2025
18-OR: Lower Incretin Effect and Reduced GIP Characterize the Metabolic Phenotype of People with Multiple Islet Autoantibodies and Normal Glucose Tolerance
GALDERISI A, MARCHIORI H, ALGUARD M, DESOUSA M, TICHY E, FLYNN A, GAGLIA J, DALLA MAN C, SHERR J. 18-OR: Lower Incretin Effect and Reduced GIP Characterize the Metabolic Phenotype of People with Multiple Islet Autoantibodies and Normal Glucose Tolerance. Diabetes 2025, 74 DOI: 10.2337/db25-18-or.Peer-Reviewed Original ResearchOral glucose tolerance testNormal glucose toleranceInsulin secretion rateGlucose tolerance testIncretin effectStage 0GLP-1Islet autoantibodiesTolerance testGlucose tolerancePreclinical type 1 diabetesStage 1Reduced incretin effectHormone GLP-1Iv glucose tolerance testType 1 diabetesMultiple islet autoantibodiesPhenotype of peopleOral minimal modelC-peptideMetabolic phenotypeGlucose profilesIncretinMeasurement of glucoseInsulin secretion1962-LB: Baseline Insulin Secretion Determines the Response to Abatacept In Stage 1 Type 1 Diabetes
CARR A, GALDERISI A, TAYLOR P, BONET J, CUTHBERTSON D, SOSENKO J, SIMS E, EVANS-MOLINA C, DALLA MAN C, SENIOR P, ISMAIL H, NATHAN B, PETRELLI A, SHERR J, HEROLD K, RUSSELL W, MORAN A, DAYAN C. 1962-LB: Baseline Insulin Secretion Determines the Response to Abatacept In Stage 1 Type 1 Diabetes. Diabetes 2025, 74 DOI: 10.2337/db25-1962-lb.Peer-Reviewed Original ResearchOral minimal modelHigh secretorsEunice Kennedy Shriver National Institute of Child HealthOral glucose tolerance testAge-adjusted ANCOVACTLA-4-immunoglobulinInsulin secretionNational Institute of AllergyImmune Tolerance NetworkRisk regression analysisNational Center for Research ResourcesNational Institute of Child HealthGlucose tolerance testInstitute of Child HealthDelay disease progressionInstitute of AllergyNational Institute of DiabetesCanadian Institutes of Health ResearchBaseline insulin secretionDigestive and Kidney DiseasesBeta cell functionQuantify insulin secretionBeta cell responses to glucoseCell response to glucoseAbatacept armsWS16.05Impact of elexacaftor/tezacaftor/ivacaftor on glucose tolerance in adolescents with cystic fibrosis. Data from the MODUL-CF study
Bonnel A, Galderisi A, Weiss L, Sermet-Gaudelus I, Besancon A, Letierce A, Sahki D, Group M. WS16.05Impact of elexacaftor/tezacaftor/ivacaftor on glucose tolerance in adolescents with cystic fibrosis. Data from the MODUL-CF study. Journal Of Cystic Fibrosis 2025, 24: s33. DOI: 10.1016/j.jcf.2025.03.586.Peer-Reviewed Original ResearchOral glucose tolerance testAbnormal glucose toleranceNormal glucose toleranceCF-related diabetesBaseline oral glucose tolerance testAbnormal glucose tolerance groupCystic fibrosisGlucose toleranceNormal glucose tolerance groupEffective CFTR modulatorsOGTT glucoseBMI z-scoreYear of treatmentImpaired fasting glucoseImpaired glucose toleranceGlucose tolerance testForced expiratory volumeCFTR modulatorsPulmonary infectionDecrease recurrenceBaseline characteristicsRelated diabetesFasting glucoseTolerance testInsulin treatmentThe Disposition Index in Autoantibody-Positive Individuals at Risk for Type 1 Diabetes
Ismail H, Cuthbertson D, Galderisi A, Libman I, Jacobsen L, Moran A, Petrelli A, Atkinson M, Redondo M, Hannon T, Mather K, Sosenko J. The Disposition Index in Autoantibody-Positive Individuals at Risk for Type 1 Diabetes. Diabetes 2025, 74: 1196-1204. PMID: 40173211, PMCID: PMC12185960, DOI: 10.2337/db24-1000.Peer-Reviewed Original ResearchConceptsFirst-phase insulin responseArea under the curveArea under the curve ratioType 1 diabetesB cell functionAutoantibody-positive individualsDPT-1Glucose tolerance testMatsuda indexDisposition indexRegression modelsDiabetic rangeAnalyzed cross-sectionallyTolerance testDiabetes Prevention Trial-Type 1Oral glucose tolerance testProgression to type 1 diabetesStudy participantsCox regression modelsAntibody-positive relativesInsulin secretionPrediction of T1DRisk scoreIntravenous glucose tolerance testMeasure of B-cell functionATGL links insulin dysregulation to insulin resistance in adolescents with obesity and hepatosteatosis
Slusher A, Santoro N, Vash-Margita A, Galderisi A, Hu P, Tokoglu F, Li Z, Tarabra E, Strober J, Vatner D, Shulman G, Caprio S. ATGL links insulin dysregulation to insulin resistance in adolescents with obesity and hepatosteatosis. Journal Of Clinical Investigation 2025, 135: e184740. PMID: 40091831, PMCID: PMC11910223, DOI: 10.1172/jci184740.Peer-Reviewed Original ResearchConceptsHyperinsulinemic-euglycemic clampSubcutaneous adipose tissueInsulin resistanceAdipose triglyceride lipaseInsulin infusionOral glucose tolerance testAbdominal fat distributionGlucose tolerance testMeasuring abdominal fat distributionLower liver fatActivating adipose triglyceride lipaseMetabolic disease riskLiver fat contentEctopic lipid storageFUNDINGThis workAdipose tissue lipolysisInhibition of adipose tissue lipolysisSubcutaneous adipose tissue samplesFat distributionTolerance testInsulin exposureLiver fatInfusionGlycerol turnoverAdipose tissueMetabolic Phenotype of Stage 1 and Stage 2 Type 1 Diabetes Using Modeling of β Cell Function
Galderisi A, Bonet J, Ismail H, Moran A, Fiorina P, Bosi E, Petrelli A. Metabolic Phenotype of Stage 1 and Stage 2 Type 1 Diabetes Using Modeling of β Cell Function. The Journal Of Clinical Endocrinology & Metabolism 2025, dgaf086. PMID: 39992257, DOI: 10.1210/clinem/dgaf086.Peer-Reviewed Original ResearchOral glucose tolerance testMetabolic phenotypeOral minimal modelInsulin secretionResponse to disease-modifying treatmentsOdds of disease progressionPhenotype of individualsPrevention trialsPreclinical type 1 diabetesIndependent of stageMeasures of beta-cell functionStage 1Glucose tolerance testAssociated with reduced oddsBeta-cell functionMeasures of insulin secretionType 1 diabetesOGTT-derived measuresIncreased insulin clearanceT1D prevention trialsIslet autoimmunityDisease-modifying treatmentsTolerance testDisease progressionProgression predictorsEffect of Elexacaftor/Tezacaftor/Ivacaftor on Glucose Tolerance in Adolescents With Cystic Fibrosis
Galderisi A, Weiss L, Besançon A, Stremler N, Reix P, Wizla N, Lustre A, Rames C, Tatopoulos A, Perisson C, Dalphin M, Troussier F, Houdouin V, Bessaci K, Cosson L, Gabsi A, Corvol H, Deneuville E, Storni V, Ramel S, Bui S, Heraud M, Remus N, Huet F, Scalbert M, Mely L, Gachelin E, Giannantonio M, Letierce A, Sahki D, Marguet C, Bonnel A, Sermet-Gaudelus I. Effect of Elexacaftor/Tezacaftor/Ivacaftor on Glucose Tolerance in Adolescents With Cystic Fibrosis. The Journal Of Clinical Endocrinology & Metabolism 2025, dgaf099. PMID: 39977216, DOI: 10.1210/clinem/dgaf099.Peer-Reviewed Original ResearchOral glucose tolerance testBaseline oral glucose tolerance testAbnormal glucose toleranceNormal glucose toleranceAbnormal glucose tolerance groupCystic fibrosisGlucose toleranceNormal glucose tolerance groupEffective CFTR modulatorsCF-related diabetesInsulin secretionImpaired fasting glucoseGlucose tolerance testImpaired glucose toleranceForced expiratory volumeBMIz-scoreCFTR modulatorsBaseline characteristicsRelated diabetesFasting glucoseTolerance testTherapeutic strategiesInsulin treatmentExpiratory volumeGlucose levels
2024
Rare variants in the melanocortin 4 receptor gene (MC4R) are associated with abdominal fat and insulin resistance in youth with obesity
Galuppo B, Mannam P, Bonet J, Pierpont B, Trico’ D, Haskell-Luevano C, Ericson M, Freeman K, Philbrick W, Bale A, Caprio S, Santoro N. Rare variants in the melanocortin 4 receptor gene (MC4R) are associated with abdominal fat and insulin resistance in youth with obesity. International Journal Of Obesity 2024, 49: 819-826. PMID: 39738493, PMCID: PMC12095050, DOI: 10.1038/s41366-024-01706-0.Peer-Reviewed Original ResearchOral glucose tolerance testVisceral adipose tissueMelanocortin-4 receptor geneSubcutaneous adipose tissueVariant groupYale Pediatric Obesity ClinicInsulin resistanceEarly-onset obesityBMI z-scorePediatric obesity clinicRare variantsAdipose tissueAbdominal fat distributionDegree of obesityGlucose tolerance testTotal body fatIntrahepatic fat contentLower insulin sensitivityIntrahepatic fat accumulationAssociated with abdominal fatAbdominal MRIObesity clinicMetabolic sequelaePathogenic variantsFat distributionGeneralizing from qualitative data: a case example using critical realist thematic analysis and mechanism mapping to evaluate a community health worker-led screening program in India
Broderick K, Vaidyanathan A, Ponticiello M, Hooda M, Kulkarni V, Chalem A, Chebrolu P, Onawale A, Baumann A, Mathad J, Sundararajan R. Generalizing from qualitative data: a case example using critical realist thematic analysis and mechanism mapping to evaluate a community health worker-led screening program in India. Implementation Science 2024, 19: 81. PMID: 39719615, PMCID: PMC11667965, DOI: 10.1186/s13012-024-01407-2.Peer-Reviewed Original ResearchConceptsThematic analysisQualitative dataGoal of implementation scienceHealth system interventionsPurposively sampled participantsThematic analysis approachEvidence-based practiceThematic analysis methodPopulation of womenScreening uptakeScreening interventionsMethodsQualitative interviewsManagement of GDMIntervention developmentImplementation scienceHealth programsOral glucose tolerance testTraditional risk factorsEvidence-based managementImprove uptakeInterview transcriptsScreening programIntervention successSystem interventionsTreatment of GDMAssociation of gestational and childhood circulating C-peptide concentrations in the hyperglycemia and adverse pregnancy outcomes follow-up study
Rajamoorthi A, Zheng H, Skowronski A, Zork N, Reddy U, Tung P, Kupsco A, Gallagher D, Salem R, Leibel R, LeDuc C, Thaker V. Association of gestational and childhood circulating C-peptide concentrations in the hyperglycemia and adverse pregnancy outcomes follow-up study. Diabetes Research And Clinical Practice 2024, 220: 111967. PMID: 39716665, PMCID: PMC11840794, DOI: 10.1016/j.diabres.2024.111967.Peer-Reviewed Original ResearchConceptsOral glucose tolerance testC-peptide concentrationsC-peptideInsulin sensitivityCord bloodFollow-up studyInsulinogenic indexHOMA-IRCirculating C-peptide concentrationsCord blood C-peptideMaternal glucose concentrationsBlood C-peptideBMI z-scoreGlucose tolerance testPancreatic beta-cell developmentBeta-cell developmentGestational ageOGTT glucoseMaternal fastingAssociations of gestationalPubertal stageTolerance testInsulin resistanceZ-scoreMaternal covariatesDaily glucose variability is associated with intrahepatic fat content, β cell sensitivity, and biomarkers of glycolysis in youth with obesity
Barbieri E, Bonet J, Fox D, Nelson R, Nelson M, Nelson L, Fernandez C, Van Name M, Samuels S, Caprio S, Sabati M, Galderisi A, Sherr J, Man C, Santoro N. Daily glucose variability is associated with intrahepatic fat content, β cell sensitivity, and biomarkers of glycolysis in youth with obesity. Obesity 2024, 33: 116-124. PMID: 39658509, PMCID: PMC11666407, DOI: 10.1002/oby.24175.Peer-Reviewed Original ResearchConceptsIntrahepatic fat contentDaily glucose variabilityLiver proton density fat fractionProton density fat fractionGlucose variabilityInsulin sensitivityOral glucose tolerance testFat fractionInsulin secretionAssociated with insulin resistanceFirst-phase insulin secretionAssociated with 2-h glucoseGlucose tolerance testGlucose standard deviationMagnetic resonance imagingOral minimal modelCoefficient of variationBasal insulin secretionPediatric obesityPostprandial glucoseTolerance testCell sensitivityInsulin resistanceObesityResonance imaging12241 Association Between Brain Glucose And Circulating Glucagon Levels In Response To Acute Hyperglycemia
Matson B, Gunawan F, Coppoli A, Jiang L, Rangel E, De Aguiar R, Rothman D, Mason G, Hwang J. 12241 Association Between Brain Glucose And Circulating Glucagon Levels In Response To Acute Hyperglycemia. Journal Of The Endocrine Society 2024, 8: bvae163.674. PMCID: PMC11454728, DOI: 10.1210/jendso/bvae163.674.Peer-Reviewed Original ResearchCentral nervous systemBrain glucose levelsPlasma glucagon levelsHyperglycemic clampType 2 diabetesGlucagon levelsGlucagon secretionGlucose levelsResponse to hyperglycemiaAcute hyperglycemiaOral glucose tolerance testBrain glucose metabolismResponse to central nervous systemPathophysiology of type 2 diabetesResponse to hypoglycemiaBrain glucoseIndices of insulin sensitivityEffect of obesityRegulation of glucagon secretionGlucose tolerance testConsequences of obesityModulating glucagon secretionOvert metabolic abnormalitiesBrain glucose uptakeCirculating glucagon levelsRevisiting the Pattern of Loss of β-Cell Function in Preclinical Type 1 Diabetes.
Martino M, Galderisi A, Evans-Molina C, Dayan C. Revisiting the Pattern of Loss of β-Cell Function in Preclinical Type 1 Diabetes. Diabetes 2024, 73: 1769-1779. PMID: 39106185, DOI: 10.2337/db24-0163.Peer-Reviewed Original ResearchB cell functionBeta cell lossType 1 diabetesLoss of B-cell functionCell lossOral glucose tolerance testPreclinical type 1 diabetesEarly stage diseaseBeta cell destructionTime of diagnosisDestruction of B cellsGlucose tolerance testMonths prior to clinical diagnosisAntibody positivityStage diseaseDisease activityAutoimmune destructionB cellsDisease accelerationInsulin therapyTolerance testInsulin secretionSubmaximal stimuliCell destructionGlucose controlModeling Glucose, Insulin, C-Peptide, and Lactate Interplay in Adolescents During an Oral Glucose Tolerance Test.
Bonet J, Barbieri E, Santoro N, Dalla Man C. Modeling Glucose, Insulin, C-Peptide, and Lactate Interplay in Adolescents During an Oral Glucose Tolerance Test. Journal Of Diabetes Science And Technology 2024, 19322968241266825. PMID: 39076151, PMCID: PMC11572107, DOI: 10.1177/19322968241266825.Peer-Reviewed Original ResearchOral glucose tolerance testArea under the curveGlucose tolerance testC-peptideTolerance testStandard oral glucose tolerance testPathological conditionsTime coursePopulation of adolescentsClinical dataLactate metabolism pathwaysLiver diseaseSteatotic liver diseaseModel glucoseMetabolic diseasesIntersubject variabilityObesityLactate metabolismAnaerobic glycolysisInsulinLactate kineticsDiseaseAdolescentsLactateMetabolic pathways899-P: Combinations of the Mitochondrial Protonophore TLC-6740 and/or the ACC2 Inhibitor TLC-3595 Provide Additive Glycemic Benefits to Semaglutide (SEMA) in db/db Mice
VIJAYAKUMAR A, SRODA N, MURAKAMI E, WENG S, MYERS R, SUBRAMANIAN M, SHULMAN G. 899-P: Combinations of the Mitochondrial Protonophore TLC-6740 and/or the ACC2 Inhibitor TLC-3595 Provide Additive Glycemic Benefits to Semaglutide (SEMA) in db/db Mice. Diabetes 2024, 73 DOI: 10.2337/db24-899-p.Peer-Reviewed Original ResearchOral glucose tolerance testGLP-1R agonistsDb/db miceIncremental AUCGlucose tolerance testMale db/db miceImproved glucose toleranceSemaglutide groupGlycemic parametersSemaglutideTolerance testFood intakeGlucose toleranceGLP-1RLiver-targeted mitochondrial uncouplerDb/dbMiceGlucose bolusVEHAgonistsEvaluation of combinationsHbA1cDiabetesMitochondrial uncouplingAssess effectsDesign, rationale and protocol for Glycemic Observation and Metabolic Outcomes in Mothers and Offspring (GO MOMs): an observational cohort study
Group T, Scholtens D, LeBlanc E, Vesco K, Amy D, Bays K, Massimino S, Robinson S, Schell K, Walters G, Hillier T, Oshiro C, Cordero S, Howick C, Kim L, Martinez Y, Pishchalenko O, Wastlova V, Zork N, Mourad M, Lonier J, Reddy U, Acevedo J, Castillo J, Gomez M, Peguero B, Facco F, Feghali M, Bocan H, Stramowski S, Powe C, Edlow A, Barth W, Nathan D, Azevedo R, Baez A, Iroajanma C, Larkin M, Maya J, Michalopoulos C, Neamonitaki N, Thangthaeng N, Yee L, Lowe W, Grobman W, Szmuilowicz E, Aguirre A, Guevara E, Mallett G, Matos S, Tyagi S, Spadola A, Catalano P, Azimirad A, Werner E, Rouse D, Malloy M, Parra F, Sherr J, Merriam A, Bitterman S, Considine E, Leventhal J, Perley L, Rink L, Steffen A, Thompson B, Zgorski M, Steffes M, Arends V, Killeen A, Siddique J, Bustamante P, Cheung Y, Freeze C, Grott T, Kuang A, Tull M, Linder B. Design, rationale and protocol for Glycemic Observation and Metabolic Outcomes in Mothers and Offspring (GO MOMs): an observational cohort study. BMJ Open 2024, 14: e084216. PMID: 38851233, PMCID: PMC11163666, DOI: 10.1136/bmjopen-2024-084216.Peer-Reviewed Original ResearchConceptsLarge-for-gestational-age birth weightMetabolic outcomesLarge-for-gestational-ageDiagnosis of gestational diabetesOral glucose tolerance testAdverse pregnancy outcomesVanderbilt University Institutional Review BoardCourse of pregnancyObservational cohort studyGlucose tolerance testNational Institute of DiabetesDigestive and Kidney DiseasesGDM treatmentWeeks gestationDetect such abnormalitiesPerinatal outcomesGDM screeningInstitutional review boardGestational diabetesFirst-trimesterPregnancy outcomesEarly pregnancyGlucose abnormalitiesBirth weightPregnant adultsModelling and assessment of glucose‐lactate kinetics in youth with overweight, obesity and metabolic dysfunction‐associated steatotic liver disease: A pilot study
Bonet J, Fox D, Nelson R, Nelson M, Nelson L, Fernandez C, Barbieri E, Man C, Santoro N. Modelling and assessment of glucose‐lactate kinetics in youth with overweight, obesity and metabolic dysfunction‐associated steatotic liver disease: A pilot study. Diabetes Obesity And Metabolism 2024, 26: 3207-3212. PMID: 38742538, DOI: 10.1111/dom.15648.Peer-Reviewed Original ResearchOral glucose tolerance testLiver diseaseSteatotic liver diseaseAssess putative differencesArea under the curveProton density fat fractionBody mass indexGlucose tolerance testTime-to-peakMann-Whitney testObese adolescentsSpearman correlation coefficientMass indexTolerance testMann-WhitneyFat fractionWilcoxon testGlucose metabolismInvestigate glucoseLactate production rateEvaluate differencesLactate metabolismObesityPutative differencesLactate kineticsAltered extracellular matrix dynamics is associated with insulin resistance in adolescent children with obesity
Slusher A, Nouws J, Tokoglu F, Vash‐Margita A, Matthews M, Fitch M, Shankaran M, Hellerstein M, Caprio S. Altered extracellular matrix dynamics is associated with insulin resistance in adolescent children with obesity. Obesity 2024, 32: 593-602. PMID: 38410080, PMCID: PMC11034857, DOI: 10.1002/oby.23974.Peer-Reviewed Original ResearchConceptsSubcutaneous adipose tissueLiver fat contentInsulin resistanceInsulin sensitivityEctopic storage of lipidOral glucose tolerance testGluteal subcutaneous adipose tissueExtracellular matrix dynamicsMagnetic resonance imaging scansAdipose tissueBody fat distribution patternsFibrogenesis in vivoAdipocyte turnoverAssociated with insulin resistanceGlucose tolerance testFat distribution patternsWhole-body IRAdipose tissue insulin signalingTissue insulin signalingTolerance testGluteal fatImaging scansPathophysiological pathwaysAssociated with ratioObesity
2023
Incretin effect determines glucose trajectory and insulin sensitivity in youths with obesity
Galderisi A, Tricò D, Lat J, Samuels S, Weiss R, Van Name M, Pierpont B, Santoro N, Caprio S. Incretin effect determines glucose trajectory and insulin sensitivity in youths with obesity. JCI Insight 2023, 8: e165709. PMID: 37847560, PMCID: PMC10721315, DOI: 10.1172/jci.insight.165709.Peer-Reviewed Original ResearchConceptsOral glucose tolerance testΒ-cell functionIncretin effectBeta-cell functionInsulin sensitivityInsulin secretionGlucose levelsCell functionIsoglycemic intravenous glucose infusionGreater insulin sensitivityIntravenous glucose infusionPubertal transitionGlucose tolerance testGLP-17Glucagon suppressionGlucose infusionObesityLongitudinal increaseBaselineOGTTEffect groupGreater increaseLongitudinal trajectoriesSecretionGroupA community health worker-led program to improve access to gestational diabetes screening in urban slums of Pune, India: Results from a mixed methods study
Chebrolu P, Chalem A, Ponticiello M, Broderick K, Vaidyanathan A, Lorenc R, Kulkarni V, Onawale A, Mathad J, Sundararajan R. A community health worker-led program to improve access to gestational diabetes screening in urban slums of Pune, India: Results from a mixed methods study. PLOS Global Public Health 2023, 3: e0001622. PMID: 37889879, PMCID: PMC10610081, DOI: 10.1371/journal.pgph.0001622.Peer-Reviewed Original ResearchUrban slum communityLow-resource settingsGDM careHome-basedPregnant womenOral glucose tolerance testUrban slums of PuneFasting oral glucose tolerance testGDM screeningClinician time constraintsSlum communitiesClinic-based testingHome-based testingGDM prevalenceImprove health educationLack of timeOral glucose tolerance test screeningLow-income populationsGestational diabetes screeningProviders' lackAssess barriersLifestyle counselingManagement of GDMHealth educationDiabetes screening
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