, Young LH, Heller GV, Iskandrian AE, Davey JA, Barrett EJ, Taillefer R, Wittlin SD, Filipchuk N, Ratner RE, Inzucchi SE. Resolution of Asymptomatic Myocardial Ischemia in Patients With Type 2 Diabetes in the Detection of Ischemia in Asymptomatic Diabetics (DIAD) Study. Diabetes Care 2007, 30: 2892-2898. PMID: 17682123, DOI: 10.2337/dc07-1250.Peer-Reviewed Original ResearchConceptsResolution of ischemiaType 2 diabetesDetection of ischemiaNew ischemiaAsymptomatic Diabetics (DIAD) studyCardiovascular risk factorsAsymptomatic myocardial ischemiaAdenosine stress myocardial perfusionRepeat stressIschemia increasesAsymptomatic patientsCardiac eventsMore patientsACE inhibitorsMyocardial ischemiaRisk factorsIntensive treatmentDiabetic studyIschemiaMyocardial perfusionPatientsMedical treatmentDiabetesInitial evaluationGreater increase
2005
Evaluating the Cardiovascular Effects of the Thiazolidinediones and Their Place in the Management of Type 2 Diabetes in Relation to the Metabolic Syndrome
Drexler AJ, Nesto RW, Abrahamson MJ, Bakris G, Bell D, Brunzell J, Dandona P, Davidson J, Fonseca V, Fowler M, Frye R, Giles T, Haffner S, Hollenberg N, Hsueh W, Law R, Plutzky J, Ratner R, Reusch J, Selwyn A, Sowers J, Wyne K, Young LH. Evaluating the Cardiovascular Effects of the Thiazolidinediones and Their Place in the Management of Type 2 Diabetes in Relation to the Metabolic Syndrome. Metabolic Syndrome And Related Disorders 2005, 3: 147-173. PMID: 18370723, DOI: 10.1089/met.2005.3.147.Peer-Reviewed Original ResearchType 2 diabetesMetabolic syndromeBeta-cell functionCardiovascular effectsEndothelial dysfunctionVascular reactivityInsulin sensitivityFuture cardiovascular eventsAdverse clinical eventsCoronary artery diseasePositive cardiovascular effectsCardiovascular disease burdenPotential adverse eventsProgression of diabetesInsulin-sensitizing effectsCardiovascular eventsCardiovascular outcomesAdverse eventsCardiovascular riskArtery diseaseGlycemic controlClinical eventsInsulin resistanceDisease burdenRisk factorsAMPK – A pivotal rheostat in the control of cardiac metabolism
Miller E, Russell R, Li J, Young L. AMPK – A pivotal rheostat in the control of cardiac metabolism. Drug Discovery Today Disease Mechanisms 2005, 2: 93-100. DOI: 10.1016/j.ddmec.2005.05.008.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsMyocardial stress responseRegulation of AMPKProtein kinaseCentral regulatorStress responseAMPKNon-metabolic actionsCoronary artery diseaseNovel cardioprotective strategiesType 2 diabetesPotential novel approachArtery diseaseCardioprotective strategiesCardiac metabolismMetabolic actionsPossible roleKinaseRheostatRegulatorRegulationMetabolismDiabetesDiseaseHeart Failure and Cardiac Dysfunction in Diabetes
Young L, Russell R, Chyun D. Heart Failure and Cardiac Dysfunction in Diabetes. Contemporary Cardiology 2005, 555-578. DOI: 10.1385/1-59259-908-7:555.Peer-Reviewed Original ResearchType 2 diabetesHeart failureHigh cardiovascular morbidityPresence of diabetesOral hypoglycemic agentsAge-adjusted riskImpact of diabetesFramingham Heart StudyNondiabetic patientsCardiovascular morbidityNondiabetic menPatient yearsOlder patientsSuch patientsCardiac dysfunctionHypoglycemic agentsHeart StudyClinical problemPatientsDiabetesType 1IncidenceRiskFailureMorbidity
2004
Detection of Silent Myocardial Ischemia in Asymptomatic Diabetic Subjects
Wackers FJ, Young LH, Inzucchi SE, Chyun DA, Davey JA, Barrett EJ, Taillefer R, Wittlin SD, Heller GV, Filipchuk N, Engel S, Ratner RE, Iskandrian AE. Detection of Silent Myocardial Ischemia in Asymptomatic Diabetic Subjects. Diabetes Care 2004, 27: 1954-1961. PMID: 15277423, DOI: 10.2337/diacare.27.8.1954.Peer-Reviewed Original ResearchConceptsSilent myocardial ischemiaType 2 diabetesCardiac risk factorsMyocardial ischemiaAsymptomatic patientsSilent ischemiaNormal perfusionRisk factorsTraditional cardiac risk factorsAmerican Diabetes Association guidelinesTomography myocardial perfusion imagingRegional myocardial perfusion abnormalitiesAbnormal stress testAsymptomatic diabetic subjectsAsymptomatic Diabetics (DIAD) studyCurrent American Diabetes AssociationPrevalence of ischemiaCardiac autonomic dysfunctionLarge perfusion defectsST-segment depressionCoronary artery diseaseAmerican Diabetes AssociationMyocardial perfusion abnormalitiesMyocardial perfusion imagingStrongest predictor
2001
Effect of 5-Aminoimidazole-4-Carboxamide-1-β-d-Ribofuranoside Infusion on In Vivo Glucose and Lipid Metabolism in Lean and Obese Zucker Rats
Bergeron R, Previs S, Cline G, Perret P, Russell III R, Young L, Shulman G. Effect of 5-Aminoimidazole-4-Carboxamide-1-β-d-Ribofuranoside Infusion on In Vivo Glucose and Lipid Metabolism in Lean and Obese Zucker Rats. Diabetes 2001, 50: 1076-1082. PMID: 11334411, DOI: 10.2337/diabetes.50.5.1076.Peer-Reviewed Original ResearchMeSH KeywordsAdenylate KinaseAminoimidazole CarboxamideAnimalsBlood GlucoseBody WeightFatty Acids, NonesterifiedGlucoseGlycerolInfusions, IntravenousInjections, IntravenousInsulinInsulin ResistanceLactatesMaleModels, AnimalMuscle, SkeletalObesityRatsRats, ZuckerReference ValuesRibonucleotidesTriglyceridesConceptsWhole-body glucose disposalInsulin-resistant rat modelObese ratsEndogenous glucose productionObese Zucker ratsRed gastrocnemius muscleInsulin infusion rateLean ratsGlucose disposalInsulin infusionRat modelInfusion rateGastrocnemius muscleZucker ratsLipid metabolismGlucose productionEndogenous glucose production rateGlucose transport activitySkeletal muscle glucose transport activityType 2 diabetesWhole-body carbohydrateInsulin-stimulated glucose uptakeInsulin-independent pathwaySkeletal muscle AMPKGlucose production rate