BACKGROUND Acute myocardial infarction(AMI)is a major cause of mortality worldwide.The stress hyperglycemia ratio(SHR),which integrates glucose and glycated hemoglobin A1c levels,better reflects acute metabolic stress...BACKGROUND Acute myocardial infarction(AMI)is a major cause of mortality worldwide.The stress hyperglycemia ratio(SHR),which integrates glucose and glycated hemoglobin A1c levels,better reflects acute metabolic stress.This study assessed the SHR and longterm prognosis of patients with AMI.METHODS This study was a post-hoc analysis based on the prospective,multicenter OPTIMAL registry(http://www.clinicaltrials.gov,NCT number:NCT03084991).A total of 3384 consecutive patients who underwent percutaneous coronary intervention(PCI)at Department of Cardiology,The 2nd Affiliated Hospital of Harbin Medical University,Harbin,China were included in the present analysis after exclusions.Patients were stratified into quartiles according to the SHR.The primary endpoint was cardiovascular death,with all-cause death and major adverse cardiovascular events as secondary endpoints.The median follow-up duration was 24.1 months,with a completion rate of 99.5%.RESULTS Kaplan-Meier survival curves showed progressively worse survival across SHR quartiles(log-rank P<0.001),with patients in Q4(SHR≥1.34)experiencing the highest risk.Multivariate Cox regression analysis confirmed that the SHR was an independent predictor of cardiovascular death[hazard ratio(HR)=1.56],all-cause death(HR=1.48),and major adverse cardiovascular events(HR=1.34)for Q4(SHR≥1.34)versus Q2(SHR:0.93–1.11).Restricted cubic spline analysis revealed a J-shaped association between SHR and outcomes,with the lowest risk observed at an SHR of approximately 1.0.CONCLUSIONS The SHR is an independent predictor of long-term adverse outcomes in patients with AMI undergoing PCI,supporting its use for early risk stratification and glycemic management.展开更多
Plant polyphenols are potential substitutes for clinicalα-glucosidase inhibitors.Our previous studies indicated that prodelphinidins from Chinese bayberry leaves(BLPs)have strongerα-glucosidase inhibitory activity t...Plant polyphenols are potential substitutes for clinicalα-glucosidase inhibitors.Our previous studies indicated that prodelphinidins from Chinese bayberry leaves(BLPs)have strongerα-glucosidase inhibitory activity than other common polyphenols,but they have no safe history of consumption.There is a reasonable prospect that prodelphinidins from Chinese bayberry fruits(BFPs)can improve postprandial hyperglycemia,though known active components are only myricetin and cyanidin-3-O-glucoside.Hence,the aim of this study was to analyze structure and hypoglycemic effect of BFPs of“Biqi”(BQPs)and“Dongkui”(DKPs)cultivars,and compare their difference with BLPs.The contents of BQPs and DKPs were(221.73±0.60)and(136.82±4.33)mg epicatechin(EC)equivalents/g dry weight,respectively.The most subunits were epigallocatechin gallate along with a small amount of epigallocatechin,epicatechin gallate and EC connected by B-type linkages and a small portion of A-type linkages with mean polymerization degree of 4.25 and 4.08,respectively.Importantly,BQPs and DKPs wereα-glucosidase inhibitors with half inhibitory concentration of 11.91 and 9.47μg/m L respectively,which were significantly stronger than BLPs.DKPs could also improve postprandial hyperglycemia of normal mice and high fat diet-induced type II diabetic mice.Therefore,edible prodelphinidins,which have stronger hypoglycemic effect than BLPs,were first found in Chinese bayberry fruits.展开更多
BACKGROUND Diabetes and its associated microvascular complications,such as nephropathy and retinopathy,significantly impact global health.These complications often begin in the prediabetic stage,emphasizing the import...BACKGROUND Diabetes and its associated microvascular complications,such as nephropathy and retinopathy,significantly impact global health.These complications often begin in the prediabetic stage,emphasizing the importance of early detection and intervention.Inflammatory pathways are key contributors to these conditions,and recent research has identified members of the tumor necrosis factor(TNF)receptor superfamily as potential biomarkers.However,their association with renal and retinal dysfunction in individuals with intermediate hyperglycemia(IH)remains underexplored.The Early Prevention of Diabetes Complications(ePREDICE)trial provides a valuable cohort to investigate these associations and improve risk assessment strategies.AIM To identify inflammatory biomarkers associated with early renal and retinal dysfunction in individuals with IH.Specifically,we evaluate the diagnostic and prognostic potential of TNF receptor superfamily members[TNF receptor 1(TNF-R1),TNF receptor 2(TNF-R2)],T-cell immunoglobulin and mucin domain 3(TIM-3)/HAVCR2,galectin-3,and interleukin-6(IL-6)in detecting kidney dysfunction and retinopathy in this high-risk population.By understanding their roles,we seek to enhance early screening methods and inform personalized intervention strategies.METHODS A cross-sectional analysis of 967 individuals with IH from the ePREDICE trial was conducted.Participants underwent comprehensive anthropometric and biochemical assessments.Key inflammatory biomarkers,including TNF-R1,TNF-R2,TIM-3/HAVCR2,galectin-3,and IL-6,were quantified using immunoassays.Renal function was assessed using estimated glomerular filtration rate(eGFR)and albuminuria,while retinopathy was evaluated through fundoscopic examination.Statistical analyses included adjusted mean comparisons,correlation studies,and receiver operating characteristic curve analysis to assess biomarker diagnostic accuracy.RESULTS TNF-R1,TNF-R2,and TIM-3/HAVCR2 were significantly associated with reduced filtration function(eGFR<60 mL/minute/1.73 m^(2))and albuminuria,with area under the curve(AUC)values between 0.815 and 0.845.TIM-3/HAVCR2 emerged as the strongest predictor of retinopathy(AUC=0.737).Strong correlations(r>0.75)were observed among TNF-R1,TNF-R2,and TIM-3/HAVCR2,suggesting a coordinated role in inflammatory pathways.CONCLUSION Our findings highlight the potential of TNF receptor superfamily members as biomarkers for early-stage renal and retinal complications in individuals with IH.Their integration into clinical screening protocols could facilitate earlier detection,improving patient stratification and personalized management strategies.Further longitudinal studies are necessary to validate their predictive value and potential for guiding therapeutic interventions in IH and early diabetes management.展开更多
Objective To elucidate the regulatory mechanism of circRNAs in diabetic retinopathy.Methods Next-generation sequencing(NGS)was employed to identify circRNAs that are abnormally expressed in endothe-lial progenitor cel...Objective To elucidate the regulatory mechanism of circRNAs in diabetic retinopathy.Methods Next-generation sequencing(NGS)was employed to identify circRNAs that are abnormally expressed in endothe-lial progenitor cells(EPCs)under hyperglycemia(HG)conditions.The regulatory mechanism and predicted targets of this circRNA were also studied via bioinformatics analysis,luciferase reporter assays,angiogenic differentiation experiments,flow cytometry,and RT-qPCR.Results Circ-astrotactin 1(circ-Astn1)expression was decreased in EPCs under HG conditions,and circ-Astn1 overexpres-sion inhibited HG-induced endothelial damage.The miR-138-5p and silencing information regulator 2 related enzyme 1(SIRT1)were identified as circ-Astn1 downstream targets,which were further verified through luciferase reporter assays.SIRT1 silencing or miR-138-5p overexpression reversed the protective effect of circ-Astn1 on HG-induced endothelial cell dysfunction,as evidenced by increased apoptosis,abnormal vascular differentiation,and inflammatory factor secretion.SIRT1 overexpression reversed miR-138-5p-induced endothelial cell dysfunction under HG conditions.In vivo experiments confirmed that circ-Astnl overexpression promoted skin wound healing through the regulation of SIRT1.Conclusions These findings suggest that circ-Astn1 promotes SIRT1 expression by sponging miR-138-5p.Circ-Astn1 over-expression suppresses HG-induced endothelial cell damage via miR-138-5p/SIRT1 axis.展开更多
BACKGROUND Diabetic cystopathy(DCP)is a complication affecting the lives of people with diabetes.However,the pathogenesis of DCP is not well known.AIM To investigate the potential mechanisms by which cAMP-responsive e...BACKGROUND Diabetic cystopathy(DCP)is a complication affecting the lives of people with diabetes.However,the pathogenesis of DCP is not well known.AIM To investigate the potential mechanisms by which cAMP-responsive elementbinding protein 3 like 3(CREB3 L3)promotes the occurrence and development of DCP.METHODS High-throughput sequencing was used to analyze differentially expressed genes(DEGs)in bladder urothelium from patients with DCP and healthy controls.Gene enrichment analysis was conducted to assess the biological functions of DEG.Small interfering RNA technology was performed to silence the CREB3 L3 gene in both in vitro and in vivo experiments.Morphological changes in bladder urothelium from a DCP rat model were observed.Immunofluorescence and western blotting assay were performed to determine associated protein expression.RESULTS We identified significant DEGs through high-throughput sequencing.These genes were primarily enriched in inflammatory activation,epithelial-mesenchymal transition(EMT)and tight junction organization.Upregulated expression of both CREB3 L3 and C-reactive protein(CRP)in bladder urothelium from patients with DCP was accompanied by upregulated EMT markers including N-cadherin and vimentin proteins,but downregulated E-cadherin.Silencing CREB3 L3 attenuated the protein expression of CRP and EMT in SV-HUC-1 urothelial cells under hyperglycemic conditions and in the diabetes mellitus rat model at 4,8,and 12 weeks.CREB3 L3 knockdown also reversed downregulation of the tight junction proteins occludin and claudin 1.CONCLUSION Hyperglycemia induces the upregulation of CREB3 L3 expression,thereby promoting the EMT and impairing tight junctions in bladder urothelial cells.Targeting CREB3 L3 in bladder urothelial cells is likely to be a key approach in preventing and treating DCP.展开更多
BACKGROUND Stress-induced hyperglycemia(SIH)is common in critically ill patients and has been associated with adverse cardiovascular outcomes.Intensive insulin therapy(IIT)has been proposed to mitigate these risks by ...BACKGROUND Stress-induced hyperglycemia(SIH)is common in critically ill patients and has been associated with adverse cardiovascular outcomes.Intensive insulin therapy(IIT)has been proposed to mitigate these risks by achieving tighter glycemic control.AIM To evaluate the efficacy of IIT for managing SIH in critically ill patients and to explore its potential effect on cardiac function.METHODS A retrospective study was conducted at our hospital from January 2021 to December 2024,adhering to STROBE guidelines.A total of 186 critically ill pa-tients were divided into normal glycemia(n=85)and SIH(n=101)groups.The SIH cohort was further subdivided into conventional treatment(n=50)and IIT(n=51)groups.Hemodynamic parameters-including right atrial pressure(RAP),pulmonary artery pressure(PAP),pulmonary capillary wedge pressure(PAWP),cardiac output(CO),cardiac index(CI),and B-type natriuretic peptide(BNP)-were measured at baseline and post-treatment.Clinical outcomes such as intensive care unit(ICU)length of stay,mechanical ventilation requirements,and mortality were also recorded.Statistical analyses were conducted using inde-pendent samples t-tests and χ^(2)/Fisher’s exact tests.RESULTS SIH markedly worsened haemodynamics versus normal glycaemia:RAP 9.8±5.1 vs 6.1±3.5 mmHg,PAP 35.2±16.0 vs 26.2±10.3 mmHg,PAWP 16.0±7.0 vs 8.6±6.4 mmHg,CO 3.3±2.3 vs 6.0±3.3 L/min,CI 1.88±0.24 vs 2.70±0.50 L/min/m2,BNP 465±250 vs 180±53 pg/mL(all P<0.001).Within the SIH cohort,IIT outperformed conventional therapy:RAP 7.0±2.2 vs 8.3±3.9 mmHg(P=0.04),PAP 21.6±3.7 vs 29.3±6.5 mmHg(P<0.001),PAWP 10.2±5.4 vs 13.8±5.3 mmHg(P=0.001),CO 4.9±2.2 vs 4.0±1.4 L/min(P=0.022),CI 2.58±0.32 vs 2.11±0.31 L/min/m2,P<0.001),BNP 202±62 vs 346±171 pg/mL(P<0.001).Clinically,IIT shortened ICU stay(10.3±3.4 vs 14.5±2.6 days,P<0.001),reduced ventilator use(56.9%vs 76.0%,P=0.042),and lowered mortality(23.5%vs 42.0%,P=0.048).CONCLUSION IIT significantly reduced cardiac filling pressures,improved cardiac function,and was associated with favorable clinical outcomes in SIH patients,suggesting potential benefits of stricter glycaemic control in critically ill patients.However,given the retrospective design and absence of glucose-variability monitoring,these findings should be interpreted with caution.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
Everolimus is an orally administered rapamycin analogue that has been approved to treat several types of solid tumors. However, some patients develop hyperglycemia after being treated with everolimus. In this meta-ana...Everolimus is an orally administered rapamycin analogue that has been approved to treat several types of solid tumors. However, some patients develop hyperglycemia after being treated with everolimus. In this meta-analysis, we aimed to evaluate the incidence and risk of hyperglycemia in patients with cancer who received everolimus. We searched the medical literature, as index in the Cochrane Library, PubMed, EMBASE, and abstracts from the top scientific meetings （AACR, ASCO, and ESMO）. Our meta-analysis included the randomly controlled trials published before November 2014. We calculated overall incidence, relative risk （RR） and 95% confidence intervals （CI） using fixed-effects or random-effects models, depending on the heterogene- ity among the trials. A total of 3377 patients （everolimus： 1971; control： 1406） from 8 randomized clinical trials were included in the meta-analysis. In the everolimus groups, the incidence of all grades of hyperglycemia was 20.0% （95% CI： 11.0%-29.0%）, while the incidence of high-grade hyperglycemia was 6.0% （95% CI： 3.0%-8.0%）. Patients treated with everolimus had an in- creased risk of hyperglycemia as compared with that of controls （all-grade RR： 2.94, 95% CI： 2.34-3.70; high-grade RR： 4.66, 95% CI： 2.75-7.89）. Everolimus significantly increased the risk of hyperglycemia. This risk may depend on the tumor type and the everolimus dosage.展开更多
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 ...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.展开更多
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 t...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.展开更多
Recent evidence suggests that admission hypergly- cemia has deleterious effects on the survival and functional outcome of patients with intracerebral hemorrhage （ICH）. In this study, we first induced acute hyperglyc...Recent evidence suggests that admission hypergly- cemia has deleterious effects on the survival and functional outcome of patients with intracerebral hemorrhage （ICH）. In this study, we first induced acute hyperglycemia in male adult Sprague-Dawley rats by intraperitoneal injection of 50% glucose （6 mL/kg）, and created the ICH model thereafter by delivering autologous whole blood or homologous normal- glucose blood into the right basal ganglia. Twenty- four hours later, we assessed the neurological injury, evaluated the hematoma and brain water content, and investigated autophagy. We found elevations of neurological deficit scores, brain water content, and microtubule-associated protein light chain-3 （LC3） and beclin-1 protein levels, and decreased SQSTM1/ p62 levels after ICH with normal-glucose blood （without hyperglycemia）. Acute hyperglycemia with ICH of high-glucose blood hematoma was associated with significantly increased forelimb-use asymmetry test scores, brain water content and SQSTM1/p62 protein levels, and evident decreases in the ratio of LC3-11/LC3-1 and beclin-1 protein levels. On the other hand, acute hyperglycemia and ICH with normal- glucose blood hematoma only slightly increased the neurological deficit scores and brain water content （P 〉0.05）. In conclusion, the autophagy pathway was activated after ICH, and acute hyperglycemia with hematoma of high-glucose blood exacerbates the neurological injury, and reduces autophagy around the hematoma.展开更多
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 an...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.展开更多
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 n...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.展开更多
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 cardioprotect...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.展开更多
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 c...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.展开更多
The Goto-Kakizaki(GK) rat is a spontaneous type 2 diabetic animal model,which is characterized by a progressive loss of beta islet cells with fibrosis.In the present study,the hypoglycemic effect of asiatic acid(AA) i...The Goto-Kakizaki(GK) rat is a spontaneous type 2 diabetic animal model,which is characterized by a progressive loss of beta islet cells with fibrosis.In the present study,the hypoglycemic effect of asiatic acid(AA) in GK rats was examined.GK rats receiving AA at a daily dose of 25 mg·kg-1 for four weeks showed a significant reduction in blood glucose levels.Age-matched normal Wistar rats were given 0.5% sodium carboxymethyl cellulose(CMC-Na) solution for the same periods and used as control.Compared to the normal Wistar rats,GK rats treated with AA showed improvement in insulin resistance partially through decreasing glucose level(P < 0.01) and insulin level(P < 0.05).Furthermore,the results of immunohistochemistry indicate that AA treatment reduced islet fibrosis in GK rats.Fibronectin,a key protein related to islet fibrosis,was over-expressed in GK rats,which was reversed significantly by AA treatment(P < 0.05).These findings suggest that AA has a beneficial effect on lowering blood glucose levels in GK rats and improves fibrosis of islets in diabetes,which may play a role in the prevention of islets展开更多
Studies have shown that targeting xanthine oxidase(XO)can be a feasible treatment for fructose-induced hyperuricemia and hyperglycemia.This study aimed to evaluate the dual regulatory effects and molecular mechanisms ...Studies have shown that targeting xanthine oxidase(XO)can be a feasible treatment for fructose-induced hyperuricemia and hyperglycemia.This study aimed to evaluate the dual regulatory effects and molecular mechanisms of diacylated anthocyanins from purple sweet potato(diacylated AF-PSPs)on hyperglycemia and hyperuricemia induced by a high-fructose/high-fat diet.The body weight,organ index,serum biochemical indexes,and liver antioxidant indexes of mice were measured,and the kidneys were observed in pathological sections.The relative expression levels of messenger RNAs(mRNAs)of fructose metabolism pathway enzymes in kidney were detected by fluorescent real-time quantitative polymerase chain(qPCR)reaction technique,and the expression of renal transporter protein and inflammatory factor pathway protein was determined by immunohistochemistry(IHC)technique.Results showed that diacylated AF-PSPs alleviated hyperuricemia in mice,and that this effect might be related to the regulation of liver XO activity,lipid accumulation,and relevant renal transporters.Diacylated AF-PSPs reduced body weight and relieved lipid metabolism disorder,liver lipid accumulation,and liver oxidative stress,thereby enhancing insulin utilization and sensitivity,lowering blood sugar,and reducing hyperglycemia in mice.Also,diacylated AF-PSPs restored mRNA levels related to renal fructose metabolism,and reduced kidney injury and inflammation.This study provided experimental evidence for the mechanisms of dual regulation of blood glucose and uric acid(UA)by diacylated AF-PSPs and their utilization as functional foods in the management of metabolic syndrome.展开更多
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....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.展开更多
OBJECTIVE:To elucidate whether Danzhi Jiangtang capsule(丹蛭降糖胶囊,DJC)has treatment effects on diabetic periodontitis and the potential mechanism.METHODS:One week after the induction of diabetes by streptozotocin(S...OBJECTIVE:To elucidate whether Danzhi Jiangtang capsule(丹蛭降糖胶囊,DJC)has treatment effects on diabetic periodontitis and the potential mechanism.METHODS:One week after the induction of diabetes by streptozotocin(STZ),60 male Wistar rats were ligated by orthodontic ligation thread in cervical portion of bilateral maxillary first molar to induce diabetic periodontitis.Periodontitis was exanimated by tooth tissue morphology after 4 weeks.And then all rats were divided into 5 groups:diabetic periodontitis group(DP,n=20),periodontal basic treatment group(DP+BT,n=20),periodontal basic treatment+DJC treatment group(DP+BT+DJC,n=20)and additional Wnt/β-catenin inhibitor group(DP+BT+DJC+WIKI4/21 H7,n=20).Eight weeks after different interventions,fasting plasma glucose(FPG),C-peptide and glycosylated hemoglobin(Hb Alc)of rats were measured and then all rats were sacrificed.The paraffin sections of periodontal tissue were executed hematoxylin-eosin(HE)staining and immunohistochemical examination.The m RNA and protein levels of inflammatory cytokines were evaluated by quantitative polymerase chain reaction(Q-PCR)and Western blotting(WB).The protein levels of Wnt/β-catenin signaling molecules were measured by WB.RESULTS:The blood glucose and C-peptide concentrations in DP,DP+BT and DP+BT+DJC groups were gradually reduced,with gradually decreased distance of CEJ-A and the percentage of periodontal ligament(PDL),as well as gradually increased Hb Alc.The number of monocytes and leukocytes in the junctional epithelium and periodontal connective tissue was markedly decreased in DP+BT+DJC group(P<0.05),which was slightly reduced in DP+BT group comparing to DP group.The protein levels of Wnt1 andβ-catenin were obviously up-regulated with DJC treatment,while the SOST and DDK1 were markedly down-regulated with DJC treatment.The expression levels of BGP were lowest in DP group and highest in DP+BT+DJC group,while the tumor necrosis factor-α(TNF-α),interferon-γ(IFN-γ)and metalloproteinase-3(MMP-3)were highest in DP group and lowest in DP+BT+DJC group.All these changes could be reversed by Wnt/β-catenin inhibitor.CONCLUSION:DJC can improve the hyperglycemia and both distal alveolar bone loss and alveolar bone loss in furcation area of diabetic periodontitis rats by reducing the inflammation of gingival tissue and regulating the expressions of BGP,TNF-α,IFN-γand MMP-3 potentially through Wnt/β-catenin signaling.展开更多
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 patie...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.展开更多
基金supported by the National Natural Science Foundation of China(No.62135002)the Key Research and Development Program of Heilongjiang Province(No.2022ZX01A28).
文摘BACKGROUND Acute myocardial infarction(AMI)is a major cause of mortality worldwide.The stress hyperglycemia ratio(SHR),which integrates glucose and glycated hemoglobin A1c levels,better reflects acute metabolic stress.This study assessed the SHR and longterm prognosis of patients with AMI.METHODS This study was a post-hoc analysis based on the prospective,multicenter OPTIMAL registry(http://www.clinicaltrials.gov,NCT number:NCT03084991).A total of 3384 consecutive patients who underwent percutaneous coronary intervention(PCI)at Department of Cardiology,The 2nd Affiliated Hospital of Harbin Medical University,Harbin,China were included in the present analysis after exclusions.Patients were stratified into quartiles according to the SHR.The primary endpoint was cardiovascular death,with all-cause death and major adverse cardiovascular events as secondary endpoints.The median follow-up duration was 24.1 months,with a completion rate of 99.5%.RESULTS Kaplan-Meier survival curves showed progressively worse survival across SHR quartiles(log-rank P<0.001),with patients in Q4(SHR≥1.34)experiencing the highest risk.Multivariate Cox regression analysis confirmed that the SHR was an independent predictor of cardiovascular death[hazard ratio(HR)=1.56],all-cause death(HR=1.48),and major adverse cardiovascular events(HR=1.34)for Q4(SHR≥1.34)versus Q2(SHR:0.93–1.11).Restricted cubic spline analysis revealed a J-shaped association between SHR and outcomes,with the lowest risk observed at an SHR of approximately 1.0.CONCLUSIONS The SHR is an independent predictor of long-term adverse outcomes in patients with AMI undergoing PCI,supporting its use for early risk stratification and glycemic management.
基金supported by grants from the National Key Research and Development Program of China(2022YFF1100204)the National Natural Science Foundation of China(31972088,32001715)。
文摘Plant polyphenols are potential substitutes for clinicalα-glucosidase inhibitors.Our previous studies indicated that prodelphinidins from Chinese bayberry leaves(BLPs)have strongerα-glucosidase inhibitory activity than other common polyphenols,but they have no safe history of consumption.There is a reasonable prospect that prodelphinidins from Chinese bayberry fruits(BFPs)can improve postprandial hyperglycemia,though known active components are only myricetin and cyanidin-3-O-glucoside.Hence,the aim of this study was to analyze structure and hypoglycemic effect of BFPs of“Biqi”(BQPs)and“Dongkui”(DKPs)cultivars,and compare their difference with BLPs.The contents of BQPs and DKPs were(221.73±0.60)and(136.82±4.33)mg epicatechin(EC)equivalents/g dry weight,respectively.The most subunits were epigallocatechin gallate along with a small amount of epigallocatechin,epicatechin gallate and EC connected by B-type linkages and a small portion of A-type linkages with mean polymerization degree of 4.25 and 4.08,respectively.Importantly,BQPs and DKPs wereα-glucosidase inhibitors with half inhibitory concentration of 11.91 and 9.47μg/m L respectively,which were significantly stronger than BLPs.DKPs could also improve postprandial hyperglycemia of normal mice and high fat diet-induced type II diabetic mice.Therefore,edible prodelphinidins,which have stronger hypoglycemic effect than BLPs,were first found in Chinese bayberry fruits.
基金Supported by the Instituto de Salud Carlos Ⅲ(ISCⅢ)Through the Project Co-Funded by the European Union,No.PI20-00487,No.PI23-00119 and No.PI24-01630.
文摘BACKGROUND Diabetes and its associated microvascular complications,such as nephropathy and retinopathy,significantly impact global health.These complications often begin in the prediabetic stage,emphasizing the importance of early detection and intervention.Inflammatory pathways are key contributors to these conditions,and recent research has identified members of the tumor necrosis factor(TNF)receptor superfamily as potential biomarkers.However,their association with renal and retinal dysfunction in individuals with intermediate hyperglycemia(IH)remains underexplored.The Early Prevention of Diabetes Complications(ePREDICE)trial provides a valuable cohort to investigate these associations and improve risk assessment strategies.AIM To identify inflammatory biomarkers associated with early renal and retinal dysfunction in individuals with IH.Specifically,we evaluate the diagnostic and prognostic potential of TNF receptor superfamily members[TNF receptor 1(TNF-R1),TNF receptor 2(TNF-R2)],T-cell immunoglobulin and mucin domain 3(TIM-3)/HAVCR2,galectin-3,and interleukin-6(IL-6)in detecting kidney dysfunction and retinopathy in this high-risk population.By understanding their roles,we seek to enhance early screening methods and inform personalized intervention strategies.METHODS A cross-sectional analysis of 967 individuals with IH from the ePREDICE trial was conducted.Participants underwent comprehensive anthropometric and biochemical assessments.Key inflammatory biomarkers,including TNF-R1,TNF-R2,TIM-3/HAVCR2,galectin-3,and IL-6,were quantified using immunoassays.Renal function was assessed using estimated glomerular filtration rate(eGFR)and albuminuria,while retinopathy was evaluated through fundoscopic examination.Statistical analyses included adjusted mean comparisons,correlation studies,and receiver operating characteristic curve analysis to assess biomarker diagnostic accuracy.RESULTS TNF-R1,TNF-R2,and TIM-3/HAVCR2 were significantly associated with reduced filtration function(eGFR<60 mL/minute/1.73 m^(2))and albuminuria,with area under the curve(AUC)values between 0.815 and 0.845.TIM-3/HAVCR2 emerged as the strongest predictor of retinopathy(AUC=0.737).Strong correlations(r>0.75)were observed among TNF-R1,TNF-R2,and TIM-3/HAVCR2,suggesting a coordinated role in inflammatory pathways.CONCLUSION Our findings highlight the potential of TNF receptor superfamily members as biomarkers for early-stage renal and retinal complications in individuals with IH.Their integration into clinical screening protocols could facilitate earlier detection,improving patient stratification and personalized management strategies.Further longitudinal studies are necessary to validate their predictive value and potential for guiding therapeutic interventions in IH and early diabetes management.
基金supported by grants from the National Natural Science Foundation of China(No.81770483)Shanghai Tenth Hospital’s improvement plan for NSFC(No.04.03.17.070).
文摘Objective To elucidate the regulatory mechanism of circRNAs in diabetic retinopathy.Methods Next-generation sequencing(NGS)was employed to identify circRNAs that are abnormally expressed in endothe-lial progenitor cells(EPCs)under hyperglycemia(HG)conditions.The regulatory mechanism and predicted targets of this circRNA were also studied via bioinformatics analysis,luciferase reporter assays,angiogenic differentiation experiments,flow cytometry,and RT-qPCR.Results Circ-astrotactin 1(circ-Astn1)expression was decreased in EPCs under HG conditions,and circ-Astn1 overexpres-sion inhibited HG-induced endothelial damage.The miR-138-5p and silencing information regulator 2 related enzyme 1(SIRT1)were identified as circ-Astn1 downstream targets,which were further verified through luciferase reporter assays.SIRT1 silencing or miR-138-5p overexpression reversed the protective effect of circ-Astn1 on HG-induced endothelial cell dysfunction,as evidenced by increased apoptosis,abnormal vascular differentiation,and inflammatory factor secretion.SIRT1 overexpression reversed miR-138-5p-induced endothelial cell dysfunction under HG conditions.In vivo experiments confirmed that circ-Astnl overexpression promoted skin wound healing through the regulation of SIRT1.Conclusions These findings suggest that circ-Astn1 promotes SIRT1 expression by sponging miR-138-5p.Circ-Astn1 over-expression suppresses HG-induced endothelial cell damage via miR-138-5p/SIRT1 axis.
基金Supported by Guangxi Natural Science Foundation,No.2024GXNSFAA010031.
文摘BACKGROUND Diabetic cystopathy(DCP)is a complication affecting the lives of people with diabetes.However,the pathogenesis of DCP is not well known.AIM To investigate the potential mechanisms by which cAMP-responsive elementbinding protein 3 like 3(CREB3 L3)promotes the occurrence and development of DCP.METHODS High-throughput sequencing was used to analyze differentially expressed genes(DEGs)in bladder urothelium from patients with DCP and healthy controls.Gene enrichment analysis was conducted to assess the biological functions of DEG.Small interfering RNA technology was performed to silence the CREB3 L3 gene in both in vitro and in vivo experiments.Morphological changes in bladder urothelium from a DCP rat model were observed.Immunofluorescence and western blotting assay were performed to determine associated protein expression.RESULTS We identified significant DEGs through high-throughput sequencing.These genes were primarily enriched in inflammatory activation,epithelial-mesenchymal transition(EMT)and tight junction organization.Upregulated expression of both CREB3 L3 and C-reactive protein(CRP)in bladder urothelium from patients with DCP was accompanied by upregulated EMT markers including N-cadherin and vimentin proteins,but downregulated E-cadherin.Silencing CREB3 L3 attenuated the protein expression of CRP and EMT in SV-HUC-1 urothelial cells under hyperglycemic conditions and in the diabetes mellitus rat model at 4,8,and 12 weeks.CREB3 L3 knockdown also reversed downregulation of the tight junction proteins occludin and claudin 1.CONCLUSION Hyperglycemia induces the upregulation of CREB3 L3 expression,thereby promoting the EMT and impairing tight junctions in bladder urothelial cells.Targeting CREB3 L3 in bladder urothelial cells is likely to be a key approach in preventing and treating DCP.
文摘BACKGROUND Stress-induced hyperglycemia(SIH)is common in critically ill patients and has been associated with adverse cardiovascular outcomes.Intensive insulin therapy(IIT)has been proposed to mitigate these risks by achieving tighter glycemic control.AIM To evaluate the efficacy of IIT for managing SIH in critically ill patients and to explore its potential effect on cardiac function.METHODS A retrospective study was conducted at our hospital from January 2021 to December 2024,adhering to STROBE guidelines.A total of 186 critically ill pa-tients were divided into normal glycemia(n=85)and SIH(n=101)groups.The SIH cohort was further subdivided into conventional treatment(n=50)and IIT(n=51)groups.Hemodynamic parameters-including right atrial pressure(RAP),pulmonary artery pressure(PAP),pulmonary capillary wedge pressure(PAWP),cardiac output(CO),cardiac index(CI),and B-type natriuretic peptide(BNP)-were measured at baseline and post-treatment.Clinical outcomes such as intensive care unit(ICU)length of stay,mechanical ventilation requirements,and mortality were also recorded.Statistical analyses were conducted using inde-pendent samples t-tests and χ^(2)/Fisher’s exact tests.RESULTS SIH markedly worsened haemodynamics versus normal glycaemia:RAP 9.8±5.1 vs 6.1±3.5 mmHg,PAP 35.2±16.0 vs 26.2±10.3 mmHg,PAWP 16.0±7.0 vs 8.6±6.4 mmHg,CO 3.3±2.3 vs 6.0±3.3 L/min,CI 1.88±0.24 vs 2.70±0.50 L/min/m2,BNP 465±250 vs 180±53 pg/mL(all P<0.001).Within the SIH cohort,IIT outperformed conventional therapy:RAP 7.0±2.2 vs 8.3±3.9 mmHg(P=0.04),PAP 21.6±3.7 vs 29.3±6.5 mmHg(P<0.001),PAWP 10.2±5.4 vs 13.8±5.3 mmHg(P=0.001),CO 4.9±2.2 vs 4.0±1.4 L/min(P=0.022),CI 2.58±0.32 vs 2.11±0.31 L/min/m2,P<0.001),BNP 202±62 vs 346±171 pg/mL(P<0.001).Clinically,IIT shortened ICU stay(10.3±3.4 vs 14.5±2.6 days,P<0.001),reduced ventilator use(56.9%vs 76.0%,P=0.042),and lowered mortality(23.5%vs 42.0%,P=0.048).CONCLUSION IIT significantly reduced cardiac filling pressures,improved cardiac function,and was associated with favorable clinical outcomes in SIH patients,suggesting potential benefits of stricter glycaemic control in critically ill patients.However,given the retrospective design and absence of glucose-variability monitoring,these findings should be interpreted with caution.
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Everolimus is an orally administered rapamycin analogue that has been approved to treat several types of solid tumors. However, some patients develop hyperglycemia after being treated with everolimus. In this meta-analysis, we aimed to evaluate the incidence and risk of hyperglycemia in patients with cancer who received everolimus. We searched the medical literature, as index in the Cochrane Library, PubMed, EMBASE, and abstracts from the top scientific meetings （AACR, ASCO, and ESMO）. Our meta-analysis included the randomly controlled trials published before November 2014. We calculated overall incidence, relative risk （RR） and 95% confidence intervals （CI） using fixed-effects or random-effects models, depending on the heterogene- ity among the trials. A total of 3377 patients （everolimus： 1971; control： 1406） from 8 randomized clinical trials were included in the meta-analysis. In the everolimus groups, the incidence of all grades of hyperglycemia was 20.0% （95% CI： 11.0%-29.0%）, while the incidence of high-grade hyperglycemia was 6.0% （95% CI： 3.0%-8.0%）. Patients treated with everolimus had an in- creased risk of hyperglycemia as compared with that of controls （all-grade RR： 2.94, 95% CI： 2.34-3.70; high-grade RR： 4.66, 95% CI： 2.75-7.89）. Everolimus significantly increased the risk of hyperglycemia. This risk may depend on the tumor type and the everolimus dosage.
文摘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.
基金Supported by A Grant-in-Aid from the Ministry of Health,Labor and Welfare,Japan
文摘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.
基金supported by a grant from the National Natural Science Foundation of China(30600195)
文摘Recent evidence suggests that admission hypergly- cemia has deleterious effects on the survival and functional outcome of patients with intracerebral hemorrhage （ICH）. In this study, we first induced acute hyperglycemia in male adult Sprague-Dawley rats by intraperitoneal injection of 50% glucose （6 mL/kg）, and created the ICH model thereafter by delivering autologous whole blood or homologous normal- glucose blood into the right basal ganglia. Twenty- four hours later, we assessed the neurological injury, evaluated the hematoma and brain water content, and investigated autophagy. We found elevations of neurological deficit scores, brain water content, and microtubule-associated protein light chain-3 （LC3） and beclin-1 protein levels, and decreased SQSTM1/ p62 levels after ICH with normal-glucose blood （without hyperglycemia）. Acute hyperglycemia with ICH of high-glucose blood hematoma was associated with significantly increased forelimb-use asymmetry test scores, brain water content and SQSTM1/p62 protein levels, and evident decreases in the ratio of LC3-11/LC3-1 and beclin-1 protein levels. On the other hand, acute hyperglycemia and ICH with normal- glucose blood hematoma only slightly increased the neurological deficit scores and brain water content （P 〉0.05）. In conclusion, the autophagy pathway was activated after ICH, and acute hyperglycemia with hematoma of high-glucose blood exacerbates the neurological injury, and reduces autophagy around the hematoma.
文摘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.
基金supported by a grant from Catholic Universitary Center(Centro Universitario Cattolico)-Conferenza Episcopale Italiana,Rome,Italy(to FF)。
文摘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.
基金supported by the National Natural Science Foundation of China grant (NSFC81970247)。
文摘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.
基金supported by the National Natural Science Foundation of China,No.30772229(to JNZ),No.81200907(to HJW)the Natural Science Foundation of Tianjin of China,No.12JCQNJC06800(to HJW)+1 种基金the Science and Technology Projects in Key Areas of Traditional Chinese Medicine of Tianjin of China,No.2018001(to ZGW)the Scientific Research Program Project of Tianjin Education Commission of China,No.2018ZD03(to ZGW)
文摘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.
基金supported by the Fundamental Research Funds for the Central Universities(No.JKP2011004)
文摘The Goto-Kakizaki(GK) rat is a spontaneous type 2 diabetic animal model,which is characterized by a progressive loss of beta islet cells with fibrosis.In the present study,the hypoglycemic effect of asiatic acid(AA) in GK rats was examined.GK rats receiving AA at a daily dose of 25 mg·kg-1 for four weeks showed a significant reduction in blood glucose levels.Age-matched normal Wistar rats were given 0.5% sodium carboxymethyl cellulose(CMC-Na) solution for the same periods and used as control.Compared to the normal Wistar rats,GK rats treated with AA showed improvement in insulin resistance partially through decreasing glucose level(P < 0.01) and insulin level(P < 0.05).Furthermore,the results of immunohistochemistry indicate that AA treatment reduced islet fibrosis in GK rats.Fibronectin,a key protein related to islet fibrosis,was over-expressed in GK rats,which was reversed significantly by AA treatment(P < 0.05).These findings suggest that AA has a beneficial effect on lowering blood glucose levels in GK rats and improves fibrosis of islets in diabetes,which may play a role in the prevention of islets
基金supported by the National Key Technologies R&D Program of China(No.2021YFE0194000)the Fundamental Research Funds for the Central Universities of China(No.2662018PY022).
文摘Studies have shown that targeting xanthine oxidase(XO)can be a feasible treatment for fructose-induced hyperuricemia and hyperglycemia.This study aimed to evaluate the dual regulatory effects and molecular mechanisms of diacylated anthocyanins from purple sweet potato(diacylated AF-PSPs)on hyperglycemia and hyperuricemia induced by a high-fructose/high-fat diet.The body weight,organ index,serum biochemical indexes,and liver antioxidant indexes of mice were measured,and the kidneys were observed in pathological sections.The relative expression levels of messenger RNAs(mRNAs)of fructose metabolism pathway enzymes in kidney were detected by fluorescent real-time quantitative polymerase chain(qPCR)reaction technique,and the expression of renal transporter protein and inflammatory factor pathway protein was determined by immunohistochemistry(IHC)technique.Results showed that diacylated AF-PSPs alleviated hyperuricemia in mice,and that this effect might be related to the regulation of liver XO activity,lipid accumulation,and relevant renal transporters.Diacylated AF-PSPs reduced body weight and relieved lipid metabolism disorder,liver lipid accumulation,and liver oxidative stress,thereby enhancing insulin utilization and sensitivity,lowering blood sugar,and reducing hyperglycemia in mice.Also,diacylated AF-PSPs restored mRNA levels related to renal fructose metabolism,and reduced kidney injury and inflammation.This study provided experimental evidence for the mechanisms of dual regulation of blood glucose and uric acid(UA)by diacylated AF-PSPs and their utilization as functional foods in the management of metabolic syndrome.
文摘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.
基金Supported by the Education Science Foundation of Anhui Province(Intervention Study on Periodontal Tissue in Rats with Experimental Diabetic Periodontitis in Danzhi Jiangtang Capsule,No.KJ2015A429)。
文摘OBJECTIVE:To elucidate whether Danzhi Jiangtang capsule(丹蛭降糖胶囊,DJC)has treatment effects on diabetic periodontitis and the potential mechanism.METHODS:One week after the induction of diabetes by streptozotocin(STZ),60 male Wistar rats were ligated by orthodontic ligation thread in cervical portion of bilateral maxillary first molar to induce diabetic periodontitis.Periodontitis was exanimated by tooth tissue morphology after 4 weeks.And then all rats were divided into 5 groups:diabetic periodontitis group(DP,n=20),periodontal basic treatment group(DP+BT,n=20),periodontal basic treatment+DJC treatment group(DP+BT+DJC,n=20)and additional Wnt/β-catenin inhibitor group(DP+BT+DJC+WIKI4/21 H7,n=20).Eight weeks after different interventions,fasting plasma glucose(FPG),C-peptide and glycosylated hemoglobin(Hb Alc)of rats were measured and then all rats were sacrificed.The paraffin sections of periodontal tissue were executed hematoxylin-eosin(HE)staining and immunohistochemical examination.The m RNA and protein levels of inflammatory cytokines were evaluated by quantitative polymerase chain reaction(Q-PCR)and Western blotting(WB).The protein levels of Wnt/β-catenin signaling molecules were measured by WB.RESULTS:The blood glucose and C-peptide concentrations in DP,DP+BT and DP+BT+DJC groups were gradually reduced,with gradually decreased distance of CEJ-A and the percentage of periodontal ligament(PDL),as well as gradually increased Hb Alc.The number of monocytes and leukocytes in the junctional epithelium and periodontal connective tissue was markedly decreased in DP+BT+DJC group(P<0.05),which was slightly reduced in DP+BT group comparing to DP group.The protein levels of Wnt1 andβ-catenin were obviously up-regulated with DJC treatment,while the SOST and DDK1 were markedly down-regulated with DJC treatment.The expression levels of BGP were lowest in DP group and highest in DP+BT+DJC group,while the tumor necrosis factor-α(TNF-α),interferon-γ(IFN-γ)and metalloproteinase-3(MMP-3)were highest in DP group and lowest in DP+BT+DJC group.All these changes could be reversed by Wnt/β-catenin inhibitor.CONCLUSION:DJC can improve the hyperglycemia and both distal alveolar bone loss and alveolar bone loss in furcation area of diabetic periodontitis rats by reducing the inflammation of gingival tissue and regulating the expressions of BGP,TNF-α,IFN-γand MMP-3 potentially through Wnt/β-catenin signaling.
文摘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.
