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 homeostasisSumatriptanPlaceboSecretionTrialsHumansObstructive 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 kinetics342-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-peptideInhibition of 11β‐Hydroxysteroid dehydrogenase‐1 with AZD4017 in patients with nonalcoholic steatohepatitis or nonalcoholic fatty liver disease: A randomized, double‐blind, placebo‐controlled, phase II study
Yadav Y, Dunagan K, Khot R, Venkatesh S, Port J, Galderisi A, Cobelli C, Wegner C, Basu A, Carter R, Basu R. Inhibition of 11β‐Hydroxysteroid dehydrogenase‐1 with AZD4017 in patients with nonalcoholic steatohepatitis or nonalcoholic fatty liver disease: A randomized, double‐blind, placebo‐controlled, phase II study. Diabetes Obesity And Metabolism 2022, 24: 881-890. PMID: 35014156, PMCID: PMC9135169, DOI: 10.1111/dom.14646.Peer-Reviewed Original ResearchConceptsNonalcoholic fatty liver diseaseLiver fat fractionFatty liver diseaseMagnetic resonance imagingMean changePlacebo groupPrimary outcomeLiver diseasePresence of NAFLDSignificant between-group differencesPhase II studyPhase 2 studyKey inclusion criteriaType 2 diabetesBetween-group differencesShort-term treatmentBiopsy positiveII studyNonalcoholic steatohepatitisWeek 12Liver steatosisHepatic fatInsulin sensitivityAZD4017Liver enzymes
2021
Relation of glomerular filtration to insulin resistance and related risk factors in obese children
Magen D, Halloun R, Galderisi A, Caprio S, Weiss R. Relation of glomerular filtration to insulin resistance and related risk factors in obese children. International Journal Of Obesity 2021, 46: 374-380. PMID: 34725443, DOI: 10.1038/s41366-021-01001-2.Peer-Reviewed Original ResearchConceptsGlomerular filtration rateInsulin sensitivityObese childrenInsulin resistanceBlood pressureFiltration rateRisk factorsWhole-body insulin sensitivityChildhood insulin resistanceFuture kidney diseaseRelation of eGFRSignificant renal morbiditySpectrum of obesityCardiovascular risk factorsPresence of microalbuminuriaSystolic blood pressureRelated risk factorsHepatic insulin sensitivityBody insulin sensitivityObjectiveChildhood obesityRenal morbidityClinical outcomesGlucose toleranceMale sexKidney diseaseEarly 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 responseMetabolic 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
1054-P: Insulin Sensitivity from Sensor and Pump Data in Youths with Type 1 Diabetes: Hybrid Closed-Loop Validation
SCHIAVON M, GALDERISI A, KRAEMER K, COBELLI C, MAN C, CENGIZ E. 1054-P: Insulin Sensitivity from Sensor and Pump Data in Youths with Type 1 Diabetes: Hybrid Closed-Loop Validation. Diabetes 2019, 68 DOI: 10.2337/db19-1054-p.Peer-Reviewed Original ResearchContinuous glucose monitoringInsulin sensitivityType 1 diabetesEuropean Medical Information FrameworkInsulin pump dataClosed-loop treatmentOral minimal modelMannKind CorporationSequential mealsInsulin therapyMeal studyPlasma glucoseGlycemic outcomesType 1Glucose monitoringSpeakers bureauMeal variationT1D.T1DInternational SocietyAdvisory PanelPump dataTreatmentSI indexDiabetes
2018
The rs7903146 Variant in the TCF7L2 Gene Increases the Risk of Prediabetes/Type 2 Diabetes in Obese Adolescents by Impairing beta-Cell Function and Hepatic Insulin Sensitivity
C C, N S, L G, C D, C C, A G, R K, B P, M G, S C. The rs7903146 Variant in the TCF7L2 Gene Increases the Risk of Prediabetes/Type 2 Diabetes in Obese Adolescents by Impairing beta-Cell Function and Hepatic Insulin Sensitivity. 2018 DOI: 10.1530/ey.15.12.3.Peer-Reviewed Original ResearchEthnicity 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