两种胰岛素方案治疗门诊初诊2型糖尿病患者的疗效及低血糖发生率比较

目的研究两种胰岛素方案治疗门诊初诊2型糖尿病患者的疗效及低血糖发生率。方法选取孝感市中心医院2013年3月—2014年8月84例门诊初诊2型糖尿病患者,抽签随机分为两组,其中42例采用餐前皮下注射门冬胰岛素治疗记为对照组,剩下42例采用餐前注射门冬胰岛素联合晚间注射甘精胰岛素强化治疗记为观察组。结果两组治疗后血糖相关指标比较无明显差异,不具有统计学意义(P0.05);观察组低血糖率11.90%较对照组30.95%显著较低,具有统计学意义(P0.05)。结论两种胰岛素方案治疗初诊2型糖尿病均较为有效,但早期采用强化治疗方案能有效稳定平衡血糖代谢、预防低血糖发生,可作为临床治疗初诊2型糖尿病的首选参考方法。     

浅析磷酸西格列汀联合二甲双胍治疗新诊断2型糖尿病的降糖效果

目的探讨磷酸西格列汀联合二甲双胍治疗新诊断2型糖尿.病的降糖效果及对胰岛功能的保护作用。方法将2015年12月—2016年12月在广州市增城区人民医院内分泌科治疗的66例新诊断2型糖尿病患者随机分为两组,对照组单服二甲双胍治疗,观察组采用磷酸西格列汀联合二甲双胍治疗,比较两组患者的血糖及胰岛素功能。结果观察组治疗后FPG、2h PG、Hb A1c明显较对照组改善,差异有统计学意义(P<0.05);观察组治疗后HOMA-β、HOMAIR、IAI、血清APN明显较对照组改善,差异有统计学意义(P<0.05)。结论磷酸西格列汀联合二甲双胍治疗新诊断2型糖尿病效果显著,有利于血糖的平稳控制,延缓胰岛功能恶化,保护胰岛β细胞功能,具有积极的临床意义。     

二甲双胍铬(Ⅲ)配合物对糖尿病合并非酒精性脂肪肝大鼠的影响

为了研究二甲双胍铬(Ⅲ)配合物的生物活性,构建糖尿病合并非酒精性脂肪肝大鼠模型,实验8周后检测各组大鼠空腹血糖、血脂、胰岛素、转氨酶水平,组织病理学观察大鼠肝脏形态变化,蛋白印迹法检测大鼠肝脏Caspase-3蛋白的表达情况。实验结果:与模型组相比,铬(Ⅲ)配合物干预可显著降低大鼠空腹血糖、血脂、胰岛素、转氨酶水平,差异有统计学意义(p0.05);可减轻大鼠肝脏细胞水肿、脂肪变性等病理变化,并且干预组大鼠肝脏Caspase-3蛋白的表达显著低于模型组(p0.05)。说明铬(Ⅲ)配合物对糖尿病合并非酒精性脂肪肝大鼠具有一定的治疗和肝脏保护作用。     

瘦素水平和妊娠期糖尿病的相关性研究

目的分析瘦素水平和妊娠期糖尿病的相关性。方法选取150例妊娠期糖尿病患者作为观察组,另选取同期的38名健康妊娠者作为对照组;对比观察组与对照组的瘦素、空腹血糖(FPG)、空腹胰岛素(FINS)水平、HOMA-IR指数,分析妊娠期糖尿病患者瘦素与FPG、FINS、HOMA-IR指数的相关性。结果观察组患者的瘦素、FPG、FINS水平均显著高于对照组,HOMA-IR指数大于对照组,差异具有统计学意义(P0.05);妊娠期糖尿病患者的瘦素与FPG、FINS、HOMA-IR指数均呈正相关,均具有统计学意义(P0.05)。结论妊娠期糖尿病的发生、发展可能与瘦素水平升高具有相关性,孕期检测瘦素水平,有利于预测妊娠期糖尿病的发病,评估严重程度。     

缬沙坦联合氨氯地平治疗社区老年原发性高血压合并糖尿病的临床效果及安全性

目的探究在治疗老年性原发性高血压合并糖尿病患者中采用缬沙坦联合氨氯地平治疗的效果以及术后安全性,评估其临床意义,为临床治疗做出指导。方法以天津市滨海新区杭州道街社区卫生服务中心2013年5月—2014年6月间收诊的80例原发性高血压合并糖尿病老年患者的临床资料作为研究对象,按治疗方式不同将患者分成氨氯地平合并缬沙坦组40例(实验组)和单纯缬沙坦组40例(对照组)。测定分析两组患者治疗后情况,包括患者血压水平变化、空腹血糖、饭后2 h血糖以及胰岛素等指标,记录治疗情况。结果治疗后实验组血压水平下降的程度优于对照组(P0.05)。实验组空腹血糖等指标对比对照组均具有显著优势(P0.05)。结论联合氨氯地平缬沙坦治疗高血压合并糖尿病患者在血压下降水平、血糖前后变化水平等方面明显优于单纯使用缬沙坦治疗,不良反应发生率低,值得临床推广使用。     

胰岛素联合沙格列汀降糖疗效及安全性的研究

目的评估胰岛素联合沙格列汀治疗2型糖尿病的有效性和安全性。方法回顾性对照研究50例2型糖尿病患者胰岛素加用沙格列汀或阿卡波糖治疗(48±8)周后血糖水平和血糖波动等指标的变化。结果治疗(48±8)周后,两组血糖、Hb A1c、MAGE均明显下降(P均≤0.001),其中沙格列汀组MAGE的降幅明显大于阿卡波糖组(P=0.024),胃肠道不良反应发生率显著低于阿卡波糖组。结论沙格列汀联合胰岛素具有更强的控制血糖波动的疗效,胃肠道不良反应发生率更低。     

Zn2+,Cu2+及Ni2+对二甲双胍的配合作用及降血糖活性研究

二甲双胍盐酸盐、硝酸盐及与Zn²⁺, Cu²⁺, Ni²⁺三种金属离子配合物的结构特点、电荷分布和二甲双胍配合物对四氧嘧啶糖尿病小鼠血糖影响的研究表明:Zn²⁺配合物表现为较为少见的单齿配位,而Cu²⁺, Ni²⁺配合物表现为双齿配位.进一步电荷分布计算发现,与端基N原子相比,二甲双胍的桥基N原子具有较高的负电荷.三种金属离子配合物对四氧嘧啶糖尿病小鼠血糖的影响研究显示,桥基N配位掩蔽后,二甲双胍的降血糖功能丧失.说明桥基N对二甲双胍的降血糖作用具有重要意义.     

二甲双胍化学反应性的密度泛函理论研究及实验研究

二甲双胍(MET)是一个非常优良的降血糖药,一直是治疗II型糖尿病(T2DM)的首选药物,但其脂溶性较差,也存在引起胃肠道不适等副作用,对其结构修饰和衍生化,特别是将其研制成前药(Prodrug)具有一定的临床意义。为了探明二甲双胍化学反应的性能特点,本文基于密度泛函理论（DFT）开展了二甲双胍的化学内禀性质研究,包括各种可能互变异构体的单点能和量子化学反应性指数。此外,还对各异构体互变过程的过渡态以及它们的反应路径进行了研究。在此基础上,本文还对二甲双胍与亲电试剂的化学反应机理进行了初探,并用化学合成反应来验证,从而让我们能够从理论上弄清楚二甲双胍化学反应的特殊性质。     

小分子GPR40激动剂作为抗Ⅱ型糖尿病候选药物的研究进展

目前治疗Ⅱ型糖尿病的主要手段依然是口服或注射降糖药物以达到控制血糖的目的.虽然已有针对不同靶点开发的多种抗Ⅱ型糖尿病药物上市,但是鉴于糖尿病治疗药物长期服用的高安全性要求以及庞大的患病人群,研发新型安全有效的抗糖尿病药物仍然是当今药物化学研究的热点.GPR40是G-蛋白偶联受体家族中的一员,激动后可以诱导葡萄糖依赖的胰岛素分泌.因为仅在血糖浓度过高时,GPR40激动剂才能促进胰岛素分泌,所以针对该靶点开发降糖药物将极大地降低目前抗糖尿病药物低血糖副作用的风险.因此,GPR40已成为抗Ⅱ型糖尿病药物研发的前沿和热门靶点,本文将围绕小分子GPR40激动剂的药效团模型,即必需的苯丙酸核心骨架及其疏水末端和连接链的结构改造,对近年来各大制药公司及研究机构报道的小分子GPR40激动剂的研发进展进行总结评述.     

N5-芳酰基- N1，N1-二甲双胍钕配合物的合成和降血糖作用

盐酸- N1,NN', N'1-二甲双胍(HDMBG∙HCl)是临床广泛应用的降血糖药物，用于非胰岛素依赖型糖尿病的治疗。本文合成了三氯三（N5-苯甲酰-N1', N'1-二甲双胍)合钕 (Nd(BDMBG)3Cl3)和一氯二（N5-邻羧基苯甲酰- N1,NN', N'1-二甲双胍）合钕（Nd(CDMBG)2Cl）两种固态配合物，并通过元素分析、ICP、IR、UV、荧光光谱等表征了它们的化学组成和结构。糖尿病小鼠模型和ESR谱测定结果显示，几种化合物的降血糖作用及对人工脂质体膜超氧自由基的清除率呈现如下顺序：Nd(SDMBG)3　[)三（N5-水杨酰-N1,N1-二甲双胍）合钕] >Nd(CDMBG)2Cl » HDMBG·HCl > Nd(BDMBG)3Cl3，表明芳酰基邻位取代基的不同对配合物的降血糖作用和对O2-的清除作用具有重要影响。     

UHPLC-MS-Based Serum and Urine Metabolomics Reveals the Anti-Diabetic Mechanism of Ginsenoside Re in Type 2 Diabetic Rats

Panax ginseng was employed in the treatment of “Xiao-Ke” symptom, which nowadays known as diabetes mellitus, in traditional Chinese medicine for more than a thousand years. Ginsenoside Re was the major pharmacologic ingredient found abundantly in ginseng. However, the anti-diabetic of Ginsenoside Re and its underlying mechanism in metabolic level are still unclear. Serum and urine metabolomic method was carried out to investigate the anti-diabetic pharmacological effects and the potential mechanism of Ginsenoside Re on high-fat diet combined streptozotocin-induced type 2 diabetes mellitus (T2DM) rats based on ultra-high-performance liquid chromatography coupled with quadrupole exactive orbitrap mass spectrometry (UHPLC-Q-Exactive Orbitrap/MS). Serum and urine samples were collected from the control group (CON), T2DM group, metformin (MET) treatment group, and ginsenoside Re treatment group after intervention. The biochemical parameters of serum were firstly analyzed. The endogenous metabolites in serum and urine were detected by UHPLC-MS. The potential metabolites were screened by multivariate statistical analysis and identified by accurate mass measurement, MS/MS, and metabolite databases. The anti-diabetic-related metabolites were analyzed by KEGG metabolic pathway, and its potential mechanism was discussed. The treatment of ginsenoside Re significantly reduced the blood glucose and serum lipid level improved the oxidative stress caused by T2DM. Biochemical parameters (urea nitrogen, uric acid) showed that ginsenoside Re could improve renal function in T2DM rats. Respective 2 and 6 differential metabolites were found and identified in serum and urine of ginsenoside Re compared with T2DM group and enriched in KEGG pathway. Metabolic pathways analysis indicated that the differential metabolites related to T2DM were mainly involved in arachidonic acid metabolism, Vitamin B6, steroid hormone biosynthesis, and bile secretion metabolic pathways. This study verified the anti-diabetic and anti-oxidation effects of ginsenoside Re, elaborated that ginsenoside Re has a good regulation of the metabolic disorder in T2DM rats, which could promote insulin secretion, stimulated cannabinoid type 1 receptor (CB₁), and CaMKK β to activate AMPK signaling pathway, inhibited insulin resistance, and improved blood glucose uptake and diabetic nephropathy, so as to play the role of anti-diabetic.     

Clinical effects of monocomponent insulin and commercial insulin preparations on insulin requiring diabetics (author's transl)

Diurnal variation of blood sugar, C-peptide immunoreactivity (CPR), free insulin and total insulin were measured in 10 insulin requiring diabetics after obtaining adequate control of diabetes with commercial lente insulin treatment. Following these tests, insulin treatment were changed to monocomponent insulin (MC-insulin) from commercial lente insulin treatment in all subjects and the same tests were performed at 7th day of MC-insulin treatment. Diurnal variations of blood sugar in both groups were not changed significantly. Also changes in CPR of both groups were nearly same magnitude and endogenous insulin secretion in these insulin treated diabetics were suggested except a case of juvenile diabetic subject. However personal variation were great in diabetics with high antibody titer, diurnal variations of total extractable insulin in both groups were quite comparable. And mean diurnal changes in free insulin were resemble to that of CPR. All of these data suggested that clinical effects of MC-insulin and commercial insulin treatment on insulin requiring diabetics were comparable except insulin antibody or proinsulinspecific antibody production.     

Injectable dual glucose-responsive hydrogel-micelle composite for mimicking physiological basal and prandial insulin delivery

For type 1 and advanced type 2 diabetic patients, insulin replacement therapy with simulating on-demand prandial and basal insulin secretion is the best option for optimal glycemic control. However, there is no insulin delivery system yet could mimic both controlled basal insulin release and rapid prandial insulin release in response to real-time blood glucose changes. Here we reported an artificial insulin delivery system, mimicking physiological basal and prandial insulin secretion, to achieve real-time glycemic control and reduce risk of hypoglycemia. A phenylboronic acid(PBA)/galactosyl-based glucose-responsive insulin delivery system was prepared with insulin-loaded micelles embedded in hydrogel matrix. At the hyperglycemic state, both the hydrogel and micelles could swell and achieve rapid glucose-responsive release of insulin, mimicking prandial insulin secretion.When the glucose level returned to the normal state, only the micelles partially responded to glucose and still released insulin gradually. The hydrogel with increased crosslinking density could slow down the diffusion speed of insulin inside, resulting in controlled release of insulin and simulating physiological basal insulin secretion. This hydrogel-micelle composite insulin delivery system could quickly reduce the blood glucose level in a mouse model of type 1 diabetes, and maintain normal blood glucose level without hypoglycemia for about 24 h. This kind of glucose-responsive hydrogel-micelle composite may be a promising candidate for delivery of insulin in the treatment of diabetes.     

Effect of the combination of metformin and fenofibrate on glucose homeostasis in diabetic Goto-Kakizaki rats

Metformin has been reported to increase the expression of the glucagon-like peptide-1 (GLP-1) receptor in pancreatic beta cells in a peroxisome proliferator-activated receptor (PPAR)-α-dependent manner. We investigated whether a PPARα agonist, fenofibrate, exhibits an additive or synergistic effect on glucose metabolism, independent of its lipid-lowering effect, when added to metformin. Non-obese diabetic Goto-Kakizaki (GK) rats were divided into four groups and treated for 28 days with metformin, fenofibrate, metformin plus fenofibrate or vehicle. The random blood glucose levels, body weights, food intake and serum lipid profiles were not significantly different among the groups. After 4 weeks, metformin, but not fenofibrate, markedly reduced the blood glucose levels during oral glucose tolerance tests, and this effect was attenuated by adding fenofibrate. Metformin increased the expression of the GLP-1 receptor in pancreatic islets, whereas fenofibrate did not. During the intraperitoneal glucose tolerance tests with the injection of a GLP-1 analog, metformin and/or fenofibrate did not alter the insulin secretory responses. In conclusion, fenofibrate did not confer any beneficial effect on glucose homeostasis but reduced metformin''s glucose-lowering activity in GK rats, thus discouraging the addition of fenofibrate to metformin to improve glycemic control.     

全科医生对社区糖尿病患者的防治

目的探讨和分析全科医生在社区糖尿病患者疾病防治中的效用。方法以2015年1月—2016年12月期间深圳市坪山新区人民医院碧岭社康中心管理的180例糖尿病患者为研究对象,并采用随机分组的方法分为观察组(n=90)和对照组(n=90),其中,观察组患者予以药物治疗,对照组患者予以非药物治疗,并观察和比较两组患者治疗前后的各种代谢指标。结果无论是在接受全科医生指导前还是指导后,观察组患者空腹血糖值和餐后2 h血糖值均明显低于对照组,且差异均具有统计学意义(P<0.05);观察组患者的糖化血红蛋白值、尿微量蛋白值、收缩压和舒张压值以及体质量指数明显低于对照组,且差异均具有统计学意义(P<0.05)。结论实施药物治疗的糖尿病患者的各项血糖及代谢指标均低于非药物治疗组的数值,全科医生在社区糖尿病患者的防治中发挥着一定的积极效用。     

Stevioside Attenuates Insulin Resistance in Skeletal Muscle by Facilitating IR/IRS-1/Akt/GLUT 4 Signaling Pathways: An In Vivo and In Silico Approach

Type-2 diabetes mellitus (T2DM), the leading global health burden of this century majorly develops due to obesity and hyperglycemia-induced oxidative stress in skeletal muscles. Hence, developing novel drugs that ameliorate these pathological events is an immediate priority. The study was designed to analyze the possible role of Stevioside, a characteristic sugar from leaves of Stevia rebaudiana (Bertoni) on insulin signaling molecules in gastrocnemius muscle of obesity and hyperglycemia-induced T2DM rats. Adult male Wistar rats rendered diabetic by administration of high fat diet (HFD) and sucrose for 60 days were orally administered with SIT (20 mg/kg/day) for 45 days. Various parameters were estimated including fasting blood glucose (FBG), serum lipid profile, oxidative stress markers, antioxidant enzymes and expression of insulin signaling molecules in diabetic gastrocnemius muscle. Stevioside treatment improved glucose and insulin tolerances in diabetic rats and restored their elevated levels of FBG, serum insulin and lipid profile to normalcy. In diabetic gastrocnemius muscles, Setvioside normalized the altered levels of lipid peroxidase (LPO), hydrogen peroxide (H₂O₂) and hydroxyl radical (OH*), antioxidant enzymes (CAT, SOD, GPx and GSH) and molecules of insulin signaling including insulin receptor (IR), insulin receptor substrate-1 (IRS-1) and Akt mRNA levels. Furthermore, Stevioside enhanced glucose uptake (GU) and oxidation in diabetic muscles by augmenting glucose transporter 4 (GLUT 4) synthesis very effectively in a similar way to metformin. Results of molecular docking analysis evidenced the higher binding affinity with IRS-1 and GLUT 4. Stevioside effectively inhibits oxidative stress and promotes glucose uptake in diabetic gastrocnemius muscles by activating IR/IRS-1/Akt/GLUT 4 pathway. The results of the in silico investigation matched those of the in vivo study. Hence, Stevioside could be considered as a promising phytomedicine to treat T2DM.