2022
342-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 trajectoriesObesitySecretionGlucoseGroupIgM-associated gut bacteria in obesity and type 2 diabetes in C57BL/6 mice and humans
Pearson JA, Ding H, Hu C, Peng J, Galuppo B, Wong FS, Caprio S, Santoro N, Wen L. IgM-associated gut bacteria in obesity and type 2 diabetes in C57BL/6 mice and humans. Diabetologia 2022, 65: 1398-1411. PMID: 35587276, PMCID: PMC9283171, DOI: 10.1007/s00125-022-05711-8.Peer-Reviewed Original ResearchConceptsFecal microbiota transplantType 2 diabetesNormal glucose toleranceB6 miceWild-type miceGlucose toleranceIgM antibodiesObese youthGut microbiotaWeight gainGut bacteriaObese young individualsImpaired glucose toleranceDiet-induced obesityConclusions/interpretationOur resultsBody weight gainGreater weight gainMice fecal microbiotaHuman stool samplesGlucose intoleranceClinical featuresC57BL/6 miceMicrobiota transplantRecipient miceStool samplesA 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-peptide
2020
Fatty 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 ResearchA 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 responseA Low ω-6 to ω-3 PUFA Ratio (n–6:n–3 PUFA) Diet to Treat Fatty Liver Disease in Obese Youth
Van Name MA, Savoye M, Chick JM, Galuppo BT, Feldstein AE, Pierpont B, Johnson C, Shabanova V, Ekong U, Valentino PL, Kim G, Caprio S, Santoro N. A Low ω-6 to ω-3 PUFA Ratio (n–6:n–3 PUFA) Diet to Treat Fatty Liver Disease in Obese Youth. Journal Of Nutrition 2020, 150: 2314-2321. PMID: 32652034, PMCID: PMC7467848, DOI: 10.1093/jn/nxaa183.Peer-Reviewed Original ResearchConceptsFatty liver diseasePNPLA3 rs738409 genotypeLiver diseaseAlanine aminotransferaseRs738409 genotypeInsulin sensitivityObese youthNonalcoholic fatty liver diseaseGenotype groupsWhole-body insulin sensitivityBody insulin sensitivityLinoleic acid metabolitesHepatic fat fractionMann-Whitney U testDiet imbalanceNormocaloric dietPrimary outcomeLDL cholesterolDietary interventionFatty liverUnblinded studyObese adolescentsPUFA dietMetabolic parametersStable weightIntrahepatic 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
2018
Trajectories of changes in glucose tolerance in a multiethnic cohort of obese youths: an observational prospective analysis
Galderisi A, Giannini C, Weiss R, Kim G, Shabanova V, Santoro N, Pierpont B, Savoye M, Caprio S. Trajectories of changes in glucose tolerance in a multiethnic cohort of obese youths: an observational prospective analysis. The Lancet Child & Adolescent Health 2018, 2: 726-735. PMID: 30236381, PMCID: PMC6190831, DOI: 10.1016/s2352-4642(18)30235-9.Peer-Reviewed Original ResearchConceptsImpaired glucose toleranceNormal glucose toleranceOral disposition indexPersistent impaired glucose toleranceGlucose toleranceDisposition indexMultiethnic cohortObese adolescentsInsulin secretionObese youthBaseline normal glucose toleranceOral glucose tolerance testHigh-risk ethnic groupsStudy periodObservational prospective analysisPediatric obesity clinicAmerican Diabetes AssociationGlucose tolerance testAmerican Heart AssociationType 2 diabetesBody insulin sensitivityEthnic originΒ-cell responseΒ-cell functionBlack ethnic originThe 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, PMCID: PMC12136689, 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 metabolism
2016
Psychosocial predictors and moderators of weight management programme outcomes in ethnically diverse obese youth
Taylor JH, Xu Y, Li F, Shaw M, Dziura J, Caprio S, Tamborlane WV, Nowicka P, Savoye M. Psychosocial predictors and moderators of weight management programme outcomes in ethnically diverse obese youth. Pediatric Obesity 2016, 12: 453-461. PMID: 27384496, PMCID: PMC5568975, DOI: 10.1111/ijpo.12165.Peer-Reviewed Original ResearchConceptsClinic careObese youthOutpatient clinic careAbnormal glucose toleranceObesity treatment outcomesObesity intervention programFamily functioningLifestyle interventionGlucose toleranceChildhood obesityLifestyle programTreatment outcomesPsychosocial predictorsIdentification of factorsIntervention programsIntervention outcomesOutcomesPoor family functioningTreatment effectsHigh anxietyBaselineCareMonthsIntervention
2015
Helpful or harmful? Prospective association between weight misperception and weight gain among overweight and obese adolescents and young adults
Sonneville K, Thurston I, Milliren C, Kamody R, Gooding H, Richmond T. Helpful or harmful? Prospective association between weight misperception and weight gain among overweight and obese adolescents and young adults. International Journal Of Obesity 2015, 40: 328-332. PMID: 26303350, DOI: 10.1038/ijo.2015.166.Peer-Reviewed Original ResearchConceptsWeight misperceptionFuture weight gainProspective associationsWeight gainBMI gainLess BMI gainLower BMI gainSubsequent BMI changeWeight perceptionWave IIAccurate weight perceptionPercent of malesBMI changeLinear regression modelingHealthy weightObese adolescentsObese youthWave IVObeseOverweightYoung adultsWeight changeNational Longitudinal StudyLongitudinal studyRegression modelingHepatic De Novo Lipogenesis in Obese Youth Is Modulated by a Common Variant in the GCKR Gene
Santoro N, Caprio S, Pierpont B, Van Name M, Savoye M, Parks EJ. Hepatic De Novo Lipogenesis in Obese Youth Is Modulated by a Common Variant in the GCKR Gene. The Journal Of Clinical Endocrinology & Metabolism 2015, 100: e1125-e1132. PMID: 26043229, PMCID: PMC4524990, DOI: 10.1210/jc.2015-1587.Peer-Reviewed Original ResearchConceptsHepatic de novo lipogenesisDe novo lipogenesisFractional de novo lipogenesisCC subjectsNovo lipogenesisLiver lipid synthesisLow-density lipoproteinCarbohydrate drinkGlucose oxidationObese adolescentsObese youthTT subjectsTT genotypeCHO loadHigh basal ratesStudy aimRisk allelesGCKR geneLipogenesisGene variantsBasal rateCommon variantsSubjectsLipid synthesisLower increase
2014
Co-occurrence of Risk Alleles in or Near Genes Modulating Insulin Secretion Predisposes Obese Youth to Prediabetes
Giannini C, Man C, Groop L, Cobelli C, Zhao H, Shaw MM, Duran E, Pierpont B, Bale AE, Caprio S, Santoro N. Co-occurrence of Risk Alleles in or Near Genes Modulating Insulin Secretion Predisposes Obese Youth to Prediabetes. Diabetes Care 2014, 37: 475-482. PMID: 24062323, PMCID: PMC3898754, DOI: 10.2337/dc13-1458.Peer-Reviewed Original ResearchConceptsIGT/T2DImpaired glucose toleranceNormal glucose toleranceInsulin secretionRisk allelesGlucose toleranceObese childrenChance of progressionType 2 diabetesHigh genetic predispositionHigh-risk scoreOral minimal modelObese subjectsPediatric obesityProgressive worseningHyperglycemic clampObese youthHigh riskLower oddsRisk scoreGenetic predispositionT2DSecretionGene variantsEarly phaseReversal of Early Abnormalities in Glucose Metabolism in Obese Youth: Results of an Intensive Lifestyle Randomized Controlled Trial
Savoye M, Caprio S, Dziura J, Camp A, Germain G, Summers C, Li F, Shaw M, Nowicka P, Kursawe R, DePourcq F, Kim G, Tamborlane WV. Reversal of Early Abnormalities in Glucose Metabolism in Obese Youth: Results of an Intensive Lifestyle Randomized Controlled Trial. Diabetes Care 2014, 37: 317-324. PMID: 24062325, PMCID: PMC3898759, DOI: 10.2337/dc13-1571.Peer-Reviewed Original ResearchConceptsStandard of careClinical careBlood glucoseObese adolescentsObese youthOral glucose tolerance test glucoseIntensive lifestyle modificationDiabetes Prevention ProgramStandard clinical careInsulin sensitivity indexHealthy lifestyle programType 2 diabetesRisk of T2DChildhood obesity epidemicΒ-cell dysfunctionLifestyle modificationControlled TrialsOGTT glucosePrimary outcomeGlucose toleranceInsulin resistanceLifestyle programAnthropometric assessmentEarly abnormalitiesGlucose levels
2012
Longitudinal Effects of MRI-Measured Hepatic Steatosis on Biomarkers of Glucose Homeostasis and Hepatic Apoptosis in Obese Youth
Kim G, Giannini C, Pierpont B, Feldstein AE, Santoro N, Kursawe R, Shaw M, Duran E, Goldberg R, Dziura J, Caprio S. Longitudinal Effects of MRI-Measured Hepatic Steatosis on Biomarkers of Glucose Homeostasis and Hepatic Apoptosis in Obese Youth. Diabetes Care 2012, 36: 130-136. PMID: 22933439, PMCID: PMC3526202, DOI: 10.2337/dc12-0277.Peer-Reviewed Original ResearchConceptsMagnetic resonance imagingWhole-body insulin sensitivityInsulin sensitivityObese youthHepatic steatosisInsulin resistanceHepatocellular apoptosisGlucose homeostasisOral glucose tolerance testHepatic apoptosisAbdominal magnetic resonance imagingCK-18 levelsFatty liver groupGlucose tolerance testHepatic fat contentLiver groupIndependent predictorsFatty liverDisposition indexTolerance testBlood glucoseMetabolic parametersCK-18Multivariate analysisResonance imagingHepatic Fat Accumulation Is Modulated by the Interaction between the rs738409 Variant in the PNPLA3 Gene and the Dietary Omega6/Omega3 PUFA Intake
Santoro N, Savoye M, Kim G, Marotto K, Shaw MM, Pierpont B, Caprio S. Hepatic Fat Accumulation Is Modulated by the Interaction between the rs738409 Variant in the PNPLA3 Gene and the Dietary Omega6/Omega3 PUFA Intake. PLOS ONE 2012, 7: e37827. PMID: 22629460, PMCID: PMC3357343, DOI: 10.1371/journal.pone.0037827.Peer-Reviewed Original ResearchConceptsALT levelsObese youthSingle nucleotide polymorphismsRs738409 single nucleotide polymorphismFatty acid intakeFatty liver developmentLiver fat contentHepatic fat accumulationNutrition Data SystemRs738409 variantPNPLA3 genotypePUFA intakeFatty liverAcid intakeHepatic steatosisHepatic fatLiver damageDietary factorsFat accumulationPNPLA3 geneMRI studiesG alleleALT measurementsPUFA ratioPotential role
2011
Variant in the glucokinase regulatory protein (GCKR) gene is associated with fatty liver in obese children and adolescents
Santoro N, Zhang CK, Zhao H, Pakstis AJ, Kim G, Kursawe R, Dykas DJ, Bale AE, Giannini C, Pierpont B, Shaw MM, Groop L, Caprio S. Variant in the glucokinase regulatory protein (GCKR) gene is associated with fatty liver in obese children and adolescents. Hepatology 2011, 55: 781-789. PMID: 22105854, PMCID: PMC3288435, DOI: 10.1002/hep.24806.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAdolescentApolipoprotein C-IIIBlack or African AmericanChildFatty LiverFemaleGene FrequencyGenetic Predisposition to DiseaseHaplotypesHispanic or LatinoHumansLipaseLipoproteins, VLDLMaleMembrane ProteinsObesityPolymorphism, Single NucleotideRisk FactorsTriglyceridesWhite PeopleConceptsFatty liverObese childrenSingle nucleotide polymorphismsTriglyceride levelsOral glucose tolerance testGlucokinase regulatory proteinGlucose tolerance testHepatic fat accumulationAccumulation of triglyceridesLow-density lipoproteinElevated triglyceridesLarge VLDLTolerance testFat accumulationObese youthGlucokinase regulatory protein geneMagnetic resonancePNPLA3LiverRs1260326African AmericansTriglyceridesLipoproteinChildrenNucleotide polymorphisms
2010
A common variant in the patatin‐like phospholipase 3 gene (PNPLA3) is associated with fatty liver disease in obese children and adolescents
Santoro N, Kursawe R, D'Adamo E, Dykas DJ, Zhang CK, Bale AE, Calí AM, Narayan D, Shaw MM, Pierpont B, Savoye M, Lartaud D, Eldrich S, Cushman SW, Zhao H, Shulman GI, Caprio S. A common variant in the patatin‐like phospholipase 3 gene (PNPLA3) is associated with fatty liver disease in obese children and adolescents. Hepatology 2010, 52: 1281-1290. PMID: 20803499, PMCID: PMC3221304, DOI: 10.1002/hep.23832.Peer-Reviewed Original ResearchConceptsPatatin-like phospholipase 3 geneNonalcoholic fatty liver diseaseFatty liver diseaseG alleleHepatic steatosisLiver diseaseLow leptinObese youthPeripheral glucose disposal rateAdipogenesis/lipogenesisHepatic glucose production ratePNPLA3 G alleleGlucose disposal ratePeripheral insulin resistanceSingle nucleotide polymorphismsSirtuin 1 expressionSubcutaneous fat biopsiesHepatic fat contentAdipocyte cell sizeSubset of subjectsAdipose cell sizeMagnetic resonance imagingAfrican AmericansCommon variantsExpression of PNPLA3High normal fasting glucose level in obese youth: a marker for insulin resistance and beta cell dysregulation
O’Malley G, Santoro N, Northrup V, D’Adamo E, Shaw M, Eldrich S, Caprio S. High normal fasting glucose level in obese youth: a marker for insulin resistance and beta cell dysregulation. Diabetologia 2010, 53: 1199-1209. PMID: 20204321, DOI: 10.1007/s00125-010-1693-0.Peer-Reviewed Original ResearchConceptsBeta-cell functionPlasma glucosePlasma glucose levelsInsulin sensitivityObese youthGlucose levelsType 2 diabetes mellitusConclusions/interpretationThese dataAdverse cardiovascular profileAims/hypothesisAImpaired glucose toleranceCell functionBMI z-scoreCross-sectional analysisAUC 2Standard OGTTCardiovascular profileDiabetes mellitusGlucose toleranceH glucoseInsulin resistanceRisk factorsInterpretationThese dataCardiovascular diseaseCell dysregulation
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