2013
Blunted glucagon but not epinephrine responses to hypoglycemia occurs in youth with less than 1 yr duration of type 1 diabetes mellitus
Arbelaez AM, Xing D, Cryer PE, Kollman C, Beck RW, Sherr J, Ruedy KJ, Tamborlane WV, Mauras N, Tsalikian E, Wilson DM, White NH, Group F. Blunted glucagon but not epinephrine responses to hypoglycemia occurs in youth with less than 1 yr duration of type 1 diabetes mellitus. Pediatric Diabetes 2013, 15: 127-134. PMID: 23992543, PMCID: PMC3858506, DOI: 10.1111/pedi.12070.Peer-Reviewed Original ResearchConceptsType 1 diabetes mellitusPeak epinephrineEpinephrine responseDiabetes mellitusT1DM subjectsRecent-onset type 1 diabetes mellitusHypoglycemia-associated autonomic failureBarrier of hypoglycemiaInsulin-induced hypoglycemiaAutonomic failureCounterregulatory hormonesSubsequent hypoglycemiaGlucagon responsePatients 9Recurrent hypoglycemiaGlycemic controlHypoglycemic clampEpinephrine levelsHypoglycemiaHormonal responsesT1DMGlucagonMellitusControl 19CR responseIncreased Brain Transport and Metabolism of Acetate in Hypoglycemia Unawareness
Gulanski BI, De Feyter HM, Page KA, Belfort-DeAguiar R, Mason GF, Rothman DL, Sherwin RS. Increased Brain Transport and Metabolism of Acetate in Hypoglycemia Unawareness. The Journal Of Clinical Endocrinology & Metabolism 2013, 98: 3811-3820. PMID: 23796565, PMCID: PMC4425818, DOI: 10.1210/jc.2013-1701.Peer-Reviewed Original ResearchConceptsHypoglycemia-associated autonomic failureHypoglycemia unawarenessT1DM individualsEpinephrine levelsBrain transportControl groupType 1 diabetes mellitusDefective glucose counterregulationHealthy nondiabetic controlsSevere hypoglycemia unawarenessIntensive insulin therapyLong-term complicationsHospital research unitEntire study populationT1DM participantsAutonomic failureGlucose counterregulationInsulin therapyDiabetes mellitusNondiabetic controlsCerebral cortexAcute hypoglycemiaT1DM controlsCerebral energeticsStudy population
2009
Blunted Counterregulatory Hormone Responses to Hypoglycemia in Young Children and Adolescents With Well-Controlled Type 1 Diabetes
Tsalikian E, Tamborlane W, Xing D, Becker D, Mauras N, Fiallo-Scharer R, Buckingham B, Weinzimer S, Steffes M, Singh R, Beck R, Ruedy K, Kollman C. Blunted Counterregulatory Hormone Responses to Hypoglycemia in Young Children and Adolescents With Well-Controlled Type 1 Diabetes. Diabetes Care 2009, 32: 1954-1959. PMID: 19675205, PMCID: PMC2768200, DOI: 10.2337/dc08-2298.Peer-Reviewed Original ResearchConceptsType 1 diabetesPlasma glucose concentrationEpinephrine responsePlasma glucoseYoung childrenInsulin pump-treated patientsHypoglycemia-associated autonomic failurePump-treated patientsLower plasma glucose concentrationsIntensive insulin therapySymptoms of hypoglycemiaInsulin infusion protocolCounterregulatory hormone concentrationsGlucose concentrationAbsence of signsClosed-loop insulin delivery systemsContinuous glucose monitoringAcute complicationsAutonomic failureCounterregulatory hormonesSympathoadrenal responseInsulin therapyPatient ageNondiabetic adolescentsSymptom scores
2008
Increased GABAergic Tone in the Ventromedial Hypothalamus Contributes to Suppression of Counterregulatory Reponses After Antecedent Hypoglycemia
Chan O, Cheng H, Herzog R, Czyzyk D, Zhu W, Wang A, McCrimmon RJ, Seashore MR, Sherwin RS. Increased GABAergic Tone in the Ventromedial Hypothalamus Contributes to Suppression of Counterregulatory Reponses After Antecedent Hypoglycemia. Diabetes 2008, 57: 1363-1370. PMID: 18375441, PMCID: PMC5518793, DOI: 10.2337/db07-1559.Peer-Reviewed Original ResearchConceptsVMH GABA levelsVentromedial hypothalamusGlutamic acid decarboxylaseHypoglycemic animalsHypoglycemic ratsSympathoadrenal responseRecurrent hypoglycemiaCounterregulatory responsesGABAergic toneInhibitory toneGABA levelsHypoglycemia-associated autonomic failureGABAergic inhibitory toneOnset of hypoglycemiaGABA synthetic enzymeQuantitative RT-PCRAntecedent hypoglycemiaAutonomic failureHypoglycemic stimulusReceptor blockadeEpinephrine releaseAcute hypoglycemiaReceptor antagonistInhibitory neurotransmitterSubsequent boutEffect of Acute and Recurrent Hypoglycemia on Changes in Brain Glycogen Concentration
Herzog RI, Chan O, Yu S, Dziura J, McNay EC, Sherwin RS. Effect of Acute and Recurrent Hypoglycemia on Changes in Brain Glycogen Concentration. Endocrinology 2008, 149: 1499-1504. PMID: 18187548, PMCID: PMC2276713, DOI: 10.1210/en.2007-1252.Peer-Reviewed Original ResearchConceptsHypoglycemia-associated autonomic failureRecurrent hypoglycemiaAcute hypoglycemiaAutonomic failureBrain glycogenGlycogen levelsBrain glucoseGlucose levelsRH groupInsulin-induced acute hypoglycemiaSimilar blood glucose levelsIntensive insulin treatmentHyperinsulinemic-hypoglycemic clamp studyBrain glycogen concentrationHypoglycemic clamp studiesBlood glucose levelsBrain glucose levelsCounterregulatory failureDiabetic patientsGlycogen supercompensationRecurrent episodesSingle boutInsulin treatmentClamp studiesAnimal models
2006
Antecedent Hypercortisolemia Is Not Primarily Responsible for Generating Hypoglycemia-Associated Autonomic Failure
Goldberg PA, Weiss R, McCrimmon RJ, Hintz EV, Dziura JD, Sherwin RS. Antecedent Hypercortisolemia Is Not Primarily Responsible for Generating Hypoglycemia-Associated Autonomic Failure. Diabetes 2006, 55: 1121-1126. PMID: 16567537, DOI: 10.2337/diabetes.55.04.06.db05-1169.Peer-Reviewed Original ResearchConceptsEndogenous cortisol productionAntecedent hypoglycemiaEpinephrine responseAutonomic failureCortisol productionHypoglycemia-associated autonomic failureSubsequent counterregulatory responsesNondiabetic human subjectsAntecedent euglycemiaMetyrapone blockadeOral metyraponeHydrocortisone infusionLongstanding diabetesSubsequent hypoglycemiaSympathoadrenal responseCounterregulatory responsesConcurrent blockadeSevere hypoglycemiaACTH levelsSelective blockadeHypercortisolemiaHypoglycemiaExperimental modelBlockadeHuman subjects
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