Post-acute ischemic stroke hyperglycemia aggravates destruction of the blood-brain barrier

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.

Rapid correction of chronic hyperglycemia and bone remodeling,warning against overdoing

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.

Balancing act:The dilemma of rapid hyperglycemia correction in diabetes management

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.

中国糖尿病行为与生活方式干预指南(2024版)

行为与生活方式干预(behavior and lifestyle interventions,BLIs)可以降低血糖和血压,调节血脂,控制肥胖,减少心血管事件,是糖尿病等慢性病的一线治疗措施。BLIs包括帮助患者维护健康饮食、坚持体育锻炼、保持正常体重、保证良好睡眠、避免吸烟和酗酒、做好心理调适、建立良好的社会支持、进行科学的血糖自我监测、坚持降糖药治疗等。除了出现严重高血糖及糖尿病急性并发症需要立即进行药物治疗外,新诊断的2型糖尿病患者应首先进行BLIs。BLIs应遵循有效性、建立互信、问题解决导向、综合性和个性化原则。常用干预策略包括应用成熟的行为改变理论、使用行为改变技术、有效运用传播策略、提高患者行为技能、实施以人为本的患者自我管理教育和支持。基本步骤包括行为与生活方式及其影响因素评估、确定行为目标、制定干预实施方案、实施干预和评价效果。BLIs效果评价指标包括过程指标、临床结局、社会心理、行为结局、患者报告和健康结局。效果评价可采用定性和定量相结合的方法进行,常用的评价工具包括糖尿病自我护理行为评价量表(summary of diabetes self-care activities,SDSCA)、患者行为量表(patient activation measurement,PAM)和糖尿病管理自我效能量表(diabetes management self-efficacy scale,DMSES)。

Enhancing metformin efficacy with cholecalciferol and taurine in diabetes therapy:Potential and limitations

Diabetes mellitus,particularly type 2 diabetes mellitus(T2DM),poses a significant global health challenge.Traditional management strategies primarily focus on glycemic control;however,there is a growing need for comprehensive approaches addressing the complex pathophysiology of diabetes complications.The recent study by Attia et al explores the potential of a novel therapy combining metformin with cholecalciferol(vitamin D3)and taurine to mitigate T2DM-related complications in a rat model.The findings indicate that this treatment combination improves glycemic control and reduces oxidative stress,inflammation,and lipid abnormalities.However,the study is limited by a lack of safety profile data and in-depth molecular mechanism insights.This editorial critically highlights the study's strengths and weaknesses,compares it against other combination therapy research in T2DM,and underscores the need to explore further the mechanisms underpinning the observed therapeutic effects and investigate the safety profile of this novel approach.

Transient extreme insulin resistance in a critically ill patient:A case report

BACKGROUND Acute hyperglycemia due to insulin resistance is common in critically ill patients,typically managed with insulin infusion.However,the occurrence of transient extreme insulin resistance(EIR)requiring exceptional high-dose insulin is rare.CASE SUMMARY We present the case of a 68-year-old woman with pneumonia who suffered an out-of-hospital cardiac arrest,subsequently developing transient EIR following a new episode of sepsis.Remarkably,insulin resistance rapidly reversed when the insulin infusion rate peaked at 960 units/hour(a total of 18224 units on that day),and it was promptly titrated down to zero upon achieving the target glucose level.CONCLUSION Exceptional high-dose insulin infusion may be required in critically ill patients with stress-related EIR,which is typically transient.Clinicians should be aware of the phenomenon and cautious to avoid hypoglycemia and fluid overload during the steep titration of high-dose insulin infusion.

三高共患潜在危险因素及防治的研究进展

高血压、高血糖及高血脂(简称三高)是代谢综合征(MS)的重要组成部分,三者往往有明显的聚集倾向并使全身多系统疾病的患病风险成倍增加。肥胖、饮食过度、活动减少等是促进三高共同患病的传统危险因素,然而近年有研究发现,部分潜在危险因素与三高的发生密切相关。因此,基于三高的高患病率和公众的低防范意识,文章就三高共患的新发潜在危险因素及干预措施进行综述,以期为三高的早期防治提供新视角,为缓解三高导致的代谢紊乱及全身性疾病的发生提供科学依据和实践指导。

Prediabetes and atrial fibrillation risk stratification,phenotyping,and possible reversal to normoglycemia

Patients admitted with prediabetes and atrial fibrillation are at high risk for major adverse cardiac or cerebrovascular events independent of confounding variables.The shared pathophysiology between these three serious but common diseases and their association with atherosclerotic cardiovascular risk factors establish a vicious circle culminating in high atherogenicity.Because of that,it is of paramount importance to perform risk stratification of patients with prediabetes to define phenotypes that benefit from various interventions.Furthermore,stress hyperglycemia assessment of hospitalized patients and consensus on the definition of prediabetes is vital.The roles lifestyle and metformin play in prediabetes are well established.However,the role of glucagon-like peptide agonists and metabolic surgery is less clear.Prediabetes is considered an intermediate between normoglycemia and diabetes along the blood glucose continuum.One billion people are expected to suffer from prediabetes by the year 2045.Therefore,realworld randomized controlled trials to assess major adverse cardiac or cerebrovascular event risk reduction and reversal/prevention of type 2 diabetes among patients are needed to determine the proper interventions.

Effects of glycemic indicators on early neurological outcomes in patients with acute ischemic stroke treated with intravenous thrombolysis

BACKGROUND Stress hyperglycemia(SH)is a common phenomenon that is present in about 50%of patients with acute ischemic stroke(AIS).It is thought to be a main risk factor for poor functional outcome among patients with AIS undergoing intravenous thrombolysis(IVT).AIM To investigate the predictive value of glycemic indicators for early neurological outcomes(ENOs)in patients with AIS treated with IVT.METHODS We retrospectively reviewed a prospectively collected database of patients with AIS who underwent IVT at the Department of Neurology,Second Affiliated Hospital of Xuzhou Medical University,between January 2017 and June 2022.ENO included early neurological improvement(ENI)and early neurological deterioration(END),defined as a decrease or increase in the National Institutes of Health Stroke Scale(NIHSS)score between baseline and 24 hours after IVT.We analyzed the associations between glycemic indicators[including admission hyperglycemia(AH),fasting blood glucose(FBG),and SH ratio(SHR)]and ENO in all patients and in subgroups stratified by diabetes mellitus(DM).RESULTS A total of 819 patients with AIS treated with IVT were included.Among these,AH was observed in 329 patients(40.2%).Compared with patients without AH,those with AH were more likely to have a higher prevalence of DM(P<0.001)and hypertension(P=0.031)and presented with higher admission NIHSS scores(P<0.001).During the first 24 hours after IVT,END occurred in 208 patients(25.4%)and ENI occurred in 156 patients(19.0%).Multivariate mixed logistic regression analyses indicated that END was independently associated with AH[odds ratio(OR):1.744,95%confidence interval(CI):1.236-2.463;P=0.002].Subjects were classified into four groups representing quartiles.Compared with Q1,patients in the higher quartiles of SHR(Q2:OR:2.306,95%CI:1.342-3.960;P=0.002)(Q3:OR:2.284,95%CI:1.346-3.876;P=0.002)(Q4:OR:3.486,95%CI:2.088-5.820;P=0.001)and FBG(Q3:OR:1.746,95%CI:1.045-2.917;P=0.033)(Q4:OR:2.436,95%CI:1.476-4.022;P=0.001)had a significantly higher risk of END in the overall population.However,none of the glycemic indicators were found to be associated with ENI in patients with or without DM.CONCLUSION Our study demonstrated that glycemic indicators in patients with stroke treated with IVT were associated with the presence of END rather than ENI during the first 24 hours after admission.

Pelvic floor dysfunction in patients with gestational diabetes mellitus

In this editorial,we comment on an article by Wang et al.Recent literature shows an increase in research on pelvic organ prolapse(POP).Although the true incidence of POP remains uncertain,its impact on quality of life is substantial.Anatomical studies report high incidence rates,surpassing those observed in symptom-based surveys.Weakness of the endopelvic fascia is a primary anatomical risk factor for POP.Additionally,gestational diabetes mellitus(GDM)has emerged as a growing concern,as poor glycemic control increases complications for both mother and fetus.GDM and POP are interconnected,with factors like maternal obesity,macrosomia,and hormonal changes exacerbating pelvic floor dysfunction.Modifiable risk factors,such as obesity and chronic hyperglycemia,along with multiparity,instrumental deliveries,and obstetric trauma,further increase susceptibility.For patients with GDM,gynecological exams,Pelvic Organ Prolapse Quantification staging,and pelvic floor ultrasonography are valuable diagnostics,with proctological exams and magnetic resonance defecography aiding in multi-compartment prolapse diagnoses.Imaging,though uncomfortable during pregnancy,is safe in the early postpartum period.This editorial emphasizes the need for further research on the pathophysiology of GDM-related POP and offers recommendations for improving diagnosis and clinical management of patients with GDM.

Steroid hyperglycemia: Prevalence, early detection and therapeutic recommendations: A narrative review

Steroids are drugs that have been used extensively in a variety of conditions. Although widely prescribed for their anti-inflammatory and immunosuppressive properties, glucocorticoids have several side effects, being hyperglycemia one of the most common and representative. In the present review, we discuss the main epidemiologic characteristics associated with steroid use, with emphasis on the identification of high risk populations. Additionally we present the pathophysiology of corticosteroid induced hyperglycemia as well as the pharmacokinetics and pharmacodynamics associated with steroid use. We propose a treatment strategy based on previous reports and the understanding of the mechanism of action of both, the different types of glucocorticoids and the treatment options, in both the ambulatory and the hospital setting. Finally, we present some of the recent scientific advances as well as some options for future use of glucocorticoids.

Hyperglycemia is a significant prognostic factor of hepatocellular carcinoma after curative therapy

AIM:To evaluate whether metabolic factors are related to distant recurrence of hepatocellular carcinoma(HCC) and survival after curative treatment.METHODS:This retrospective study included 344 patients whose HCC was treated curatively by radiofrequency ablation(RFA) therapy.The mean age was 67.6 years and the mean observation period was 4.04 years.The etiological background of liver disease was hepatitis B virus infection in 30,hepatitis C virus infection in 278,excessive alcohol drinking in 9,and other in 27 patients.The Child-Pugh classification grade was A(n = 307) or B(n = 37).The number of HCC nodules was one in 260,two in 61,and three in 23 patients.For surveillance of HCC recurrence after curative therapy with RFA,patients were radiologically evaluated every 3 mo.Factors associated with distant recurrence of HCC or survival were studied.RESULTS:Inadequate maintenance of blood glucose in diabetic patients was associated with higher incidence of distant recurrence.The 1-,2-,and 3-year recurrence rates were significantly higher in diabetic patients with inadequate maintenance of blood glucose compared with the others:50.6% vs 26.8%,83.5% vs 54.4%,and 93.8% vs 73.0%,respectively(P = 0.0001).Inadequate maintenance of blood glucose was an independent predictor of distant recurrence [adjusted relative risk 1.97(95%CI,1.33-2.91),(P = 0.0007)] after adjustment for other risk factors,such as number of HCC nodules [2.03(95%CI,1.51-2.73),P < 0.0001] and initial level of serum alpha fetoprotein(AFP) [1.43(95%CI,1.04-1.97),P = 0.028].Obesity was not an independent predictor of recurrence.The incidence of distant recurrence did not differ between diabetic patients with adequate maintenance of blood glucose and non-diabetic patients.Among 232 patients who had HCC recurrence,138 had a second recurrence.The 1-,2-,and 3-year rates of second recurrence were significantly higher in diabetic patients with inadequate maintenance of blood glucose than in the others:9.0% vs 5.9%,53.1% vs 24.3%,and 69.6% vs 42.3%,respectively(P = 0.0021).Inadequate maintenance of blood glucose in diabetic patients [1.99(95%CI,1.23-3.22),P = 0.0049] and presence of multiple HCC nodules [1.53(95%CI,1.06-2.22),P = 0.024] were again significantly associated with second HCC recurrence.Inadequate maintenance of blood glucose in diabetic patients was also a significant predictor of poor survival [2.77(95%CI,1.38-5.57),P = 0.0046] independent of excessive alcohol drinking [6.34(95%CI,1.35-29.7),P = 0.019],initial level of serum AFP [3.40(95%CI,1.88-6.18),P < 0.0001] and Child-Pugh classification grade B [2.24(95%CI,1.12-4.46),P = 0.022].Comparing diabetic patients with inadequate maintenance of blood glucose vs the others,the 1-,2-,and 3-year survival rates were significantly lower in diabetic patients with inadequate maintenance of blood glucose:92% vs 99%,85% vs 96%,and 70% vs 92%,respectively(P = 0.0003).CONCLUSION:Inadequate maintenance of blood glucose in diabetic patients is a significant risk factor for recurrence of HCC and for poor survival after curative RFA therapy.

Postprandial hyperglycemia and postprandial hypertriglyceridemia in type 2 diabetes

Postprandial glucose level is an independent risk factor for cardiovascular disease that exerts effects greater than glucose levels at fasting state, whereas increase in serum triglyceride level, under both fasting and postprandial conditions, contributes to the development of arteriosclerosis. Insulin resistance is a prevailing cause of abnormalities in postabsorptive excursion of blood glucose and postprandial lipid profile. Excess fat deposition renders a vicious cycle of hyperglycemia and hypertriglyceridemia in the postprandial state, and both of which are contributors to atherosclerotic change of vessels especially in patients with type 2 diabetes mellitus. Several therapeutic approaches for ameliorating each of these abnormalities have been attempted, including various antidiabetic agents or new compounds targeting lipid metabolism.

Hyperglycemia in poor controlled diabetes from crude tamarind herbal pill:a case study

Hyperglycemia is an important finding in the diabetic patient with poor glycemic control.There are several possible causes of hyperglycemic.Here,the author presents an interesting case study on a female diabetic patient presenting with hyperglycemic due to intake of crude tamarind herbal pill.General practitioner should realize that the use of alternative medicine can be a cause of unexplained hyperglycemic episode in diabetic patient.

Hyperglycemia induces protein nonenzymeatic glycosylation in brain neurons of diabetic rats at early stage

BACKGROUND： Protein nonenzymatic glycosylation is supposed to be one of mechanisms for chronic complications development in diabetes mellitus, and therefore, might play an important role in the neuronal degeneration. OBJECTIVE： To study the protein nonenzymatic glycosylation in brain neurons of diabetic rats, and to analyze the pathway of neuronal degeneration at the early stage of hyperglymecia. DESIGN： Randomized controlled animal experiment. SETTING： Department of Endocrinology, First hospital Affiliated to General Hospital of Chinese PLA and Beijing Laboratory for Brain Aging, Xuanwu Hospital Affiliated to Capital Medical University. MATERIALS： Thirty-five male Wistar rats （grade Ⅱ ）, aged 3 months old, and 11 male purebred Kunming mice （grade Ⅲ） without special pathogen, aged 3 months old, were provided by the Animal Room of Capital Medical University. METHODS： This experiment was carried out in the Beijing Laboratory for Brain Aging, Xuanwu Hospital Affiliated to Capital Medical University in 1998. The rats in the diabetic model group were intraperitoneally injected into 10 g/L STZ according to 60 mg/kg to establish rat models of diabetes mellitus. The blood glucose and body mass of rats in each group were determined respectively at 1, 2 and 3 months after modeling. The antibodies of advanced glycosylation end products （AGEs） of bovine serum albumin （anti-BSA） were self-prepared： ①The antigen of AGEs-BSA was prepared.②Eleven male Kuming mice （grade Ⅱ） of 3 months old without special pathogen were selected to inoculate AGEs-BSA. ③The animals were immunized. ④Primary purification and detection of poly-antibodies of AGEs： the AGEs were performed immtmohistochemical examination at 1 month after diabetic modeling by ELISA method. MAIN OUTCOME MEASURES： ① Detection results of blood glucose and body mass of rats in two groups at different time points. ②Determination of polyclonal antibody titer of AGEs-BSA. ③Changes in immtmohistochemical image of AGEs in brain tissue of rats in two groups. RESULTS： Thirteen rats in the diabetic model group and fifteen rats in the normal model group entered the stage of final analysis. ①Changes of blood glucose and body mass： At 1, 2 and 3 months after modeling, the blood glucose of rats in the diabetic model group were respectively（28.8 ± 2.8）, （23.1 ± 5.5）, （25.4 ± 5.1） mmol/L, which were significantly higher than those in the normal control group [（6.2± 0.9）, （6.1 ± 0.8）, （6.1±0.7） mmol/L, P 〈 0.01]; At 1, 2 and 3 months after modeling, the body mass of rats in the diabetic model group were respectively （250.1 ± 52.2）, （263.8± 50.0）, （261.5 ± 42.6） g, which were significantly lower than those in the normal control group [（422.6±36.2）, （462.6±39.0）, （485.0±28.8） g, P 〈 0.01]. ②Determination of antibody titer of immune serum： The mice were treated by AGEs-BSA of different concentrations twice. After that, the titer of AGEs -BSA was determined, and the results of which indicated that a higher absorbance existed at 1： 1 000. ③Determination of antigen concentration： The final titer of antibody in the abdominal dropsy was determined, and the results of which suggested that there was a much higher absorbance in the AGEs-BSA at the concentration of 5 - 50 mg/L. ④Determination of antibody titer in abdominal dropsy： The antibody titer in abdominal dropsy was detected by ELISA method with antigen at 20 mg/L, which indicated that the maximum absorbance （1.265 ±0.039） existed at 1 ： 4 000, and very larger absorbance （0.982±0.067） at 1 ： 20 000. The polyclonal antibody of AGEs-BSA was successfully prepared. ⑤Immtmohistochemical detection results： The immtmohistochemical staining of AGEs showed there were positive neurons in the first month in the diabetic model group, whereas it was not significant in the normal control group. The positive substances were found mainly in the cytoplasm. CONCLUSION： Hyperglycemia at the early stage of diabetes mellitus （1 month after modeling） can lead to protein nonenzymeatic glycosylation in brain neurons, and no obvious reactions mentioned above are found in the normal control group. It suggests that the degenerative changes of tissue structure of central nervous system are related with protein nonenzymeatic glycosylation caused by hyperglycemia.

The effect of hyperglycemia on blood brain barrier of rats with focal cerebral ischemia/reperfusion injury

Objective： To determine whether hyperglycemia could aggravate the microvascular damage in ischemic stroke. Methods： Hyperglycemia model was made by injection of streptozocin through subcutaneous injection in wistar rats. Using the suture model, the rats were subjected to 3h of focal ischemia and different times of reperfusion, including 6,12,24,48,96h and 7d. TIC dyeing was used to Show the infarction area of rats. The infarctive volume of rats were calculated by computer imaging analysis system;Matrix metalloproteinase （MMP-2） and （MMP-9）were detected by immunohistochemistly and in situ hybridization histochemistly in Wistar rats. Results： The infarctive volume was siginificantly larger in hyperglycemic rats than that of nonhyperglycemic rats. The level of MMP-2, MMP-9 expression in the group of hyperglycemic rats was higher than that of nonhyperglycemic rats. Conclusion： Hyperglycemia aggravated the injury of focal ischmia-repeffusion in wistar rats and the higher expression of MMP-2,MMP-9 might be one of the mechanism in aggravation of focal ischemia/repeffusion injury.

Decreased numbers of circulating endothelial progenitor cells are associated with hyperglycemia in patients with traumatic brain injury

Hyperglycemia reduces the number of circulating endothelial progenitor cells, accelerates their senescence and impairs their function.However, the relationship between blood glucose levels and endothelial progenitor cells in peripheral blood of patients with traumatic brain injury is unclear. In this study, 101 traumatic brain injury patients admitted to the Department of Neurosurgery, Tianjin Medical University General Hospital or the Department of Neurosurgery, Tianjin Huanhu Hospital, China, were enrolled from April 2005 to March 2007. The number of circulating endothelial progenitor cells and blood glucose levels were measured at 1, 4, 7, 14 and 21 days after traumatic brain injury by flow cytometry and automatic biochemical analysis, respectively. The number of circulating endothelial progenitor cells and blood sugar levels in 37 healthy control subjects were also examined. Compared with controls, the number of circulating endothelial progenitor cells in traumatic brain injury patients was decreased at 1 day after injury, and then increased at 4 days after injury,and reached a peak at 7 days after injury. Compared with controls, blood glucose levels in traumatic brain injury patients peaked at 1 day and then decreased until 7 days and then remained stable. At 1, 4, and 7 days after injury, the number of circulating endothelial progenitor cells was negatively correlated with blood sugar levels(r =-0.147, P < 0.05). Our results verify that hyperglycemia in patients with traumatic brain injury is associated with decreased numbers of circulating endothelial progenitor cells. This study was approved by the Ethical Committee of Tianjin Medical University General Hospital, China(approval No. 200501) in January 2015.

Impact of Admission Hyperglycemia on Stroke-Associated Pneumoniain Acute Cerebral Hemorrhage: A Retrospective Observational Study

Background: Hyperglycemia is always seen amongst acute intra-cerebral hemorrhage (ICH) and usually has been reported in literature and studied in relation to mortality and poor recovery. However, literature specific to stroke-associated pneumonia (SAP) on this topic is very small. Further, how to differentiate the predictive value of hyperglycemia with and without abnormal HbA1C in such patients is still a matter of debate and no universal consensus. We evaluated hyperglycemia as a marker for SAP in patients with ICH to assess its usefulness as a potential predictor. Materials and methods: Clinical characteristics for a sample of 551 patients with acute ICH were collected from the Beijing Tiantan Hospital of Capital Medical University, Beijing, China. Possible associated risk factors of SAP were reviewed. Hyperglycemia and HbA1C on admission were the main hypothetic predictor, SAP occurring within the first 7 days is the primary outcome. Results: The cohort study includes 551 hospitalized patients. The prevalence of hyperglycemia was 52.5% and SAP occurred in 147 (26.7%). The incidence of SAP was higher in the group with hyperglycemia than those without hyperglycemia (37.7% versus 14.5%, p 6.5) (OR, 1.57;95%CI, 0.81 - 3.23) had not been shown to be associated with SAP. Conclusions: In this hospital-based cohort of patients presenting with acute intra-hemorrhage, hyperglycemia on admission was associated significantly with SAP. The association was stronger for hyperglycemia with normal HgbA1C than for hyperglycemia with high HgbA1C. Hyperglycemia with normal HgbA1C might be a more sensitive predictor of early acute complication, such as SAP.

The Area under the Curve (AUC) of Oral Glucose Tolerance Test (OGTT) Could Be a Measure Method of Hyperglycemia in All Pregnant Women

Objective: We adopted the area under the curve (AUC) of oral glucose tolerance test (OGTT) as a measure method of the severity of maternal hyperglycemia and investigated its relationship with adverse perinatal outcomes among women with and without gestational diabetes mellitus (GDM). Research design and methods: This is a retrospective cohort study. Our study group collected the medical records of 15,296 women who received perinatal care in 15 hospitals in Beijing and who delivered from July 1, 2013, to December 31, 2013. And several original articles on this cohort have been published. In this study, we analyze the relationship between AUC and adverse perinatal outcomes, so that in multiple pregnant cases, patients with pre-pregnancy diabetes, hypertension, and abnormal kidney function and those who did not receive a 75-g OGTT were excluded. A Chi-squared test and logistic regression analysis were used to determine the associations. Results: In total, 13,561 women were included. As the AUC of OGTT increased, the prevalence of macrosomia (odds ratio [OR] 1.059, 95% confidence interval [95% CI] 1.029 - 1.090, p < 0.001) and hypertensive diseases (OR 1.106, 95% CI 1.064 - 1.149, p < 0.001) also increased. For patients with same levels of AUC values, no significant differences in the risk of macrosomia, preterm birth and neonatal complications were observed between the GDM and non-GDM groups. Women with an AUC higher than 14.20 (mmol * h/L) had a higher risk of adverse outcomes regardless of the presence of GDM. Conclusions: The AUC could be a measure method of the severity of maternal hyperglycemia, and women with a high AUC should undergo aggressive management to avoid adverse outcomes regardless of the presence of GDM.

Propofol postconditioning ameliorates hypoxia/reoxygenation induced H9c2 cell apoptosis and autophagy via upregulating forkhead transcription factors under hyperglycemia

Background:Administration of propofol,an intravenous anesthetic with antioxidant property,immediately at the onset of post-ischemic reperfusion(propofol postconditioning,P-PostC) has been shown to confer cardioprotection against ischemia–reperfusion(I/R) injury,while the underlying mechanism remains incompletely understood.The forkhead box O(FoxO) transcription factors are reported to play critical roles in activating cardiomyocyte survival signaling throughout the process of cellular injuries induced by oxidative stress and are also involved in hypoxic postconditioning mediated neuroprotection,however,the role of FoxO in postconditioning mediated protection in the heart and in particular in high glucose condition is unknown.Methods:Rat heart-derived H9c2 cells were exposed to high glucose(HG) for 48 h,then subjected to hypoxia/reoxygenation(H/R,composed of 8 h of hypoxia followed by 12 h of reoxygenation) in the absence or presence of postconditioning with various concentrations of propofol(P-PostC) at the onset of reoxygenation.After having identified the optical concentration of propofol,H9c2 cells were subjected to H/R and P-PostC in the absence or presence of FoxO1 or FoxO3a gene silencing to explore their roles in P-PostC mediated protection against apoptotic and autophagic cell deaths under hyperglycemia.Results:The results showed that HG with or without H/R decreased cell viability,increased lactate dehydrogenase(LDH) leakage and the production of reactive oxygen species(ROS) in H9c2 cells,all of which were significantly reversed by propofol(P-PostC),especially at the concentration of 25 μmol/L(P25)(P<0.05,NC vs.HG;HG vs.HG+HR;HG+HR+P12.5 or HG+HR+P25 or HG+HR+P50 vs.HG+HR).Moreover,we found that propofol(P25) decreased H9c2 cells apoptosis and autophagy that were concomitant with increased FoxO1 and FoxO3a expression(P<0.05,HG+HR+P25 vs.HG+HR).The protective effects of propofol(P25) against H/R injury were reversed by silencing FoxO1 or FoxO3a(P<0.05,HG+HR+P25 vs.HG+HR+P25+siRNA-1 or HG+HR+P25+siRNA-5).Conclusions:It is concluded that propofol postconditioning attenuated H9c2 cardiac cells apoptosis and autophagy induced by H/R injury through upregulating FoxO1 and FoxO3a under hyperglycemia.