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 indexRevisiting 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 control
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 trajectoriesSecretionGroupQuantifying beta cell function in the preclinical stages of type 1 diabetes
Galderisi A, Carr A, Martino M, Taylor P, Senior P, Dayan C. Quantifying beta cell function in the preclinical stages of type 1 diabetes. Diabetologia 2023, 66: 2189-2199. PMID: 37712956, PMCID: PMC10627950, DOI: 10.1007/s00125-023-06011-5.Peer-Reviewed Original ResearchConceptsType 1 diabetesBeta-cell functionInsulin secretionFunctional beta-cell massEarly pre-symptomatic stagesCell functionPre-symptomatic phaseBeta-cell massDisease-modifying interventionsPre-symptomatic stageContinuous glucose monitoringIslet autoimmunityInsulin sensitivityDisease progressionGlucose profilesInvasive measuresPreclinical stageMetabolic testsProgressive lossDiabetesMetabolic changesGlucose monitoringAvailable testsMeasurable changesOGTTSumatriptan, a serotonin 5HT1B receptor agonist, acutely reduces insulin secretion and sensitivity and glucose effectiveness in overweight humans: A double‐blinded placebo‐controlled cross‐over trial
Golubic R, Ismail M, Josipovic M, Kennet J, Galderisi A, Evans M. Sumatriptan, a serotonin 5HT1B receptor agonist, acutely reduces insulin secretion and sensitivity and glucose effectiveness in overweight humans: A double‐blinded placebo‐controlled cross‐over trial. Diabetes Obesity And Metabolism 2023, 25: 3059-3063. PMID: 37312648, DOI: 10.1111/dom.15176.Peer-Reviewed Original ResearchConceptsPlacebo-controlled cross-over trialIntravenous glucose tolerance testGlucose tolerance testCross-over trialGlucose effectivenessTolerance testInsulin sensitivityInsulin secretionHyperinsulinaemic euglycaemic clampControl blood glucoseGlucoregulatory roleOverweight adultsOverweight humansEuglycaemic clampInsulin levelsGlucose excursionsBlood glucoseReceptor agonistMouse modelGlucose homeostasisSumatriptanPlaceboSecretionTrialsHumansIn silico design and validation of a time-varying PID controller for an artificial pancreas with intraperitoneal insulin delivery and glucose sensing
Libera A, Toffanin C, Drecogna M, Galderisi A, Pillonetto G, Cobelli C. In silico design and validation of a time-varying PID controller for an artificial pancreas with intraperitoneal insulin delivery and glucose sensing. APL Bioengineering 2023, 7: 026105. PMID: 37229215, PMCID: PMC10205143, DOI: 10.1063/5.0145446.Peer-Reviewed Original ResearchIP insulin deliveryInsulin deliveryPeritoneal spaceMeal announcementChronic autoimmune diseaseInsulin kineticsParadigm of treatmentBeta-cell functionIntraperitoneal insulin deliveryType 1 diabetesInpatient trialPeripheral hyperinsulinemiaMacrovascular complicationsGlycemic controlTwo-compartment modelInsulin replacementAutoimmune diseasesInsulin delivery systemsInsulin secretionDaily burdenInsulin pumpAid useCell functionArtificial pancreasDiseaseBeta cell function in the early stages of type 1 diabetes: still a long way ahead of us
Galderisi A. Beta cell function in the early stages of type 1 diabetes: still a long way ahead of us. Pediatric Endocrinology Diabetes And Metabolism 2023, 29: 1-3. PMID: 37218722, PMCID: PMC10226454, DOI: 10.5114/pedm.2023.126360.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsBeta-cell functionType 1 diabetesIslet autoimmunityCell functionFunctional beta-cell massDisease-modifier drugsUnderlying autoimmune processPre-symptomatic phaseBeta-cell massSymptomatic diabetesAutoimmune processClinical onsetSurrogate markerDiabetes progressionC-peptideInsulin secretionModifier drugsEarly changesDiabetesMetabolic changesDysglycaemiaAutoimmunityT1DOnsetModifier treatmentObstructive sleep apnea (OSA) is associated with the impairment of beta-cell response to glucose in children and adolescents with obesity
Umano G, Galderisi A, Aiello F, Martino M, Camponesco O, Di Sessa A, Marzuillo P, Alfonso P, Miraglia del Giudice E. Obstructive sleep apnea (OSA) is associated with the impairment of beta-cell response to glucose in children and adolescents with obesity. International Journal Of Obesity 2023, 47: 257-262. PMID: 36670156, PMCID: PMC10113157, DOI: 10.1038/s41366-023-01257-w.Peer-Reviewed Original ResearchConceptsMild obstructive sleep apneaObstructive sleep apneaOral glucose tolerance testSevere obstructive sleep apneaInsulin secretionSleep apneaPlasma glucoseCardio-respiratory polygraphyTotal insulin secretionApnea-hypopnea indexOxygen desaturation indexBeta-cell responseGlucose tolerance testBeta-cell functionDynamic insulin secretionSpearman correlation testOral minimal modelOGTT studyReleasable insulinOSA severityDesaturation indexPediatric clinicTolerance testInsulin sensitivityLow prevalence
2022
342-OR: Low Incretin Effect Is Associated with Longitudinal Decline of Beta-Cell Function and Insulin Sensitivity in Obese Youth
GALDERISI A, LAT J, SAMUELS S, PIERPONT B, VAN NAME M, SANTORO N, CAPRIO S. 342-OR: Low Incretin Effect Is Associated with Longitudinal Decline of Beta-Cell Function and Insulin Sensitivity in Obese Youth. Diabetes 2022, 71 DOI: 10.2337/db22-342-or.Peer-Reviewed Original ResearchBeta-cell functionIncretin effectInsulin sensitivityInsulin secretionCell functionFirst-phase insulin secretionIsoglycemic intravenous glucose infusionLongitudinal declineReduced β-cell functionEarly insulin secretionLower insulin sensitivityIntravenous glucose infusionΒ-cell functionOral minimal modelIncretin groupsObese youthGlucose infusionRelative increaseNational InstituteTertileLongitudinal trajectoriesObesitySecretionGlucoseGroupA low n‐6 to n‐3 polyunsaturated fatty acid ratio diet improves hyperinsulinaemia by restoring insulin clearance in obese youth
Tricò D, Galderisi A, Van Name MA, Caprio S, Samuels S, Li Z, Galuppo BT, Savoye M, Mari A, Feldstein AE, Santoro N. A low n‐6 to n‐3 polyunsaturated fatty acid ratio diet improves hyperinsulinaemia by restoring insulin clearance in obese youth. Diabetes Obesity And Metabolism 2022, 24: 1267-1276. PMID: 35297549, PMCID: PMC9177628, DOI: 10.1111/dom.14695.Peer-Reviewed Original ResearchConceptsOral glucose tolerance testΒ-cell glucose sensitivityInsulin clearanceΒ-cell functionObese youthInsulin secretionRatio dietGlucose-dependent insulin secretionAbdominal magnetic resonance imagingWhole-body insulin sensitivityImpaired insulin clearancePostload insulin levelsWorse metabolic profileGlucose tolerance testHepatic fat contentDietary-induced changesGlucose sensitivityMagnetic resonance imagingInsulin levelsHepatic fatInsulin resistancePlasma insulinTolerance testInsulin sensitivityC-peptideLack of Evidence for a Causal Role of Hyperinsulinemia in the Progression of Obesity in Children and Adolescents: A Longitudinal Study.
Halloun R, Galderisi A, Caprio S, Weiss R. Lack of Evidence for a Causal Role of Hyperinsulinemia in the Progression of Obesity in Children and Adolescents: A Longitudinal Study. Diabetes Care 2022, 45: 1400-1407. PMID: 35235641, PMCID: PMC9210872, DOI: 10.2337/dc21-2210.Peer-Reviewed Original ResearchConceptsDegree of obesityOral glucose tolerance testCarbohydrate-insulin modelLower postprandial glucosePostprandial glucoseInsulin secretionMultivariate analysisPostprandial glucose levelsPediatric obesity clinicProgression of obesityGlucose tolerance testCurve of insulinDevelopment of obesityGreater insulin secretionGreater increaseLack of evidenceInsulinogenic indexObesity clinicLower BMIObesity managementTolerance testGlucose levelsPeak insulinHyperinsulinemiaObesity
2020
A Reduced Incretin Effect Mediated by the rs7903146 Variant in the TCF7L2 Gene Is an Early Marker of β-Cell Dysfunction in Obese Youth
Galderisi A, Tricò D, Pierpont B, Shabanova V, Samuels S, Man C, Galuppo B, Santoro N, Caprio S. A Reduced Incretin Effect Mediated by the rs7903146 Variant in the TCF7L2 Gene Is an Early Marker of β-Cell Dysfunction in Obese Youth. Diabetes Care 2020, 43: 2553-2563. PMID: 32788279, PMCID: PMC7510033, DOI: 10.2337/dc20-0445.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAllelesBiomarkersEarly DiagnosisFemaleGenotypeGlucose IntoleranceGlucose Tolerance TestHumansIncretinsInsulinInsulin ResistanceInsulin SecretionInsulin-Secreting CellsMalePancreatic DiseasesPediatric ObesityPolymorphism, Single NucleotideTranscription Factor 7-Like 2 ProteinYoung AdultConceptsOral glucose tolerance testIncretin effectRs7903146 variantObese youthVariant rs7903146Obese adolescentsHyperglycemic clampInsulin sensitivityInsulin secretionC-peptide secretion rateIsoglycemic intravenous glucose infusionGlucose-induced insulin secretionImpaired glucose toleranceMetabolic phenotypeGlucose tolerance testLower insulin secretionPlasma glucose peakIntravenous glucose infusionΒ-cell functionPlasma glucose concentrationΒ-cell dysfunctionT risk alleleTranscription factor 7Wild-type genotypeIncretin response