2024
Evolving 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 carePathophysiologyDiseaseTeplizumab induces persistent changes in the antigen‐specific repertoire in individuals at‐risk for type 1 diabetes
Lledó-Delgado A, Preston-Hurlburt P, Currie S, Clark P, Linsley P, Long S, Liu C, Koroleva G, Martins A, Tsang J, Herold K. Teplizumab induces persistent changes in the antigen‐specific repertoire in individuals at‐risk for type 1 diabetes. Journal Of Clinical Investigation 2024, 134: e177492. PMID: 39137044, PMCID: PMC11405034, DOI: 10.1172/jci177492.Peer-Reviewed Original ResearchCD8+ T cellsAutoreactive T cellsT cellsType 1 diabetesPeripheral blood CD8+ T cellsBlood CD8+ T cellsExpansion of autoreactive T cellsOperational toleranceExpression of CD127Progression of type 1 diabetesAnti-CD3 mAbAntigen-specific repertoireT cell receptorAt-risk patientsAnalysis of study participantsStudy participantsIL7R expressionTeplizumab groupCD8+Placebo groupCD4+Clinical respondersFree intervalTeplizumabReduced expression of genesComparisons of Metabolic Measures to Predict T1D vs Detect a Preventive Treatment Effect in High-Risk Individuals
Sims E, Cuthbertson D, Jacobsen L, Ismail H, Nathan B, Herold K, Redondo M, Sosenko J. Comparisons of Metabolic Measures to Predict T1D vs Detect a Preventive Treatment Effect in High-Risk Individuals. The Journal Of Clinical Endocrinology & Metabolism 2024, 109: 2116-2123. PMID: 38267821, PMCID: PMC11244203, DOI: 10.1210/clinem/dgae048.Peer-Reviewed Original ResearchSix-month changesPrevention trialsC-peptidePredicting diabetesMetabolic endpointsPreventive treatment effectsMetabolic measuresEffect of disease-modifying therapiesProportional hazards regressionTreatment effectsResponse to immunotherapyMeasurement of glucoseNatural history studiesPrevention StudyHazards regressionInclusion criteriaDisease-modifying therapiesT1D prevention trialsComparing placeboTreatment armsTeplizumabTrialNet PathwayHigh riskDetect treatment effectsCombined glucose
2019
An Anti-CD3 Antibody, Teplizumab, in Relatives at Risk for Type 1 Diabetes
Herold KC, Bundy BN, Long SA, Bluestone JA, DiMeglio LA, Dufort MJ, Gitelman SE, Gottlieb PA, Krischer JP, Linsley PS, Marks JB, Moore W, Moran A, Rodriguez H, Russell WE, Schatz D, Skyler JS, Tsalikian E, Wherrett DK, Ziegler AG, Greenbaum CJ. An Anti-CD3 Antibody, Teplizumab, in Relatives at Risk for Type 1 Diabetes. New England Journal Of Medicine 2019, 381: 603-613. PMID: 31180194, PMCID: PMC6776880, DOI: 10.1056/nejmoa1902226.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAntibodies, Monoclonal, HumanizedCD3 ComplexChildDiabetes Mellitus, Type 1Disease ProgressionDouble-Blind MethodExanthemaFemaleGlucose Tolerance TestHLA-DR3 AntigenHLA-DR4 AntigenHumansLymphocyte CountLymphopeniaMaleMiddle AgedProportional Hazards ModelsT-LymphocytesYoung AdultConceptsType 1 diabetesClinical type 1 diabetesTeplizumab groupPlacebo groupOral glucose tolerance testInsulin-producing beta cellsDouble-blind trialChronic autoimmune diseaseGlucose tolerance testRelatives of patientsRate of diagnosisHigh-risk participantsTransient lymphopeniaAdverse eventsHazard ratioHLA-DR3HLA-DR4Median timeClinical progressionAutoimmune diseasesExogenous insulinCD3 antibodyT cellsTeplizumabClinical disease