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 ResearchMeSH KeywordsAdolescentBlood GlucoseDiabetes Mellitus, Type 2GlucoseHumansIncretinsInsulinInsulin ResistanceObesityConceptsOral 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 homeostasisSumatriptanPlaceboSecretionTrialsHumansA New Index of Insulin Sensitivity from Glucose Sensor and Insulin Pump Data: In Silico and In Vivo Validation in Youths with Type 1 Diabetes
Schiavon M, Galderisi A, Basu A, Kudva Y, Cengiz E, Man C. A New Index of Insulin Sensitivity from Glucose Sensor and Insulin Pump Data: In Silico and In Vivo Validation in Youths with Type 1 Diabetes. Diabetes Technology & Therapeutics 2023, 25: 270-278. PMID: 36648253, PMCID: PMC10066780, DOI: 10.1089/dia.2022.0397.Peer-Reviewed Original Research
2022
β-Cell Function and Insulin Sensitivity in Youth With Early Type 1 Diabetes From a 2-Hour 7-Sample OGTT
Galderisi A, Evans-Molina C, Martino M, Caprio S, Cobelli C, Moran A. β-Cell Function and Insulin Sensitivity in Youth With Early Type 1 Diabetes From a 2-Hour 7-Sample OGTT. The Journal Of Clinical Endocrinology & Metabolism 2022, 108: 1376-1386. PMID: 36546354, PMCID: PMC10188312, DOI: 10.1210/clinem/dgac740.Peer-Reviewed Original ResearchAdipose 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 ResearchMeSH KeywordsAdipocytesAdipose TissueAdolescentBody Mass IndexChildHumansInsulinInsulin ResistancePediatric ObesityConceptsAdipose 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 ResearchMeSH KeywordsAdolescentBlood GlucoseGlucoseGlucose IntoleranceHumansInsulinInsulin ResistanceObesityConceptsOral 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 kineticsSGLT2i Improves Glycemic Control in Patients With Congenital Severe Insulin Resistance.
Galderisi A, Tamborlane W, Taylor SI, Attia N, Moretti C, Barbetti F. SGLT2i Improves Glycemic Control in Patients With Congenital Severe Insulin Resistance. Pediatrics 2022, 150 PMID: 35652305, DOI: 10.1542/peds.2021-055671.Peer-Reviewed Original ResearchConceptsRabson-Mendenhall syndromeGlycemic controlHemoglobin A1cRenal calcium excretionInsulin-resistant diabetesSevere insulin resistanceCalcium excretionUrinary calciumAntidiabetic treatmentDay doseDose escalationSecond patientFirst patientInsulin levelsInsulin resistanceUrinary excretionSerum glucosePatientsEmpagliflozinMild increaseDapagliflozinΒ-hydroxybutyrateTarget rangeA1CExcretionA 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 ResearchMeSH KeywordsAdolescentBlood GlucoseDietFatty Acids, Omega-3GlucoseHumansHyperinsulinismInsulinInsulin ResistanceInsulin, Regular, HumanObesityConceptsOral 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 ResearchMeSH KeywordsAdolescentBlood GlucoseBody Mass IndexChildFemaleHumansHyperinsulinismInsulinInsulin ResistanceLongitudinal StudiesMalePediatric ObesityConceptsDegree 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
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 ResearchMeSH KeywordsAdolescentBody Mass IndexChildFemaleGlomerular Filtration RateHumansInsulin ResistanceKidneyMalePediatric ObesityRisk FactorsConceptsGlomerular 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 testMetabolic syndrome and insulin resistance in pre-pubertal children with psoriasis
Caroppo F, Galderisi A, Ventura L, Belloni Fortina A. Metabolic syndrome and insulin resistance in pre-pubertal children with psoriasis. European Journal Of Pediatrics 2021, 180: 1739-1745. PMID: 33483797, PMCID: PMC8105196, DOI: 10.1007/s00431-020-03924-w.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultBody Mass IndexChildChild, PreschoolHumansInsulinInsulin ResistanceMetabolic SyndromeProspective StudiesPsoriasisRisk FactorsConceptsPre-pubertal childrenMetabolic syndromeInsulin resistanceMetabolic diseasesMetabolic syndrome risk factorsSingle-center prospective studyHomeostatic model assessmentAge-specific percentilesCardiometabolic comorbiditiesChildhood psoriasisProspective studyRisk factorsHigh prevalencePsoriasisModel assessmentSyndromePrevalenceLimited dataYoung childrenChildrenAdultsDiseaseComorbiditiesHOMADiagnosis
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 levels
2019
Lower Insulin Clearance Parallels a Reduced Insulin Sensitivity in Obese Youths and Is Associated With a Decline in β-Cell Function Over Time
Galderisi A, Polidori D, Weiss R, Giannini C, Pierpont B, Tricò D, Caprio S. Lower Insulin Clearance Parallels a Reduced Insulin Sensitivity in Obese Youths and Is Associated With a Decline in β-Cell Function Over Time. Diabetes 2019, 68: 2074-2084. PMID: 31399433, PMCID: PMC6804624, DOI: 10.2337/db19-0120.Peer-Reviewed Original Research
2013
Six cases with severe insulin resistance (SIR) associated with mutations of insulin receptor: Is a Bartter-like syndrome a feature of congenital SIR?
Grasso V, Colombo C, Favalli V, Galderisi A, Rabbone I, Gombos S, Bonora E, Massa O, Meschi F, Cerutti F, Iafusco D, Bonfanti R, Monciotti C, Barbetti F. Six cases with severe insulin resistance (SIR) associated with mutations of insulin receptor: Is a Bartter-like syndrome a feature of congenital SIR? Acta Diabetologica 2013, 50: 951-957. PMID: 23824322, DOI: 10.1007/s00592-013-0490-x.Peer-Reviewed Case Reports and Technical NotesConceptsSevere insulin resistanceRabson-Mendenhall syndromeDonohue syndromePatient 3Insulin resistanceAbsence of hypertensionGene mutationsINSR mutationsInsulin receptor gene mutationsBartter-like syndromeBartter syndrome type IIReceptor gene mutationsYear of birthSevere hirsutismClinical featuresFifth patientPotassium supplementationAcanthosis nigricansHyperreninemic hyperaldosteronismRenal abnormalitiesCongenital syndromePatientsPubertal femalesSyndromeINSR gene