2023
A pref-1-controlled non-inflammatory mechanism of insulin resistance
Huang Y, Cui D, Chen L, Tong H, Wu H, Muller G, Qi Y, Wang S, Xu J, Gao X, Fifield K, Wang L, Xia Z, Vanderluit J, Liu S, Leng L, Sun G, McGuire J, Young L, Bucala R, Qi D. A pref-1-controlled non-inflammatory mechanism of insulin resistance. IScience 2023, 26: 106923. PMID: 37283810, PMCID: PMC10239698, DOI: 10.1016/j.isci.2023.106923.Peer-Reviewed Original ResearchInsulin resistanceMIF secretionPref-1 expressionPref-1Fat-induced insulin resistancePlasma MIF levelsNon-inflammatory mechanismsActivation of PAR2Palmitic acid dietHigh fat-induced insulin resistanceWhite adipose tissueSubsequent insulin resistanceMIF levelsPAR2 expressionM2 macrophagesAcid dietAdipose tissueAMPK-dependent mannerEndothelial cellsSecretionIntegrin β1CellsExpressionHigh levelsInflammation
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 strokeAchievement of Guideline-Recommended Weight Loss Among Patients With Ischemic Stroke and Obesity
Dearborn JL, Viscoli CM, Young LH, Gorman MJ, Furie KL, Kernan WN. Achievement of Guideline-Recommended Weight Loss Among Patients With Ischemic Stroke and Obesity. Stroke 2019, 50: 713-717. PMID: 30786849, PMCID: PMC6391736, DOI: 10.1161/strokeaha.118.024008.Peer-Reviewed Original ResearchConceptsTransient ischemic attackBody mass indexProportion of patientsIschemic strokeMass indexVascular eventsBaseline weightWeight lossAchievement of guidelineDays of randomizationRecent ischemic strokeAcute ischemic strokeFuture vascular eventsIschemic attackPlacebo groupObese patientsDiabetes mellitusMedian ageTrial entryIRIS trialMedian timeFunctional outcomeInsulin resistanceClinical trialsPatients
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 patientsMacrophage migration inhibitory factor mediates metabolic dysfunction induced by atypical antipsychotic therapy
Cui D, Peng Y, Zhang C, Li Z, Su Y, Qi Y, Xing M, Li J, Kim GE, Su KN, Xu J, Wang M, Ding W, Piecychna M, Leng L, Hirasawa M, Jiang K, Young L, Xu Y, Qi D, Bucala R. Macrophage migration inhibitory factor mediates metabolic dysfunction induced by atypical antipsychotic therapy. Journal Of Clinical Investigation 2018, 128: 4997-5007. PMID: 30295645, PMCID: PMC6205380, DOI: 10.1172/jci93090.Peer-Reviewed Original ResearchConceptsMacrophage migration inhibitory factorAtypical antipsychotic therapyMIF expressionMigration inhibitory factorInsulin resistanceAntipsychotic therapyAtypical antipsychoticsMetabolic dysfunctionOlanzapine-induced insulin resistanceInhibitory factorDrug-naive schizophrenic patientsMetabolic side effectsPlasma lipid concentrationsAbnormal fat depositionAdverse metabolic sequelaeMIF concentrationsOlanzapine monotherapyMetabolic sequelaeOlanzapine administrationIntracerebroventricular injectionMIF antibodyFood intakeClinical utilitySchizophrenic patientsSide effectsHeart Failure After Ischemic Stroke or Transient Ischemic Attack in Insulin-Resistant Patients Without Diabetes Mellitus Treated With Pioglitazone
Young LH, Viscoli CM, Schwartz GG, Inzucchi SE, Curtis JP, Gorman MJ, Furie KL, Conwit R, Spatz E, Lovejoy A, Abbott JD, Jacoby DL, Kolansky DM, Ling FS, Pfau SE, Kernan WN. Heart Failure After Ischemic Stroke or Transient Ischemic Attack in Insulin-Resistant Patients Without Diabetes Mellitus Treated With Pioglitazone. Circulation 2018, 138: 1210-1220. PMID: 29934374, PMCID: PMC6202153, DOI: 10.1161/circulationaha.118.034763.Peer-Reviewed Original ResearchConceptsRisk of HFTransient ischemic attackEffect of pioglitazoneHF riskHeart failureInsulin-resistant patientsMyocardial infarctionIschemic attackCardiovascular benefitsIschemic strokeDiabetes mellitusInsulin resistanceHigher C-reactive proteinComposite of strokeHF risk scoreHigher HF riskDrug dose reductionHospitalized heart failureIncident myocardial infarctionLower mean doseC-reactive proteinBaseline patient featuresHF hospitalizationCardiovascular eventsPlacebo groupWhat Mediated Pioglitazone's Cardiovascular (CV) Benefit in the IRIS Trial?
INZUCCHI S, VISCOLI C, YOUNG L, GORMAN M, CONWIT R, SCHWARTZ G, KERNAN W. What Mediated Pioglitazone's Cardiovascular (CV) Benefit in the IRIS Trial? Diabetes 2018, 67 DOI: 10.2337/db18-17-lb.Peer-Reviewed Original ResearchTransient ischemic attackDensity lipoprotein cholesterolInsulin resistanceCV benefitsLog HRCardiovascular benefitsLipoprotein cholesterolBlood pressureStroke/transient ischemic attackHigh-sensitivity C-reactive proteinHigh-density lipoprotein cholesterolLow-density lipoprotein cholesterolMeasures of IRInsulin Resistance InterventionHomeostatic model assessmentDiastolic blood pressureEffect of pioglitazoneSystolic blood pressureC-reactive proteinFavorable effectBoehringer Ingelheim PharmaceuticalsPIO effectIschemic attackNondiabetic patientsHOMA-IR
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 Prevents Stroke in Patients With a Recent Transient Ischemic Attack or Ischemic Stroke
Yaghi S, Furie KL, Viscoli CM, Kamel H, Gorman M, Dearborn J, Young LH, Inzucchi SE, Lovejoy AM, Kasner SE, Conwit R, Kernan WN. Pioglitazone Prevents Stroke in Patients With a Recent Transient Ischemic Attack or Ischemic Stroke. Circulation 2017, 137: 455-463. PMID: 29084736, DOI: 10.1161/circulationaha.117.030458.Peer-Reviewed Original ResearchConceptsTransient ischemic attackIschemic strokeIschemic attackNondiabetic patientsStroke outcomeStroke eventsInsulin resistanceRecent transient ischemic attackCox proportional hazards modelQualifying ischemic strokeEffect of pioglitazoneFirst stroke eventProportional hazards modelPrevents strokeHemorrhagic eventsComposite outcomeSecondary preventionRecent strokeIRIS trialMyocardial infarctionTreatment groupsHazards modelPioglitazoneConsensus criteriaSurvival analysisEffects of pioglitazone on cognitive function in patients with a recent ischaemic stroke or TIA: a report from the IRIS trial
Furie KL, Viscoli CM, Gorman M, Ford GA, Young LH, Inzucchi SE, Guarino PD, Lovejoy AM, Conwit R, Tanne D, Kernan WN. Effects of pioglitazone on cognitive function in patients with a recent ischaemic stroke or TIA: a report from the IRIS trial. Journal Of Neurology Neurosurgery & Psychiatry 2017, 89: 21. PMID: 28939682, DOI: 10.1136/jnnp-2017-316361.Peer-Reviewed Original ResearchConceptsTransient ischemic attackRecent ischemic strokeIschemic strokeCognitive functionHomeostasis model assessment insulin resistance scoreModified Mini-Mental State Examination scoresAssessment-insulin resistance scoreMini-Mental State Examination scoreInsulin Resistance InterventionPoststroke cognitive functionVascular risk factorsEffect of pioglitazoneInsulin-resistant patientsState Examination scoreIschemic attackPioglitazone groupPlacebo groupIRIS trialStroke trialsCerebrovascular diseaseInsulin resistanceRisk factorsCognitive dysfunctionPatientsResistance InterventionPioglitazone 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 riskResponse to Comment on Inzucchi et al. Pioglitazone Prevents Diabetes in Patients With Insulin Resistance and Cerebrovascular Disease. Diabetes Care 2016;39:1684–1692
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. Response to Comment on Inzucchi et al. Pioglitazone Prevents Diabetes in Patients With Insulin Resistance and Cerebrovascular Disease. Diabetes Care 2016;39:1684–1692. Diabetes Care 2017, 40: e47-e48. PMID: 28325804, PMCID: PMC5360290, DOI: 10.2337/dci16-0048.Peer-Reviewed Case Reports and Technical NotesCardiac Outcomes After Ischemic Stroke or Transient Ischemic Attack
Young LH, Viscoli CM, Curtis JP, Inzucchi SE, Schwartz GG, Lovejoy AM, Furie KL, Gorman MJ, Conwit R, Abbott JD, Jacoby DL, Kolansky DM, Pfau SE, Ling FS, Kernan WN. Cardiac Outcomes After Ischemic Stroke or Transient Ischemic Attack. Circulation 2017, 135: 1882-1893. PMID: 28246237, PMCID: PMC5511545, DOI: 10.1161/circulationaha.116.024863.Peer-Reviewed Original ResearchConceptsAcute coronary syndromeType 1 myocardial infarctionTransient ischemic attackMyocardial infarctionCoronary syndromeInsulin resistanceIschemic attackIschemic strokeDiabetes mellitusSerum troponinAcute coronary syndrome episodeMean age 63 yearsAcute coronary syndrome eventIndependent clinical events committeeType 2 myocardial infarctionIRIS participantsImpact of pioglitazoneRecent cerebrovascular eventsRecent ischemic strokeClinical events committeeAge 63 yearsEffect of pioglitazoneSmall myocardial infarctionCoronary artery diseaseST-segment elevation
2016
Pioglitazone 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
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
2007
Aging-Associated Reductions in AMP-Activated Protein Kinase Activity and Mitochondrial Biogenesis
Reznick RM, Zong H, Li J, Morino K, Moore IK, Yu HJ, Liu ZX, Dong J, Mustard KJ, Hawley SA, Befroy D, Pypaert M, Hardie DG, Young LH, Shulman GI. Aging-Associated Reductions in AMP-Activated Protein Kinase Activity and Mitochondrial Biogenesis. Cell Metabolism 2007, 5: 151-156. PMID: 17276357, PMCID: PMC1885964, DOI: 10.1016/j.cmet.2007.01.008.Peer-Reviewed Original ResearchConceptsIntracellular lipid metabolismMitochondrial biogenesisAMPK activityMitochondrial functionProtein kinase activityLipid metabolismProtein kinaseKinase activityAge-associated reductionBiogenesisOld ratsAMPKSkeletal muscleRecent studiesInsulin resistanceChronic activationMetabolismAcute stimulationFat oxidationImportant roleAcid feedingKinaseRatsActivityRegulation
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 factors
2003
Insulin resistance and the effects of thiazolidinediones on cardiac metabolism
Young LH. Insulin resistance and the effects of thiazolidinediones on cardiac metabolism. The American Journal Of Medicine 2003, 115: 75-80. PMID: 14678870, DOI: 10.1016/j.amjmed.2003.09.013.BooksConceptsMyocardial metabolismFree fatty acidsAdministration of thiazolidinedionesImproved glucose metabolismEffects of thiazolidinedionesInsulin-sensitizing effectsRecovery of functionCardiac contractile activityPotential beneficial effectsPostischemic periodDiabetes mellitusMyocardial injuryFFA metabolismInsulin resistanceFatty acid concentrationsContractile activityGlucose metabolismAnimal studiesCardiac metabolismPharmacologic manipulationThiazolidinedionesBeneficial effectsSkeletal muscleHigh rateMetabolism