2024
Revisiting 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 trajectoriesSecretionGroupSumatriptan, 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 homeostasisSumatriptanPlaceboSecretionTrialsHumansScreening strategies for glucose tolerance abnormalities and diabetes in people with cystic fibrosis
Weiss L, Reix P, Mosnier-Pudar H, Ronsin O, Beltrand J, Reynaud Q, Mely L, Burgel P, Stremler N, Rakotoarisoa L, Galderisi A, Perge K, Bendelac N, Abely M, Kessler L. Screening strategies for glucose tolerance abnormalities and diabetes in people with cystic fibrosis. Diabetes & Metabolism 2023, 49: 101444. PMID: 37030530, DOI: 10.1016/j.diabet.2023.101444.Peer-Reviewed Original ResearchConceptsGlucose tolerance abnormalitiesCystic fibrosis-related diabetesTolerance abnormalitiesCystic fibrosisAnnual oral glucose tolerance testOral glucose tolerance testGlucose tolerance testLong asymptomatic periodStage of diabetesNew comorbiditiesAsymptomatic periodClinical profileTolerance testNew diagnostic toolsPathophysiological knowledgeDiabetesNutritional outcomesPatientsFibrosisAbnormalitiesScreening strategyLife expectancyDiagnostic toolScreening methodComorbiditiesObstructive 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
Adipose Tissue Insulin Resistance Is Not Associated With Changes in the Degree of Obesity in Children and Adolescents
Halloun R, Galderisi A, Caprio S, Weiss R. Adipose Tissue Insulin Resistance Is Not Associated With Changes in the Degree of Obesity in Children and Adolescents. The Journal Of Clinical Endocrinology & Metabolism 2022, 108: 1053-1060. PMID: 36469736, PMCID: PMC10306082, DOI: 10.1210/clinem/dgac700.Peer-Reviewed Original ResearchConceptsAdipose tissue insulin resistanceDegree of obesityTissue insulin resistanceWhole-body insulin sensitivityTissue insulin sensitivityInsulin resistanceInsulin sensitivityMultivariate analysisSecondary analysisBody mass index z-scorePediatric weight management clinicOral glucose tolerance testInsulin sensitivity/resistanceSkeletal muscle insulin resistanceFree fatty acid concentrationsWeight management clinicGlucose tolerance testMain outcome measuresDevelopment of obesityIndex z-scoreCarbohydrate-insulin modelMuscle insulin resistanceSensitivity/resistanceManagement clinicTolerance testMechanistic Insights Into the Heterogeneity of Glucose Response Classes in Youths With Obesity: A Latent Class Trajectory Approach
Tricò D, McCollum S, Samuels S, Santoro N, Galderisi A, Groop L, Caprio S, Shabanova V. Mechanistic Insights Into the Heterogeneity of Glucose Response Classes in Youths With Obesity: A Latent Class Trajectory Approach. Diabetes Care 2022, 45: 1841-1851. PMID: 35766976, PMCID: PMC9346992, DOI: 10.2337/dc22-0110.Peer-Reviewed Original ResearchConceptsOral glucose tolerance testΒ-cell functionΒ-cell glucose sensitivityInsulin sensitivityGenetic risk profileMultiple oral glucose tolerance testsDifferent genetic risk profilesRisk profileMin oral glucose tolerance testLatent class trajectory analysisGlucose tolerance testImpaired insulin sensitivityPlasma glucose responseGlucose sensitivityClass 3Model-predicted probabilityClass 1Tolerance testProgressive impairmentMultiethnic cohortGlucose responseLongitudinal changesObesityTransient reductionInsulin kineticsA 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
2021
Early Impairment of Insulin Sensitivity, β-Cell Responsiveness, and Insulin Clearance in Youth with Stage 1 Type 1 Diabetes
Galderisi A, Moran A, Evans-Molina C, Martino M, Santoro N, Caprio S, Cobelli C. Early Impairment of Insulin Sensitivity, β-Cell Responsiveness, and Insulin Clearance in Youth with Stage 1 Type 1 Diabetes. The Journal Of Clinical Endocrinology & Metabolism 2021, 106: 2660-2669. PMID: 34000022, PMCID: PMC8372628, DOI: 10.1210/clinem/dgab344.Peer-Reviewed Original ResearchConceptsOral glucose tolerance testΒ-cell responsivenessInsulin secretion rateΒ-cell functionInsulin sensitivityInsulin clearanceIslet autoantibodiesGlucose toleranceMultiple islet autoantibodiesOGTT glucose concentrationsPlasma insulin AUCImpaired glucose toleranceNormal glucose toleranceGlucose tolerance testType 1 diabetesReduced insulin sensitivityRatio of AUCOral minimal modelLean youthInsulin AUCClinical onsetInsulin levelsDisposition indexPresymptomatic phaseTolerance test
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 responseIntrahepatic fat, irrespective of ethnicity, is associated with reduced endogenous insulin clearance and hepatic insulin resistance in obese youths: A cross‐sectional and longitudinal study from the Yale Pediatric NAFLD cohort
Tricò D, Galderisi A, Mari A, Polidori D, Galuppo B, Pierpont B, Samuels S, Santoro N, Caprio S. Intrahepatic fat, irrespective of ethnicity, is associated with reduced endogenous insulin clearance and hepatic insulin resistance in obese youths: A cross‐sectional and longitudinal study from the Yale Pediatric NAFLD cohort. Diabetes Obesity And Metabolism 2020, 22: 1628-1638. PMID: 32363679, PMCID: PMC8174801, DOI: 10.1111/dom.14076.Peer-Reviewed Original ResearchConceptsHepatic insulin resistance indexNon-alcoholic fatty liver diseaseEndogenous insulin clearanceInsulin secretion rateInsulin clearanceHepatic insulin resistanceObese youthInsulin resistanceOral glucose tolerance testIntrahepatic fat accumulationIntrahepatic fat contentReduced insulin clearanceInsulin resistance indexFatty liver diseaseGlucose tolerance testWaist-hip ratioIntrahepatic lipid accumulationHepatic insulin sensitivityPlasma glucose levelsMulti-ethnic cohortC-peptide dataNAFLD cohortIntrahepatic fatLiver diseaseInsulin levelsMetabolic and Genetic Determinants of Glucose Shape After Oral Challenge in Obese Youths: A Longitudinal Study
Galderisi A, Tricò D, Man C, Santoro N, Pierpont B, Groop L, Cobelli C, Caprio S. Metabolic and Genetic Determinants of Glucose Shape After Oral Challenge in Obese Youths: A Longitudinal Study. The Journal Of Clinical Endocrinology & Metabolism 2020, 105: dgz207. PMID: 31972003, PMCID: PMC6977541, DOI: 10.1210/clinem/dgz207.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAllelesChildCross-Sectional StudiesDiabetes Mellitus, Type 2FemaleGenetic Predisposition to DiseaseGenotypeGlucoseGlucose IntoleranceGlucose Tolerance TestHumansInsulin SecretionInsulin-Secreting CellsLongitudinal StudiesMalePediatric ObesityPrediabetic StateTime FactorsTranscription Factor 7-Like 2 ProteinYoung AdultConceptsOral glucose tolerance testTCF7L2 rs7903146 variantΒ-cell responsivenessObese youthT risk alleleDisposition indexGlucose peakRs7903146 variantTCF7L2 rs7903146Lower disposition indexGlucose tolerance testOral minimal modelGlucose toleranceOral challengeDiabetes riskTolerance testInsulin sensitivityHigh glucose concentrationsLate peak groupMetabolic phenotypeGlucose concentrationLongitudinal studyReproducible markerPrevalenceRs7903146
2019
Fructose Consumption Contributes to Hyperinsulinemia in Adolescents With Obesity Through a GLP-1–Mediated Mechanism
Galderisi A, Giannini C, Van Name M, Caprio S. Fructose Consumption Contributes to Hyperinsulinemia in Adolescents With Obesity Through a GLP-1–Mediated Mechanism. The Journal Of Clinical Endocrinology & Metabolism 2019, 104: 3481-3490. PMID: 30938760, PMCID: PMC6599430, DOI: 10.1210/jc.2019-00161.Peer-Reviewed Original ResearchConceptsLean adolescentsGLP-1Insulin responseFructose consumptionBaseline oral glucose tolerance testGlucagon-like peptide-1 secretionOral glucose tolerance testGlucose-dependent insulinotropic polypeptideHigher GLP-1Plasma glucose excursionsGLP-1 responsePeptide-1 secretionGlucose tolerance testIngestion of glucoseΒ-cell functionMeasures of glucoseEligible subjectsGlucose ingestionGlucose toleranceLean adultsAnorexic effectFructose challengeGreater insulinInsulinotropic polypeptideLean group
2018
Ethnicity and Common Genetic Variants Modulate Nonalcoholic Fatty Liver Disease (NAFLD) Metabolic Phenotype in Obese Youth
TRICO D, CAPRIO S, UMANO G, GALDERISI A, MATA M, NOUWS J, PIERPONT B, KIM G, SANTORO N. Ethnicity and Common Genetic Variants Modulate Nonalcoholic Fatty Liver Disease (NAFLD) Metabolic Phenotype in Obese Youth. Diabetes 2018, 67 DOI: 10.2337/db18-313-or.Peer-Reviewed Original ResearchNonalcoholic fatty liver diseasePediatric nonalcoholic fatty liver diseaseType 2 diabetesInsulin resistanceObese adolescentsInsulin sensitivityPrevalence of NAFLDHigher C-peptide levelsOral glucose tolerance testAfrican AmericansC-peptide levelsHigh fasting glucoseFatty liver diseaseGlucose tolerance testLower insulin sensitivityMajor risk factorZ-score BMIHepatic fat contentStrongest predictorCommon gene variantsFasting GlucoseNAFLD developmentGlucose toleranceLiver diseaseTolerance test