2022
Pathophysiology and management of hypoglycemia in diabetes
Sanchez‐Rangel E, Deajon‐Jackson J, Hwang JJ. Pathophysiology and management of hypoglycemia in diabetes. Annals Of The New York Academy Of Sciences 2022, 1518: 25-46. PMID: 36202764, DOI: 10.1111/nyas.14904.Peer-Reviewed Original ResearchConceptsType 1 diabetes mellitusCounter-regulatory hormonal responsesMechanism of hypoglycemiaDuration of diabetesManageable chronic diseaseOptimal glycemic controlManagement of hypoglycemiaTreatment of hypoglycemiaNew insulin formulationsDiscovery of insulinGlycemic controlDiabetes mellitusTherapeutic optionsBrain glucoseChronic diseasesNovel therapiesDiabetes managementHypoglycemiaPharmacologic targetHormonal responsesInsulin formulationsDiabetesPatientsCurrent literatureDelivery devicesStress-level glucocorticoids increase fasting hunger and decrease cerebral blood flow in regions regulating eating
Bini J, Parikh L, Lacadie C, Hwang JJ, Shah S, Rosenberg SB, Seo D, Lam K, Hamza M, De Aguiar RB, Constable T, Sherwin RS, Sinha R, Jastreboff AM. Stress-level glucocorticoids increase fasting hunger and decrease cerebral blood flow in regions regulating eating. NeuroImage Clinical 2022, 36: 103202. PMID: 36126514, PMCID: PMC9486604, DOI: 10.1016/j.nicl.2022.103202.Peer-Reviewed Original ResearchConceptsCerebral blood flowRegional cerebral blood flowBlood flowMetabolic hormonesRandomized double-blind cross-over designDouble-blind cross-over designStress level glucocorticoidsPrimary sensory cortexPerfusion magnetic resonanceCross-over designMedial temporal gyrusWhole-brain voxelMedial brainstemSaline daysOvernight infusionCBF responseHunger ratingsPlasma insulinGlucocorticoid effectsHedonic signalsObesity riskLimbic regionsFood intakeNeural regulationDistinct brain networksInsulin increases placental triglyceride as a potential mechanism for fetal adiposity in maternal obesity
Anam AK, Cooke KM, Dratver MB, O'Bryan JV, Perley LE, Guller SM, Hwang JJ, Taylor HS, Goedeke L, Kliman HJ, Vatner DF, Flannery CA. Insulin increases placental triglyceride as a potential mechanism for fetal adiposity in maternal obesity. Molecular Metabolism 2022, 64: 101574. PMID: 35970449, PMCID: PMC9440306, DOI: 10.1016/j.molmet.2022.101574.Peer-Reviewed Original ResearchConceptsDe novo lipogenesisFetal adiposityFatty acid uptakeMaternal obesityObese womenNormal weightExcess adiposityVillous explantsInsulin receptorNewborns of mothersNormal-weight womenAcid uptakePlacental villous explantsTranscription factor SREBP-1Insulin-like growth factor 2Effect of insulinFatty acid oxidationPlacental triglyceridesPlacental responsesElevated triglyceridesMaternal hyperglycemiaWeight womenGrowth factor 2Diabetes riskPlacental metabolismReversibility of brain glucose kinetics in type 2 diabetes mellitus
Sanchez-Rangel E, Gunawan F, Jiang L, Savoye M, Dai F, Coppoli A, Rothman DL, Mason GF, Hwang JJ. Reversibility of brain glucose kinetics in type 2 diabetes mellitus. Diabetologia 2022, 65: 895-905. PMID: 35247067, PMCID: PMC8960594, DOI: 10.1007/s00125-022-05664-y.Peer-Reviewed Original ResearchConceptsType 2 diabetesBrain glucose levelsGlucose levelsHyperglycaemic clampGlycaemic controlBrain glucoseUncontrolled type 2 diabetesType 2 diabetes mellitusConclusions/interpretationThese findingsAims/hypothesisWePlasma glucose levelsLinear mixed-effects regression modelsMixed-effects regression modelsContinuous glucose monitoringMinimal weight changeMagnitude of improvementAge 44.8MethodsEight individualsSD HbA1cDiabetes mellitusCerebral glucoseInterpretationThese findingsWeek interventionRegimen intensificationPost intervention
2020
Glycemic Variability and CNS Inflammation: Reviewing the Connection
Watt C, Sanchez-Rangel E, Hwang JJ. Glycemic Variability and CNS Inflammation: Reviewing the Connection. Nutrients 2020, 12: 3906. PMID: 33371247, PMCID: PMC7766608, DOI: 10.3390/nu12123906.Peer-Reviewed Original ResearchConceptsBlood-brain barrierGlycemic variabilityOxidative stressCentral nervous system outcomesImpact of hyperglycemiaType 2 diabetesCNS inflammationVascular complicationsVascular inflammationCognitive dysfunctionTherapeutic implicationsCognitive deficitsType 1Brain functionNeuroinflammationInflammationDysfunctionGlucoseLow levelsSystem outcomesHigh levelsComplicationsHyperglycemiaDiabetesLatest dataCharacterizing the Effects of Diabetes and Obesity on Insulin and Leptin Levels amongst Pregnant Women
Johnson AW, Snegovskikh D, Parikh L, DeAguiar RB, Han CS, Hwang JJ. Characterizing the Effects of Diabetes and Obesity on Insulin and Leptin Levels amongst Pregnant Women. American Journal Of Perinatology 2020, 37: 1094-1101. PMID: 32120424, DOI: 10.1055/s-0040-1702988.Peer-Reviewed Original ResearchConceptsDiabetes mellitusLeptin levelsCerebrospinal fluidLean mothersPlasma ratioMaternal cerebrospinal fluidMaternal metabolic environmentElective cesarean deliveryImpact of obesityCord blood insulinEffect of diabetesLow cerebrospinal fluidUncomplicated singleton pregnanciesMaternal plasma ratioArtery plasmaDM mothersCesarean deliveryObese patientsSingleton pregnanciesFetal exposureBlood insulinLower cordPregnant womenMaternal brainLean individuals
2018
Verapamil is a potential therapy for hypoglycaemic brain injury
Hwang JJ, Sherwin RS. Verapamil is a potential therapy for hypoglycaemic brain injury. Nature Reviews Endocrinology 2018, 14: 443-444. PMID: 29967401, DOI: 10.1038/s41574-018-0056-7.Peer-Reviewed Original ResearchHypoglycemia unawareness in type 1 diabetes suppresses brain responses to hypoglycemia
Hwang JJ, Parikh L, Lacadie C, Seo D, Lam W, Hamza M, Schmidt C, Dai F, Sejling AS, Belfort-DeAguiar R, Constable RT, Sinha R, Sherwin R. Hypoglycemia unawareness in type 1 diabetes suppresses brain responses to hypoglycemia. Journal Of Clinical Investigation 2018, 128: 1485-1495. PMID: 29381484, PMCID: PMC5873861, DOI: 10.1172/jci97696.Peer-Reviewed Original ResearchConceptsMild hypoglycemiaHypoglycemia awarenessType 1 diabetes mellitus patientsPrefrontal cortexHormonal counterregulatory responsesDiabetes mellitus patientsImpaired hypoglycemia awarenessAltered activation patternsAngular gyrusType 1 diabetesBlood glucose levelsHypoglycemia-induced changesBrain responsesBrain activityHypoglycemia symptom scoresAlters brain activityClinical Translational Science AwardsHyperinsulinemic euglycemicHypoglycemia unawarenessCounterregulatory responsesHypoglycemic clampMellitus patientsMRI brainSymptom scoresNondiabetic individuals
2017
Blunted rise in brain glucose levels during hyperglycemia in adults with obesity and T2DM
Hwang JJ, Jiang L, Hamza M, Rangel E, Dai F, Belfort-DeAguiar R, Parikh L, Koo BB, Rothman DL, Mason G, Sherwin RS. Blunted rise in brain glucose levels during hyperglycemia in adults with obesity and T2DM. JCI Insight 2017, 2: e95913. PMID: 29046482, PMCID: PMC5846903, DOI: 10.1172/jci.insight.95913.Peer-Reviewed Original ResearchConceptsGlucose levelsPlasma free fatty acid levelsSimilar plasma glucose levelsFree fatty acid levelsCerebral glucose metabolismPlasma glucose levelsBrain glucose levelsFatty acid levelsAltered feeding behaviorGlucose incrementHyperglycemic clampBrain glucoseCerebral functionLean participantsOccipital lobeRodent modelsGlucose metabolismObesityT2DMGlucose responseHyperglycemiaNeurocognitive consequencesSimilar findingsAcid levelsIntracerebral glucoseThe human brain produces fructose from glucose
Hwang JJ, Jiang L, Hamza M, Dai F, Belfort-DeAguiar R, Cline G, Rothman DL, Mason G, Sherwin RS. The human brain produces fructose from glucose. JCI Insight 2017, 2: e90508. PMID: 28239653, PMCID: PMC5313070, DOI: 10.1172/jci.insight.90508.Peer-Reviewed Original ResearchConceptsPolyol pathwayFructose levelsIntracerebral glucoseBlood-brain barrierPathogenesis of obesityType 2 diabetesEffects of fructoseHuman brainRegression model analysisCNS deliveryCNS effectsHyperglycemic clampHealthy subjectsDietary consumptionGlucoseBaselineBrainMixed-effects regression model analysisFeeding behaviorMinutesCN productionObesityDiabetesLevelsPathogenesis
2015
Fructose Levels Are Markedly Elevated in Cerebrospinal Fluid Compared to Plasma in Pregnant Women
Hwang JJ, Johnson A, Cline G, Belfort-DeAguiar R, Snegovskikh D, Khokhar B, Han CS, Sherwin RS. Fructose Levels Are Markedly Elevated in Cerebrospinal Fluid Compared to Plasma in Pregnant Women. PLOS ONE 2015, 10: e0128582. PMID: 26035307, PMCID: PMC4452737, DOI: 10.1371/journal.pone.0128582.Peer-Reviewed Original ResearchConceptsCerebrospinal fluidPregnant womenSorbitol levelsCSF glucoseGlucose levelsCord blood glucoseVenous cord bloodElective cesarean sectionHuman brainBlood-brain barrierPlasma glucose levelsEffects of fructoseCesarean sectionSpinal anesthesiaPlasma levelsBlood glucoseCord bloodObservational studyDietary consumptionPlasma fructoseMaternal plasmaPolyol pathwayBrainDifferential effectsFructose levels