2015
Blunted suppression of acyl‐ghrelin in response to fructose ingestion in obese adolescents: The role of insulin resistance
Van Name M, Giannini C, Santoro N, Jastreboff AM, Kubat J, Li F, Kursawe R, Savoye M, Duran E, Dziura J, Sinha R, Sherwin RS, Cline G, Caprio S. Blunted suppression of acyl‐ghrelin in response to fructose ingestion in obese adolescents: The role of insulin resistance. Obesity 2015, 23: 653-661. PMID: 25645909, PMCID: PMC4548801, DOI: 10.1002/oby.21019.Peer-Reviewed Original ResearchConceptsAcyl ghrelinObese insulinGlucose ingestionInsulin resistanceObese adolescentsCross-over designFructose ingestionGut hormonesChildhood obesityInsulin sensitivityFructose consumptionEffect of glucoseDiminished suppressionRandom orderIngestionObesityPYYAdolescentsInsulinSuppression differencesGlucoseMinutesResponseGhrelinOIR
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 imaging
2011
Cellular mechanism of insulin resistance in nonalcoholic fatty liver disease
Kumashiro N, Erion DM, Zhang D, Kahn M, Beddow SA, Chu X, Still CD, Gerhard GS, Han X, Dziura J, Petersen KF, Samuel VT, Shulman GI. Cellular mechanism of insulin resistance in nonalcoholic fatty liver disease. Proceedings Of The National Academy Of Sciences Of The United States Of America 2011, 108: 16381-16385. PMID: 21930939, PMCID: PMC3182681, DOI: 10.1073/pnas.1113359108.Peer-Reviewed Original ResearchConceptsNonalcoholic fatty liver diseaseFatty liver diseaseHepatic DAG contentInsulin resistanceHepatic insulin resistanceLiver diseaseHepatic steatosisCellular mechanismsHomeostatic model assessmentInsulin resistance indexMarkers of inflammationType 2 diabetesER stress markersLipid dropletsHepatic diacylglycerol contentEndoplasmic reticulum stressActivation of PKCεLiver biopsyNondiabetic individualsHepatocellular lipidsInsulin sensitivityCytoplasmic lipid dropletsDAG contentResistance indexAnimal models
2009
Glucose dysregulation and hepatic steatosis in obese adolescents: Is there a link?
Cali AM, De Oliveira AM, Kim H, Chen S, Reyes‐Mugica M, Escalera S, Dziura J, Taksali SE, Kursawe R, Shaw M, Savoye M, Pierpont B, Constable RT, Caprio S. Glucose dysregulation and hepatic steatosis in obese adolescents: Is there a link? Hepatology 2009, 49: 1896-1903. PMID: 19434725, PMCID: PMC2692562, DOI: 10.1002/hep.22858.Peer-Reviewed Original ResearchConceptsHepatic fat fractionObese adolescentsHepatic fat contentGlucose dysregulationHepatic steatosisMetabolic syndromeFatty liverInsulin sensitivityTotal fatHigher hepatic fat fractionStandard oral glucose tolerance testOral glucose tolerance testTwo-hour plasma glucoseSubcutaneous fat ratioHomeostasis model assessmentAbdominal fat distributionGlucose tolerance testProinflammatory milieuHMW adiponectinIL-6Insulin resistanceMatsuda indexTolerance testPlasma glucoseFat distribution
2008
Primary Defects in β-Cell Function Further Exacerbated by Worsening of Insulin Resistance Mark the Development of Impaired Glucose Tolerance in Obese Adolescents
Cali AM, Man CD, Cobelli C, Dziura J, Seyal A, Shaw M, Allen K, Chen S, Caprio S. Primary Defects in β-Cell Function Further Exacerbated by Worsening of Insulin Resistance Mark the Development of Impaired Glucose Tolerance in Obese Adolescents. Diabetes Care 2008, 32: 456-461. PMID: 19106382, PMCID: PMC2646028, DOI: 10.2337/dc08-1274.Peer-Reviewed Original ResearchConceptsImpaired glucose toleranceNormal glucose toleranceBeta-cell functionBeta-cell responsivityObese adolescentsGlucose toleranceDisposition indexOral glucose tolerance testProgressive declinePre-diabetic stateGlucose tolerance testBMI z-scorePrimary defectGlucose intoleranceGlucose areaTolerance testPlasma glucoseInsulin sensitivityC-peptideInsulin secretionNonprogressorsZ-scoreNatural historyProgressorsPercent fatEffect of a Successful Intensive Lifestyle Program on Insulin Sensitivity and Glucose Tolerance in Obese Youth
Shaw M, Savoye M, Cali A, Dziura J, Tamborlane WV, Caprio S. Effect of a Successful Intensive Lifestyle Program on Insulin Sensitivity and Glucose Tolerance in Obese Youth. Diabetes Care 2008, 32: 45-47. PMID: 18840769, PMCID: PMC2606827, DOI: 10.2337/dc08-0808.Peer-Reviewed Original ResearchConceptsIntensive lifestyle programLifestyle programInsulin sensitivityObese youthBody fatGlucose metabolismLarge randomized clinical trialsOral glucose tolerance testGlucose tolerance testRandomized clinical trialsGlucose toleranceObese childrenControl subjectsTolerance testClinical trialsBody compositionBody weightSubject changesGreater decreaseSubjectsFatMetabolismBMIResearch designBright bodiesSleep-Disordered Breathing in Children With Metabolic Syndrome: The Role of Leptin and Sympathetic Nervous System Activity and the Effect of Continuous Positive Airway Pressure
Nakra N, Bhargava S, Dzuira J, Caprio S, Bazzy-Asaad A. Sleep-Disordered Breathing in Children With Metabolic Syndrome: The Role of Leptin and Sympathetic Nervous System Activity and the Effect of Continuous Positive Airway Pressure. Pediatrics 2008, 122: e634-e642. PMID: 18762497, PMCID: PMC5117807, DOI: 10.1542/peds.2008-0154.Peer-Reviewed Original ResearchConceptsContinuous positive airway pressureSleep-disordered breathingSympathetic nervous system activityPositive airway pressureNervous system activityWhole-body insulin sensitivityMetabolic syndromeAirway pressureLeptin levelsInsulin sensitivitySystem activityExact testContinuous positive airway pressure (CPAP) treatmentPositive airway pressure treatmentC-reactive protein levelsOral glucose tolerance testGlucose tolerance testRole of leptinBMI z-scoreFisher's exact testOvernight polysomnographyBreathing groupMetabolic derangementsInsulin resistanceSleep QuestionnaireShort‐term metabolic and cardiovascular effects of metformin in markedly obese adolescents with normal glucose tolerance
Burgert TS, Duran EJ, Goldberg‐Gell R, Dziura J, Yeckel CW, Katz S, Tamborlane WV, Caprio S. Short‐term metabolic and cardiovascular effects of metformin in markedly obese adolescents with normal glucose tolerance. Pediatric Diabetes 2008, 9: 567-576. PMID: 18761646, DOI: 10.1111/j.1399-5448.2008.00434.x.Peer-Reviewed Original ResearchConceptsNormal glucose toleranceInsulin sensitivityGlucose toleranceObese childrenDouble-blind clinical trialType 2 diabetes mellitusSubcutaneous fatCardio-metabolic consequencesBaseline insulin sensitivityImproved insulin sensitivityInsulin-resistant adolescentsHeart rate recoveryLong-term treatmentDeep subcutaneous fatShort-term useMagnetic resonance imagingPlacebo groupCardiovascular effectsDiabetes mellitusMetS groupClinical effectsLipid parametersInsulin sensitizersInflammatory cytokinesObese adolescents
2007
Interethnic Differences in Muscle, Liver and Abdominal Fat Partitioning in Obese Adolescents
Liska D, Dufour S, Zern TL, Taksali S, Calí AM, Dziura J, Shulman GI, Pierpont BM, Caprio S. Interethnic Differences in Muscle, Liver and Abdominal Fat Partitioning in Obese Adolescents. PLOS ONE 2007, 2: e569. PMID: 17593968, PMCID: PMC1892806, DOI: 10.1371/journal.pone.0000569.Peer-Reviewed Original ResearchConceptsMagnetic resonance imagingLiver fat contentHepatic fat contentInsulin resistanceObese adolescentsAfrican AmericansOral glucose tolerance testingObese Hispanic adolescentsAbdominal fat distributionGlucose tolerance testingType 2 diabetesTotal body fatEthnic differencesClear ethnic differencesVisceral fatInsulin sensitivityFat distributionTolerance testingIMCL levelsMultiethnic cohortObese youthFat contentAbdominal cavityBody fatSoleus muscleDegree of Obesity and Glucose Allostasis Are Major Effectors of Glucose Tolerance Dynamics in Obese Youth
Weiss R, Cali AM, Dziura J, Burgert TS, Tamborlane WV, Caprio S. Degree of Obesity and Glucose Allostasis Are Major Effectors of Glucose Tolerance Dynamics in Obese Youth. Diabetes Care 2007, 30: 1845-1850. PMID: 17475938, DOI: 10.2337/dc07-0325.Peer-Reviewed Original ResearchConceptsOral glucose tolerance testDegree of obesityElevated glucose levelsObese youthGlucose toleranceAmbient glycemiaInsulin sensitivityGlucose levelsSecond oral glucose tolerance testBaseline BMI z-scoreGlucose tolerance testBMI z-scoreAltered glucose metabolismCross-sectional analysisTolerance testInsulin sensitizationGlucose metabolismObesityZ-scoreLongitudinal assessmentLongitudinal changesMajor effectorGlycemiaSignificant reduction
2006
Increased prevalence of insulin resistance and nonalcoholic fatty liver disease in Asian-Indian men
Petersen KF, Dufour S, Feng J, Befroy D, Dziura J, Man C, Cobelli C, Shulman GI. Increased prevalence of insulin resistance and nonalcoholic fatty liver disease in Asian-Indian men. Proceedings Of The National Academy Of Sciences Of The United States Of America 2006, 103: 18273-18277. PMID: 17114290, PMCID: PMC1693873, DOI: 10.1073/pnas.0608537103.Peer-Reviewed Original ResearchConceptsAsian Indian menInsulin resistanceInsulin sensitivity indexLiver diseaseNonalcoholic fatty liver diseaseOral glucose tolerance testType 2 diabetes mellitusAsian IndiansWhole-body insulin sensitivityFatty liver diseaseIL-6 concentrationsTreatment of T2DMIntramyocellular lipid contentGlucose tolerance testPathogenesis of T2DMProton magnetic resonance spectroscopyImportant therapeutic implicationsEthnic groupsDiabetes mellitusImportant ethnic differencesCaucasian manTolerance testInsulin sensitivityIntramyocellular lipidsLean individualsAlanine Aminotransferase Levels and Fatty Liver in Childhood Obesity: Associations with Insulin Resistance, Adiponectin, and Visceral Fat
Burgert TS, Taksali SE, Dziura J, Goodman TR, Yeckel CW, Papademetris X, Constable RT, Weiss R, Tamborlane WV, Savoye M, Seyal AA, Caprio S. Alanine Aminotransferase Levels and Fatty Liver in Childhood Obesity: Associations with Insulin Resistance, Adiponectin, and Visceral Fat. The Journal Of Clinical Endocrinology & Metabolism 2006, 91: 4287-4294. PMID: 16912127, DOI: 10.1210/jc.2006-1010.Peer-Reviewed Original ResearchConceptsIntrahepatic fat accumulationAlanine aminotransferase levelsHepatic fat fractionVisceral fatInsulin sensitivityMagnetic resonance imagingFat accumulationAminotransferase levelsMetabolic syndromeFatty liverInsulin resistanceChildhood obesityResonance imagingLipid metabolismNonalcoholic fatty liver diseaseHispanic race/ethnicityAbdominal fat partitioningSerum aminotransferase elevationFatty liver diseaseBiomarkers of inflammationHepatic fat accumulationReduced insulin sensitivityFat fractionRace/ethnicityAminotransferase elevationEthnic differences in beta cell adaptation to insulin resistance in obese children and adolescents
Weiss R, Dziura JD, Burgert TS, Taksali SE, Tamborlane WV, Caprio S. Ethnic differences in beta cell adaptation to insulin resistance in obese children and adolescents. Diabetologia 2006, 49: 571-579. PMID: 16456682, DOI: 10.1007/s00125-005-0109-z.Peer-Reviewed Original ResearchConceptsEarly insulin responseObese childrenInsulin resistanceInsulin clearanceInsulin responseAims/hypothesisThe prevalenceObesity-related insulin resistanceOral glucose loadLower insulin clearanceType 2 diabetesAcute insulin responseGlucose tolerance levelsAltered glucose metabolismSevere insulin resistanceBeta-cell adaptationAfrican American subjectsEthnic groupsHypothesisThe prevalenceGlucose toleranceGlucose loadInsulin sensitivityGlucose metabolismMethodsSeven hundredClearanceHispanic origin
2005
Exercise and improved insulin sensitivity in older women: evidence of the enduring benefits of higher intensity training
DiPietro L, Dziura J, Yeckel CW, Neufer PD. Exercise and improved insulin sensitivity in older women: evidence of the enduring benefits of higher intensity training. Journal Of Applied Physiology 2005, 100: 142-149. PMID: 16141382, DOI: 10.1152/japplphysiol.00474.2005.Peer-Reviewed Original ResearchConceptsHigh-intensity exercise trainingIntensity exercise trainingExercise trainingAerobic trainingInsulin sensitivityExercise volumeOlder womenGlucose utilizationModerate-intensity aerobic trainingTwo-step euglycemic-hyperinsulinemic clampInsulin-stimulated glucose utilizationHigh-intensity aerobic trainingDual-energy X-ray absorptiometryHigher insulin doseLower insulin doseHealthy older womenEuglycemic hyperinsulinemic clampLow-intensity exerciseTotal body fatAdipose tissue lipolysisImproved glucose utilizationX-ray absorptiometrySuppression of lipolysisFinal exercise boutInsulin-stimulated suppressionThe “Obese Insulin-Sensitive” Adolescent: Importance of Adiponectin and Lipid Partitioning
Weiss R, Taksali SE, Dufour S, Yeckel CW, Papademetris X, Cline G, Tamborlane WV, Dziura J, Shulman GI, Caprio S. The “Obese Insulin-Sensitive” Adolescent: Importance of Adiponectin and Lipid Partitioning. The Journal Of Clinical Endocrinology & Metabolism 2005, 90: 3731-3737. PMID: 15797955, DOI: 10.1210/jc.2004-2305.Peer-Reviewed Original ResearchConceptsInsulin sensitivityVisceral fatLipid depositionObese insulin-resistant adolescentsObese insulin-sensitive subjectsNormal glucose tolerancePeripheral insulin sensitivityIntramyocellular lipid contentBody mass indexInsulin-sensitive subjectsHyperinsulinemic-euglycemic clampInsulin-resistant adolescentsInsulin-sensitive controlsWide interindividual variationLipid partitioningLower lipid depositionPercent body fatMagnetic resonance imagingImportance of adiponectinObese insulinObese groupGlucose toleranceMass indexObese adolescentsIntramyocellular lipids
2004
The Normal Glucose Tolerance Continuum in Obese Youth: Evidence for Impairment in β-Cell Function Independent of Insulin Resistance
Yeckel CW, Taksali SE, Dziura J, Weiss R, Burgert TS, Sherwin RS, Tamborlane WV, Caprio S. The Normal Glucose Tolerance Continuum in Obese Youth: Evidence for Impairment in β-Cell Function Independent of Insulin Resistance. The Journal Of Clinical Endocrinology & Metabolism 2004, 90: 747-754. PMID: 15522932, DOI: 10.1210/jc.2004-1258.Peer-Reviewed Original ResearchConceptsBeta-cell responsivenessNormal glucose tolerancePlasma glucose levelsGlucose levelsGlucose toleranceInsulin sensitivityPlasma glucoseObese youthOral glucose tolerance testType 2 diabetes mellitusDecreased insulinogenic indexGlucose tolerance continuumGlucose tolerance testInsulin sensitivity indexContinuum of riskDelta insulinInsulinogenic indexDiabetes mellitusInsulin resistancePlasma levelsTolerance testNormal rangeFunction IndependentDlGlucose concentrationValidation of Insulin Sensitivity Indices from Oral Glucose Tolerance Test Parameters in Obese Children and Adolescents
Yeckel CW, Weiss R, Dziura J, Taksali SE, Dufour S, Burgert TS, Tamborlane WV, Caprio S. Validation of Insulin Sensitivity Indices from Oral Glucose Tolerance Test Parameters in Obese Children and Adolescents. The Journal Of Clinical Endocrinology & Metabolism 2004, 89: 1096-1101. PMID: 15001593, DOI: 10.1210/jc.2003-031503.Peer-Reviewed Original ResearchConceptsWhole-body insulin sensitivity indexOral glucose tolerance testInsulin sensitivity indexIntramyocellular lipid contentInsulin sensitivityInsulin resistanceObese youthLarge cohortComposite whole body insulin sensitivity indexOral glucose tolerance test parametersSurrogate indexClamp-derived insulin sensitivityImpaired glucose toleranceGlucose tolerance testType 2 diabetesEuglycemic hyperinsulinemic clampInsulin sensitivity measurementsGlucose toleranceMetabolic syndromeObese childrenObese populationPoor functionPlasma glucoseTolerance testInsulin response
2003
Prediabetes in obese youth: a syndrome of impaired glucose tolerance, severe insulin resistance, and altered myocellular and abdominal fat partitioning
Weiss R, Dufour S, Taksali SE, Tamborlane WV, Petersen KF, Bonadonna RC, Boselli L, Barbetta G, Allen K, Rife F, Savoye M, Dziura J, Sherwin R, Shulman GI, Caprio S. Prediabetes in obese youth: a syndrome of impaired glucose tolerance, severe insulin resistance, and altered myocellular and abdominal fat partitioning. The Lancet 2003, 362: 951-957. PMID: 14511928, PMCID: PMC2995523, DOI: 10.1016/s0140-6736(03)14364-4.Peer-Reviewed Original ResearchConceptsImpaired glucose toleranceNormal glucose toleranceGlucose toleranceObese childrenInsulin resistanceObese adolescentsGlucose disposalInsulin sensitivitySevere peripheral insulin resistanceNon-oxidative glucose metabolismSubcutaneous fatH plasma glucose concentrationsAbdominal fat partitioningVisceral lipid contentsPeripheral glucose disposalHigher intramyocellular lipid contentAbdominal fat distributionDegree of obesityIntramyocellular lipid contentPeripheral insulin resistanceHigh visceral fatAbdominal subcutaneous fatEuglycaemic hyperinsulinaemic clampSevere insulin resistancePlasma glucose concentrationLow Adiponectin Levels in Adolescent Obesity: A Marker of Increased Intramyocellular Lipid Accumulation
Weiss R, Dufour S, Groszmann A, Petersen K, Dziura J, Taksali SE, Shulman G, Caprio S. Low Adiponectin Levels in Adolescent Obesity: A Marker of Increased Intramyocellular Lipid Accumulation. The Journal Of Clinical Endocrinology & Metabolism 2003, 88: 2014-2018. PMID: 12727947, DOI: 10.1210/jc.2002-021711.Peer-Reviewed Original ResearchConceptsAdiponectin levelsInsulin sensitivityAdolescent obesityObese adolescentsPutative modulatory effectsLower adiponectin levelsAbdominal fat distributionIntramyocellular lipid contentPlasma adiponectin levelsIntramyocellular lipid accumulationEuglycemic hyperinsulinemic clampTotal body fatMagnetic resonance imagingCentral adiposityPediatric populationInsulin resistanceIntramuscular lipid contentTriglyceride levelsFat distributionLipid contentPlasma triglyceridesFree fatty acidsBody fatModulatory effectsAdiponectin