2019
Screening eye exams in youth with type 1 diabetes under 18 years of age: Once may be enough?
Gubitosi‐Klug R, Bebu I, White NH, Malone J, Miller R, Lorenzi GM, Hainsworth DP, Trapani VR, Lachin JM, Tamborlane WV, Group* F. Screening eye exams in youth with type 1 diabetes under 18 years of age: Once may be enough? Pediatric Diabetes 2019, 20: 743-749. PMID: 31206973, PMCID: PMC7217664, DOI: 10.1111/pedi.12877.Peer-Reviewed Original ResearchConceptsYears of ageType 1 diabetesDiabetic retinopathyEye examEarly Treatment Diabetic Retinopathy Study (ETDRS) scaleMild non-proliferative diabetic retinopathyDiabetic Retinopathy Study scaleNon-proliferative diabetic retinopathyDiabetic retinopathy assessmentDiabetic retinopathy statusBaseline glycated hemoglobinClinical trial evidenceSignificant macular edemaProliferative diabetic retinopathyStandardized clinical trialsDiabetic retinopathy examinationsRetinopathy assessmentRetinopathy statusBaseline characteristicsComplications TrialMacular edemaCase seriesDiabetes controlIncident casesTrial evidenceRisk Factors for Kidney Disease in Type 1 Diabetes
Perkins BA, Bebu I, de Boer IH, Molitch M, Tamborlane W, Lorenzi G, Herman W, White NH, Pop-Busui R, Paterson AD, Orchard T, Cowie C, Lachin JM, Group O. Risk Factors for Kidney Disease in Type 1 Diabetes. Diabetes Care 2019, 42: dc182062. PMID: 30833370, PMCID: PMC6489116, DOI: 10.2337/dc18-2062.Peer-Reviewed Original ResearchConceptsHigher systolic blood pressureHigher mean triglyceridesSystolic blood pressureRisk factorsKidney diseaseBlood pressureIncident macroalbuminuriaMean triglyceridesMultivariable Cox proportional hazards modelsGlomerular filtration rate lossCox proportional hazards modelComplications Trial (DCCT) cohortNonglycemic risk factorsModifiable risk factorsFrequency of screeningAssociation of baselineType 1 diabetesProportional hazards modelGlycemic exposureTrial cohortDiabetes controlMale sexHazards modelClinical strategiesAdvanced stage
2017
Insulin Pump Use in Young Children with Type 1 Diabetes: Sociodemographic Factors and Parent-Reported Barriers
Commissariat PV, Boyle CT, Miller KM, Mantravadi MG, DeSalvo DJ, Tamborlane WV, Van Name MA, Anderson BJ, DiMeglio LA, Laffel LM. Insulin Pump Use in Young Children with Type 1 Diabetes: Sociodemographic Factors and Parent-Reported Barriers. Diabetes Technology & Therapeutics 2017, 19: 363-369. PMID: 28581817, PMCID: PMC6435342, DOI: 10.1089/dia.2016.0375.Peer-Reviewed Original ResearchMeSH KeywordsBlood GlucoseBlood Glucose Self-MonitoringChildChild, PreschoolCohort StudiesCross-Sectional StudiesDiabetes Mellitus, Type 1FemaleGlycated HemoglobinHealth Care SurveysHumansHypoglycemic AgentsInsulinInsulin Infusion SystemsMaleMonitoring, AmbulatoryParentsPatient Acceptance of Health CarePatient PreferenceRegistriesSocioeconomic FactorsUnited StatesConceptsBlood glucose monitoringContinuous glucose monitoringGlycemic controlGlucose monitoringMore frequent blood glucose monitoringPump usersYoung childrenFrequent blood glucose monitoringParent-reported reasonsDuration of diabetesOverall glycemic controlInsulin pump useT1D Exchange RegistryParent-reported barriersType 1 diabetesAnnual household incomeClinical characteristicsT1D durationParents of childrenPump therapyCGM usePump useSociodemographic factorsTherapeutic effectivenessType 1The Risk of Severe Hypoglycemia in Type 1 Diabetes Over 30 Years of Follow-up in the DCCT/EDIC Study
Gubitosi-Klug RA, Braffett BH, White NH, Sherwin RS, Service FJ, Lachin JM, Tamborlane WV, Group T. The Risk of Severe Hypoglycemia in Type 1 Diabetes Over 30 Years of Follow-up in the DCCT/EDIC Study. Diabetes Care 2017, 40: dc162723. PMID: 28550194, PMCID: PMC5521975, DOI: 10.2337/dc16-2723.Peer-Reviewed Original ResearchConceptsSevere hypoglycemiaTreatment groupsMean HbADiabetes therapyDCCT/EDIC cohortDCCT/EDIC studyIntensive diabetes therapyIntensive treatment groupSevere hypoglycemia ratesConventional treatment groupDuration of diabetesConventional diabetes therapyType 1 diabetesComplications (DCCT/EDIC) cohortEDIC studySimilar HbAComplications TrialHypoglycemia ratesLower HbADiabetes controlDCCT studyRisk factorsRelative riskHypoglycemiaLower risk
2016
Clinical outcomes in youth beyond the first year of type 1 diabetes: Results of the Pediatric Diabetes Consortium (PDC) type 1 diabetes new onset (NeOn) study
Cengiz E, Cheng P, Ruedy KJ, Kollman C, Tamborlane WV, Klingensmith GJ, Gal RL, Silverstein J, Lee J, Redondo MJ, Beck RW, Consortium F. Clinical outcomes in youth beyond the first year of type 1 diabetes: Results of the Pediatric Diabetes Consortium (PDC) type 1 diabetes new onset (NeOn) study. Pediatric Diabetes 2016, 18: 566-573. PMID: 27758023, PMCID: PMC5397378, DOI: 10.1111/pedi.12459.Peer-Reviewed Original ResearchMeSH KeywordsAcademic Medical CentersAdolescentChildChild, PreschoolCohort StudiesDiabetes Mellitus, Type 1Diabetic KetoacidosisDisease ProgressionDrug MonitoringFemaleFollow-Up StudiesGlycated HemoglobinHumansHyperglycemiaHypoglycemiaHypoglycemic AgentsInsulinInsulin SecretionInsulin-Secreting CellsMaleProspective StudiesRiskSeverity of Illness IndexUnited StatesConceptsType 1 diabetesPercentage of participantsClinical outcomesDiabetic ketoacidosisGlycemic controlResidual endogenous insulin secretionCourse of T1D.Pediatric Diabetes ConsortiumYears of diabetesOnset StudyEndogenous insulin secretionOptimal glycemic controlTime of diagnosisDuration of T1DNew insulin analoguesNovel treatment strategiesAdjunctive pharmacologic agentsFirst yearPartial remissionDiabetes CenterInsulin doseYears postdiagnosisMonths postdiagnosisGlycated hemoglobinPharmacologic agentsA cross‐sectional view of the current state of treatment of youth with type 2 diabetes in the USA: enrollment data from the Pediatric Diabetes Consortium Type 2 Diabetes Registry
Nambam B, Silverstein J, Cheng P, Ruedy KJ, Beck RW, Wadwa R, Klingensmith G, Willi SM, Wood JR, Bacha F, Thomas IH, Tamborlane WV, Consortium F. A cross‐sectional view of the current state of treatment of youth with type 2 diabetes in the USA: enrollment data from the Pediatric Diabetes Consortium Type 2 Diabetes Registry. Pediatric Diabetes 2016, 18: 222-229. PMID: 26970319, DOI: 10.1111/pedi.12377.Peer-Reviewed Original ResearchMeSH KeywordsAcademic Medical CentersAdolescentAdultChildCohort StudiesCombined Modality TherapyComorbidityCross-Sectional StudiesDiabetes Mellitus, Type 2Glycated HemoglobinHumansHyperglycemiaHypoglycemiaMedical RecordsPractice Patterns, Physicians'PrevalenceRegistriesRisk FactorsUnited StatesYoung AdultGlucagon Nasal Powder: A Promising Alternative to Intramuscular Glucagon in Youth With Type 1 Diabetes
Sherr JL, Ruedy KJ, Foster NC, Piché CA, Dulude H, Rickels MR, Tamborlane WV, Bethin KE, DiMeglio LA, Fox LA, Wadwa RP, Schatz DA, Nathan BM, Marcovina SM, Rampakakis E, Meng L, Beck RW. Glucagon Nasal Powder: A Promising Alternative to Intramuscular Glucagon in Youth With Type 1 Diabetes. Diabetes Care 2016, 39: 555-562. PMID: 26884472, PMCID: PMC4806770, DOI: 10.2337/dc15-1606.Peer-Reviewed Original ResearchMeSH KeywordsAdministration, IntranasalAdolescentBlood GlucoseChildChild, PreschoolCohort StudiesCross-Over StudiesDiabetes Mellitus, Type 1Dose-Response Relationship, DrugDouble-Blind MethodDrug-Related Side Effects and Adverse ReactionsFemaleGlucagonHumansHypoglycemiaInjections, IntramuscularInsulinMaleNauseaPowdersConceptsIntramuscular glucagonType 1 diabetesIntranasal dosesIntranasal glucagonYounger cohortsWeight-based doseMin of dosingTreatment of hypoglycemiaDose-response relationshipTransient nauseaDl riseSevere hypoglycemiaGlucagon levelsIntranasal doseClinical centersPlasma glucosePharmacodynamic studiesHospital settingGlucagon preparationPotential efficacyGlucagonType 1Adverse effectsCohortAge range
2015
Vitamin D status in youth with type 1 and type 2 diabetes enrolled in the Pediatric Diabetes Consortium (PDC) is not worse than in youth without diabetes
Wood JR, Connor CG, Cheng P, Ruedy KJ, Tamborlane WV, Klingensmith G, Schatz D, Gregg B, Cengiz E, Willi S, Bacha F, Beck RW, Consortium T. Vitamin D status in youth with type 1 and type 2 diabetes enrolled in the Pediatric Diabetes Consortium (PDC) is not worse than in youth without diabetes. Pediatric Diabetes 2015, 17: 584-591. PMID: 26611890, PMCID: PMC4882286, DOI: 10.1111/pedi.12340.Peer-Reviewed Original ResearchConceptsPediatric Diabetes ConsortiumVitamin D levelsType 2 diabetesD levelsRace/ethnicityNHANES surveyVitamin D deficiency/insufficiencyVitamin D supplementationDeficiency/insufficiencyVitamin D deficiencyVitamin D statusVitamin D sufficiencyType 1 diabetesAge-matched youthNon-Hispanic whitesD sufficiencyD supplementationD deficiencyD statusVitamin DDiabetesSocio-economic statusType 1InsufficiencySubstantial proportionPrevalence of cardiovascular risk factors in youth with type 1 diabetes and elevated body mass index
Redondo MJ, Foster NC, Libman IM, Mehta SN, Hathway JM, Bethin KE, Nathan BM, Ecker MA, Shah AC, DuBose SN, Tamborlane WV, Hoffman RP, Wong JC, Maahs DM, Beck RW, DiMeglio LA. Prevalence of cardiovascular risk factors in youth with type 1 diabetes and elevated body mass index. Acta Diabetologica 2015, 53: 271-277. PMID: 26077171, DOI: 10.1007/s00592-015-0785-1.Peer-Reviewed Original ResearchConceptsType 1 diabetesCardiovascular risk factorsHealthy weight participantsWeight participantsRisk factorsElevated body mass indexHealthy weight peersFrequency of hypertensionDiagnosis of hypertensionHealthy weight childrenBody mass indexYears of ageWarrants further investigationConclusionsObese childrenMass indexObese participantsT1D ExchangeWeight childrenMedical recordsPrevention criteriaWeight statusAimThe prevalenceHigh prevalenceChildren 2Dyslipidemia
2013
Pediatric diabetes consortium T1D New Onset (NeOn) study: clinical outcomes during the first year following diagnosis
Cengiz E, Connor CG, Ruedy KJ, Beck RW, Kollman C, Klingensmith GJ, Tamborlane WV, Lee JM, Haller MJ, Consortium F. Pediatric diabetes consortium T1D New Onset (NeOn) study: clinical outcomes during the first year following diagnosis. Pediatric Diabetes 2013, 15: 287-293. PMID: 23944865, PMCID: PMC3844085, DOI: 10.1111/pedi.12068.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentChildChild, PreschoolCohort StudiesDiabetes Mellitus, Type 1Diabetic KetoacidosisDrug MonitoringFemaleFollow-Up StudiesGlycated HemoglobinHumansHyperglycemiaHypoglycemiaHypoglycemic AgentsIncidenceInfantInsulinKaplan-Meier EstimateMaleProportional Hazards ModelsProspective StudiesUnited StatesConceptsPediatric Diabetes ConsortiumDiabetic ketoacidosisClinical outcomesNatural historyFirst yearCourse of T1DDiagnosis of T1D.Onset of T1DTime of diagnosisSevere hypoglycemic eventsType 1 diabetesMean HbA1cMulticenter studyHypoglycemic eventsClinical measuresLarge cohortIntervention studiesDiagnosisFuture interventionsMonthsOnset StudyHbA1cT1D.T1DOutcomesPediatric Diabetes Consortium Type 1 Diabetes New Onset (NeOn) Study: factors associated with HbA1c levels one year after diagnosis
Redondo MJ, Connor CG, Ruedy KJ, Beck RW, Kollman C, Wood JR, Buckingham B, Klingensmith GJ, Silverstein J, Tamborlane WV, Consortium F. Pediatric Diabetes Consortium Type 1 Diabetes New Onset (NeOn) Study: factors associated with HbA1c levels one year after diagnosis. Pediatric Diabetes 2013, 15: 294-302. PMID: 23889707, PMCID: PMC3858510, DOI: 10.1111/pedi.12061.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentBlood Glucose Self-MonitoringChildChild, PreschoolCohort StudiesDiabetes Mellitus, Type 1Diabetic KetoacidosisFemaleFollow-Up StudiesGlycated HemoglobinHumansHyperglycemiaHypoglycemiaHypoglycemic AgentsInfantInsulinMaleNuclear FamilyProspective StudiesSocioeconomic FactorsUnited StatesConceptsPediatric Diabetes ConsortiumLower insulin requirementsBody mass indexDiabetic ketoacidosisInsulin requirementsWhite raceNon-Hispanic white raceDeterminants of hemoglobinOnset of T1DType 1 diabetesLevels one yearHigher socioeconomic statusFirst yearPositive autoantibodiesSD HbA1cNew onsetMass indexBlood glucoseClinical centersDiabetes physiciansPrivate health insuranceTanner stageNumber of visitsFrequent SMBGIntervention studiesSevere hypoglycemia and diabetic ketoacidosis among youth with type 1 diabetes in the T1D Exchange clinic registry
Cengiz E, Xing D, Wong JC, Wolfsdorf JI, Haymond MW, Rewers A, Shanmugham S, Tamborlane WV, Willi SM, Seiple DL, Miller KM, DuBose SN, Beck RW, Network F. Severe hypoglycemia and diabetic ketoacidosis among youth with type 1 diabetes in the T1D Exchange clinic registry. Pediatric Diabetes 2013, 14: 447-454. PMID: 23469984, PMCID: PMC4100244, DOI: 10.1111/pedi.12030.Peer-Reviewed Original ResearchConceptsType 1 diabetesT1D Exchange Clinic RegistryDiabetic ketoacidosisSevere hypoglycemiaClinic registryFrequency of SHOccurrence of SHRisk of DKASerious acute complicationsPoor glycemic controlHigh-risk groupAssociation of baselineNew treatment paradigmSeparate logistic regression modelsNon-white raceLower household incomeLogistic regression modelsYoung adult cohortDKA frequencyAcute complicationsClinical factorsGlycemic controlHigher HbA1cT1D ExchangeTreatment paradigm
2012
Body Mass Index at the Time of Diagnosis of Autoimmune Type 1 Diabetes in Children
Kaminski BM, Klingensmith GJ, Beck RW, Tamborlane WV, Lee J, Hassan K, Schatz D, Kollman C, Redondo MJ, Consortium P. Body Mass Index at the Time of Diagnosis of Autoimmune Type 1 Diabetes in Children. The Journal Of Pediatrics 2012, 162: 736-740.e1. PMID: 23092524, DOI: 10.1016/j.jpeds.2012.09.017.Peer-Reviewed Original ResearchConceptsAutoimmune type 1 diabetesType 1 diabetesGeneral populationDiabetic ketoacidosisT1D onsetHigher BMI z-scoreHispanic race/ethnicityDisease control populationsMedian BMI percentilePediatric Diabetes ConsortiumDiagnosis of T1DPediatric diabetes centersTime of diagnosisDays of diagnosisBody mass indexSame clinical characteristicsBody mass index distributionBMI z-scoreType 2 diabetesChildren ages 2Race/ethnicityClinical characteristicsDiabetes autoantibodiesDiabetes CenterLower hemoglobin
2011
A Bridge to Insulin Pump Therapy: Twice-Daily Regimen with NPH and Detemir Insulins During Initial Treatment of Youth with Type 1 Diabetes Mellitus
Cengiz E, Sherr JL, Erkin-Cakmak A, Weinzimer SA, Burke EN, Sikes KA, Urban AD, Tamborlane WV. A Bridge to Insulin Pump Therapy: Twice-Daily Regimen with NPH and Detemir Insulins During Initial Treatment of Youth with Type 1 Diabetes Mellitus. Endocrine Practice 2011, 17: 862-866. PMID: 21550949, DOI: 10.4158/ep11031.or.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentChildCohort StudiesDiabetes Mellitus, Type 1Diabetic KetoacidosisDrug Administration ScheduleDrug MonitoringDrug Therapy, CombinationFemaleFollow-Up StudiesGlycated HemoglobinHospitals, PediatricHospitals, UniversityHumansHypoglycemiaHypoglycemic AgentsInjections, SubcutaneousInsulin DetemirInsulin Infusion SystemsInsulin, IsophaneInsulin, Long-ActingInsulin, Short-ActingMaleConceptsRapid-acting insulin analoguesInsulin detemirNPH insulinYounger patientsA1c levelsInitial treatmentInsulin dosesNew-onset type 1 diabetes mellitusInsulin analoguesBasal/bolus insulinTotal daily insulin dosesType 1 diabetes mellitusInsulin injection treatmentPump-treated patientsDaily insulin dosesHemoglobin A1c levelsTwice daily regimenEffective initial treatmentSevere hypoglycemic eventsNew-onset T1DMInsulin pump therapyDetemir insulinDaily regimenInsulin regimenDiabetes mellitus
2010
Characteristics of Adolescents and Youth with Recent-Onset Type 2 Diabetes: The TODAY Cohort at Baseline
Copeland KC, Zeitler P, Geffner M, Guandalini C, Higgins J, Hirst K, Kaufman FR, Linder B, Marcovina S, McGuigan P, Pyle L, Tamborlane W, Willi S. Characteristics of Adolescents and Youth with Recent-Onset Type 2 Diabetes: The TODAY Cohort at Baseline. The Journal Of Clinical Endocrinology & Metabolism 2010, 96: 159-167. PMID: 20962021, PMCID: PMC3038479, DOI: 10.1210/jc.2010-1642.Peer-Reviewed Original ResearchConceptsType 2 diabetesBlood pressureFamily historyBiochemical abnormalitiesRecent-onset type 2 diabetesLow high-density lipoprotein levelsRecent-Onset Type 2Body mass index z-scoreHigh-density lipoprotein levelsDiabetes care clinicMean diabetes durationYr of diagnosisTODAY cohortBody mass indexIndex z-scoreNon-Hispanic blacksLow socioeconomic statusBaseline data collectionParents/guardiansDiabetes durationBaseline characteristicsHigh triglyceridesCare clinicsLipoprotein levelsMass index
2007
Decompensated Hyperglycemic Hyperosmolarity Without Significant Ketoacidosis in the Adolescent and Young Adult Population
Canarie MF, Bogue CW, Banasiak KJ, Weinzimer SA, Tamborlane WV. Decompensated Hyperglycemic Hyperosmolarity Without Significant Ketoacidosis in the Adolescent and Young Adult Population. Journal Of Pediatric Endocrinology And Metabolism 2007, 20: 1115-1124. PMID: 18051930, DOI: 10.1515/jpem.2007.20.10.1115.Peer-Reviewed Original ResearchConceptsHyperglycemic hyperosmolar syndromeDiabetic ketoacidosisSignificant ketoacidosisSerious complicationsPoor outcomeRisk factorsSerum osmolarityExact testDiagnosis of DKANew-onset diabeticsTertiary care teachingRetrospective cohort studyHours of admissionSecondary discharge diagnosisYear old patientInadequate fluid resuscitationMOsm/Fisher's exact testYoung adult populationInitial study criteriaAfrican AmericansHours of treatmentHospital stayHyperglycemic crisisHyperosmolar syndromeThe transition to young adulthood in youth with type 1 diabetes on intensive treatment
Insabella G, Grey M, Knafl G, Tamborlane W. The transition to young adulthood in youth with type 1 diabetes on intensive treatment. Pediatric Diabetes 2007, 8: 228-234. PMID: 17659065, DOI: 10.1111/j.1399-5448.2007.00266.x.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultCohort StudiesDepressionDiabetes Mellitus, Type 1FemaleHumansMaleQuality of LifeConceptsQuality of lifeDepressive symptomsYoung adulthoodIntensive treatmentPsychosocial outcomesDisease-related worriesPediatric diabetes clinicType 1 diabetesChart reviewComplications TrialDiabetes clinicIntensive therapyDiabetes complicationsDiabetes controlTreatment groupsSuch symptomsMetabolic controlIntervention studiesSymptomsDiabetesYoung adultsEarly adulthoodLonger durationHigh levelsAdulthood
2006
Alanine 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
Single‐ and Multiple‐Dose Pharmacokinetics of Pioglitazone in Adolescents With Type 2 Diabetes
Christensen ML, Meibohm B, Capparelli EV, Velasquez‐Mieyer P, Burghen GA, Tamborlane WV. Single‐ and Multiple‐Dose Pharmacokinetics of Pioglitazone in Adolescents With Type 2 Diabetes. The Journal Of Clinical Pharmacology 2005, 45: 1137-1144. PMID: 16172178, DOI: 10.1177/0091270005279578.Peer-Reviewed Original ResearchConceptsMultiple-dose pharmacokineticsType 2 diabetesMultiple dosingDoses of pioglitazoneDaily dose administrationTotal serum concentrationsLast doseFirst doseSystemic exposureDose administrationSerum concentrationsBlood samplesPioglitazoneDose levelsActive metaboliteDosingDoseDiabetesPharmacokineticsAdolescentsHoursActive compoundsAdministrationDoses