AIM To investigate possible changes of blood glucose levels after oral intake of lactulose in healthy subjects.METHODS The study was performed as prospective, randomized, two-part study with 4-way cross-over design wi...AIM To investigate possible changes of blood glucose levels after oral intake of lactulose in healthy subjects.METHODS The study was performed as prospective, randomized, two-part study with 4-way cross-over design with n = 12 in each study arm. Capillary blood glucose levels were determined over a time period of 180 min after intake of a single dose of 10 g or 20 g lactulose provided as crystal or liquid formulation. During the manufacturing process of lactulose, impurities with sugars(e.g., lactose, fructose, galactose) occur. Water and 20 g glucose were used as control and reference. Because lactulose is used as a functional food ingredient, it may also be consumed by people with impaired glucose tolerance, including diabetics. Therefore, it is of interest to determine whether the described carbohydrate impurities may increase blood glucose levels after ingestion. RESULTS The blood glucose concentration-time curves after intake of 10 g lactulose, 20 g lactulose, and water were almost identical. None of the three applications showed any changes in blood glucose levels. After intake of 20 g glucose, blood glucose concentration increased by approximately 3 mmol/L(mean Cmax = 8.3 mmol/L), reaching maximum levels after approximately 30 min and returning to baseline within approximately 90 min, which was significantly different to the corresponding 20 g lactulose formulations(P < 0.0001). Comparing the two lactulose formulations, crystals and liquid, in the dosage of 10 g and 20 g, there was no difference in the blood glucose profile and calculated pharmacokinetic parameters despite the different amounts of carbohydrate impurities(1.5% for crystals and 26.45% for liquid). Anyhow, the absolute amount of single sugars was low with 0.3 g in crystals and 5.29 g in liquid formulation in the 20 g dosages. Lactulose was well tolerated by most volunteers, and only some reported mild to moderate mainly gastrointestinal side effects. CONCLUSION The unchanged blood glucose levels after lactulose intake in healthy subjects suggest its safe use in subjects with impaired glucose tolerance.展开更多
Objective:To investigate the effect of different blood glucose levels on viscera injury, oxidative stress response and Wnt5a inflammatory pathway in children with sepsis.Methods:70 children with sepsis treated in our ...Objective:To investigate the effect of different blood glucose levels on viscera injury, oxidative stress response and Wnt5a inflammatory pathway in children with sepsis.Methods:70 children with sepsis treated in our hospital between January 2014 and December 2015 were retrospectively collected and divided into the sepsis group A (blood glucose>10 mmol/L) (n=29) and the sepsis group B (blood glucose ≤10 mmol/L) (n=41) according to the different blood glucose levels, and 50 healthy children who accepted vaccination and were with normal blood glucose levels in our hospital during the same period were selected as healthy control group. The day after admission, RIA method was used to determine liver function indexes;automatic biochemical analyzer was used to determine oxidative stress indexes;enzyme-linked immunosorbent assay (ELISA) was used to detect Wnt5a inflammatory pathway index levels.Results: Liver function indexes total bilirubin (TBIL), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels of sepsis group A were higher than those of sepsis group B and healthy control group (P<0.05);oxidative stress indexes advanced protein oxidation products (AOPPs), lipid hydrogen peroxide (LHP), reactive oxygen species (ROS), and malondialdehyde (MDA) levels were higher than those of sepsis group B and healthy control group while glutathione peroxidase (GSH-Px) level was lower than that of sepsis group B and healthy control group (P<0.05);serum Wnt5a inflammatory pathway indexes interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-12 (IL-12) and macrophage inflammatory protein-1β (MIP-1β) levels were higher than those of sepsis group B and healthy control group (P<0.05).Conclusions:Sepsis children with high blood glucose are with severe liver function damage as well as intense oxidative stress and inflammatory response, which are the important indexes for severe illness and poor prognosis.展开更多
Shuxuetong injection composed of leech(Hirudo nipponica Whitman) and earthworm(Pheretima aspergillum) has been used for the clinical treatment of acute stroke for many years in China. However, the precise neuroprotect...Shuxuetong injection composed of leech(Hirudo nipponica Whitman) and earthworm(Pheretima aspergillum) has been used for the clinical treatment of acute stroke for many years in China. However, the precise neuroprotective mechanism of Shuxuetong injection remains poorly understood. Here, cerebral microvascular endothelial cells(bEnd.3) were incubated in glucose-free Dulbecco's modified Eagle's medium containing 95% N_2/5% CO_2 for 6 hours, followed by high-glucose medium containing 95% O_2 and 5% CO_2 for 18 hours to establish an oxygen-glucose deprivation/reperfusion model. This in vitro cell model was administered Shuxuetong injection at 1/32, 1/64, and 1/128 concentrations(diluted 32-, 64-, and 128-times). Cell Counting Kit-8 assay was used to evaluate cell viability. A fluorescence method was used to measure lactate dehydrogenase, and a fluorescence microplate reader used to detect intracellular reactive oxygen species. A fluorescent probe was also used to measure mitochondrial superoxide production. A cell resistance meter was used to measure transepithelial resistance and examine integrity of monolayer cells. The fluorescein isothiocyanate-dextran test was performed to examine blood-brain barrier permeability. Real-time reverse transcription polymerase chain reaction was performed to analyze mRNA expression levels of tumor necrosis factor alpha, interleukin-1β, interleukin-6, and inducible nitric oxide synthase. Western blot assay was performed to analyze expression of caspase-3, intercellular adhesion molecule 1, vascular cell adhesion molecule 1, occludin, vascular endothelial growth factor, cleaved caspase-3, B-cell lymphoma 2, phosphorylated extracellular signal-regulated protein kinase, extracellular signal-regulated protein kinase, nuclear factor-κB p65, I kappa B alpha, phosphorylated I kappa B alpha, I kappa B kinase, phosphorylated I kappa B kinase, claudin-5, and zonula occludens-1. Our results show that Shuxuetong injection increases bEnd.3 cell viability and B-cell lymphoma 2 expression, reduces cleaved caspase-3 expression, inhibits production of reactive oxygen species and mitochondrial superoxide, suppresses expression of tumor necrosis factor alpha, interleukin-1β, interleukin-6, inducible nitric oxide synthase mRNA, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1, markedly increases transepithelial resistance, decreases blood-brain barrier permeability, upregulates claudin-5, occludin, and zonula occludens-1 expression, reduces nuclear factor-κB p65 and vascular endothelial growth factor expression, and reduces I kappa B alpha, extracellular signal-regulated protein kinase 1/2, and I kappa B kinase phosphorylation levels. Overall, these findings suggest that Shuxuetong injection has protective effects on brain microvascular endothelial cells after oxygen-glucose deprivation/reperfusion. Moreover, its protective effect is associated with reduction of mitochondrial superoxide production, inhibition of the inflammatory response, and inhibition of vascular endothelial growth factor, extracellular signal-regulated protein kinase 1/2, and the nuclear factor-κB p65 signaling pathway.展开更多
Background and Objective:Self-monitoring of blood glucose(SMBG)is crucial for achieving a glycemic target and upholding blood glucose stability,both of which are the primary purpose of anti-diabetic treatments.However...Background and Objective:Self-monitoring of blood glucose(SMBG)is crucial for achieving a glycemic target and upholding blood glucose stability,both of which are the primary purpose of anti-diabetic treatments.However,the association between time in range(TIR),as assessed by SMBG,andβ-cell insulin secretion as well as insulin sensitivity remains unexplored.Therefore,this study aims to investigate the connections between TIR,derived from SMBG,and indices representingβ-cell functionality and insulin sensitivity.The primary objective of this study was to elucidate the relationship between short-term glycemic control(measured as points in range[PIR])and bothβ-cell function and insulin sensitivity.Methods:This cross-sectional study enrolled 472 hospitalized patients with type 2 diabetes mellitus(T2DM).To assessβ-cell secretion capacity,we employed the insulin secretion-sensitivity index-2(ISSI-2)and(ΔC-peptide_(0-120)/Δglucose_(0-120))×Matsuda index,while insulin sensitivity was evaluated using the Matsuda index and HOMA-IR.Since SMBG offers glucose data at specific point-in-time,we substituted TIR with PIR.According to clinical guidelines,values falling within the range of 3.9-10 mmol were considered"in range,"and the corresponding percentage was calculated as PIR.Results:We observed significant associations between higher PIR quartiles and increased ISSI-2,(ΔC-peptide_(0-120)/Δglucose_(0-120))×Matsuda index,Matsuda index(increased)and HOMA-IR(decreased)(all P<0.001).PIR exhibited positive correlations with log ISSI-2(r=0.361,P<0.001),log(ΔC-peptide_(0-120)/Δglucose_(0-120))×Matsuda index(r=0.482,P<0.001),and log Matsuda index(r=0.178,P<0.001)and negative correlations with log HOMA-IR(r=-0.288,P<0.001).Furthermore,PIR emerged as an independent risk factor for log ISSI-2,log(ΔC-peptide_(0-120)/Δglucose_(0-120))×Matsuda index,log Matsuda index,and log HOMA-IR.Conclusion:PIR can serve as a valuable tool for assessingβ-cell function and insulin sensitivity.展开更多
Objective: To observe the influence of high blood glucose fluctuation on the endothelial function of type 2 diabetes mellitus (T2DM) rats and the effects of Panax Quinquefolius Saponin (PQS) of stem and leaf. Met...Objective: To observe the influence of high blood glucose fluctuation on the endothelial function of type 2 diabetes mellitus (T2DM) rats and the effects of Panax Quinquefolius Saponin (PQS) of stem and leaf. Methods: The T2DM model was induced by intraperitoneal injection of a small dose of streptozotocin (STZ, 35 mg/kg) plus high fat and high caloric laboratory chow. Then, diabetic rats were divided into steady high blood glucose (SHG) group and fluctuant high blood glucose (FHG) group according to fasting blood glucose coefficient of variation (FBG-CV), and then, the FHG group rats were divided into 4 groups according to the level of FBG-CV and fasting blood glucose: PQS 30 mg/(kg·d) group, PQS 60 mg/(kg·d) group, metformin hydrochloride control (MHC) group, and FHG control group, 10 in each group. Meanwhile, 10 rats without any treatment were used as normal control (NOR) group. Eight weeks later, the aortic arteries histology, plasma hepatocyte growth factor (HGF), and serum nitric oxide (NO), endothelin-1 (ET-1), tumor necrosis factor α (TNF-α), and soluble intercellular adhesion molecule 1 (slCAM-1) were measured. Results: In comparison with the NOR group, the level of plasma HGF and serum NO, ET-1 and TNF-α, and slCAM-1 in SHG and FHG control groups were all significantly increased (P〈0.01); in comparison with the SHG group, plasma HGF and serum NO, ET-1, TNF-α, and slCAM-1 in FHG group were all significantly increased further (P〈0.01 or P〈0.05); meanwhile, in comparison with the FHG control group, the level of plasma HGF and serum NO, ET-1, TNF- α, and slCAM-1 in PQS and MHC groups were all decreased significantly (P〈0.01). However, comparison of the aortic arteries histology among groups showed no significant differences either before or after treatment. Conclusion: Blood glucose fluctuation could facilitate the development of vascular endothelial dysfunction in T2DM rats, while PQS could improve the endothelial function of T2DM rats with high blood glucose fluctuation, which may be related to its effects of relieving vessel stress, decreasing vasoconstrictor ET-1 production, preventing compensated increase of NO, and reducing inflammatory reaction.展开更多
BACKGROUND Progressive pancreaticβ-cell dysfunction is a fundamental part of the pathology of type 2 diabetes mellitus(T2DM).Cellular therapies offer novel opportunities for the treatment of T2DM to improve the funct...BACKGROUND Progressive pancreaticβ-cell dysfunction is a fundamental part of the pathology of type 2 diabetes mellitus(T2DM).Cellular therapies offer novel opportunities for the treatment of T2DM to improve the function of isletβ-cells.AIM To evaluate the effectiveness and safety of human umbilical cord-mesenchymal stem cell(hUC-MSC)infusion in T2DM treatment.METHODS Sixteen patients were enrolled and received 1×10^(6) cells/kg per week for 3 wk as intravenous hUC-MSC infusion.The effectiveness was evaluated by assessing fasting blood glucose,C-peptide,normal glycosylated hemoglobin A1c(HbA1c),insulin resistance index(homeostatic model assessment for insulin resistance),and isletβ-cell function(homeostasis model assessment ofβ-cell function).The dosage of hypoglycemic agents and safety were evaluated by monitoring the occurrence of any adverse events(AEs).RESULTS During the entire intervention period,the fasting plasma glucose level was significantly reduced[baseline:9.3400(8.3575,11.7725),day 14±3:6.5200(5.2200,8.6900);P<0.01].The HbA1c level was significantly reduced on day 84±3[baseline:7.8000(7.5250,8.6750),day 84±3:7.150(6.600,7.925);P<0.01].The patients’isletβ-cell function was significantly improved on day 28±3 of intervention[baseline:29.90(16.43,37.40),day 28±3:40.97(19.27,56.36);P<0.01].The dosage of hypoglycemic agents was reduced in all patients,of whom 6(50%)had a decrement of more than 50%and 1(6.25%)discontinued the hypoglycemic agents.Four patients had transient fever,which occurred within 24 h after the second or third infusion.One patient(2.08%)had asymptomatic nocturnal hypoglycemia after infusion on day 28±3.No liver damage or other side effects were reported.CONCLUSION The results of this study suggest that hUC-MSC infusion can improve glycemia,restore isletβ-cell function,and reduce the dosage of hypoglycemic agents without serious AEs.Thus,hUC-MSC infusion may be a novel option for the treatment of T2DM.展开更多
目的:探讨二甲双胍恩格列净片治疗2型糖尿病(T2DM)合并射血分数保留性心力衰竭(HFpEF)患者的临床效果和安全性。方法:选取2021年10月—2022年9月保定市第一中心医院80例T2DM合并HFpEF患者,通过随机数字表法将其分为观察组(n=40)和对照组...目的:探讨二甲双胍恩格列净片治疗2型糖尿病(T2DM)合并射血分数保留性心力衰竭(HFpEF)患者的临床效果和安全性。方法:选取2021年10月—2022年9月保定市第一中心医院80例T2DM合并HFpEF患者,通过随机数字表法将其分为观察组(n=40)和对照组(n=40)。对照组给予常规药物治疗,观察组在对照组的用药基础上联合二甲双胍恩格列净片治疗。两组均接受为期6个月的连续治疗。对比两组血糖指标、心功能指标及不良反应发生情况。结果:治疗后,两组空腹血糖(FBG)、餐后2 h血糖(2 h PG)、糖化血红蛋白(HbA1c)均较治疗前下降,且观察组均低于对照组(P<0.05)。治疗后,两组左室射血分数(LVEF)、左室舒张末径(LVEDD)、左室收缩末径(LVESD)、脑钠肽(BNP)均优于治疗前,且观察组均优于对照组(P<0.05)。观察组不良反应发生率(5.0%)低于对照组(22.5%),差异有统计学意义(P<0.05)。结论:二甲双胍恩格列净片治疗2型糖尿病合并HFpEF临床效果显著,能够使患者的血糖水平下降并提高心功能相关指标,同时安全性较高。展开更多
文摘AIM To investigate possible changes of blood glucose levels after oral intake of lactulose in healthy subjects.METHODS The study was performed as prospective, randomized, two-part study with 4-way cross-over design with n = 12 in each study arm. Capillary blood glucose levels were determined over a time period of 180 min after intake of a single dose of 10 g or 20 g lactulose provided as crystal or liquid formulation. During the manufacturing process of lactulose, impurities with sugars(e.g., lactose, fructose, galactose) occur. Water and 20 g glucose were used as control and reference. Because lactulose is used as a functional food ingredient, it may also be consumed by people with impaired glucose tolerance, including diabetics. Therefore, it is of interest to determine whether the described carbohydrate impurities may increase blood glucose levels after ingestion. RESULTS The blood glucose concentration-time curves after intake of 10 g lactulose, 20 g lactulose, and water were almost identical. None of the three applications showed any changes in blood glucose levels. After intake of 20 g glucose, blood glucose concentration increased by approximately 3 mmol/L(mean Cmax = 8.3 mmol/L), reaching maximum levels after approximately 30 min and returning to baseline within approximately 90 min, which was significantly different to the corresponding 20 g lactulose formulations(P < 0.0001). Comparing the two lactulose formulations, crystals and liquid, in the dosage of 10 g and 20 g, there was no difference in the blood glucose profile and calculated pharmacokinetic parameters despite the different amounts of carbohydrate impurities(1.5% for crystals and 26.45% for liquid). Anyhow, the absolute amount of single sugars was low with 0.3 g in crystals and 5.29 g in liquid formulation in the 20 g dosages. Lactulose was well tolerated by most volunteers, and only some reported mild to moderate mainly gastrointestinal side effects. CONCLUSION The unchanged blood glucose levels after lactulose intake in healthy subjects suggest its safe use in subjects with impaired glucose tolerance.
文摘Objective:To investigate the effect of different blood glucose levels on viscera injury, oxidative stress response and Wnt5a inflammatory pathway in children with sepsis.Methods:70 children with sepsis treated in our hospital between January 2014 and December 2015 were retrospectively collected and divided into the sepsis group A (blood glucose>10 mmol/L) (n=29) and the sepsis group B (blood glucose ≤10 mmol/L) (n=41) according to the different blood glucose levels, and 50 healthy children who accepted vaccination and were with normal blood glucose levels in our hospital during the same period were selected as healthy control group. The day after admission, RIA method was used to determine liver function indexes;automatic biochemical analyzer was used to determine oxidative stress indexes;enzyme-linked immunosorbent assay (ELISA) was used to detect Wnt5a inflammatory pathway index levels.Results: Liver function indexes total bilirubin (TBIL), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels of sepsis group A were higher than those of sepsis group B and healthy control group (P<0.05);oxidative stress indexes advanced protein oxidation products (AOPPs), lipid hydrogen peroxide (LHP), reactive oxygen species (ROS), and malondialdehyde (MDA) levels were higher than those of sepsis group B and healthy control group while glutathione peroxidase (GSH-Px) level was lower than that of sepsis group B and healthy control group (P<0.05);serum Wnt5a inflammatory pathway indexes interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-12 (IL-12) and macrophage inflammatory protein-1β (MIP-1β) levels were higher than those of sepsis group B and healthy control group (P<0.05).Conclusions:Sepsis children with high blood glucose are with severe liver function damage as well as intense oxidative stress and inflammatory response, which are the important indexes for severe illness and poor prognosis.
基金supported in part by the National Natural Science Foundation of China,No.81573644(to LMH),81573733(to SWX)the Tianjin 131 Innovative Team Project,China(to HW)+5 种基金the National Major Science and Technology Project of China,No.2012ZX09101201-004(to SWX)the Science and Technology Plan Project of Tianjin of China,No.16PTSYJC00120(to LMH)the Applied Foundation and Frontier Technology Research Program of Tianjin of China(General Project),No.14JCYBJC28900(to SXW)the National International Science and Technology Cooperation Project of China,No.2015DFA30430(to HW)the Key Program of the Natural Science Foundation of Tianjin of China,No.16ICZDJC36300(to HW)the Scientific Research and Technology Development Plan Project of Guangxi Zhuang Autonomous Region of China,No.14125008-2-5(to SXW)
文摘Shuxuetong injection composed of leech(Hirudo nipponica Whitman) and earthworm(Pheretima aspergillum) has been used for the clinical treatment of acute stroke for many years in China. However, the precise neuroprotective mechanism of Shuxuetong injection remains poorly understood. Here, cerebral microvascular endothelial cells(bEnd.3) were incubated in glucose-free Dulbecco's modified Eagle's medium containing 95% N_2/5% CO_2 for 6 hours, followed by high-glucose medium containing 95% O_2 and 5% CO_2 for 18 hours to establish an oxygen-glucose deprivation/reperfusion model. This in vitro cell model was administered Shuxuetong injection at 1/32, 1/64, and 1/128 concentrations(diluted 32-, 64-, and 128-times). Cell Counting Kit-8 assay was used to evaluate cell viability. A fluorescence method was used to measure lactate dehydrogenase, and a fluorescence microplate reader used to detect intracellular reactive oxygen species. A fluorescent probe was also used to measure mitochondrial superoxide production. A cell resistance meter was used to measure transepithelial resistance and examine integrity of monolayer cells. The fluorescein isothiocyanate-dextran test was performed to examine blood-brain barrier permeability. Real-time reverse transcription polymerase chain reaction was performed to analyze mRNA expression levels of tumor necrosis factor alpha, interleukin-1β, interleukin-6, and inducible nitric oxide synthase. Western blot assay was performed to analyze expression of caspase-3, intercellular adhesion molecule 1, vascular cell adhesion molecule 1, occludin, vascular endothelial growth factor, cleaved caspase-3, B-cell lymphoma 2, phosphorylated extracellular signal-regulated protein kinase, extracellular signal-regulated protein kinase, nuclear factor-κB p65, I kappa B alpha, phosphorylated I kappa B alpha, I kappa B kinase, phosphorylated I kappa B kinase, claudin-5, and zonula occludens-1. Our results show that Shuxuetong injection increases bEnd.3 cell viability and B-cell lymphoma 2 expression, reduces cleaved caspase-3 expression, inhibits production of reactive oxygen species and mitochondrial superoxide, suppresses expression of tumor necrosis factor alpha, interleukin-1β, interleukin-6, inducible nitric oxide synthase mRNA, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1, markedly increases transepithelial resistance, decreases blood-brain barrier permeability, upregulates claudin-5, occludin, and zonula occludens-1 expression, reduces nuclear factor-κB p65 and vascular endothelial growth factor expression, and reduces I kappa B alpha, extracellular signal-regulated protein kinase 1/2, and I kappa B kinase phosphorylation levels. Overall, these findings suggest that Shuxuetong injection has protective effects on brain microvascular endothelial cells after oxygen-glucose deprivation/reperfusion. Moreover, its protective effect is associated with reduction of mitochondrial superoxide production, inhibition of the inflammatory response, and inhibition of vascular endothelial growth factor, extracellular signal-regulated protein kinase 1/2, and the nuclear factor-κB p65 signaling pathway.
文摘Background and Objective:Self-monitoring of blood glucose(SMBG)is crucial for achieving a glycemic target and upholding blood glucose stability,both of which are the primary purpose of anti-diabetic treatments.However,the association between time in range(TIR),as assessed by SMBG,andβ-cell insulin secretion as well as insulin sensitivity remains unexplored.Therefore,this study aims to investigate the connections between TIR,derived from SMBG,and indices representingβ-cell functionality and insulin sensitivity.The primary objective of this study was to elucidate the relationship between short-term glycemic control(measured as points in range[PIR])and bothβ-cell function and insulin sensitivity.Methods:This cross-sectional study enrolled 472 hospitalized patients with type 2 diabetes mellitus(T2DM).To assessβ-cell secretion capacity,we employed the insulin secretion-sensitivity index-2(ISSI-2)and(ΔC-peptide_(0-120)/Δglucose_(0-120))×Matsuda index,while insulin sensitivity was evaluated using the Matsuda index and HOMA-IR.Since SMBG offers glucose data at specific point-in-time,we substituted TIR with PIR.According to clinical guidelines,values falling within the range of 3.9-10 mmol were considered"in range,"and the corresponding percentage was calculated as PIR.Results:We observed significant associations between higher PIR quartiles and increased ISSI-2,(ΔC-peptide_(0-120)/Δglucose_(0-120))×Matsuda index,Matsuda index(increased)and HOMA-IR(decreased)(all P<0.001).PIR exhibited positive correlations with log ISSI-2(r=0.361,P<0.001),log(ΔC-peptide_(0-120)/Δglucose_(0-120))×Matsuda index(r=0.482,P<0.001),and log Matsuda index(r=0.178,P<0.001)and negative correlations with log HOMA-IR(r=-0.288,P<0.001).Furthermore,PIR emerged as an independent risk factor for log ISSI-2,log(ΔC-peptide_(0-120)/Δglucose_(0-120))×Matsuda index,log Matsuda index,and log HOMA-IR.Conclusion:PIR can serve as a valuable tool for assessingβ-cell function and insulin sensitivity.
基金Supported by the National Natural Science Foundation of China(No.81041038)
文摘Objective: To observe the influence of high blood glucose fluctuation on the endothelial function of type 2 diabetes mellitus (T2DM) rats and the effects of Panax Quinquefolius Saponin (PQS) of stem and leaf. Methods: The T2DM model was induced by intraperitoneal injection of a small dose of streptozotocin (STZ, 35 mg/kg) plus high fat and high caloric laboratory chow. Then, diabetic rats were divided into steady high blood glucose (SHG) group and fluctuant high blood glucose (FHG) group according to fasting blood glucose coefficient of variation (FBG-CV), and then, the FHG group rats were divided into 4 groups according to the level of FBG-CV and fasting blood glucose: PQS 30 mg/(kg·d) group, PQS 60 mg/(kg·d) group, metformin hydrochloride control (MHC) group, and FHG control group, 10 in each group. Meanwhile, 10 rats without any treatment were used as normal control (NOR) group. Eight weeks later, the aortic arteries histology, plasma hepatocyte growth factor (HGF), and serum nitric oxide (NO), endothelin-1 (ET-1), tumor necrosis factor α (TNF-α), and soluble intercellular adhesion molecule 1 (slCAM-1) were measured. Results: In comparison with the NOR group, the level of plasma HGF and serum NO, ET-1 and TNF-α, and slCAM-1 in SHG and FHG control groups were all significantly increased (P〈0.01); in comparison with the SHG group, plasma HGF and serum NO, ET-1, TNF-α, and slCAM-1 in FHG group were all significantly increased further (P〈0.01 or P〈0.05); meanwhile, in comparison with the FHG control group, the level of plasma HGF and serum NO, ET-1, TNF- α, and slCAM-1 in PQS and MHC groups were all decreased significantly (P〈0.01). However, comparison of the aortic arteries histology among groups showed no significant differences either before or after treatment. Conclusion: Blood glucose fluctuation could facilitate the development of vascular endothelial dysfunction in T2DM rats, while PQS could improve the endothelial function of T2DM rats with high blood glucose fluctuation, which may be related to its effects of relieving vessel stress, decreasing vasoconstrictor ET-1 production, preventing compensated increase of NO, and reducing inflammatory reaction.
基金Supported by Shenzhen Science and Technology Innovation Committee Projects,No.JCYJ20170816105416349Shenzhen High-level Hospital Construction FundShenzhen Key Medical Discipline Construction Fund,No.SZXK010.
文摘BACKGROUND Progressive pancreaticβ-cell dysfunction is a fundamental part of the pathology of type 2 diabetes mellitus(T2DM).Cellular therapies offer novel opportunities for the treatment of T2DM to improve the function of isletβ-cells.AIM To evaluate the effectiveness and safety of human umbilical cord-mesenchymal stem cell(hUC-MSC)infusion in T2DM treatment.METHODS Sixteen patients were enrolled and received 1×10^(6) cells/kg per week for 3 wk as intravenous hUC-MSC infusion.The effectiveness was evaluated by assessing fasting blood glucose,C-peptide,normal glycosylated hemoglobin A1c(HbA1c),insulin resistance index(homeostatic model assessment for insulin resistance),and isletβ-cell function(homeostasis model assessment ofβ-cell function).The dosage of hypoglycemic agents and safety were evaluated by monitoring the occurrence of any adverse events(AEs).RESULTS During the entire intervention period,the fasting plasma glucose level was significantly reduced[baseline:9.3400(8.3575,11.7725),day 14±3:6.5200(5.2200,8.6900);P<0.01].The HbA1c level was significantly reduced on day 84±3[baseline:7.8000(7.5250,8.6750),day 84±3:7.150(6.600,7.925);P<0.01].The patients’isletβ-cell function was significantly improved on day 28±3 of intervention[baseline:29.90(16.43,37.40),day 28±3:40.97(19.27,56.36);P<0.01].The dosage of hypoglycemic agents was reduced in all patients,of whom 6(50%)had a decrement of more than 50%and 1(6.25%)discontinued the hypoglycemic agents.Four patients had transient fever,which occurred within 24 h after the second or third infusion.One patient(2.08%)had asymptomatic nocturnal hypoglycemia after infusion on day 28±3.No liver damage or other side effects were reported.CONCLUSION The results of this study suggest that hUC-MSC infusion can improve glycemia,restore isletβ-cell function,and reduce the dosage of hypoglycemic agents without serious AEs.Thus,hUC-MSC infusion may be a novel option for the treatment of T2DM.
文摘目的 分析利拉鲁肽治疗冠心病合并2型糖尿病患者的临床效果。方法 102例冠心病合并2型糖尿病患者,应用电脑随机选择方式将患者分为对照组和观察组,每组51例。对照组给予二甲双胍治疗,观察组给予二甲双胍结合利拉鲁肽治疗。对比两组心功能指标(左室射血分数、左室舒张末内径、心排血量以及QT离散度)、血糖指标[空腹血糖(FPG)、餐后2 h血糖(2 h PG)、糖化血红蛋白(HbA1c)]、胰岛素抵抗情况[胰岛β细胞功能指数(HOMA-β)、胰岛素抵抗指数(HOMA-IR)]。结果 治疗后,观察组左室射血分数(56.10±9.06)%、左室舒张末内径(45.80±6.64)mm、心排血量(5.60±1.18)L/min、QT离散度(45.03±6.31)ms优于对照组的(50.50±7.90)%、(50.20±7.07)mm、(4.88±1.01)L/min、(53.77±8.50)ms(P<0.05)。治疗后,观察组2 h PG(7.28±1.30)mmol/L、FPG(6.06±0.27)mmol/L、HbA1c(5.88±0.32)%优于对照组的(8.71±1.20)mmol/L、(7.01±0.76)mmol/L、(6.65±0.52)%(P<0.05)。治疗后,观察组HOMA-β、HOMA-IR优于对照组(P<0.05)。结论 结合冠心病合并2型糖尿病患者实际情况应用二甲双胍结合利拉鲁肽治疗,能够有效改善患者的心功能指标、血糖指标及胰岛素抵抗情况,具有优良的应用前景,在今后的工作过程中能够进一步应用。
文摘目的:探讨二甲双胍恩格列净片治疗2型糖尿病(T2DM)合并射血分数保留性心力衰竭(HFpEF)患者的临床效果和安全性。方法:选取2021年10月—2022年9月保定市第一中心医院80例T2DM合并HFpEF患者,通过随机数字表法将其分为观察组(n=40)和对照组(n=40)。对照组给予常规药物治疗,观察组在对照组的用药基础上联合二甲双胍恩格列净片治疗。两组均接受为期6个月的连续治疗。对比两组血糖指标、心功能指标及不良反应发生情况。结果:治疗后,两组空腹血糖(FBG)、餐后2 h血糖(2 h PG)、糖化血红蛋白(HbA1c)均较治疗前下降,且观察组均低于对照组(P<0.05)。治疗后,两组左室射血分数(LVEF)、左室舒张末径(LVEDD)、左室收缩末径(LVESD)、脑钠肽(BNP)均优于治疗前,且观察组均优于对照组(P<0.05)。观察组不良反应发生率(5.0%)低于对照组(22.5%),差异有统计学意义(P<0.05)。结论:二甲双胍恩格列净片治疗2型糖尿病合并HFpEF临床效果显著,能够使患者的血糖水平下降并提高心功能相关指标,同时安全性较高。