Post-acute ischemic stroke hyperglycemia increases the risk of hemorrhagic transformation,which is associated with blood-brain barrier disruption.Brain microvascular endothelial cells are a major component of the bloo...Post-acute ischemic stroke hyperglycemia increases the risk of hemorrhagic transformation,which is associated with blood-brain barrier disruption.Brain microvascular endothelial cells are a major component of the blood-brain barrier.Intercellular mitochondrial transfer has emerged as a novel paradigm for repairing cells with mitochondrial dysfunction.In this study,we first investigated whether mitochondrial transfer exists between brain microvascular endothelial cells,and then investigated the effects of post-acute ischemic stroke hyperglycemia on mitochondrial transfer between brain microvascular endothelial cells.We found that healthy brain microvascular endothelial cells can transfer intact mitochondria to oxygen glucose deprivation-injured brain microvascular endothelial cells.However,post-oxygen glucose deprivation hyperglycemia hindered mitochondrial transfer and exacerbated mitochondrial dysfunction.We established an in vitro brain microvascular endothelial cell model of the blood-brain barrier.We found that post-acute ischemic stroke hyperglycemia reduced the overall energy metabolism levels of brain microvascular endothelial cells and increased permeability of the blood-brain barrier.In a clinical study,we retrospectively analyzed the relationship between post-acute ischemic stroke hyperglycemia and the severity of hemorrhagic transformation.We found that post-acute ischemic stroke hyperglycemia serves as an independent predictor of severe hemorrhagic transformation.These findings suggest that post-acute ischemic stroke hyperglycemia can aggravate disruption of the blood-brain barrier by inhibiting mitochondrial transfer.展开更多
Dietary flavonoids are abundant in natural plants and possess multiple pharmacological and nutritional activities.In this study,apigenin,luteolin,and baicalein were chosen to evaluate their anti-diabetic effect in hig...Dietary flavonoids are abundant in natural plants and possess multiple pharmacological and nutritional activities.In this study,apigenin,luteolin,and baicalein were chosen to evaluate their anti-diabetic effect in high-glucose and dexamethasone induced insulin-resistant(IR)HepG2 cells.All flavonoids improves the glucose consumption and glycogen synthesis abilities in IR-HepG2 cells via activating glucose transporter protein 4(GLUT4)and phosphor-glycogen synthase kinase(GSK-3β).These fl avonoids signifi cantly inhibited the production of reactive oxygen species(ROS)and advanced glycation end-products(AGEs),which were closely related to the suppression of the phosphorylation form of NF-κB and P65.The expression levels of insulin receptor substrate-1(IRS-1),insulin receptor substrate-2(IRS-2)and phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)pathway in IR-HepG2 cells were all partially activated by the fl avonoids,with variable effects.Furthermore,the intracellular metabolic conditions of the fl avonoids were also evaluated.展开更多
It is widely recognized that chronic hyperglycemia decreases bone quality,although little is known about the impact of the rapid correction of chronic hyperglycemia on the quality of bone remodeling.This spotlight art...It is widely recognized that chronic hyperglycemia decreases bone quality,although little is known about the impact of the rapid correction of chronic hyperglycemia on the quality of bone remodeling.This spotlight article explores this correlation by focusing on the stages of bone remodeling linked to glucose levels.展开更多
The global diabetes surge poses a critical public health challenge,emphasizing the need for effective glycemic control.However,rapid correction of chronic hyperglycemia can unexpectedly trigger microvascular complicat...The global diabetes surge poses a critical public health challenge,emphasizing the need for effective glycemic control.However,rapid correction of chronic hyperglycemia can unexpectedly trigger microvascular complications,necessitating a reevaluation of the speed and intensity of glycemic correction.Theories suggest swift blood sugar reductions may cause inflammation,oxidative stress,and neurovascular changes,resulting in complications.Healthcare providers should cautiously approach aggressive glycemic control,especially in long-standing,poorly controlled diabetes.Preventing and managing these complications requires a personalized,comprehensive approach with education,monitoring,and interdisciplinary care.Diabetes management must balance short and longterm goals,prioritizing overall well-being.This editorial underscores the need for a personalized,nuanced approach,focusing on equilibrium between glycemic control and avoiding overcorrection.展开更多
BACKGROUND The correction and control of chronic hyperglycemia are the management goals of patients living with diabetes.Chronic hyperglycemia is the main factor inducing diabetes-related complications.However,in cert...BACKGROUND The correction and control of chronic hyperglycemia are the management goals of patients living with diabetes.Chronic hyperglycemia is the main factor inducing diabetes-related complications.However,in certain situations,the rapid and intense correction of chronic hyperglycemia can paradoxically favor the onset of microvascular complications.CASE SUMMARY In this case report,we describe the case of a 25-year-old woman living with type 1 diabetes since the age of 9 years.Her diabetes was chronic and unstable but without complications.During an unplanned pregnancy,her diabetes was intensely managed with the rapid correction of her hyperglycemia.However,over the following 2 years,she developed numerous degenerative microvascular complications:Charcot neuroarthropathy with multiple joint involvement,severe proliferative diabetic retinopathy,gastroparesis,bladder voiding disorders,and end-stage renal failure requiring hemodialysis.CONCLUSION In the literature to date,the occurrence of multiple microvascular complications following the rapid correction of chronic hyperglycemia has been rarely described in the same individual.展开更多
BACKGROUND New onset hyperglycemia is common in patients with severe coronavirus disease 2019(COVID-19)infection.Cytokine storm due to COVID-19 infection is an essential etiology for new-onset hyperglycemia,but factor...BACKGROUND New onset hyperglycemia is common in patients with severe coronavirus disease 2019(COVID-19)infection.Cytokine storm due to COVID-19 infection is an essential etiology for new-onset hyperglycemia,but factors like direct severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)-induced pancreaticβ-cell failure have also been postulated to play a role.AIM We plan to investigate further the mechanisms underlying SARS-CoV-2 infection-induced hyperglycemia,particularly the rationale of the cytokine-induced hyperglycemia hypothesis,by evaluating the association between inflammatory markers and new onset hyperglycemia in non-diabetic patients with COVID-19 infection.METHODS We conducted a retrospective case-control study on adults without diabetes mellitus hospitalized for COVID-19 infection.The serum levels of glucose and inflammatory markers at presentation before initiation of corticosteroid were collected.Hyperglycemia was defined as glucose levels≥140 mg/dL.C-Reactive protein(CRP)≥100 mg/L,ferritin≥530 ng/mL,lactate dehydrogenase(LDH)≥590 U/L,and D-dimer≥0.5 mg/L were considered elevated.We used theχ2 test for categorical variables and the Mann-Whitney U test for continuous variables and calculated the logistic regression for hyperglycemia.RESULTS Of the 520 patients screened,248 met the inclusion criteria.Baseline demographics were equally distributed between patients with hyperglycemia and those who were normoglycemic.Serum inflammatory markers in patients with or without new-onset hyperglycemia were elevated as follows:CRP(58.1%vs 65.6%,P=0.29),ferritin(48.4%vs 34.9%,P=0.14),D-dimer(37.1%vs 37.1%,P=0.76)and LDH(19.4%vs 11.8%,P=0.02).Logistic regression analysis showed LDH odds ratio(OR)=1.623(P=0.256).We observed significantly higher mortality(24.2%vs 9.1%,P=0.001;OR=2.528,P=0.024)and length of stay(8.89 vs 6.69,P=0.026)in patients with hyperglycemia.CONCLUSION Our study showed no association between CRP,ferritin,LDH,D-dimer levels,and new-onset hyperglycemia in non-diabetic patients with COVID-19 infection.It also shows an increased mortality risk and length of stay in patients with hyperglycemia.With new-onset hyperglycemia being closely associated with poor prognostic indices,it becomes pivotal to understand the underlying pathophysiological mechanisms behind the SARS-CoV-2 infection-induced hyperglycemia.We conclude that the stress hyperglycemia hypothesis is not the only mechanism of SARS-CoV-2 infection-induced hyperglycemia but rather a multicausal pathogenesis leading to hyperglycemia that requires further research and understanding.This would help us improve not only the clinical outcomes of COVID-19 disease and inpatient hyperglycemia management but also understand the long-term effects of SARS-CoV-2 infection and further management.展开更多
“Intermediate hyperglycemia in early pregnancy(IHEP)”refers to mild hyperglycemia detected before 24 gestational weeks(GW),satisfying the criteria for the diagnosis of gestational diabetes mellitus.Many professional...“Intermediate hyperglycemia in early pregnancy(IHEP)”refers to mild hyperglycemia detected before 24 gestational weeks(GW),satisfying the criteria for the diagnosis of gestational diabetes mellitus.Many professional bodies recommend routine screening for“overt diabetes”in early pregnancy,which identifies a significant number of women with mild hyperglycemia of undetermined significance.A literature search revealed that one-third of GDM women in South Asian countries are diagnosed before the conventional screening period of 24 GW to 28 GW;hence,they belong in the IHEP category.Most hospitals in this region diagnose IHEP by oral glucose tolerance test(OGTT)using the same criteria used for GDM diagnosis after 24 GW.There is some evidence to suggest that South Asian women with IHEP are more prone to adverse pregnancy events than women with a diagnosis of GDM after 24 GW,but this observation needs to be proven by randomized control trials.Fasting plasma glucose is a reliable screening test for GDM that can obviate the need for OGTT for GDM diagnosis among 50%of South Asian pregnant women.HbA1c in the first trimester predicts GDM in later pregnancy,but it is not a reliable test for IHEP diagnosis.There is evidence to suggest that HbA1c in the first trimester is an independent risk factor for several adverse pregnancy events.Further research to identify the pathogenetic mechanisms behind the fetal and maternal effects of IHEP is strongly recommended.展开更多
基金supported by the Ningbo Public Welfare Science and Technology Program,No.2022S023(to JY)Ningbo Natural Science Foundation,No.2022J211(to JS)+2 种基金Ningbo Medical and Health Brand Discipline,No.PPXK2018-04(to XG)Ningbo Top Medical and Health Research Program,No.2022020304(to XG)Key Laboratory of Precision Medicine for Atherosclerotic Diseases of Zhejiang Province,No.2022E10026(to YH)。
文摘Post-acute ischemic stroke hyperglycemia increases the risk of hemorrhagic transformation,which is associated with blood-brain barrier disruption.Brain microvascular endothelial cells are a major component of the blood-brain barrier.Intercellular mitochondrial transfer has emerged as a novel paradigm for repairing cells with mitochondrial dysfunction.In this study,we first investigated whether mitochondrial transfer exists between brain microvascular endothelial cells,and then investigated the effects of post-acute ischemic stroke hyperglycemia on mitochondrial transfer between brain microvascular endothelial cells.We found that healthy brain microvascular endothelial cells can transfer intact mitochondria to oxygen glucose deprivation-injured brain microvascular endothelial cells.However,post-oxygen glucose deprivation hyperglycemia hindered mitochondrial transfer and exacerbated mitochondrial dysfunction.We established an in vitro brain microvascular endothelial cell model of the blood-brain barrier.We found that post-acute ischemic stroke hyperglycemia reduced the overall energy metabolism levels of brain microvascular endothelial cells and increased permeability of the blood-brain barrier.In a clinical study,we retrospectively analyzed the relationship between post-acute ischemic stroke hyperglycemia and the severity of hemorrhagic transformation.We found that post-acute ischemic stroke hyperglycemia serves as an independent predictor of severe hemorrhagic transformation.These findings suggest that post-acute ischemic stroke hyperglycemia can aggravate disruption of the blood-brain barrier by inhibiting mitochondrial transfer.
基金supported by National Natural Science Foundation of China(32072212)Multi-Year Research Grant of University of Macao(MYRG2018-00169-ICMS)+5 种基金Science and Technology Development Fund of Macao(FDCT)(0098/2020/A)MICINN supporting the Ramón y Cajal grant for M.A.Prieto(RYC-201722891)Jianbo Xiao(RYC2020-030365-I)Xunta de Galicia supporting the Axudas Conecta Peme,the IN852A 2018/58 Neuro Food Project,the program EXCELENCIA-ED431F 2020/12the pre-doctoral grants of P.García-Oliveira(ED481A-2019/295)to Ibero-American Program on Science and Technology(CYTED-AQUA-CIBUS,P317RT0003).
文摘Dietary flavonoids are abundant in natural plants and possess multiple pharmacological and nutritional activities.In this study,apigenin,luteolin,and baicalein were chosen to evaluate their anti-diabetic effect in high-glucose and dexamethasone induced insulin-resistant(IR)HepG2 cells.All flavonoids improves the glucose consumption and glycogen synthesis abilities in IR-HepG2 cells via activating glucose transporter protein 4(GLUT4)and phosphor-glycogen synthase kinase(GSK-3β).These fl avonoids signifi cantly inhibited the production of reactive oxygen species(ROS)and advanced glycation end-products(AGEs),which were closely related to the suppression of the phosphorylation form of NF-κB and P65.The expression levels of insulin receptor substrate-1(IRS-1),insulin receptor substrate-2(IRS-2)and phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)pathway in IR-HepG2 cells were all partially activated by the fl avonoids,with variable effects.Furthermore,the intracellular metabolic conditions of the fl avonoids were also evaluated.
文摘It is widely recognized that chronic hyperglycemia decreases bone quality,although little is known about the impact of the rapid correction of chronic hyperglycemia on the quality of bone remodeling.This spotlight article explores this correlation by focusing on the stages of bone remodeling linked to glucose levels.
文摘The global diabetes surge poses a critical public health challenge,emphasizing the need for effective glycemic control.However,rapid correction of chronic hyperglycemia can unexpectedly trigger microvascular complications,necessitating a reevaluation of the speed and intensity of glycemic correction.Theories suggest swift blood sugar reductions may cause inflammation,oxidative stress,and neurovascular changes,resulting in complications.Healthcare providers should cautiously approach aggressive glycemic control,especially in long-standing,poorly controlled diabetes.Preventing and managing these complications requires a personalized,comprehensive approach with education,monitoring,and interdisciplinary care.Diabetes management must balance short and longterm goals,prioritizing overall well-being.This editorial underscores the need for a personalized,nuanced approach,focusing on equilibrium between glycemic control and avoiding overcorrection.
文摘BACKGROUND The correction and control of chronic hyperglycemia are the management goals of patients living with diabetes.Chronic hyperglycemia is the main factor inducing diabetes-related complications.However,in certain situations,the rapid and intense correction of chronic hyperglycemia can paradoxically favor the onset of microvascular complications.CASE SUMMARY In this case report,we describe the case of a 25-year-old woman living with type 1 diabetes since the age of 9 years.Her diabetes was chronic and unstable but without complications.During an unplanned pregnancy,her diabetes was intensely managed with the rapid correction of her hyperglycemia.However,over the following 2 years,she developed numerous degenerative microvascular complications:Charcot neuroarthropathy with multiple joint involvement,severe proliferative diabetic retinopathy,gastroparesis,bladder voiding disorders,and end-stage renal failure requiring hemodialysis.CONCLUSION In the literature to date,the occurrence of multiple microvascular complications following the rapid correction of chronic hyperglycemia has been rarely described in the same individual.
基金The study was reviewed and approved by our local Medical Center Institutional Review Board(Approval No.2020-035).
文摘BACKGROUND New onset hyperglycemia is common in patients with severe coronavirus disease 2019(COVID-19)infection.Cytokine storm due to COVID-19 infection is an essential etiology for new-onset hyperglycemia,but factors like direct severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)-induced pancreaticβ-cell failure have also been postulated to play a role.AIM We plan to investigate further the mechanisms underlying SARS-CoV-2 infection-induced hyperglycemia,particularly the rationale of the cytokine-induced hyperglycemia hypothesis,by evaluating the association between inflammatory markers and new onset hyperglycemia in non-diabetic patients with COVID-19 infection.METHODS We conducted a retrospective case-control study on adults without diabetes mellitus hospitalized for COVID-19 infection.The serum levels of glucose and inflammatory markers at presentation before initiation of corticosteroid were collected.Hyperglycemia was defined as glucose levels≥140 mg/dL.C-Reactive protein(CRP)≥100 mg/L,ferritin≥530 ng/mL,lactate dehydrogenase(LDH)≥590 U/L,and D-dimer≥0.5 mg/L were considered elevated.We used theχ2 test for categorical variables and the Mann-Whitney U test for continuous variables and calculated the logistic regression for hyperglycemia.RESULTS Of the 520 patients screened,248 met the inclusion criteria.Baseline demographics were equally distributed between patients with hyperglycemia and those who were normoglycemic.Serum inflammatory markers in patients with or without new-onset hyperglycemia were elevated as follows:CRP(58.1%vs 65.6%,P=0.29),ferritin(48.4%vs 34.9%,P=0.14),D-dimer(37.1%vs 37.1%,P=0.76)and LDH(19.4%vs 11.8%,P=0.02).Logistic regression analysis showed LDH odds ratio(OR)=1.623(P=0.256).We observed significantly higher mortality(24.2%vs 9.1%,P=0.001;OR=2.528,P=0.024)and length of stay(8.89 vs 6.69,P=0.026)in patients with hyperglycemia.CONCLUSION Our study showed no association between CRP,ferritin,LDH,D-dimer levels,and new-onset hyperglycemia in non-diabetic patients with COVID-19 infection.It also shows an increased mortality risk and length of stay in patients with hyperglycemia.With new-onset hyperglycemia being closely associated with poor prognostic indices,it becomes pivotal to understand the underlying pathophysiological mechanisms behind the SARS-CoV-2 infection-induced hyperglycemia.We conclude that the stress hyperglycemia hypothesis is not the only mechanism of SARS-CoV-2 infection-induced hyperglycemia but rather a multicausal pathogenesis leading to hyperglycemia that requires further research and understanding.This would help us improve not only the clinical outcomes of COVID-19 disease and inpatient hyperglycemia management but also understand the long-term effects of SARS-CoV-2 infection and further management.
文摘“Intermediate hyperglycemia in early pregnancy(IHEP)”refers to mild hyperglycemia detected before 24 gestational weeks(GW),satisfying the criteria for the diagnosis of gestational diabetes mellitus.Many professional bodies recommend routine screening for“overt diabetes”in early pregnancy,which identifies a significant number of women with mild hyperglycemia of undetermined significance.A literature search revealed that one-third of GDM women in South Asian countries are diagnosed before the conventional screening period of 24 GW to 28 GW;hence,they belong in the IHEP category.Most hospitals in this region diagnose IHEP by oral glucose tolerance test(OGTT)using the same criteria used for GDM diagnosis after 24 GW.There is some evidence to suggest that South Asian women with IHEP are more prone to adverse pregnancy events than women with a diagnosis of GDM after 24 GW,but this observation needs to be proven by randomized control trials.Fasting plasma glucose is a reliable screening test for GDM that can obviate the need for OGTT for GDM diagnosis among 50%of South Asian pregnant women.HbA1c in the first trimester predicts GDM in later pregnancy,but it is not a reliable test for IHEP diagnosis.There is evidence to suggest that HbA1c in the first trimester is an independent risk factor for several adverse pregnancy events.Further research to identify the pathogenetic mechanisms behind the fetal and maternal effects of IHEP is strongly recommended.
