2024
Human induced pluripotent stem cell-derived cardiomyocytes to study inflammation-induced aberrant calcium transient
Tatekoshi Y, Chen C, Shapiro J, Chang H, Blancard M, Lyra-Leite D, Burridge P, Feinstein M, D'Aquila R, Hsue P, Ardehali H. Human induced pluripotent stem cell-derived cardiomyocytes to study inflammation-induced aberrant calcium transient. ELife 2024, 13: rp95867. PMID: 39331464, PMCID: PMC11434618, DOI: 10.7554/elife.95867.Peer-Reviewed Original ResearchConceptsHuman induced pluripotent stem cell-derived cardiomyocytesPluripotent stem cell-derived cardiomyocytesStem cell-derived cardiomyocytesCell-derived cardiomyocytesUptake in vitroHIV viremiaDiastolic dysfunctionHIV patientsCardiomyocyte relaxationSarcoplasmic reticulumSGLT2 inhibitorsHeart failurePotential new interventionsInflammatory cytokinesAnimal modelsHFpEFStudy molecular mechanismsMito-TEMPOCardiomyocytesCytokinesHIVPatientsRelaxation defectsPLWHSerumHuman induced pluripotent stem cell-derived cardiomyocytes to study inflammation-induced aberrant calcium transient
Tatekoshi Y, Chen C, Shapiro J, Chang H, Blancard M, Lyra-Leite D, Burridge P, Feinstein M, D'Aquila R, Hsue P, Ardehali H. Human induced pluripotent stem cell-derived cardiomyocytes to study inflammation-induced aberrant calcium transient. ELife 2024, 13 DOI: 10.7554/elife.95867.3.Peer-Reviewed Original ResearchHuman induced pluripotent stem cell-derived cardiomyocytesPluripotent stem cell-derived cardiomyocytesStem cell-derived cardiomyocytesCell-derived cardiomyocytesUptake in vitroCa 2HIV viremiaDiastolic dysfunctionCardiomyocyte relaxationHIV patientsSarcoplasmic reticulumSGLT2 inhibitorsHeart failurePotential new interventionsInflammatory cytokinesAnimal modelsHFpEFStudy molecular mechanismsMito-TEMPOCardiomyocytesHIVCytokinesRelaxation defectsPatientsPLWHA kidney-hypothalamus axis promotes compensatory glucose production in response to glycosuria
Faniyan T, Zhang X, Morgan D, Robles J, Bathina S, Brookes P, Rahmouni K, Perry R, Chhabra K. A kidney-hypothalamus axis promotes compensatory glucose production in response to glycosuria. ELife 2024, 12 DOI: 10.7554/elife.91540.4.Peer-Reviewed Original ResearchGlucose productionEndogenous glucose productionReabsorption of nutrientsLoss of glucoseHypothalamic-pituitary-adrenal axisNormal energy supplyProteomic analysisCompensatory increaseAfferent renal nervesAfferent renal denervationPlasma proteomic analysisDefense mechanismsAcute phase proteinsRenal denervationKO miceSGLT2 inhibitorsKnockout miceRenal nervesAfferent nervesEfficiency of drugsBody's defense mechanismsGlycosuriaGlucosePhase proteinsTreat hyperglycemiaComparative Effectiveness of Glucagon-Like Peptide-1 Receptor Agonists, Sodium-Glucose Cotransporter 2 Inhibitors, Dipeptidyl Peptidase-4 Inhibitors, and Sulfonylureas for Sight-Threatening Diabetic Retinopathy
Barkmeier A, Herrin J, Swarna K, Deng Y, Polley E, Umpierrez G, Galindo R, Ross J, Mickelson M, McCoy R. Comparative Effectiveness of Glucagon-Like Peptide-1 Receptor Agonists, Sodium-Glucose Cotransporter 2 Inhibitors, Dipeptidyl Peptidase-4 Inhibitors, and Sulfonylureas for Sight-Threatening Diabetic Retinopathy. Ophthalmology Retina 2024, 8: 943-952. PMID: 38735641, DOI: 10.1016/j.oret.2024.05.003.Peer-Reviewed Original Research
2023
SGLT2 Inhibitor Use and Risk of Clinical Events in Patients With Cancer Therapy–Related Cardiac Dysfunction
Avula V, Sharma G, Kosiborod M, Vaduganathan M, Neilan T, Lopez T, Dent S, Baldassarre L, Scherrer-Crosbie M, Barac A, Liu J, Deswal A, Khadke S, Yang E, Ky B, Lenihan D, Nohria A, Dani S, Ganatra S. SGLT2 Inhibitor Use and Risk of Clinical Events in Patients With Cancer Therapy–Related Cardiac Dysfunction. JACC Heart Failure 2023, 12: 67-78. PMID: 37897456, DOI: 10.1016/j.jchf.2023.08.026.Peer-Reviewed Original ResearchConceptsCancer therapy-related cardiac dysfunctionSGLT2 inhibitor useGuideline-directed medical therapyHeart failureInhibitor useSGLT2 inhibitorsMedical therapyCardiac dysfunctionAntineoplastic therapyAtrial fibrillation/flutterType 2 diabetes mellitusAcute HF exacerbationCox proportional HRsAcute kidney injuryRenal replacement therapyRetrospective cohort analysisIschemic heart diseaseRisk of cardiomyopathyAggregate patient dataTriNetX Research NetworkProportional HRsCause hospitalizationCause mortalityHF exacerbationKidney injuryCritical Analysis of the Effects of SGLT2 Inhibitors on Renal Tubular Sodium, Water and Chloride Homeostasis and Their Role in Influencing Heart Failure Outcomes
Packer M, Wilcox C, Testani J. Critical Analysis of the Effects of SGLT2 Inhibitors on Renal Tubular Sodium, Water and Chloride Homeostasis and Their Role in Influencing Heart Failure Outcomes. Circulation 2023, 148: 354-372. PMID: 37486998, PMCID: PMC10358443, DOI: 10.1161/circulationaha.123.064346.Peer-Reviewed Original ResearchConceptsSGLT2 inhibitorsProximal renal tubulesRenal tubulesProximal tubular effectHeart failure outcomesHeart failure eventsSodium-hydrogen exchanger 3Renal tubular sodiumProgressive volume lossLong-term treatmentReabsorption of glucoseTreatment-related changesChronic diuresisPharmacological toleranceTubular effectsClinical courseFractional excretionHeart failureTubular sodiumCardioprotective effectsRenal compensationDiuretic effectIndividual patientsDurable improvementDegree of upregulation164-LB: Durable Improvement in HbA1c in Youth-Onset T2D—A Post Hoc Analysis of the DINAMO Trial of Empagliflozin and Linagliptin vs. Placebo
LAFFEL L, DANNE T, TAMBORLANE W, KLINGENSMITH G, NEUBACHER D, TARTAKOVSKY I, MARQUARD J, ZEITLER P, WILLI S. 164-LB: Durable Improvement in HbA1c in Youth-Onset T2D—A Post Hoc Analysis of the DINAMO Trial of Empagliflozin and Linagliptin vs. Placebo. Diabetes 2023, 72 DOI: 10.2337/db23-164-lb.Peer-Reviewed Original ResearchHbA1c <Increasing prevalence of childhood overweightGlycemic controlPrevalence of childhood overweightSafety of empagliflozinLinagliptin 5 mgClinically meaningful responseYouth-onset T2DOnset of complicationsBeta-cell functionPost Hoc AnalysisEmpagliflozin groupClinical courseFPG levelsChildhood overweightSGLT2 inhibitorsEmpagliflozinYouth-onsetPlaceboHbA1c changeMeaningful responseHbA1cHigher HbA1cHoc AnalysisIncreased prevalenceSGLT2 inhibitors and diuretics in heart failure: clicking reset on the renal volume setpoint?
Borlaug B, Testani J. SGLT2 inhibitors and diuretics in heart failure: clicking reset on the renal volume setpoint? European Heart Journal 2023, 44: 2944-2946. PMID: 37220086, DOI: 10.1093/eurheartj/ehad345.Commentaries, Editorials and LettersUpdate on Measuring Ketones
Huang J, Yeung A, Bergenstal R, Castorino K, Cengiz E, Dhatariya K, Niu I, Sherr J, Umpierrez G, Klonoff D. Update on Measuring Ketones. Journal Of Diabetes Science And Technology 2023, 18: 714-726. PMID: 36794812, PMCID: PMC11089855, DOI: 10.1177/19322968231152236.Peer-Reviewed Original ResearchDiabetic ketoacidosisInsulin deficiencyKetone bodiesImmune checkpoint inhibitor therapyRisk of DKACheckpoint inhibitor therapyLow-carbohydrate dietLow carbohydrate availabilityInhibitor therapyInterstitial fluidSGLT2 inhibitorsUrine ketonesInsulin insufficiencyFree fatty acidsBlood ketonesCarbohydrate dietDiabetes treatmentUS FoodDrug AdministrationCare testAlcohol useKetone testEnergy substratesLipolysis increasesKetone concentrationsChapter 13 Sodium-glucose Co-transporter-2 inhibitors: a new era of cardioprotection and renoprotection
Balasubramanian P, Inzucchi S. Chapter 13 Sodium-glucose Co-transporter-2 inhibitors: a new era of cardioprotection and renoprotection. 2023, 337-363. DOI: 10.1016/b978-0-323-99991-5.00006-1.Peer-Reviewed Original ResearchSGLT2 inhibitorsType 2 diabetesSodium-glucose cotransporter 2 inhibitorsGlucose cotransporter 2 inhibitorsLarge cardiovascular outcome trialsInduction of glucosuriaRenal protective benefitsCardiovascular risk factorsGlucose-lowering medicationsCardiovascular outcome trialsCotransporter 2 inhibitorsClinical practice guidelinesMechanism of actionRenal benefitsCardiorenal benefitsDiabetes statusOutcome trialsBlood pressureChronic kidneyHeart failureRisk factorsLipid profileCardiovascular diseasePractice guidelinesBody weight
2022
Dapagliflozin in patients with heart failure with mildly reduced and preserved ejection fraction treated with a mineralocorticoid receptor antagonist or sacubitril/valsartan
Yang M, Butt J, Kondo T, Jering K, Docherty K, Jhund P, de Boer R, Claggett B, Desai A, Hernandez A, Inzucchi S, Kosiborod M, Lam C, Langkilde A, Martinez F, Petersson M, Shah S, Vaduganathan M, Wilderäng U, Solomon S, McMurray J. Dapagliflozin in patients with heart failure with mildly reduced and preserved ejection fraction treated with a mineralocorticoid receptor antagonist or sacubitril/valsartan. European Journal Of Heart Failure 2022, 24: 2307-2319. PMID: 36342375, PMCID: PMC11497302, DOI: 10.1002/ejhf.2722.Peer-Reviewed Original ResearchConceptsAngiotensin receptor neprilysin inhibitorMineralocorticoid receptor antagonistsSafety of dapagliflozinHeart failureEjection fractionPrimary outcomeReceptor antagonistRecent guidelinesSodium-glucose cotransporter 2 inhibitorsLower systolic blood pressureBenefit of dapagliflozinPrior HF hospitalizationSacubitril/valsartanCotransporter 2 inhibitorsEffect of dapagliflozinSystolic blood pressureARNI therapyHF hospitalizationCardiovascular deathAdverse eventsHazard ratioBlood pressureSGLT2 inhibitorsPatientsDapagliflozinKetones: the double-edged sword of SGLT2 inhibitors?
Lupsa BC, Kibbey RG, Inzucchi SE. Ketones: the double-edged sword of SGLT2 inhibitors? Diabetologia 2022, 66: 23-32. PMID: 36255460, DOI: 10.1007/s00125-022-05815-1.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsSGLT2 inhibitorsDrug categoriesSodium-glucose cotransporter 2 inhibitorsCardio-renal benefitsNormal blood glucose concentrationsCotransporter 2 inhibitorsClasses of medicationsAnti-inflammatory effectsSerious adverse effectsType 1 diabetesBlood glucose levelsBlood glucose concentrationKidney outcomesRare complicationBlood pressureSGLT2 inhibitionGlucose levelsKetone levelsBody weightType 2Ketone bodiesAdverse effectsGlucose concentrationInhibitorsEdged sword122-LB: Effect of Dapagliflozin on Mitochondrial Metabolism and Cardiac Function in the Failing Heart
GOEDEKE L, MA Y, ZHANG J, GUERRERA N, WU X, ZHANG D, KAHN M, ZHANG X, YOUNG L, SHULMAN G. 122-LB: Effect of Dapagliflozin on Mitochondrial Metabolism and Cardiac Function in the Failing Heart. Diabetes 2022, 71 DOI: 10.2337/db22-122-lb.Peer-Reviewed Original ResearchDAPA treatmentLV ejection fractionEjection fractionHeart failureMI ratsCardiac outputMyocardial infarctionCardiac functionLeft ventricularEffect of dapagliflozinMale Sprague-DawleyPlasma glucose concentrationMalonyl-CoA contentMitochondrial oxidationKetone availabilityΒOHB levelsVehicle treatmentPermanent ligationSGLT2 inhibitionSGLT2 inhibitorsCardioprotective effectsCoronary arteryAcetyl-CoA contentFailing HeartMitochondrial metabolismA precision medicine approach to metabolic therapy for breast cancer in mice
Akingbesote ND, Norman A, Zhu W, Halberstam AA, Zhang X, Foldi J, Lustberg MB, Perry RJ. A precision medicine approach to metabolic therapy for breast cancer in mice. Communications Biology 2022, 5: 478. PMID: 35595952, PMCID: PMC9122928, DOI: 10.1038/s42003-022-03422-9.Peer-Reviewed Original ResearchConceptsPrecision medicine approachBreast cancerSodium-glucose transport protein 2 inhibitorsBreast tumorsMedicine approachCanonical insulinSGLT2 inhibitor dapagliflozinEfficacy of paclitaxelBreast tumor-bearing miceTumor glucose uptakeTumor-bearing miceChemotherapy correlatesNeoadjuvant approachNeoadjuvant settingPaclitaxel chemotherapyInhibitor dapagliflozinSGLT2 inhibitorsProlonging survivalAntihyperglycemic drugsPotential adjuvantMetabolic therapyDapagliflozinTumorsDriver mutationsGlucose uptakeNewer Glucose-Lowering Medications and Potential Role in Metabolic Management of PCOS
Anam A, Inzucchi S. Newer Glucose-Lowering Medications and Potential Role in Metabolic Management of PCOS. 2022, 527-553. DOI: 10.1007/978-3-030-92589-5_26.ChaptersPolycystic ovary syndromeType 2 diabetes mellitusDiabetes mellitusSodium-glucose cotransporter 2 inhibitorsGLP-1 receptor agonistsDipeptidyl peptidase-4 inhibitorsWeight lossGLP-1 RAsCV risk factorsGlucose-lowering medicationsCotransporter 2 inhibitorsGlucose lowering medicationsPeptidase-4 inhibitorsHigh-risk populationCategories of medicationsAbnormal carbohydrate metabolismPart of standardCV outcomesLifestyle interventionOvary syndromeMetabolic sequelaeMetabolic abnormalitiesMetabolic managementSGLT2 inhibitorsPatient populationPhenomapping-Derived Tool to Individualize the Effect of Canagliflozin on Cardiovascular Risk in Type 2 Diabetes.
Oikonomou EK, Suchard MA, McGuire DK, Khera R. Phenomapping-Derived Tool to Individualize the Effect of Canagliflozin on Cardiovascular Risk in Type 2 Diabetes. Diabetes Care 2022, 45: 965-974. PMID: 35120199, PMCID: PMC9016734, DOI: 10.2337/dc21-1765.Peer-Reviewed Original ResearchConceptsCanagliflozin Cardiovascular Assessment StudyMajor adverse cardiovascular eventsType 2 diabetesHazard ratioSodium-glucose cotransporter 2 inhibitorsCardiovascular disease benefitAdverse cardiovascular eventsCotransporter 2 inhibitorsEffects of canagliflozinCanagliflozin dosesCanagliflozin's effectsCardiovascular eventsCardiovascular riskPatients 5Cardioprotective effectsSGLT2 inhibitorsDisease benefitBaseline variablesOriginal trialCanagliflozinType 2DiabetesPatientsRisk estimatesEffect estimatesThe Enhanced Cardiac Outcome of Conjugated SGLT2 Inhibitors and GLP-1RA Therapy in Diabetic Patients
Fadah K, Alashi A, Deoker A. The Enhanced Cardiac Outcome of Conjugated SGLT2 Inhibitors and GLP-1RA Therapy in Diabetic Patients. Current Cardiology Reports 2022, 24: 17-22. PMID: 35000149, DOI: 10.1007/s11886-021-01619-8.Peer-Reviewed Original ResearchConceptsDiabetic populationDiabetic patientsSGLT2 inhibitorsGlucagon-like peptide-1 receptor agonistsSodium-glucose cotransporter 2 inhibitorsMajor adverse cardiovascular eventsReal-world cohort studyPeptide-1 receptor agonistsAdditional cardiovascular benefitsGLP-1RA therapyAdverse cardiovascular eventsCotransporter 2 inhibitorsMechanism of actionGLP-1RAsAntihyperglycemic therapyCardiac complicationsCardiac mortalityCardiovascular eventsCardiac outcomesCardiovascular benefitsCohort studyDrug therapyReceptor agonistCardioprotective processesReviewCardiovascular disease
2021
Abstract 13182: Dapagliflozin and Changes in Metabolic Syndrome in Patients With Type 2 Diabetes: A DECLARE TIMI 58 Sub-Analysis
Moura F, Itamar R, Cahn A, Goodrich E, Bhatt D, Leiter L, WILDING J, Gause-nilsson I, Mosenzon O, Sabatine M, Wiviott S. Abstract 13182: Dapagliflozin and Changes in Metabolic Syndrome in Patients With Type 2 Diabetes: A DECLARE TIMI 58 Sub-Analysis. Circulation 2021, 144: a13182-a13182. DOI: 10.1161/circ.144.suppl_1.13182.Peer-Reviewed Original ResearchHDL-CMetabolic syndromeProgression to MetSAssociation of MetSClassification of MetSPrevalence of MetSHDL-C <Prediction of CV deathRandomized to dapagliflozinComponents of MetSPresence of MetSEffects of dapagliflozinLow HDL-CType 2 diabetes mellitusFollow-up visitAssociated with outcomeType 2 diabetesIDF criteriaBaseline characteristicsCV deathSGLT2 inhibitorsDapagliflozin armHeart failureSub-analysisElevated BPImpact of SGLT2 inhibitors in comparison with DPP4 inhibitors on ascites and death in veterans with cirrhosis on metformin
Saffo S, Kaplan DE, Mahmud N, Serper M, John BV, Ross JS, Taddei T. Impact of SGLT2 inhibitors in comparison with DPP4 inhibitors on ascites and death in veterans with cirrhosis on metformin. Diabetes Obesity And Metabolism 2021, 23: 2402-2408. PMID: 34227216, PMCID: PMC8429193, DOI: 10.1111/dom.14488.Peer-Reviewed Original ResearchConceptsSodium-glucose cotransporter 2 inhibitorsDipeptidyl peptidase-4 inhibitorsPeptidase-4 inhibitorsDiabetes mellitusLiver diseaseNon-alcoholic fatty liver diseaseCotransporter 2 inhibitorsChronic liver diseaseFatty liver diseaseVeterans Affairs hospitalIncidence of ascitesAdditional pharmacotherapyTreat analysisElectronic health dataSGLT2 inhibitorsSGLT2i usersSurrogate biomarkerDPP4 inhibitorsMetabolic effectsPatientsCirrhosisPropensity scoreAscitesConfirmatory studiesMetforminCould Sodium/Glucose Co-Transporter-2 Inhibitors Have Antiarrhythmic Potential in Atrial Fibrillation? Literature Review and Future Considerations
Vrachatis DA, Papathanasiou KA, Iliodromitis KE, Giotaki SG, Kossyvakis C, Raisakis K, Kaoukis A, Lambadiari V, Avramides D, Reimers B, Stefanini GG, Cleman M, Giannopoulos G, Lansky A, Deftereos SG. Could Sodium/Glucose Co-Transporter-2 Inhibitors Have Antiarrhythmic Potential in Atrial Fibrillation? Literature Review and Future Considerations. Drugs 2021, 81: 1381-1395. PMID: 34297330, DOI: 10.1007/s40265-021-01565-3.Peer-Reviewed Original ResearchConceptsAtrial fibrillationSGLT2 inhibitorsCardiorenal protectionAntiarrhythmic effectsClinical dataSodium/glucose co-transporter-2 inhibitorClinical data implyDate available evidenceGlucose-lowering medicationsEffective therapeutic optionPotential pathophysiological linkLarge clinical trialsPre-specified endpointsType 2 diabetesPossible beneficial effectsPost Hoc AnalysisNormoglycemic adultsAF burdenAF preventionPathophysiologic mechanismsPathophysiological linkSGLT2 inhibitionAntiarrhythmic potentialSodium glucoseTherapeutic options
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