2024
Trajectory of beta cell function and insulin clearance in stage 2 type 1 diabetes: natural history and response to teplizumab
Galderisi A, Sims E, Evans-Molina C, Petrelli A, Cuthbertson D, Nathan B, Ismail H, Herold K, Moran A. Trajectory of beta cell function and insulin clearance in stage 2 type 1 diabetes: natural history and response to teplizumab. Diabetologia 2024, 1-16. PMID: 39560746, DOI: 10.1007/s00125-024-06323-0.Peer-Reviewed Original ResearchProgrammed death-1AUC C-peptideSlow progressorsRapid progressorsInsulin secretionInsulin clearanceC-peptideDisease-free survival ratesT effector memory cellsCD8+ T effector memory cellsNatural historyImpact of immunotherapyPlacebo-treated individualsT memory cellsBaseline insulin secretionBeta cell functionInterpreting clinical trialsLoss of insulin secretionDeath-1Elevated insulin secretionPlacebo-treatedTreatment armsTeplizumabClinical trialsDisposition indexEvolving Concepts in Pathophysiology, Screening, and Prevention of Type 1 Diabetes: Report of Diabetes Mellitus Interagency Coordinating Committee Workshop.
Greenbaum C, Nepom G, Wood-Heickman L, Wherrett D, DiMeglio L, Herold K, Krischer J. Evolving Concepts in Pathophysiology, Screening, and Prevention of Type 1 Diabetes: Report of Diabetes Mellitus Interagency Coordinating Committee Workshop. Diabetes 2024, 73: 1780-1790. PMID: 39167668, PMCID: PMC11493760, DOI: 10.2337/dbi24-0020.Peer-Reviewed Original ResearchConceptsType 1 diabetesClinical trialsType 1 Diabetes TrialNetEtiology of type 1 diabetesImmune Tolerance NetworkFood and Drug AdministrationU.S. Food and Drug AdministrationNational Institute of DiabetesDigestive and Kidney DiseasesMultiple immune pathwaysDisease-modifying therapiesMechanism of actionTherapeutic responsePrognostic markerKidney diseaseDrug AdministrationTrialNetClinical diagnosisImmune pathwaysDiabetesTeplizumabRegulatory approvalClinical carePathophysiologyDisease68-OR: Influence of the Type 1 Diabetes Genetic Risk Score on Response to Immunotherapies for Type 1 Diabetes Prevention
REDONDO M, BUNDY B, PARIKH H, YOU L, TRIOLO T, FERRAT L, TEMPLEMAN E, TOSUR M, STECK A, GOTTLIEB P, ONENGUT-GUMUSCU S, RICH S, ORAM R, HEROLD K, KRISCHER J. 68-OR: Influence of the Type 1 Diabetes Genetic Risk Score on Response to Immunotherapies for Type 1 Diabetes Prevention. Diabetes 2024, 73 DOI: 10.2337/db24-68-or.Peer-Reviewed Original ResearchT1D riskAssociated with higher risk of progressionMarkers of response to treatmentNon-HLA single nucleotide polymorphismsEvaluate risk-benefit ratiosHigh risk of progressionGenetic risk scoreSingle nucleotide polymorphismsCox modelType 1 diabetes genetic risk scoreResponse to immunotherapyRisk of progressionIncreased T1D riskAssociated with higher riskResponse to treatmentRisk-benefit ratioInteraction termsT1D preventionType 1 diabetes preventionPrevent T1DTreatment armsHazard ratioScore 2Treated armClinical trialsEarly Metabolic Endpoints Identify Persistent Treatment Efficacy in Recent-Onset Type 1 Diabetes Immunotherapy Trials.
Jacobsen L, Cuthbertson D, Bundy B, Atkinson M, Moore W, Haller M, Russell W, Gitelman S, Herold K, Redondo M, Sims E, Wherrett D, Moran A, Pugliese A, Gottlieb P, Sosenko J, Ismail H. Early Metabolic Endpoints Identify Persistent Treatment Efficacy in Recent-Onset Type 1 Diabetes Immunotherapy Trials. Diabetes Care 2024, 47: 1048-1055. PMID: 38621411, PMCID: PMC11294635, DOI: 10.2337/dc24-0171.Peer-Reviewed Original ResearchConceptsC-peptide area-under-the-curveArea under the curveC-peptideRecent-onset type 1 diabetesTreatment efficacyEarly-phase clinical trialsC-peptide preservationPrimary end pointB cell functionDetect treatment efficacyType 1 diabetesPost hoc analysisRandomized controlled trialsImmune therapyImmunotherapy trialsMonths posttherapyClinical trialsTreatment effectsEnd pointsMetabolic indicesHoc analysisControlled trialsType 1 diabetes trialsMetabolic endpointsIntervention trials
2012
Teplizumab Induces Human Gut-Tropic Regulatory Cells in Humanized Mice and Patients
Waldron-Lynch F, Henegariu O, Deng S, Preston-Hurlburt P, Tooley J, Flavell R, Herold KC. Teplizumab Induces Human Gut-Tropic Regulatory Cells in Humanized Mice and Patients. Science Translational Medicine 2012, 4: 118ra12. PMID: 22277969, PMCID: PMC4131554, DOI: 10.1126/scitranslmed.3003401.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, Monoclonal, HumanizedCD3 ComplexCell MovementDiabetes Mellitus, Type 1Forkhead Transcription FactorsGastrointestinal TractHumansHypoglycemic AgentsInterleukin-10Intestine, SmallL-SelectinMiceMucous MembraneNatalizumabOligonucleotide Array Sequence AnalysisReceptors, CCR6T-Lymphocytes, RegulatoryConceptsHumanized micePeripheral circulationSmall intestineType 1 diabetes mellitusNovel immunologic mechanismIL-10 expressionTreatment of patientsType 1 diabetesSecondary lymph organsHuman immune cellsT cell migrationMechanism of actionGut-tropicImmunologic mechanismsRegulatory cellsDiabetes mellitusImmune therapyInterleukin-10Immune cellsRegulatory cytokinesClinical trialsPreclinical modelsClinical studiesT cellsHuman hematopoietic stem cells