2022
Efficacy of lower doses of pioglitazone after stroke or transient ischaemic attack in patients with insulin resistance
Spence JD, Viscoli C, Kernan WN, Young LH, Furie K, DeFronzo R, Abdul‐Ghani M, Dandona P, Inzucchi SE. Efficacy of lower doses of pioglitazone after stroke or transient ischaemic attack in patients with insulin resistance. Diabetes Obesity And Metabolism 2022, 24: 1150-1158. PMID: 35253334, DOI: 10.1111/dom.14687.Peer-Reviewed Original ResearchConceptsNew-onset diabetesAdjusted hazard ratioHazard ratioLow dosesAdverse effectsInsulin Resistance InterventionTransient ischemic attackSecondary prevention strategiesAnti-atherosclerotic propertiesInsulin-sensitizing drugsLess adverse effectsIschemic attackStudy drugHeart failureStroke trialsAdverse outcomesInsulin resistancePioglitazonePrevention strategiesHigh dosesResistance InterventionFull doseWeight gainDiabetesPatients
2019
Pioglitazone Therapy in Patients With Stroke and Prediabetes
Spence JD, Viscoli CM, Inzucchi SE, Dearborn-Tomazos J, Ford GA, Gorman M, Furie KL, Lovejoy AM, Young LH, Kernan WN. Pioglitazone Therapy in Patients With Stroke and Prediabetes. JAMA Neurology 2019, 76: 526-535. PMID: 30734043, PMCID: PMC6515584, DOI: 10.1001/jamaneurol.2019.0079.Peer-Reviewed Original ResearchMeSH KeywordsAcute Coronary SyndromeAgedDiabetes Mellitus, Type 2Disease ProgressionFemaleGlycated HemoglobinHeart FailureHospitalizationHumansHypoglycemic AgentsInsulin ResistanceMaleMedication AdherenceMiddle AgedMyocardial InfarctionPioglitazonePrediabetic StateProportional Hazards ModelsRecurrenceSecondary PreventionStrokeConceptsAcute coronary syndromeStroke/myocardial infarctionTransient ischemic attackMyocardial infarctionCoronary syndromeHeart failureIRIS trialInsulin resistanceGood adherenceIschemic attackRecurrent strokeHazard ratioClinical trialsStroke/transient ischemic attackRandomized multicenter clinical trialAmerican Diabetes Association criteriaInsulin Resistance InterventionHemoglobin A1c levelsEffect of pioglitazoneInsulin-sensitizing agentsMulticenter clinical trialPlasma glucose levelsSerious bone fracturesPlacebo cohortPrior stroke
2018
Metabolic syndrome identifies normal weight insulin-resistant stroke patients at risk for recurrent vascular disease
Dearborn JL, Viscoli CM, Inzucchi SE, Young LH, Kernan WN. Metabolic syndrome identifies normal weight insulin-resistant stroke patients at risk for recurrent vascular disease. International Journal Of Stroke 2018, 14: 639-645. PMID: 30507360, DOI: 10.1177/1747493018816425.Peer-Reviewed Original ResearchConceptsNormal weight patientsMetabolic syndromeMyocardial infarctionWeight patientsCause mortalityInsulin resistanceHigh riskInsulin Resistance InterventionRecent ischemic strokeRecurrent vascular diseaseNon-diabetic patientsTransient ischemic attackAdverse cardiovascular outcomesMajor comorbid conditionsIschemic attackCardiovascular outcomesObesity paradoxIschemic strokeNormal BMIObese patientsStroke populationBetter prognosisComorbid conditionsNormal weightStroke patients
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 preventionSmoking cessation and outcome after ischemic stroke or TIA
Epstein KA, Viscoli CM, Spence JD, Young LH, Inzucchi SE, Gorman M, Gerstenhaber B, Guarino PD, Dixit A, Furie KL, Kernan WN, Bladin C, Davis S, Wijeratne T, Levi C, Parsons M, Brodtmann A, Ng S, Archer J, Delcourt C, Winder T, Berger L, Boulanger J, Chan R, Spence J, Durocher A, Mackey A, Verreault S, Minuk J, Penn A, Shuaib A, Cote R, Selchen D, Bayer N, Sweet M, Malik S, Stotts G, Griewing B, Soda H, Weinhardt R, Berrouschot J, Stoll A, Witte O, Günther A, Bodechtel U, Schminke U, Hobohm C, Hetzel A, Lambeck J, Wartenberg K, Huttner H, Dittrich R, Nabavi D, Gröschel K, Thomalla G, Rosenkranz M, Jander S, Meisel A, Ludolph A, Althaus K, Huber R, Lorenz M, Tanne D, Merzlyak O, Bornstein N, Telman G, Lampl Y, Streifler J, Weller B, Ifergane G, Wirgin Y, Carolei A, Toni D, Stanzione P, Micieli G, Agnelli G, Caso V, Gandolfo C, Comi G, Consoli D, Rasura M, Di Lazzaro V, Dixit A, Jupp B, Shaw L, Salih I, Esisi B, Power M, Strain W, Elyas S, Manawadu D, Kalra L, O'Brien E, Warburton E, Chatterjee K, Hargroves D, Blight A, Moynihan B, Markus H, Macleod M, Broughton D, Rodgers H, Hlaing T, Muir S, Sajid M, Bath P, Price C, Sekaran L, Vahidassr D, Muir K, McIlmoyle J, Datta P, Davey R, Langhorne P, Stott D, Datta P, England T, Muhidden K, O'Connell J, Majmudar N, Schindler J, Clark W, Sethi P, Rordorf G, Kleindorfer D, Silliman S, Gorman M, Kelly M, Singleton L, Meyer B, Jackson C, Walker J, Ehtisham A, Goodpasture H, Wang D, Fayad P, Cordina S, Naritoku D, Chiu D, Lukovits T, Goddeau R, Clark‐Arbogast R, Leigh R, Wityk R, Pettigrew L, Tayal A, Jarouse J, Friday G, Sen S, Kim A, Johnston S, Elkins J, Barrett A, Leira E, Kelly A, Burgin S, Rempe D, Jacoby M, Hughes D, Majersik J, Skalabrin E, Lee J, Hsu C, Sundararajan S, Slivka A, Minagar A, Alicic R, Geraghty M, Kase C, Lansberg M, Albers G, Dietrich D, Hanna J, Gentile N, Santiago F, Katzan I, Ching M, Sawyer, Warwick T, Yilmaz E, Pedelty L, Schneck M, Coull B, Solenski N, Johnston K, Lee V, Prabhakaran S, Johnson M, Silverman I, Salgado M, Birkhahn R, Strawsburg R, Altafullah I, Cohen D, Zweifler R, Lee Kwen P, Hammer M, Vora N, Tietjen G, Albakri E, Dandapani B, Jickling G, Verro P, Roller M, Hughes R, Simpson J, Vidic T, Lash S, Sigsbee B, Rosenbaum D, Fonzetti P, Fleck J, Goldszmidt A, Alexandrov A, Halsey J, Hart R, Sattin J, Kumar S, Book D, Torbey M, Poock J, King M, Graham G, Sung G, Mirsen T, Dromerick A, Runheim A, Jackson C, Feen E, Reichwein R, Waters M, Amory C, Bernardini G, Bell R, Diamond B, Rosenbaum D, Palestrant D, Segal A, Burger K, Schwartz R, Mitsias P, Kramer J, Kramer J, Robbins D, Silver B, Easton J, Feldmann E, Rymer M, Dorssom J, Ali L, Ovbiagele B, Kirshner H. Smoking cessation and outcome after ischemic stroke or TIA. Neurology 2017, 89: 1723-1729. PMID: 28887378, PMCID: PMC5644463, DOI: 10.1212/wnl.0000000000004524.Peer-Reviewed Original ResearchMeSH KeywordsAgedCohort StudiesFemaleHumansIschemic Attack, TransientMaleMiddle AgedMyocardial InfarctionProportional Hazards ModelsSmokingSmoking CessationStrokeConceptsMyocardial infarctionIschemic strokeIndex eventProspective observational cohort studyInsulin Resistance InterventionHistory of hypertensionObservational cohort studyDiastolic blood pressureHistory of strokeCoronary artery diseaseTime of randomizationTobacco use historySignificant health benefitsRecurrent strokeNondiabetic menCohort studyCurrent smokersTrial cohortArtery diseaseBlood pressurePrimary outcomeIRIS trialStroke trialsCigarette smokingSmoking cessationMIF family cytokines in cardiovascular diseases and prospects for precision-based therapeutics
Tilstam PV, Qi D, Leng L, Young L, Bucala R. MIF family cytokines in cardiovascular diseases and prospects for precision-based therapeutics. Expert Opinion On Therapeutic Targets 2017, 21: 671-683. PMID: 28562118, PMCID: PMC6130320, DOI: 10.1080/14728222.2017.1336227.BooksConceptsMacrophage migration inhibitory factorMIF family membersCardiovascular diseaseFamily cytokinesTherapeutic opportunitiesIschemia-reperfusion injuryChemokine-like functionsMigration inhibitory factorNovel therapeutic opportunitiesPro-survival mediatorsFamily membersInflammatory pathogenesisMyocardial infarctionMyocardial ischemiaClinical studiesPleiotropic cytokineImmune systemInhibitory factorReceptor pathwayCytokinesDiseaseMIF-2Active investigationMIF familyClinical translation
2016
Pioglitazone after Ischemic Stroke or Transient Ischemic Attack.
Viscoli C, Kernan W, Young L. Pioglitazone after Ischemic Stroke or Transient Ischemic Attack. New England Journal Of Medicine 2016, 375: 704. PMID: 27532845, DOI: 10.1056/nejmc1605904.Peer-Reviewed Original ResearchPioglitazone Prevents Diabetes in Patients With Insulin Resistance and Cerebrovascular Disease.
Inzucchi SE, Viscoli CM, Young LH, Furie KL, Gorman M, Lovejoy AM, Dagogo-Jack S, Ismail-Beigi F, Korytkowski MT, Pratley RE, Schwartz GG, Kernan WN. Pioglitazone Prevents Diabetes in Patients With Insulin Resistance and Cerebrovascular Disease. Diabetes Care 2016, 39: 1684-92. PMID: 27465265, PMCID: PMC5033078, DOI: 10.2337/dc16-0798.Peer-Reviewed Original ResearchConceptsTransient ischemic attackRecent ischemic strokeInsulin resistanceIschemic strokeHOMA-IRInsulin Resistance InterventionMajor cardiovascular eventsMean HOMA-IRHistory of diabetesSubsequent ischemic eventsHomeostasis model assessmentRisk of diabetesΜIU/mLFPG testingPioglitazone groupCardiovascular eventsIschemic attackPlacebo groupFirst medicationIschemic eventsMean FPGDiabetes onsetDiabetes preventionCerebrovascular diseaseStroke trialsPioglitazone after Ischemic Stroke or Transient Ischemic Attack
Kernan WN, Viscoli CM, Furie KL, Young LH, Inzucchi SE, Gorman M, Guarino PD, Lovejoy AM, Peduzzi PN, Conwit R, Brass LM, Schwartz GG, Adams HP, Berger L, Carolei A, Clark W, Coull B, Ford GA, Kleindorfer D, O'Leary JR, Parsons MW, Ringleb P, Sen S, Spence JD, Tanne D, Wang D, Winder TR. Pioglitazone after Ischemic Stroke or Transient Ischemic Attack. New England Journal Of Medicine 2016, 374: 1321-1331. PMID: 26886418, PMCID: PMC4887756, DOI: 10.1056/nejmoa1506930.Peer-Reviewed Original ResearchConceptsTransient ischemic attackIschemic strokeInsulin resistanceMyocardial infarctionIschemic attackPrimary outcomeRecent ischemic strokeDouble-blind trialFuture cardiovascular eventsHomeostasis model assessmentInsulin resistance indexRisk of strokeEligible patientsNonfatal strokePioglitazone groupCardiovascular eventsCause mortalityPlacebo groupPreventive therapyCerebrovascular diseaseInsulin sensitivityRisk factorsResistance indexHigh riskLower risk
2015
AMPK is critical for mitochondrial function during reperfusion after myocardial ischemia
Zaha VG, Qi D, Su KN, Palmeri M, Lee HY, Hu X, Wu X, Shulman GI, Rabinovitch PS, Russell RR, Young LH. AMPK is critical for mitochondrial function during reperfusion after myocardial ischemia. Journal Of Molecular And Cellular Cardiology 2015, 91: 104-113. PMID: 26746142, PMCID: PMC4839186, DOI: 10.1016/j.yjmcc.2015.12.032.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisCatalaseGene Expression RegulationHydrogen PeroxideMAP Kinase Kinase 4MiceMice, Inbred C57BLMice, TransgenicMitochondria, HeartMitochondrial Membrane Transport ProteinsMitochondrial Permeability Transition PoreMyocardial InfarctionMyocardial ReperfusionMyocardiumNecrosisProtein Kinase InhibitorsSignal TransductionTransgenesConceptsWild typeProtein kinase kinase 4Mitochondrial functionMitochondrial catalaseKinase-dead AMPKMitochondrial reactive oxygen productionStress-responsive kinaseMPTP openingC-Jun terminal kinaseInhibition of JNKPermeability transition pore openingMitochondrial permeability transition pore openingTransition pore openingAMPK inactivationResponsive kinaseTerminal kinaseCellular metabolismJNK activationMitochondrial integrityReactive oxygen productionTransgenic expressionCell survivalAMPKKinase 4Kinase
2014
Pioglitazone for secondary prevention after ischemic stroke and transient ischemic attack: Rationale and design of the Insulin Resistance Intervention after Stroke Trial
Viscoli CM, Brass LM, Carolei A, Conwit R, Ford GA, Furie KL, Gorman M, Guarino PD, Inzucchi SE, Lovejoy AM, Parsons MW, Peduzzi PN, Ringleb PA, Schwartz GG, Spence JD, Tanne D, Young LH, Kernan WN, investigators I. Pioglitazone for secondary prevention after ischemic stroke and transient ischemic attack: Rationale and design of the Insulin Resistance Intervention after Stroke Trial. American Heart Journal 2014, 168: 823-829.e6. PMID: 25458644, PMCID: PMC4254508, DOI: 10.1016/j.ahj.2014.07.016.Peer-Reviewed Original ResearchMeSH KeywordsAdultCognition DisordersDose-Response Relationship, DrugDouble-Blind MethodFemaleHumansHypoglycemic AgentsInsulin ResistanceIschemic Attack, TransientMaleMiddle AgedMyocardial InfarctionPatient Outcome AssessmentPioglitazoneRisk AssessmentRisk FactorsSecondary PreventionStrokeSurvival AnalysisThiazolidinedionesConceptsTransient ischemic attackMyocardial infarctionIschemic attackVascular eventsIschemic strokeSecondary preventionIRIS trialInsulin resistanceHomeostasis model assessment-insulin resistanceModel assessment-insulin resistanceEffectiveness of pioglitazoneInsulin Resistance InterventionRecent ischemic strokeRecurrent vascular eventsAssessment-insulin resistanceIschemic vascular eventsAcute coronary syndromeInsulin-resistant patientsInsulin-sensitizing drugsEligible patientsIndex strokeNondiabetic patientsCardiovascular outcomesCause mortalityCoronary syndrome
2013
Limiting Cardiac Ischemic Injury by Pharmacological Augmentation of Macrophage Migration Inhibitory Factor–AMP-Activated Protein Kinase Signal Transduction
Wang J, Tong C, Yan X, Yeung E, Gandavadi S, Hare AA, Du X, Chen Y, Xiong H, Ma C, Leng L, Young LH, Jorgensen WL, Li J, Bucala R. Limiting Cardiac Ischemic Injury by Pharmacological Augmentation of Macrophage Migration Inhibitory Factor–AMP-Activated Protein Kinase Signal Transduction. Circulation 2013, 128: 225-236. PMID: 23753877, PMCID: PMC3781594, DOI: 10.1161/circulationaha.112.000862.Peer-Reviewed Original ResearchMeSH KeywordsAMP-Activated Protein KinasesAnimalsAntigens, Differentiation, B-LymphocyteCardiotonic AgentsCells, CulturedGlucoseHistocompatibility Antigens Class IIIntramolecular OxidoreductasesIsoxazolesMacrophage Migration-Inhibitory FactorsMaleMiceMice, Inbred C57BLMice, KnockoutMyocardial InfarctionMyocardial IschemiaMyocytes, CardiacRecombinant ProteinsSignal TransductionConceptsMacrophage migration inhibitory factorCardiac ischemic injuryIschemic injuryProtective effectPostischemic left ventricular functionGlucose uptakeLeft coronary artery occlusionLeft ventricular functionCoronary artery occlusionIschemic tissue injuryMigration inhibitory factorMyocardial glucose uptakeAMPK activationTreatment of cardiomyocytesArtery occlusionMIF receptorVentricular functionIschemic myocardiumCellular glucose uptakeTissue injuryIschemia modelPharmacological augmentationFlow ischemiaSuch agonistsInhibitory factor
2011
A small molecule AMPK activator protects the heart against ischemia–reperfusion injury
Kim AS, Miller EJ, Wright TM, Li J, Qi D, Atsina K, Zaha V, Sakamoto K, Young LH. A small molecule AMPK activator protects the heart against ischemia–reperfusion injury. Journal Of Molecular And Cellular Cardiology 2011, 51: 24-32. PMID: 21402077, PMCID: PMC4005884, DOI: 10.1016/j.yjmcc.2011.03.003.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphateAMP-Activated Protein KinasesAnimalsApoptosisBiphenyl CompoundsCardiotonic AgentsEnzyme ActivatorsHeartIschemic PreconditioningMiceMice, Inbred C57BLMice, TransgenicMyocardial InfarctionMyocardial Reperfusion InjuryNecrosisNitric Oxide Synthase Type IIIPeptide Elongation Factor 2PyronesThiophenesConceptsIschemia-reperfusion injuryLeft ventricular contractile functionMyocardial ischemia-reperfusion injuryMouse heartsEndothelial nitric oxide synthase activationNitric oxide synthase activationLess myocardial necrosisCoronary artery occlusionIschemia-reperfusion damageVentricular contractile functionEukaryotic elongation factor 2Isolated mouse heartsPost-ischemic reperfusionAMPK activatorArtery occlusionIschemic contractureIschemic injuryInfarct sizeMyocardial stunningMyocardial necrosisCardioprotective mechanismsContractile functionSolid organsTherapeutic targetMyocardial apoptosis
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 Trials
2002
Cardiac outcomes after myocardial infarction in elderly patients with diabetes mellitus.
Chyun D, Vaccarino V, Murillo J, Young LH, Krumholz HM. Cardiac outcomes after myocardial infarction in elderly patients with diabetes mellitus. American Journal Of Critical Care 2002, 11: 504-19. PMID: 12425401, DOI: 10.4037/ajcc2002.11.6.504.Peer-Reviewed Original ResearchConceptsRecurrent myocardial infarctionInsulin-treated diabetes mellitusDiabetes mellitusMyocardial infarctionElderly patientsHeart failureVentricular functionComorbid conditionsClinical findingsIndex myocardial infarctionPoor ventricular functionInsulin-treated diabetesAcute myocardial infarctionCardiac outcomesPoor outcomeMedical recordsMellitusInfarctionMedicare beneficiariesPatientsGreater riskInsulinMortalityRiskOutcomesAcute myocardial infarction in the elderly with diabetes
Chyun D, Vaccarino V, Murillo J, Young LH, Krumholz HM. Acute myocardial infarction in the elderly with diabetes. Heart & Lung 2002, 31: 327-339. PMID: 12487011, DOI: 10.1067/mhl.2002.126049.Peer-Reviewed Original ResearchMeSH KeywordsAgedComorbidityDiabetes MellitusFemaleHumansMaleMyocardial InfarctionRetrospective StudiesRisk AssessmentStatistics as TopicSurvival AnalysisTime FactorsConceptsAcute myocardial infarctionDiabetes mellitusMyocardial infarctionHeart failureComorbid conditionsMortality rateNon-Q-wave myocardial infarctionHistory of DMInsulin-treated diabetes mellitusRetrospective medical record reviewHigher body mass indexAcute MI settingPoor functional statusBlood pressure managementMedical record reviewSpecific comorbid conditionsSecondary preventive interventionsBody mass indexShort-term mortalityCooperative Cardiovascular ProjectEntire Medicare populationShort-term riskAggressive lipidDM statusChest pain