2024
Continuous 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, Man C, Galderisi A. Continuous Glucose Monitoring among Infants Born Very Preterm: Evidence for Accuracy in Neonatal Intensive Care. The Journal Of Pediatrics 2024, 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 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 statesEight-year national multicenter experience on the use of glucarpidase as effective rescue therapy for delayed methotrexate elimination after high-dose methotrexate cycles administered in children with hemato-oncological diseases
Peccatori N, Coppola M, Colombini A, Silvestri D, Bertorello N, Kiren V, Melchionda F, Mura R, Onofrillo D, Gobbi S, Mattera R, Vinti L, Casini T, Santoro N, Sperlì D, D’Ippolito C, Conter V, Biondi A, Rizzari C. Eight-year national multicenter experience on the use of glucarpidase as effective rescue therapy for delayed methotrexate elimination after high-dose methotrexate cycles administered in children with hemato-oncological diseases. 2024, 100202. DOI: 10.1016/j.ejcped.2024.100202.Peer-Reviewed Original ResearchDelayed methotrexate eliminationHigh-dose methotrexateAcute kidney injuryHigh-dose methotrexate cyclesHemato-oncological diseasesRescue therapyMethotrexate eliminationPediatric patientsMedical records of pediatric patientsRecords of pediatric patientsRecovery of renal functionPediatric hemato-oncology patientsElimination of MTXEffective rescue therapyPlasma MTX levelsTreat acute kidney injuryHemato-oncological patientsMethotrexate cyclesChemotherapy blockMulticenter experienceMTX levelsRenal functionMedian timeRetrospective studyRe-challengeModeling 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, 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
2021
Nonalcoholic Fatty Liver Disease (NAFLD) Association with Pediatric Diabetes
Santoro N, Goldberg-Gel R, Caprio S. Nonalcoholic Fatty Liver Disease (NAFLD) Association with Pediatric Diabetes. Contemporary Endocrinology 2021, 181-189. DOI: 10.1007/978-3-030-64133-7_17.BooksNonalcoholic fatty liver diseaseLiver diseaseDevelopment of NAFLDDevelopment of cirrhosisCommon liver diseaseFatty liver diseaseType 2 diabetesType 1 diabetesClinical characteristicsPediatric groupChronic conditionsPediatric diabetesCurrent treatmentHepatocellular carcinomaDiabetesDisease associationsDiseaseCirrhosisCarcinomaPathophysiologyPediatrics
2020
rs641738C>T near MBOAT7 is associated with liver fat, ALT and fibrosis in NAFLD: A meta-analysis
Teo K, Abeysekera KWM, Adams L, Aigner E, Anstee QM, Banales JM, Banerjee R, Basu P, Berg T, Bhatnagar P, Buch S, Canbay A, Caprio S, Chatterjee A, Chen Y, Chowdhury A, Daly AK, Datz C, de Gracia Hahn D, DiStefano JK, Dong J, Duret A, Investigators E, Vreugdenhil A, Alisi A, Socha P, Jańczyk W, Baumann U, Rajwal S, van Mourik I, Lacaille F, Dabbas M, Kelly D, Nobili V, Emdin C, Fairey M, Gerhard G, Consortium G, Eiriksdottir G, Garcia M, Gudnason V, Harris T, Kim L, Launer L, Nalls M, Smith A, Clark J, Hernaez R, Kao W, Mitchell B, Shuldiner A, Yerges-Armstrong L, Borecki I, Carr J, Feitosa M, Wu J, Butler J, Fox C, Hirschhorn J, Hoffmann U, Hwang S, Massaro J, O'Donnell C, Palmer C, Sahani D, Speliotes E, Guo X, Hampe J, Hickman M, Heintz L, Hudert C, Hunter H, Kelly M, Kozlitina J, Krawczyk M, Lammert F, Langenberg C, Lavine J, Li L, Lim H, Loomba R, Luukkonen P, Melton P, Mori T, Palmer N, Parisinos C, Pillai S, Qayyum F, Reichert M, Romeo S, Rotter J, Im Y, Santoro N, Schafmayer C, Speliotes E, Stender S, Stickel F, Still C, Strnad P, Taylor K, Tybjærg-Hansen A, Umano G, Utukuri M, Valenti L, Wagenknecht L, Wareham N, Watanabe R, Wattacheril J, Yaghootkar H, Yki-Järvinen H, Young K, Mann J. rs641738C>T near MBOAT7 is associated with liver fat, ALT and fibrosis in NAFLD: A meta-analysis. Journal Of Hepatology 2020, 74: 20-30. PMID: 32882372, PMCID: PMC7755037, DOI: 10.1016/j.jhep.2020.08.027.Peer-Reviewed Original ResearchConceptsFatty liver diseaseLiver diseaseAlanine aminotransferaseLiver fatRisk factorsSevere fatty liver diseaseCaucasian adultsHigh liver fatSpectrum of NAFLDDiagnosis of NAFLDSerum alanine aminotransferaseSeverity of NAFLDLower serum triglyceridesHigher alanine aminotransferaseCT/MRIDominant genetic modelRelated metabolic phenotypesGenome-wide association studiesPopulation-level dataNAFLD histologyAdvanced fibrosisLiver inflammationSerum triglyceridesHepatic fatAdvanced histologyFatty liver, irrespective of ethnicity, is associated with reduced insulin clearance and insulin resistance in obese youths
Trico D, Galderisi A, Galuppo B, Pierpont B, Samuels S, Santoro N, Caprio S. Fatty liver, irrespective of ethnicity, is associated with reduced insulin clearance and insulin resistance in obese youths. Endocrine Abstracts 2020 DOI: 10.1530/endoabs.70.aep256.Peer-Reviewed Original ResearchEffect of Gut Microbiota and PNPLA3 rs738409 Variant on Nonalcoholic Fatty Liver Disease (NAFLD) in Obese Youth
Kravetz A, Testerman T, Galuppo B, Graf J, Pierpont B, Siebel S, Feinn R, Santoro N. Effect of Gut Microbiota and PNPLA3 rs738409 Variant on Nonalcoholic Fatty Liver Disease (NAFLD) in Obese Youth. The Journal Of Clinical Endocrinology & Metabolism 2020, 105: dgaa382. PMID: 32561908, PMCID: PMC7458486, DOI: 10.1210/clinem/dgaa382.Peer-Reviewed Original ResearchConceptsNon-alcoholic fatty liver diseaseHepatic fat fractionFatty liver diseasePNPLA3 rs738409Obese youthLiver diseaseGut microbiotaDifferent gut microbiota compositionNonalcoholic fatty liver diseaseOral glucose tolerance testPNPLA3 rs738409 variantPediatric obesity clinicGlucose tolerance testCross-sectional studyGut microbiota compositionAbdominal magnetic resonanceNAFLD statusRs738409 variantObesity clinicPNPLA3 genotypeObese childrenTolerance testBacteroidetes ratioCommon causeRs738409
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 Research