2024
Genetic drivers of heterogeneity in type 2 diabetes pathophysiology
Suzuki K, Hatzikotoulas K, Southam L, Taylor H, Yin X, Lorenz K, Mandla R, Huerta-Chagoya A, Melloni G, Kanoni S, Rayner N, Bocher O, Arruda A, Sonehara K, Namba S, Lee S, Preuss M, Petty L, Schroeder P, Vanderwerff B, Kals M, Bragg F, Lin K, Guo X, Zhang W, Yao J, Kim Y, Graff M, Takeuchi F, Nano J, Lamri A, Nakatochi M, Moon S, Scott R, Cook J, Lee J, Pan I, Taliun D, Parra E, Chai J, Bielak L, Tabara Y, Hai Y, Thorleifsson G, Grarup N, Sofer T, Wuttke M, Sarnowski C, Gieger C, Nousome D, Trompet S, Kwak S, Long J, Sun M, Tong L, Chen W, Nongmaithem S, Noordam R, Lim V, Tam C, Joo Y, Chen C, Raffield L, Prins B, Nicolas A, Yanek L, Chen G, Brody J, Kabagambe E, An P, Xiang A, Choi H, Cade B, Tan J, Broadaway K, Williamson A, Kamali Z, Cui J, Thangam M, Adair L, Adeyemo A, Aguilar-Salinas C, Ahluwalia T, Anand S, Bertoni A, Bork-Jensen J, Brandslund I, Buchanan T, Burant C, Butterworth A, Canouil M, Chan J, Chang L, Chee M, Chen J, Chen S, Chen Y, Chen Z, Chuang L, Cushman M, Danesh J, Das S, de Silva H, Dedoussis G, Dimitrov L, Doumatey A, Du S, Duan Q, Eckardt K, Emery L, Evans D, Evans M, Fischer K, Floyd J, Ford I, Franco O, Frayling T, Freedman B, Genter P, Gerstein H, Giedraitis V, González-Villalpando C, González-Villalpando M, Gordon-Larsen P, Gross M, Guare L, Hackinger S, Hakaste L, Han S, Hattersley A, Herder C, Horikoshi M, Howard A, Hsueh W, Huang M, Huang W, Hung Y, Hwang M, Hwu C, Ichihara S, Ikram M, Ingelsson M, Islam M, Isono M, Jang H, Jasmine F, Jiang G, Jonas J, Jørgensen T, Kamanu F, Kandeel F, Kasturiratne A, Katsuya T, Kaur V, Kawaguchi T, Keaton J, Kho A, Khor C, Kibriya M, Kim D, Kronenberg F, Kuusisto J, Läll K, Lange L, Lee K, Lee M, Lee N, Leong A, Li L, Li Y, Li-Gao R, Ligthart S, Lindgren C, Linneberg A, Liu C, Liu J, Locke A, Louie T, Luan J, Luk A, Luo X, Lv J, Lynch J, Lyssenko V, Maeda S, Mamakou V, Mansuri S, Matsuda K, Meitinger T, Melander O, Metspalu A, Mo H, Morris A, Moura F, Nadler J, Nalls M, Nayak U, Ntalla I, Okada Y, Orozco L, Patel S, Patil S, Pei P, Pereira M, Peters A, Pirie F, Polikowsky H, Porneala B, Prasad G, Rasmussen-Torvik L, Reiner A, Roden M, Rohde R, Roll K, Sabanayagam C, Sandow K, Sankareswaran A, Sattar N, Schönherr S, Shahriar M, Shen B, Shi J, Shin D, Shojima N, Smith J, So W, Stančáková A, Steinthorsdottir V, Stilp A, Strauch K, Taylor K, Thorand B, Thorsteinsdottir U, Tomlinson B, Tran T, Tsai F, Tuomilehto J, Tusie-Luna T, Udler M, Valladares-Salgado A, van Dam R, van Klinken J, Varma R, Wacher-Rodarte N, Wheeler E, Wickremasinghe A, van Dijk K, Witte D, Yajnik C, Yamamoto K, Yamamoto K, Yoon K, Yu C, Yuan J, Yusuf S, Zawistowski M, Zhang L, Zheng W, Raffel L, Igase M, Ipp E, Redline S, Cho Y, Lind L, Province M, Fornage M, Hanis C, Ingelsson E, Zonderman A, Psaty B, Wang Y, Rotimi C, Becker D, Matsuda F, Liu Y, Yokota M, Kardia S, Peyser P, Pankow J, Engert J, Bonnefond A, Froguel P, Wilson J, Sheu W, Wu J, Hayes M, Ma R, Wong T, Mook-Kanamori D, Tuomi T, Chandak G, Collins F, Bharadwaj D, Paré G, Sale M, Ahsan H, Motala A, Shu X, Park K, Jukema J, Cruz M, Chen Y, Rich S, McKean-Cowdin R, Grallert H, Cheng C, Ghanbari M, Tai E, Dupuis J, Kato N, Laakso M, Köttgen A, Koh W, Bowden D, Palmer C, Kooner J, Kooperberg C, Liu S, North K, Saleheen D, Hansen T, Pedersen O, Wareham N, Lee J, Kim B, Millwood I, Walters R, Stefansson K, Ahlqvist E, Goodarzi M, Mohlke K, Langenberg C, Haiman C, Loos R, Florez J, Rader D, Ritchie M, Zöllner S, Mägi R, Marston N, Ruff C, van Heel D, Finer S, Denny J, Yamauchi T, Kadowaki T, Chambers J, Ng M, Sim X, Below J, Tsao P, Chang K, McCarthy M, Meigs J, Mahajan A, Spracklen C, Mercader J, Boehnke M, Rotter J, Vujkovic M, Voight B, Morris A, Zeggini E. Genetic drivers of heterogeneity in type 2 diabetes pathophysiology. Nature 2024, 627: 347-357. PMID: 38374256, PMCID: PMC10937372, DOI: 10.1038/s41586-024-07019-6.Peer-Reviewed Original ResearchMeSH KeywordsAdipocytesChromatinCoronary Artery DiseaseDiabetes Mellitus, Type 2Diabetic NephropathiesDisease ProgressionEndothelial CellsEnteroendocrine CellsEpigenomicsGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansIslets of LangerhansMultifactorial InheritancePeripheral Arterial DiseaseSingle-Cell AnalysisConceptsGenome-wide association study dataIndividuals of diverse ancestryRegions of open chromatinAncestry groupsGenome-wide significanceSingle-cell epigenomicsCases of T2DT2D signalsAssociation signalsObesity-related processesOpen chromatinDiverse ancestryTrait associationsDrivers of heterogeneityGenetic driversProgression of T2DEnteroendocrine cellsType 2 diabetes pathophysiologyGenetic contributionMolecular mechanismsPolygenic scoresAncestryLociPancreatic isletsStudy data
2023
Risk Assessment of Kidney Disease Progression and Efficacy of SGLT2 Inhibition in Patients With Type 2 Diabetes
Moura F, Berg D, Bellavia A, Dwyer J, Mosenzon O, Scirica B, Wiviott S, Bhatt D, Raz I, Feinberg M, Braunwald E, Morrow D, Sabatine M. Risk Assessment of Kidney Disease Progression and Efficacy of SGLT2 Inhibition in Patients With Type 2 Diabetes. Diabetes Care 2023, 46: 1807-1815. PMID: 37556796, PMCID: PMC10516252, DOI: 10.2337/dc23-0492.Peer-Reviewed Original ResearchConceptsSodium-glucose cotransporter 2Kidney disease progressionPredictors of kidney disease progressionAbsolute risk reductionDisease progressionValidation cohortType 2 diabetesSodium-glucose cotransporter 2 inhibitionUrine albumin-to-creatinine ratioAlbumin-to-creatinine ratioEfficacy of dapagliflozinMedian follow-upRisk categoriesMultivariate Cox regressionRelative risk reductionHigh-risk groupAtherosclerotic cardiovascular diseaseSystolic blood pressureRisk reductionMagnitude of benefitDapagliflozin EffectT2D durationCotransporter 2SGLT2 inhibitionStratify riskEfficacy and safety of the dual GIP and GLP-1 receptor agonist tirzepatide for weight loss: a meta-analysis of randomized controlled trials
de Mesquita Y, Pera Calvi I, Reis Marques I, Almeida Cruz S, Padrao E, Carvalho P, da Silva C, Cardoso R, Moura F, Rafalskiy V. Efficacy and safety of the dual GIP and GLP-1 receptor agonist tirzepatide for weight loss: a meta-analysis of randomized controlled trials. International Journal Of Obesity 2023, 47: 883-892. PMID: 37460681, DOI: 10.1038/s41366-023-01337-x.Peer-Reviewed Original ResearchMeSH KeywordsDiabetes Mellitus, Type 2Gastric Inhibitory PolypeptideGlucagon-Like Peptide-1 ReceptorHumansHypoglycemic AgentsRandomized Controlled Trials as TopicWeight LossConceptsMean differenceRandomized controlled trialsOdds ratioGlucagon-like peptide-1 receptor agonistsMeta-analysis of randomized controlled trialsPeptide-1 receptor agonistsControlled trialsMeta-analysisCo-primary endpointsMethodsWe searched PubMedType 2 diabetesAgonist tirzepatideRisk of biasReview Manager 5.4.1Receptor agonistsReduced BMITherapeutic optionsWaist circumferenceAdverse eventsTirzepatideGastrointestinal symptomsPooled analysisGLP-1PlaceboWeight managementAssessment of Atherothrombotic Risk in Patients With Type 2 Diabetes Mellitus
Berg D, Moura F, Bellavia A, Scirica B, Wiviott S, Bhatt D, Raz I, Bohula E, Giugliano R, Park J, Feinberg M, Braunwald E, Morrow D, Sabatine M. Assessment of Atherothrombotic Risk in Patients With Type 2 Diabetes Mellitus. Journal Of The American College Of Cardiology 2023, 81: 2391-2402. PMID: 37344040, PMCID: PMC11466046, DOI: 10.1016/j.jacc.2023.04.031.Peer-Reviewed Original ResearchMeSH KeywordsDiabetes Mellitus, Type 2HumansMyocardial InfarctionProprotein Convertase 9Risk AssessmentSodium-Glucose Transporter 2 InhibitorsConceptsType 2 diabetes mellitusSecondary preventionIschemic strokePredictor of MIValidation cohortClinical decision-makingRates of MIMyocardial infarctionAtherothrombotic eventsRisk quintileRisk of atherothrombotic eventsRisk modelSelection of pharmacotherapyRisk scoreAssessed clinical variablesMultivariate Cox regressionClinical trial cohortPooled cohortCandidate variablesCox regressionIS ratesDECLARE-TIMIAbsolute reductionTrial cohortCohort
2022
Evolocumab on top of empagliflozin improves endothelial function of individuals with diabetes: randomized active-controlled trial
Sposito A, Breder I, Barreto J, Breder J, Bonilha I, Lima M, Oliveira A, Wolf V, Luchiari B, do Carmo H, Munhoz D, Oliveira D, Coelho-Filho O, Coelho O, Matos-Souza J, Moura F, de Carvalho L, Nadruz W, Quinaglia T, Kimura-Medorima S. Evolocumab on top of empagliflozin improves endothelial function of individuals with diabetes: randomized active-controlled trial. Cardiovascular Diabetology 2022, 21: 147. PMID: 35933413, PMCID: PMC9356512, DOI: 10.1186/s12933-022-01584-8.Peer-Reviewed Original ResearchConceptsFlow-mediated dilationEndothelial functionPost-treatment changesPlasma levelsPlasma levels of nitric oxide metabolitesBackgroundSodium-glucose cotransporter 2 inhibitorsCardiovascular eventsInhibitors reduce cardiovascular eventsLevels of nitric oxide metabolitesE groupPlasma levels of nitrateEE groupHigh-risk patientsProprotein convertase subtilisin/kexin 9Nitric oxide metabolitesRandomized active-controlled trialActive-controlled trialReduce cardiovascular eventsType 2 diabetesPCSK9-iSGLT2i treatmentPrimary endpointSGLT2-iEndothelial dysfunctionSecondary outcomes
2021
Dapagliflozin effect on endothelial dysfunction in diabetic patients with atherosclerotic disease: a randomized active-controlled trial
Sposito A, Breder I, Soares A, Kimura-Medorima S, Munhoz D, Cintra R, Bonilha I, Oliveira D, Breder J, Cavalcante P, Moreira C, Moura F, de Lima-Junior J, do Carmo H, Barreto J, Nadruz W, Carvalho L, Quinaglia T. Dapagliflozin effect on endothelial dysfunction in diabetic patients with atherosclerotic disease: a randomized active-controlled trial. Cardiovascular Diabetology 2021, 20: 74. PMID: 33771149, PMCID: PMC8004411, DOI: 10.1186/s12933-021-01264-z.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedBenzhydryl CompoundsBiomarkersBlood GlucoseBrazilCarotid Artery DiseasesDiabetes Mellitus, Type 2Drug Therapy, CombinationEndothelium, VascularFemaleGlucosidesGlyburideGlycated HemoglobinHumansMaleMetforminMiddle AgedProspective StudiesSodium-Glucose Transporter 2 InhibitorsTime FactorsTreatment OutcomeVasodilationConceptsFlow-mediated dilationSodium-glucose cotransporter-2 inhibitorsCoprimary endpointsAtherosclerotic diseaseWeeks of therapyResultsNinety-seven patientsMacrovascular endothelial functionCotransporter-2 inhibitorsType 2 diabetes mellitusRandomized active-controlled trialActive-controlled trialCarotid intima-media thicknessRandomized clinical trialsIntima-media thicknessDapagliflozin EffectGlibenclamide armsDapagliflozin groupArterial wall functionOpen-labelSGLT2i treatmentGlibenclamide groupResultsNinety-sevenSingle-centerMedian HbA1cCarotid atherosclerotic disease
2019
Inhibition of the sodium-glucose co-transporter 2 in the elderly: clinical and mechanistic insights into safety and efficacy
Cintra R, Moura F, Carvalho L, Barreto J, Tambascia M, Pecoits-Filho R, Sposito A. Inhibition of the sodium-glucose co-transporter 2 in the elderly: clinical and mechanistic insights into safety and efficacy. Revista Da Associação Médica Brasileira 2019, 65: 70-86. PMID: 30758423, DOI: 10.1590/1806-9282.65.1.70.Peer-Reviewed Original ResearchConceptsSodium-glucose cotransporter 2 inhibitorsRisk of hypoglycemiaAntidiabetic therapySodium-glucose co-transporter 2High risk of hypoglycemiaIncreased risk of hypoglycemiaPrevalence of type 2 diabetes mellitusType 2 diabetes mellitusRenal proximal convoluted tubulesChronic kidney diseaseCo-morbid diseasesSystolic blood pressurePost hoc studyProximal convoluted tubulesReduced insulin sensitivitySGLT2i therapyMedian ageSodium-glucoseSodium reabsorptionOlder individualsClinical trialsIncreased riskKidney diseaseBlood pressureConvoluted tubules
2013
Validation of surrogate indexes of insulin sensitivity in acute phase of myocardial infarction based on euglycemic-hyperinsulinemic clamp
Moura F, Carvalho L, Cintra R, Martins N, Figueiredo V, Quinaglia e Silva J, Almeida O, Coelho O, Sposito A. Validation of surrogate indexes of insulin sensitivity in acute phase of myocardial infarction based on euglycemic-hyperinsulinemic clamp. AJP Endocrinology And Metabolism 2013, 306: e399-e403. PMID: 24347056, DOI: 10.1152/ajpendo.00566.2013.Peer-Reviewed Original ResearchMeSH KeywordsAgedBlood GlucoseDiabetes Mellitus, Type 2FastingFemaleGlucose Clamp TechniqueHumansInsulinInsulin ResistanceMaleMiddle AgedMyocardial InfarctionConceptsQuantitative insulin sensitivity check indexEuglycemic-hyperinsulinemic clampHomeostatic model assessmentHOMA-IRInsulin sensitivityMyocardial infarctionSurrogate indexHomeostatic model assessment of insulin resistanceModel assessment of insulin resistanceConsecutive nondiabetic patientsHomeostatic model assessment of insulin sensitivityAssessment of insulin resistanceST-segment elevation MISurrogate indexes of insulin sensitivityInsulin sensitivity check indexIndices of insulin sensitivityAcute phase of myocardial infarctionReceiver operating characteristic curveAcute MI patientsAssessment of insulin sensitivityPhase of myocardial infarctionGold standard reference methodBland-Altman plotsOperating characteristics curvePoor patient outcomes