2024
Daily glucose variability is associated with intrahepatic fat content, β cell sensitivity, and biomarkers of glycolysis in youth with obesity
Barbieri E, Bonet J, Fox D, Nelson R, Nelson M, Nelson L, Fernandez C, Van Name M, Samuels S, Caprio S, Sabati M, Galderisi A, Sherr J, Man C, Santoro N. Daily glucose variability is associated with intrahepatic fat content, β cell sensitivity, and biomarkers of glycolysis in youth with obesity. Obesity 2024, 33: 116-124. PMID: 39658509, PMCID: PMC11666407, DOI: 10.1002/oby.24175.Peer-Reviewed Original ResearchConceptsIntrahepatic fat contentDaily glucose variabilityLiver proton density fat fractionProton density fat fractionGlucose variabilityInsulin sensitivityOral glucose tolerance testFat fractionInsulin secretionAssociated with insulin resistanceFirst-phase insulin secretionAssociated with 2-h glucoseGlucose tolerance testGlucose standard deviationMagnetic resonance imagingOral minimal modelCoefficient of variationBasal insulin secretionPediatric obesityPostprandial glucoseTolerance testCell sensitivityInsulin resistanceObesityResonance imagingContinuous Glucose Monitoring among Infants Born Very Preterm: Evidence for Accuracy in Neonatal Intensive Care
Bonet J, Guiducci S, Res G, Brigadoi S, Sen S, Montaldo P, Priante E, Santoro N, Trevisanuto D, Baraldi E, Dalla Man C, Galderisi A. Continuous Glucose Monitoring among Infants Born Very Preterm: Evidence for Accuracy in Neonatal Intensive Care. The Journal Of Pediatrics 2024, 278: 114416. PMID: 39579867, DOI: 10.1016/j.jpeds.2024.114416.Peer-Reviewed Original ResearchBlood glucoseContinuous glucose monitoringSensor glucoseNeonatal intensive care unitInfants born pretermWeeks of gestationNeonatal intensive careIntensive care unitVery pretermGlucose monitoringCare unitIntensive carePoint-of-care blood glucoseInfantsPretermNeonatesPaired measurementsCGM accuracyHoursBirthweightGestationGlucoseBirthWeeksAdipose tissue insulin resistance in children and adolescents: linking glucose and free fatty acid metabolism to hepatic injury markers
Bonet J, Weiss R, Galderisi A, Man C, Caprio S, Santoro N. Adipose tissue insulin resistance in children and adolescents: linking glucose and free fatty acid metabolism to hepatic injury markers. AJP Endocrinology And Metabolism 2024, 327: e723-e728. PMID: 39503461, DOI: 10.1152/ajpendo.00270.2024.Peer-Reviewed Original ResearchImpaired glucose toleranceInsulin sensitivity indexAlanine transaminaseInsulin resistanceFree fatty acid metabolismInsulin sensitivityP<10<sup>-6</sup>Years of follow-upMeasurement of liver function testsLiver function testsFree fatty acidsAdipose tissue insulin resistanceAdipose tissue insulin sensitivityHepatic injury markersPlasma alanine transaminaseEstimated insulin sensitivity indexTissue insulin sensitivityMann-Whitney testTissue insulin resistanceType 2 diabetesDevelopment of insulin resistanceProgression of insulin resistanceOral minimal modelCardiometabolic complicationsInsulin-resistant statesModeling Glucose, Insulin, C-Peptide, and Lactate Interplay in Adolescents During an Oral Glucose Tolerance Test.
Bonet J, Barbieri E, Santoro N, Dalla Man C. Modeling Glucose, Insulin, C-Peptide, and Lactate Interplay in Adolescents During an Oral Glucose Tolerance Test. Journal Of Diabetes Science And Technology 2024, 19322968241266825. PMID: 39076151, PMCID: PMC11572107, DOI: 10.1177/19322968241266825.Peer-Reviewed Original ResearchOral glucose tolerance testArea under the curveGlucose tolerance testC-peptideTolerance testStandard oral glucose tolerance testPathological conditionsTime coursePopulation of adolescentsClinical dataLactate metabolism pathwaysLiver diseaseSteatotic liver diseaseModel glucoseMetabolic diseasesIntersubject variabilityObesityLactate metabolismAnaerobic glycolysisInsulinLactate kineticsDiseaseAdolescentsLactateMetabolic pathwaysModelling and assessment of glucose‐lactate kinetics in youth with overweight, obesity and metabolic dysfunction‐associated steatotic liver disease: A pilot study
Bonet J, Fox D, Nelson R, Nelson M, Nelson L, Fernandez C, Barbieri E, Man C, Santoro N. Modelling and assessment of glucose‐lactate kinetics in youth with overweight, obesity and metabolic dysfunction‐associated steatotic liver disease: A pilot study. Diabetes Obesity And Metabolism 2024, 26: 3207-3212. PMID: 38742538, DOI: 10.1111/dom.15648.Peer-Reviewed Original ResearchOral glucose tolerance testLiver diseaseSteatotic liver diseaseAssess putative differencesArea under the curveProton density fat fractionBody mass indexGlucose tolerance testTime-to-peakMann-Whitney testObese adolescentsSpearman correlation coefficientMass indexTolerance testMann-WhitneyFat fractionWilcoxon testGlucose metabolismInvestigate glucoseLactate production rateEvaluate differencesLactate metabolismObesityPutative differencesLactate kineticsObesity, Growth, Development, Metabolic Disorder, and Insulin Resistance in Pediatrics
Santoro N, Galderisi A, Caprio S. Obesity, Growth, Development, Metabolic Disorder, and Insulin Resistance in Pediatrics. 2024, vol1:608-vol1:616. DOI: 10.1201/9781003437734-70.ChaptersNonalcoholic fatty liver diseaseType 2 diabetesInsulin resistanceAdolescent obesityAssociated with precocious pubertyDevelopment of prediabetesCardiometabolic risk factorsPathogenesis of insulin resistanceFatty liver diseasePrecocious pubertyClinical peculiaritiesPediatric obesityLiver diseaseRisk factorsGlobal health challengeMetabolic disordersObesityFatty liverPathological complicationsPotential mechanismsInsulinHealth challengesChildrenComplicationsDyslipidemia
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 trajectoriesSecretionGroupHigh-frequency variants in PKA signaling-related genes within a large pediatric cohort with obesity or metabolic abnormalities
Bloyd M, Sinaii N, Faucz F, Iben J, Coon S, Caprio S, Santoro N, Stratakis C, London E. High-frequency variants in PKA signaling-related genes within a large pediatric cohort with obesity or metabolic abnormalities. Frontiers In Endocrinology 2023, 14: 1272939. PMID: 38027204, PMCID: PMC10679389, DOI: 10.3389/fendo.2023.1272939.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesSignaling-related genesProtein kinaseHigh-frequency variantsCAMP-dependent protein kinaseLarge-scale genome-wide association studiesNew genetic associationsPDE11A geneGenomic DNAAssociation studiesMonogenic obesityTargeted exome sequencingGenesGenetic variantsEnergy metabolismGenetic associationExome sequencingNovel variantsVariant searchMetabolic characteristicsVariantsKinaseType II diabetesLociSequencingThe lncOb rs10487505 polymorphism impairs insulin sensitivity and glucose tolerance in children and adolescents with obesity
Umano G, Cirillo G, Sanchez G, Rondinelli G, Foderini M, Ferrara S, Di Sessa A, Marzuillo P, Papparella A, Santoro N, del Giudice E. The lncOb rs10487505 polymorphism impairs insulin sensitivity and glucose tolerance in children and adolescents with obesity. Obesity 2023, 31: 2359-2364. PMID: 37550829, DOI: 10.1002/oby.23835.Peer-Reviewed Original ResearchConceptsHomeostasis model assessmentInsulin resistanceDisposition indexLower whole-body insulin sensitivity indexModel assessmentWhole-body insulin sensitivity indexRisk of prediabetesHigher fasting insulinLower disposition indexPlasma leptin levelsInsulin sensitivity indexBMI z-scoreLeptin plasma levelsLeptin gene transcriptionFasting insulinGlucose toleranceLeptin levelsCC patientsRetrospective studyPlasma levelsAnthropometrical evaluationInsulin sensitivityHormone levelsHigh prevalenceHigh riskProatherogenic changes in lipoprotein particles associated with a high triglyceride to high‐density lipoprotein cholesterol ratio in youths
Chiriacò M, Nesti L, Natali A, Santoro N, Caprio S, Tricò D. Proatherogenic changes in lipoprotein particles associated with a high triglyceride to high‐density lipoprotein cholesterol ratio in youths. Obesity 2023, 31: 1894-1902. PMID: 37227148, PMCID: PMC10330115, DOI: 10.1002/oby.23767.Peer-Reviewed Original ResearchConceptsTG/HDL ratioHigh TG/HDL ratioHigh-density lipoprotein cholesterol ratioLipoprotein cholesterol ratioHDL ratioLow-density lipoproteinHigh triglyceridesCholesterol ratioLipoprotein subclassesElevated TG/HDL ratioOral glucose tolerance testAbdominal magnetic resonance imagingIncreased cardiovascular riskTG/HDLOverweight/obesityGlucose tolerance testLipoprotein particle concentrationsIntermediate density lipoproteinPlasma lipoprotein subclassesMagnetic resonance imagingRace/ethnicityProatherogenic changesCardiovascular eventsCardiovascular riskSmall LDLComparison of Metabolic Response to Colonic Fermentation in Lean Youth vs Youth With Obesity
Galuppo B, Umano G, Li Z, Van Name M, Samuels S, Kien C, Cline G, Wagner D, Barbieri E, Tricò D, Santoro N. Comparison of Metabolic Response to Colonic Fermentation in Lean Youth vs Youth With Obesity. JAMA Network Open 2023, 6: e2312530. PMID: 37159195, PMCID: PMC10170343, DOI: 10.1001/jamanetworkopen.2023.12530.Peer-Reviewed Original ResearchConceptsInsulin sensitivity indexCross-sectional studyFree fatty acidsColonic fermentationActive glucagon-like peptide-1Plasma free fatty acidsGlucagon-like peptide-1Indigestible dietary carbohydratesReduction of ghrelinActive GLP-1Health care burdenBody mass indexMetabolic responseInsulin-resistant groupLean youthObese insulinOIS groupPYY responseAnorexigenic responsePediatric obesityMass indexTyrosine tyrosineInsulin resistanceIntravenous infusionHormone secretionStudy protocol for a randomized, controlled trial using a novel, family-centered diet treatment to prevent NAFLD in Hispanic children
Welsh J, Pyo E, Huneault H, Ramirez L, Alazraki A, Alli R, Dunbar S, Khanna G, Knight-Scott J, Pimentel A, Reed B, Rodney-Somersall C, Santoro N, Umpierrez G, Vos M. Study protocol for a randomized, controlled trial using a novel, family-centered diet treatment to prevent NAFLD in Hispanic children. Contemporary Clinical Trials 2023, 129: 107170. PMID: 37019180, PMCID: PMC10734403, DOI: 10.1016/j.cct.2023.107170.Peer-Reviewed Original ResearchConceptsNon-alcoholic fatty liver diseaseHispanic childrenFuture dietary guidelinesFatty liver diseasePrimary study outcomeLiver fat accumulationHigh-risk childrenSignificant hepatic steatosisOne-year interventionPercentile BMIElevated liverSecondary outcomesNAFLD preventionLiver diseaseLiver steatosisNAFLD pathogenesisPrevious diagnosisHepatic fatHepatic steatosisStudy protocolDietary guidelinesFat accumulationLiver disordersMetabolic markersEligibility criteria
2019
Exome sequencing of 20,791 cases of type 2 diabetes and 24,440 controls
Flannick J, Mercader JM, Fuchsberger C, Udler MS, Mahajan A, Wessel J, Teslovich TM, Caulkins L, Koesterer R, Barajas-Olmos F, Blackwell TW, Boerwinkle E, Brody JA, Centeno-Cruz F, Chen L, Chen S, Contreras-Cubas C, Córdova E, Correa A, Cortes M, DeFronzo RA, Dolan L, Drews KL, Elliott A, Floyd JS, Gabriel S, Garay-Sevilla ME, García-Ortiz H, Gross M, Han S, Heard-Costa NL, Jackson AU, Jørgensen ME, Kang HM, Kelsey M, Kim BJ, Koistinen HA, Kuusisto J, Leader JB, Linneberg A, Liu CT, Liu J, Lyssenko V, Manning AK, Marcketta A, Malacara-Hernandez JM, Martínez-Hernández A, Matsuo K, Mayer-Davis E, Mendoza-Caamal E, Mohlke KL, Morrison AC, Ndungu A, Ng MCY, O’Dushlaine C, Payne AJ, Pihoker C, Post W, Preuss M, Psaty B, Vasan R, Rayner N, Reiner A, Revilla-Monsalve C, Robertson N, Santoro N, Schurmann C, So W, Soberón X, Stringham H, Strom T, Tam C, Thameem F, Tomlinson B, Torres J, Tracy R, van Dam R, Vujkovic M, Wang S, Welch R, Witte D, Wong T, Atzmon G, Barzilai N, Blangero J, Bonnycastle L, Bowden D, Chambers J, Chan E, Cheng C, Cho Y, Collins F, de Vries P, Duggirala R, Glaser B, Gonzalez C, Gonzalez M, Groop L, Kooner J, Kwak S, Laakso M, Lehman D, Nilsson P, Spector T, Tai E, Tuomi T, Tuomilehto J, Wilson J, Aguilar-Salinas C, Bottinger E, Burke B, Carey D, Chan J, Dupuis J, Frossard P, Heckbert S, Hwang M, Kim Y, Kirchner H, Lee J, Lee J, Loos R, Ma R, Morris A, O’Donnell C, Palmer C, Pankow J, Park K, Rasheed A, Saleheen D, Sim X, Small K, Teo Y, Haiman C, Hanis C, Henderson B, Orozco L, Tusié-Luna T, Dewey F, Baras A, Gieger C, Meitinger T, Strauch K, Lange L, Grarup N, Hansen T, Pedersen O, Zeitler P, Dabelea D, Abecasis G, Bell G, Cox N, Seielstad M, Sladek R, Meigs J, Rich S, Rotter J, Altshuler D, Burtt N, Scott L, Morris A, Florez J, McCarthy M, Boehnke M. Exome sequencing of 20,791 cases of type 2 diabetes and 24,440 controls. Nature 2019, 570: 71-76. PMID: 31118516, PMCID: PMC6699738, DOI: 10.1038/s41586-019-1231-2.Peer-Reviewed Original ResearchConceptsExome-wide significanceProtein-coding genetic variantsDrug targetsRare variantsGene-level associationsType 2 diabetesRare variant associationsGene setsCandidate genesExome sequencing analysisGenetic variantsNon-diabetic control participantsExome sequencingGenesKnockout micePrioritization effortsDisease riskVariantsFuture targetsControl participantsTargetDiabetesEffect sizeSequencingHeritabilityChapter 11 Pediatric Nonalcoholic Fatty Liver Disease (NAFLD) and Type 2 Diabetes Pathophysiologic Links and Potential Implications
Galderisi A, Martino M, Santoro N. Chapter 11 Pediatric Nonalcoholic Fatty Liver Disease (NAFLD) and Type 2 Diabetes Pathophysiologic Links and Potential Implications. 2019, 91-99. DOI: 10.1016/b978-0-323-55138-0.00011-5.BooksNonalcoholic fatty liver diseaseFatty liver diseaseType 2 diabetesLiver diseasePediatric nonalcoholic fatty liver diseasePathophysiology of NAFLDEnd-stage liver diseaseIndependent risk factorPathophysiologic linkCommon complicationSimple steatosisPediatric obesityInsulin resistanceRisk factorsType 2Disease severityDiseaseDiabetesWide spectrumComplicationsPotential implicationsSteatosisObesityPathophysiologySeverity
2018
Metabolic Features of Nonalcoholic Fatty Liver (NAFL) in Obese Adolescents: Findings From a Multiethnic Cohort
Tricò D, Caprio S, Umano G, Pierpont B, Nouws J, Galderisi A, Kim G, Mata MM, Santoro N. Metabolic Features of Nonalcoholic Fatty Liver (NAFL) in Obese Adolescents: Findings From a Multiethnic Cohort. Hepatology 2018, 68: 1376-1390. PMID: 29665034, PMCID: PMC6173637, DOI: 10.1002/hep.30035.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAdolescentBiopsy, NeedleBody Mass IndexCross-Sectional StudiesFemaleGene Expression RegulationGlucose Tolerance TestHumansImmunohistochemistryInsulin ResistanceMagnetic Resonance ImagingMaleMembrane ProteinsNon-alcoholic Fatty Liver DiseasePediatric ObesityPolymerase Chain ReactionPolymorphism, Single NucleotidePrognosisProspective StudiesROC CurveConceptsNonalcoholic fatty liverNonalcoholic fatty liver diseaseOral glucose tolerance testHepatic fat fractionObese adolescentsFatty liverMagnetic resonance imagingLiver diseaseMultiethnic cohortAbdominal magnetic resonance imagingC-peptide levelsChronic liver diseaseFatty liver diseaseGlucose tolerance testSingle nucleotide polymorphismsAltered glucose homeostasisGlucose toleranceLiver steatosisProspective studyInsulin resistanceTolerance testInsulin sensitivityRisk factorsCommon causeHigh prevalenceThe 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 testThe rs626283 Variant in the MBOAT7 Gene is Associated with Insulin Resistance and Fatty Liver in Caucasian Obese Youth
Umano GR, Caprio S, Di Sessa A, Chalasani N, Dykas DJ, Pierpont B, Bale AE, Santoro N. The rs626283 Variant in the MBOAT7 Gene is Associated with Insulin Resistance and Fatty Liver in Caucasian Obese Youth. The American Journal Of Gastroenterology 2018, 113: 376. PMID: 29485130, DOI: 10.1038/ajg.2018.1.Peer-Reviewed Original ResearchMeSH KeywordsAcyltransferasesAdolescentAllelesBlack or African AmericanChildFemaleGenetic Predisposition to DiseaseGenotypeGlucose Tolerance TestHispanic or LatinoHumansInsulin ResistanceLiverMagnetic Resonance ImagingMaleMembrane ProteinsNon-alcoholic Fatty Liver DiseasePediatric ObesityPolymorphism, Single NucleotideWhite PeopleConceptsCaucasian obese childrenMBOAT7 geneObese childrenLiver diseaseHepatic steatosisInsulin resistanceInsulin sensitivityAlcoholic fatty liver diseaseBody mass index z-scoreOral glucose tolerance testWhole-body insulin sensitivityAlcoholic liver diseaseFatty liver diseaseCurve of glucoseGlucose tolerance testIndex z-scoreMagnetic resonance imagingFatty liverPNPLA3 rs738409Liver damageTolerance testLeading causeMultiethnic cohortObese youthGlucose metabolismChapter 4 Obesity and Type 2 Diabetes in Youths New Challenges to Overcome
Santoro N, Giannini C, Caprio S. Chapter 4 Obesity and Type 2 Diabetes in Youths New Challenges to Overcome. 2018, 43-52. DOI: 10.1016/b978-0-12-812019-4.00004-0.ChaptersInsulin resistanceAge groupsΒ-cellsChapter 4 ObesityPediatric age groupEctopic fat depositionProgression of obesityType 2 diabetesOvert diabetesObesity complicationsObese childrenChildhood obesityMore insulinSerum glucoseInsulin secretionPediatric diseasesNormal rangeType 2Progressive deteriorationObesityFat depositionDiabetesDiseaseComplicationsGroup
2017
Oxidized Derivatives of Linoleic Acid in Pediatric Metabolic Syndrome: Is Their Pathogenic Role Modulated by the Genetic Background and the Gut Microbiota?
Tricò D, Di Sessa A, Caprio S, Chalasani N, Liu W, Liang T, Graf J, Herzog R, Johnson CD, Umano GR, Feldstein AE, Santoro N. Oxidized Derivatives of Linoleic Acid in Pediatric Metabolic Syndrome: Is Their Pathogenic Role Modulated by the Genetic Background and the Gut Microbiota? Antioxidants & Redox Signaling 2017, 30: 241-250. PMID: 28279074, PMCID: PMC6277079, DOI: 10.1089/ars.2017.7049.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAge FactorsBiomarkersChildDelta-5 Fatty Acid DesaturaseDisease SusceptibilityFatty Acid DesaturasesFemaleGastrointestinal MicrobiomeGenetic BackgroundGenetic Predisposition to DiseaseHaplotypesHumansLinoleic AcidLipid MetabolismLipoproteinsMaleMetabolic SyndromeMetabolomeObesityOxidation-ReductionConceptsProatherogenic lipoprotein profilePediatric metabolic syndromeLipoprotein profileGut microbiotaGut bacterial loadMetabolic syndromeObese adolescentsSmall dense low-density lipoproteinBacterial loadAdverse lipoprotein profileLow-density lipoprotein particlesHigher plasma concentrationsLow-density lipoproteinLinoleic acid metabolitesPlasma 9Haplotype AAPathogenic rolePlasma concentrationsGenetic predispositionAcid metabolitesGenetic backgroundLipoprotein particlesMetSSyndromeMicrobiota