Impact of hypoglycemic agents on myocardial ischemic preconditioning

Murry et al in 1986 discovered the intrinsic mechanism of profound protection called ischemic preconditioning. The complex cellular signaling cascades underlying this phenomenon remain controversial and are only partially understood. However, evidence suggests that adenosine, released during the initial ischemic insult, activates a variety of G protein-coupled agonists, such as opioids, bradykinin, and catecholamines, resulting in the activation of protein kinases, especially protein kinase C(PKC). This leads to the translocation of PKC from the cytoplasm to the sarcolemma, where it stimulates the opening of the ATP-sensitive K+ channel, which confers resistance to ischemia. It is known that a range of different hypoglycemic agents that activate the same signaling cascades at various cellular levels can interfere with protection from ischemic preconditioning. This review examines the effects of several hypoglycemic agents on myocardial ischemic preconditioning in animal studies and clinical trials.

Utilization Pattern of Oral Hypoglycemic Agents for Diabetes Mellitus Type 2 Patients Attending Out-Patient Department at a University Hospital in New Delhi

Diabetes mellitus is the chronic disorder emerging as major world health problem which increases the rate of morbidity and mortality. The aim of the present study was to ascertain patterns of prescription of oral hypoglycemic agents to type 2 diabetic patients attending a university hospital, and to assess patient compliance. A prospective, observational and non comparative study was conducted in 200 established diabetes mellitus type 2 patients attending outpatient department at Majeedia Hospital, New Delhi, India. Prescriptions from registered patients were included in the study. Once the consultation by the physician was over, the prescriptions were reviewed and the patients were interviewed. The information was collected in an inhouse designed documentation proforma. In a pool of 200 type 2 diabetics, more than half were female (n=106, 53%). The mean age of the patients were found to be 50.4 ± 11.7 years and mean body mass index, 25.8 ± 4.4 kg/m2. A total of 432 oral hypoglycemic agents were prescribed to the patients. Highly significant number of patients were prescribed combination therapy, (n=143, 71.5%) as compared to monotherapy (n=57, 28.5%),

A Preliminary Investigation of the Possible Hypoglycemic Activity of Hibiscus rosa-sinensis

The hypoglycemic activity of an ethanol extract of Hibiscus rosa-sinsnsis was studied in glucose located rats. Afer a single dose of the extract, a slight but insignificant hypoglycemic effect was observed at 30 and 90 min. At 120 min it was mild but significant. After repeated administration of the extract (once a day for seven consecutive days) a statistically significant (P < 0 .001 ) reduction in blood glucose levels was observed at 30, 90 and 120 min after glucose loading. The average hypoglycemic activity, after repeated administration of 250 mg kg-1 leaf extract was 81 %, under similar conditions average activity of tolbutamide was 96%. At 250 mg·kg-1 the efficacy of the extract was found to be 84% of tolbutawhde (100mg·kg- 1 ). Repeated treatment of animals either with tolbutandde a sulphonylurea or H. rosa-sinensis caused a 2-3-fold improvement in glucose tolerance as compared to those receiving only once. These data suggest that the leaf extract acts like tolbutamide and the meehanism of action may be a stimulation of pancreatic hata cells to produce more insulin or an increase of the glycogen deposition in liver. It appeare that the active principle in the tested extract has the sulphonylurea Skeleton in which -SO2-NH-CO- group and the substituents (S1 and S2) may be the possible active sites responsible for its hypolycemic activity.

Hypoglycemic Therapy in Chronic Hepatic Disease Literature Review

Chronic liver disease (CLD) refers to a structural and functional change of the liver, which modifies the pharmacokinetics of multiple drugs, including hypoglycemic agents. This alteration depends on the severity degree of the liver disease, clinical characteristics of the patient, and comorbidities presence such as kidney disease and drug biochemistry. Insulin is considered a safe therapeutic strategy in patients with CLD, however, for many oral hypoglycemic agents, its use and dose adjustment will depend on the Child-Pugh score, based on the risk of hypoglycemia in this type of patient.

Opportunities and challenges of incretin-based hypoglycemic agents treating type 2 diabetes mellitus from the perspective of physiological disposition

The treatment of patients with diabetes mellitus, which is characterized by defective insulin secretion and/or the inability of tissues to respond to insulin, has been studied for decades. Many studies have focused on the use of incretin-based hypoglycemic agents in treating type 2 diabetes mellitus(T2DM). These drugs are classified as GLP-1 receptor agonists, which mimic the function of GLP-1,and DPP-4 inhibitors, which avoid GLP-1 degradation. Many incretin-based hypoglycemic agents have been approved and are widely used, and their physiological disposition and structural characteristics are crucial in the discovery of more effective drugs and provide guidance for clinical treatment of T2DM.Here, we summarize the functional mechanisms and other information of the drugs that are currently approved or under research for T2DM treatment. In addition, their physiological disposition, including metabolism, excretion, and potential drug drug interactions, is thoroughly reviewed. We also discuss similarities and differences in metabolism and excretion between GLP-1 receptor agonists and DPP-4 inhibitors. This review may facilitate clinical decision making based on patients' physical conditions and the avoidance of drug drug interactions. Moreover, the identification and development of novel drugs with appropriate physiological dispositions might be inspired.

偏头痛患者TCD、MRA及其相关生化因子变化的意义

目的 :观察颅内血管形态 ,血管舒缩变化 ,相关生化因子的变化与偏头痛的关系和在评价临床意义中的价值。方法 :30例临床确诊为偏头痛的患者 ,经颅多谱勒 (TCD)和复式彩码双功能多谱勒测定颅内外血流情况、头颅磁共振血管像 (MRA)探查颅内血管形态 ,此外 ,采用放免等方法测定发作间歇期血小板 5 羟色胺 ( 5 HT)、β 内啡肽 ( β EP)、神经降压素 (NT)、精氨酸加压素 (AVP)和血栓烷A2 (TXA2 )含量 ,并与 2 0例健康对照组进行比较。结果 :偏头痛间歇期双侧大脑中动脉(MCA)和基底动脉 (BA)血流速度明显增高 (P <0 .0 1) ,颞浅动脉 (STA)没有显著性变化 (P >0 .0 5) ;MRA显示 6例患者颅内动脉异常 ;血浆 5 HT、NT含量偏头痛组显著高于对照组 (P <0 .0 1) ,血浆 β EP、AVP、TXB2 偏头痛组显著低于对照组 (P <0 .0 5)。结论 :偏头痛患者可能有先天血管发育异常 ,发作间歇期颅内动脉存在血流速度增快 ,血浆 5 HT、β EP、NT、AVP和TXB2 与偏头痛发病有关。

Vitamin D,selenium,and antidiabetic drugs in the treatment of type 2 diabetes mellitus with Hashimoto's thyroiditis

BACKGROUND Diabetes and thyroiditis are closely related.They occur in combination and cause significant damage to the body.There is no clear treatment for type-2 diabetes mellitus(T2DM)with Hashimoto's thyroiditis(HT).While single symptomatic drug treatment of the two diseases is less effective,combined drug treatment may improve efficacy.AIM To investigate the effect of a combination of vitamin D,selenium,and hypoglycemic agents in T2DM with HT.METHODS This retrospective study included 150 patients with T2DM and HT treated at The Central Hospital of Shaoyang from March 2020 to February 2023.Fifty patients were assigned to the control group,test group A,and test group B according to different treatment methods.The control group received low-iodine diet guidance and hypoglycemic drug treatment.Test group A received the control treatment plus vitamin D treatment.Test group B received the group A treatment plus selenium.Blood levels of markers of thyroid function[free T3(FT3),thyroid stimulating hormone(TSH),free T4(FT4)],autoantibodies[thyroid peroxidase antibody(TPOAB)and thyroid globulin antibody(TGAB)],blood lipid index[low-density lipoprotein cholesterol(LDL-C),total cholesterol(TC),triacylglycerol(TG)],blood glucose index[fasting blood glucose(FBG),and hemoglobin A1c(HbA1c)]were measured pre-treatment and 3 and 6 months after treatment.The relationships between serum 25-hydroxyvitamin D3[25(OH)D3]level and each of these indices were analyzed.RESULTS The levels of 25(OH)D3,FT3,FT4,and LDL-C increased in the order of the control group,test group A,and test group B(all P<0.05).The TPOAB,TGAB,TC,TG,FBG,HbA1c,and TSH levels increased in the order of test groups B,A,and the control group(all P<0.05).All the above indices were compared after 3 and 6 months of treatment.Pre-treatment,there was no divergence in serum 25(OH)D3 level,thyroid function-related indexes,autoantibodies level,blood glucose,and blood lipid index between the control group,test groups A and B(all P>0.05).The 25(OH)D3 levels in test groups A and B were negatively correlated with FT4 and TGAB(all P<0.05).CONCLUSION The combination drug treatment for T2DM with HT significantly improved thyroid function,autoantibody,and blood glucose and lipid levels.

调中益气汤治疗老年气虚型慢传输便秘的疗效研究

背景调中益气汤最早用来治疗脾虚湿滞所导致的胃肠病。多年临证经验发现,调中益气汤加减可治疗老年慢传输型便秘(STC)。目的评价调中益气汤治疗老年气虚型STC临床疗效及对肠动力的影响。方法选取银川市中医医院2022年5月—2023年4月肛肠科、治未病中心就诊的中医辨证为气虚型STC患者100例,选用1∶1随机数字表法将患者随机分为观察组50例和对照组50例。观察组采用调中益气汤煎汤口服,对照组50例口服琥珀酸普芦卡必利片,各治疗4周。分别于治疗前、治疗4周后记录并比较每周完全自主排便次数(CSBM)积分、中医证候积分、临床症状积分和48、72 h标记物排出率,检测胃肠激素水平,观察不良反应发生情况。随访3个月,观察两组患者便秘复发情况。结果治疗4周后,观察组每周CSBM积分、中医证候积分和临床症状各积分均低于对照组(P<0.05),48、72 h标记物排出率高于对照组(P<0.05);观察组血清5-羟色胺、血管活性肽、生长抑素低于对照组,而胃泌素高于对照组(P<0.05)。治疗4周后观察组临床总有效率高于对照组(χ^(2)=4.031,P=0.046);随访3个月,观察组复发率低于对照组(χ^(2)=5.134,P=0.023)。研究过程中观察组有2例服用调中益气汤后出现腹胀,对照组4例口服琥珀酸普芦卡必利片出现口干、恶心、头晕等,均未进行对症治疗,试验终止后症状自行消失。结论调中益气汤能够改善老年STC患者中医证候、胃肠传输时间和临床症状,调节胃肠神经激素水平,促进胃肠动力,且临床复发率较低,值得临床推广。

Causes of Fasting-Evoked en Route Hypoglycemia in Diabetes (FEEHD): A Case Series Study

Background: A recent study reported that some patients with diabetes who fast overnight for laboratory tests are at risk of developing hypoglycemia, which could occur while patients are in risky situations which could result in harm to patients or others. Due to limitation in study design of the aforementioned study, the causes of hypoglycemia could not be elucidated. Objective: To better understand fasting-evoked en route hypoglycemia in diabetes (FEEHD), a recently recognized overlooked safety problem in diabetes management. Methods and Patients: A recent study reported that some patients with diabetes who fast overnight for laboratory tests are at risk of developing hypoglycemia, which could occur while patients are in risky situations which could result in harm to patients or others. Due to limitation in study design of the aforementioned study, the causes of hypoglycemia could not be elucidated. We undertook this retrospective case series study, which enrolled 4 consecutive cases of fasting hypoglycemia in patients with diabetes who were on diverse antidiabetic medications. The study duration was June 1, 2010 to June 1, 2012. Results: The 4 cases (3 women, 1 man), with either type 1 or type 2 diabetes, revealed multiple defects in either the patients’ knowledge and education regarding preparation for lab tests requiring fasting. The degree of hypoglycemia ranged from mild (65 mg/dl) to severe (31 mg/dl), and the events were either mildly symptomatic or asymptomatic. The possible causes of, and contributing factors to hypoglycemia are discussed, and recommendations for preventive measures are provided. Conclusion: Some patients with diabetes who fast for lab tests are at risk of hypoglycemia, and there seems to be an overall lack of proper education of patients with diabetes about this form of hypoglycemia. This overlooked problem can be prevented by proper education and preparation.

Effect of Yanggyuksanhwa-Tang on Non-Insulin-Dependent Diabetes Mellitus Unresponsive to Oral Hypoglycemic Agents:A Case Report

Diabetes mellitus is the fourth leading cause of death worldwide, following cancer, cerebrovascular disease, and heart disease. It is triggered by hyperglycemia and other metabolic disorders. Diabetes is a complex endocrine disease that causes chronic vascular complications such as diabetic nephropathy, retinopathy, and polyneuropathy.

住院患者高血糖的个体化目标管理

住院患者发生高血糖状况在临床中广泛存在。其与多种住院不良结局相关,增加了重症患者的死亡率、延长了非重症患者的住院时间。目前国内外内分泌及代谢学科的多个指南均建议将住院患者的高血糖状况进行系统化管理,同时强调个体化管理原则,推荐根据不同患者的情况设立个体化的血糖控制目标。本文对国内外不同指南中住院患者高血糖定义、管理现状、控制目标及监测方法进行综述,通过比较这些指南对不同人群以及不同状态的住院患者血糖控制目标的异同,来探讨住院患者高血糖管理的进展。通过综述,明确目前住院患者高血糖管理仍需坚持个体化管理原则,以期达到更低的并发症发生率及全因死亡率。

参黄降糖胶囊对糖尿病合并高血压病人血管内皮功能、血液流变学的影响

目的 探讨参黄降糖胶囊对糖尿病合并高血压病人血管内皮功能、血液流变学及血压、血糖水平的影响。方法 选取2019年5月至2020年5月在河北省沧州中西医结合医院接受治疗的糖尿病合并高血压病人98例,采用随机数字表法分为参黄降糖组(49例)和常规组(49例),常规组给予硝苯地平及二甲双胍治疗,参黄降糖组在常规组基础上给予参黄降糖胶囊治疗,比较两组病人血管内皮功能指标[内皮素-1、一氧化氮、血管内皮生长因子(VEGF)水平]、血压水平(24 h平均舒张压、24 h平均收缩压)、血糖指标、血液流变学指标及临床疗效的变化。结果 两组病人内皮素-1水平、24 h平均舒张压、24 h平均收缩压水平、血液流变学指标、血糖指标治疗后[24 h平均舒张压:(75.52±10.27)mmHg、(91.46±10.21)mmHg;24 h平均收缩压:(112.64±20.18)mmHg、(127.52±20.21)mmHg;空腹血糖:(6.18±1.09)mmol/L、(6.92±1.24)mmol/L;餐后2 h血糖(2hPG):(8.87±1.44)mmol/L、(10.28±2.01)mmol/L;空腹胰高血糖素(PGG):(78.64±12.17)ng/L、(85.16±11.69)ng/L;糖化血红蛋白(HbAlc):(6.56±1.14)%、(7.91±1.53)%]均较治疗前[24 h平均舒张压:(104.46±9.23)mmHg、(106.28±9.26)mmHg;24 h平均收缩压:(148.72±21.46)mmHg、(146.78±22.17)mmHg;空腹血糖:(9.87±1.62)mmol/L、(9.94±1.57)mmol/L;2hPG:(13.61±2.58)mmol/L、(13.59±2.54)mmol/L;PGG:(94.36±15.31)ng/L、(94.28±15.27)ng/L;HbAlc:(8.92±1.21)%、(8.96±1.31)%]降低(P<0.05),且参黄降糖组低于常规组(P<0.05),一氧化氮、VEGF水平治疗后较治疗前升高(P<0.05),且参黄降糖组高于常规组(P<0.05);参黄降糖组总有效率93.88%高于常规组总有效率77.55%(P<0.05)。结论 参黄降糖胶囊与常规药物联合用于治疗糖尿病合并高血压病人,能够降低病人血糖及血压水平、改善血液流变学指标及血管内皮功能,提高临床效果。

早期胰岛素强化与口服降糖药治疗老年2型糖尿病的临床疗效分析

目的观察早期胰岛素强化与口服降糖药治疗老年2型糖尿病临床疗效。方法选取2021年1月—2022年1月常州市德安医院收治的82例老年2型糖尿病患者,以随机数表法分组,基础组采用口服降糖药治疗(41例),强化组采取早期胰岛素强化治疗(41例),比较两组血糖指标改善情况、疗效、胰岛素指标。结果强化组患者用药后空腹血糖(FBG)、餐后2 h血糖(2 hPG)及糖化血红蛋白(HbA1c)低于基础组,治疗总有效率显著高于基础组,用药后30 min的C肽/血糖(ΔCP30/ΔG30)、120 min的C肽/血糖(ΔCP120/ΔG120)显著高于基础组,胰岛素抵抗指数(HOMA-IR)及餐后2 h胰岛素(2 hFINS)含量低于基础组,差异有统计学意义(P<0.05)。结论与口服降糖药相比,早期胰岛素强化疗法用于临床老年2型糖尿病治疗中具有更为显著的疗效,胰岛素指标改善效果更佳。

新型降糖药物替西帕肽的临床研究进展

目前全球有多种治疗糖尿病的药物,但仍有很多糖尿病患者未能达到推荐的目标血糖水平,研发和应用新型降糖药迫在眉睫。2022年5月,美国食品药品监督管理局(FDA)批准葡萄糖依赖性促胰岛素多肽(GIP)和胰高糖素样肽-1(GLP-1)双重受体激动剂替西帕肽上市,辅助饮食和运动,每周注射1次以改善成人2型糖尿病患者的血糖控制。多项临床研究已验证其用于2型糖尿病的有效性和安全性,同时该药在肥胖症、心血管风险相关疾病、非酒精性脂肪性肝炎等疾病治疗方面也具有潜在的应用价值。本文通过对替西帕肽的作用机制、有效性和安全性进行综述,为其在我国上市后的临床应用提供参考。

国家集采的口服降糖药对糖尿病患者的用药影响分析

目的统计某院门诊口服降糖药的使用情况和药品的日均费用,分析降糖药进入国家集采后对糖尿病患者的用药影响。方法采用世界卫生组织推荐的限定日剂量分析方法,对某院门诊常用的口服降糖药使用情况和日均费用进行统计分析。结果盐酸二甲双胍片、阿卡波糖片、恩格列净片的用药频度(DDDs)分别排在前三位(三者均为国家集采药品),而日均费用(DDC)分别排在第11、16和8位。对同类降血糖药进行比较,集采药品的使用量绝大多数均大于非集采药品,而日均费用均低于非集采药品。结论国家药品集中带量采购的实施,对糖尿病患者的用药产生了很大的影响。在某院,双胍类、α糖苷酶抑制剂仍是某院临床一线治疗药物,而SGLT⁃Ⅱ抑制剂作为新型口服降糖药,对糖尿病患者的肾脏和心血管均有保护作用,弥补了传统降血糖药的不足,满足了更多2型糖尿病患者的用药需求,所以在临床上的使用越来越广泛。

2019年到2022年国家医保目录协议期内谈判药品的变化分析

目的统计2019年到2022年国家医保目录协议期内谈判药品中各类西药的数量分布,分析国家谈判药品各类西药数量变化的原因。方法以表格的形式罗列出2019年到2022年四版国家医保目录中西药、中成药、协议期内谈判药品的个数分布,了解这4年各类药品的变化趋势,并重点将协议期内谈判药品西药部分按药理作用进行分类统计。结果四版医保目录的药品总数逐年递增,从2709个增加到2967个。变化最大的是协议期内谈判药品的品种数,从114个增加到363个,其中西药从91个增加到293个。从国家谈判药品各类西药的数量分布可以看出:四个版本药品品种数排在前4位的均是:抗肿瘤药、全身用抗病毒药、免疫抑制剂和降血糖药。结论肿瘤患者、病毒感染患者(如乙肝、丙肝、艾滋病)、免疫缺陷患者和糖尿病患者是国家特别重视的群体,由于这几类患者需要长期用药,而药品价格又相对昂贵,所以需要国家干预,从而降低药品价格,满足特殊人群的用药需求和可及性,减轻患者经济负担,从而提高生活质量。

基础胰岛素联合口服降糖药治疗效果不佳的2型糖尿病患者的治疗策略选择:伞形评价

目的对基础胰岛素联合一线口服降糖药(二甲双胍/磺脲类药物)治疗效果不佳的2型糖尿病(T2DM)患者的不同治疗策略进行伞形评价,为患者推荐最佳治疗策略提供科学依据。方法计算机检索PubMed、Embase、Cochrane Library、SinoMed、CNKI、WanFang Data和VIP数据库,搜集基础胰岛素联合一线口服降糖药治疗T2DM效果不佳的系统评价(SR)/Meta分析(MA),其原始研究为随机对照试验(RCT),检索时限均从建库至2023年9月13日,由2名研究者独立进行文献筛选、数据提取和文献质量评估,采用R 4.2.2软件中的metaumbrella包进行伞形评价。结果共纳入1篇SR和8篇MA,包括72个RCT,24095例患者,涉及的后续治疗措施有胰高糖素样肽1受体激动剂(GLP-1RA)、二肽基肽酶Ⅳ抑制剂(DPP-4i)、钠葡萄糖共转运蛋白2抑制剂(SGLT-2i)、噻唑烷二酮类药(TZD)等。结果显示,与安慰剂相比,GLP-1RA[WMD=-3.67,95%CI(-5.81,-1.53),P=0.001]、DPP-4i[WMD=-5.56,95%CI(-7.40,-3.73),P<0.001]和SGLT-2i[WMD=-5.34,95%CI(-9.56,-1.13),P=0.013]均可显著降低糖化血红蛋白(%)水平;阳性药物比较中,GLP-1RA vs.甘精胰岛素利司那肽固定比例复方制剂(IGlarLixi)[WMD=7.49,95%CI(7.01,7.92),P<0.001],GLP-1RA vs.德谷胰岛素利拉鲁肽注射液(IDegLira)[WMD=0.83,95%CI(0.11,1.54),P=0.023],显示GLP-1RA的降血糖效果不及IGlarLixi和IDegLira。与安慰剂相比,GLP-1RA可显著减轻体重(kg)[WMD=-3.46,95%CI(-5.30,-1.63),P<0.001];阳性药物比较中,GLP-1RA vs.IGlarLixi[WMD=-8.40,95%CI(-8.86,-7.93),P<0.001],GLP-1RA vs.IDegLira[WMD=-0.53,95%CI(-0.99,-0.07),P=0.025],显示GLP-1RA的降体重效果优于IGlarLixi和IDegLira。与安慰剂相比,TZD[OR=1.51,95%CI(1.11,2.05),P=0.009]和GLP-1RA[OR=1.24,95%CI(1.03,1.49),P=0.023]均会增加低血糖发生风险;阳性药物比较中,GLP-1RA vs.IDegLira[OR=1.22,95%CI(1.04,1.43),P=0.014],显示GLP-1RA导致的低血糖发生风险高于IDegLira。结论后续治疗使用GLP-1RA、DPP-4i、SGLT-2i能更好地控制血糖,且GLP-1RA有降低体重优势,但使用GLP-1RA的患者低血糖风险较高。

中成药联合口服降糖西药治疗2型糖尿病效果的网状Meta分析

目的:评估临床常用的中成药分别联合常用口服降糖西药治疗2型糖尿病的有效性。方法:检索国家知识基础设施数据库(CNKI)、中国学术期刊数据库(CSPD)、中文科技期刊数据库(CCD)、中国生物医学文献数据库(CBM)、PubMed、Embase、Cochrane Library等数据库,文献时间范围为建库至2020年12月23日,根据纳入、排除标准进行文献筛选、资料提取并评价纳入研究的偏倚风险后,分别对不同结局指标包括空腹血糖、餐后2 h血糖、糖化血红蛋白采用网状Meta分析进行有效性比较及排序。结果:1)空腹血糖方面:7种中成药联合口服降糖西药均优于单纯口服降糖西药治疗,参芪降糖颗粒联用口服降糖西药疗效更为显著。2)餐后血糖方面:除消渴丸外,其余6种中成药联合口服降糖西药治疗效果均优于单纯口服降糖西药治疗,参芪降糖颗粒联用口服降糖西药疗效最为显著;3)糖化血红蛋白方面:除参芪降糖颗粒外,其余6种中成药联合口服降糖西药治疗效果均优于单纯口服降糖西药治疗,其中消渴丸疗效最佳。结论:7种中成药均能改善空腹血糖、餐后血糖、糖化血红蛋白,但由于临床试验的局限性,仍需要更多严谨、科学的临床试验为临床治疗提供切实有效的依据。

SGLT2抑制剂对心衰的作用研究的进展

除降糖作用外,钠-葡萄糖共转运蛋白2抑制剂(SGLT2i)的心肾保护功能也日益引起重视。本文就SGLT2i对心衰的作用研究的进展作一综述,旨在为心衰的治疗提供新思路。