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.

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.

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.

Rapid correction of hyperglycemia:A necessity but at what price?A brief report of a patient living with type 1 diabetes

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.

Hyperglycemia in COVID-19 infection without diabetes mellitus:Association with inflammatory markers

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.

Intermediate hyperglycemia in early pregnancy:A South Asian perspective

“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.

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.

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.

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.

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.

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.

Hyperglycemia in acute ischemic stroke: physiopathological and therapeutic complexity

Diabetes mellitus and associated chronic hyperglycemia enhance the risk of acute ischemic stroke and lead to worsened clinical outcome and increased mortality. However, post-stroke hyperglycemia is also present in a number of non-diabetic patients after acute ischemic stroke, presumably as a stress response. The aim of this review is to summarize the main effects of hyperglycemia when associated to ischemic injury in acute stroke patients, highlighting the clinical and neurological outcomes in these conditions and after the administration of the currently approved pharmacological treatment, i.e. insulin. The disappointing results of the clinical trials on insulin(including the hypoglycemic events) demand a change of strategy based on more focused therapies. Starting from the comprehensive evaluation of the physiopathological alterations occurring in the ischemic brain during hyperglycemic conditions, the effects of various classes of glucose-lowering drugs are reviewed, such as glucose-like peptide-1 receptor agonists, DPP-4 inhibitors and sodium glucose cotransporter 2 inhibitors, in the perspective of overcoming the up-to-date limitations and of evaluating the effectiveness of new potential therapeutic strategies.

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.

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.

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.

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.

Citrus peel extract and powder attenuate hypercholesterolemia and hyperglycemia using rodent experimental modeling

Objective: To investigate hypocholesterolemic and hypoglycemic potential of citrus peel extract and powder using rodent experimental modeling.Methods: Considering the fact, rat feeding trial was carried out for a period of 56 d to access the prophylaxis of citrus peel flavonoids by employing normal(study Ⅰ),hyperglycemic(study Ⅱ) and hypercholesterolemic(study Ⅲ) rats. Each study was further divided into three groups to ensure the provision of selected diets, i.e.,control, functional and nutraceutical diets. Each study was further divided into three groups to ensure the provision of selected diets, i.e., control, functional and nutraceutical diets.Results: Declining trend for total cholesterol was observed in all studies with maximum reduction(8.55%) in rat group fed on nutraceutical diet in study Ⅲ. Likewise, levels of low density lipoproteins and triglycerides reduced 11.39% and 7.89% respectively in hypercholesterolemic rats. Moreover, nutraceutical diet alleviated the sera glucose level by 8.96% in study Ⅱ.Conclusions: Conclusively, inclusion of citrus peel bioflavonoids in dietary therapies is a promising strategy to modulate lipidemic and glycemic attributes without imparting any deleterious effect on hematological parameters.

New-onset hyperglycemia immediately after liver transplantation:A national survey from China Liver Transplant Registry

Background: New-onset hyperglycemia(NOH) is a common phenomenon after liver transplantation(LT),but its impact on clinical outcomes has not yet been fully assessed. We aimed to evaluate the etiology and prognosis of NOH within 1 month after LT.Methods: The data of 3339 adult patients who underwent primary LT from donation after citizen death between January 2010 and June 2016 were extracted from China Liver Transplant Registry database and analyzed. NOH was defined as fasting blood glucose ≥7.0 mmol/L confirmed on at least two occasions within the first post-transplant month with or without hypoglycemic agent.Results: Of 3339 liver recipients, 1416(42.4%) developed NOH. Recipients with NOH had higher incidence of post-transplant complications such as graft and kidney failure, infection, biliary stricture, cholangitis,and tumor recurrence in a glucose concentration-dependent manner as compared to non-NOH recipients(P < 0.05). The independent risk factors of NOH were donor warm ischemic time >10 min, cold ischemic time >10 h, anhepatic time >60 min, recipient model for end-stage liver disease score >30, moderate ascites and corticosteroid usage(P < 0.05). Liver enzymes(alanine aminotransferase and gammaglutamyltranspeptidase) on post-transplant day 7 significantly correlated with NOH(P < 0.001).Conclusions: NOH leads to increased morbidity and mortality in liver recipients. Close surveillance and tight control of blood glucose are desiderated immediately following LT particularly in those with delayed graft function and receiving corticosteroid. Strategic targeting graft ischemic injury may help maintain glucose homeostasis.

Involvement of CaSR in Hyperglycemia-induced Macroangiopathy and Related Mechanism

In order to clarify the potential role of calcium sensing receptor（Ca SR）, a typical G protein coupled receptor（GPCR）, in hyperglacemia-induced macroangiopathy, experimental hyperglycemia models in vivo and in vitro were prepared. Firstly, SD rats were divided into control group（n=10） and diabetes group（n=10）, and diabetic model was induced via high-fat diet feeding and streptozotocin（STZ, 30 mg/kg） injection. Hydroxyproline level, determined via Choramnie T oxidation method, in vessel wall in diabetic rats was 30% more than that in control group. The gene transcription and expression levels were detected by real-time PCR and Western blotting, respectively. Both of collagen Ⅰ and Ⅲ mR NA levels in diabetic aorta were nearly twice those in normal aorta. The cleaved caspase-3 and-9 were elevated 1.5 and 2.5 times respectively in diabetic vascular cells. As compared with controls, m RNA and protein levels of CaS R in aorta were increased by 3 and 1.5 times in diabetes group. The expression levels of Bax as well as pro-apoptotic kinases（phospho-p38 and phosphor-JNK） were also increased 2, 0.5 and 0.5 times respectively in diabetic rats. To further validate the involvement of Ca SR in cell apoptosis and explore the potential mechanism, the endothelial cell line（human umbilical vascular endothelial cells, HUVECs） was stimulated with high concentration of glucose（33 mmol/L） to mimic hyperglycemia in vitro. Cell-based assays also showed that the Ca SR level and key apoptotic proteins（cleaved caspase-3 and-9, Bax, phospho-p38 and phosphor-JNK） were elevated in response to stimulation, and inhibition of Ca SR by using specific inhibitor（NPS-2143, 10 μmol/L） could protect cells against apoptosis. Our results demonstrated that Ca SR might take important part in the development of diabetic macroangiopathy through promoting cell apoptosis induced by hyperglycemia.