2024
SGLT2 inhibition alters substrate utilization and mitochondrial redox in healthy and failing rat hearts
Goedeke L, Ma Y, Gaspar R, Nasiri A, Lee J, Zhang D, Galsgaard K, Hu X, Zhang J, Guerrera N, Li X, LaMoia T, Hubbard B, Haedersdal S, Wu X, Stack J, Dufour S, Butrico G, Kahn M, Perry R, Cline G, Young L, Shulman G. SGLT2 inhibition alters substrate utilization and mitochondrial redox in healthy and failing rat hearts. Journal Of Clinical Investigation 2024, 134: e176708. PMID: 39680452, PMCID: PMC11645152, DOI: 10.1172/jci176708.Peer-Reviewed Original ResearchConceptsSodium-glucose cotransporter type 2Heart failureKetone oxidationGas chromatography-mass spectrometryFatty acid oxidationLeft ventricular ejection fractionReduced myocardial oxidative stressVentricular ejection fractionKetone supplementationWeeks of treatmentMyocardial oxidative stressDecreased pyruvate oxidationInduce heart failurePlasma glucose levelsIn vivo effectsSGLT2i treatmentEjection fractionAssociated with improvementsAwake ratsSGLT2 inhibitionCardioprotective benefitsLiquid chromatography-tandem mass spectrometryPlasma ketonesRates of ketonizationChromatography-tandem mass spectrometry
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