Increased frequency of micronuclei in diabetes mellitus patients using pioglitazone and glimepiride in combination

Micronuclei frequency is a sensitive biomarker used to evaluate the genotoxicity induced by xenobiotics. Pioglitazone and glimepiride were associated with genotoxicity in experimental studies conducted in rats. Considering the lack of published reports on genotoxicity in T2DM patients using pioglitazone and glimepiride drugs in combination, current study aimed to assess whether the case and control groups significantly differ from each other in the frequency of micronuclei. Subjects comprise 127 T2DM patients (35–65 years old) under pioglitazone and glimepiride treatment for >5 years and control group of 140 age matched healthy controls (38–69 years old). Exfoliated oral mucosa cells were collected from buccal mucosa of all subjects and Feulgen/Fast-Green method was followed to screen for micronuclei. Factors such as gender, food habits, living areas and occupation have not shown significant association with the variation in micronuclei frequency among the studied subjects. However, T2DM patients under long term treatment of pioglitazone and glimepiride in combination, showed increased frequency of micronuclei as compared to controls (p < 0.001). Current study suggests that the micronuclei assay can be used as a constituent among the panel of biomarkers to assess genotoxicity in T2DM patients under long term antihyperglycemic drug therapy.     

格列美脲联合二甲双胍对老年糖尿病的治疗作用研究

目的探讨格列美脲联合二甲双胍对老年糖尿病的治疗作用。方法100例老年糖尿病患者,随机分为二甲双胍组与格列美脲联合二甲双胍组,各50例。二甲双胍组患者采取二甲双胍治疗,格列美脲联合二甲双胍组采取格列美脲联合二甲双胍治疗。比较两组疗效;空腹、餐后血糖达标时间和糖化血红蛋白降低至<6%时间;治疗前后患者血糖、血脂;不良反应发生率。结果格列美脲联合二甲双胍组总有效率为100.00%,高于二甲双胍组的82.00%,差异有统计学意义(P<0.05)。治疗后,格列美脲联合二甲双胍组患者的餐后2 h血糖、空腹血糖、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)均低于二甲双胍组,差异有统计学意义(P<0.05)。格列美脲联合二甲双胍组空腹、餐后血糖达标时间和糖化血红蛋白降低至<6%时间均短于二甲双胍组,差异有统计学意义(P<0.05)。格列美脲联合二甲双胍组用药期间出现腹泻症状1例(2.00%);二甲双胍组用药期间出现腹泻症状1例(2.00%),两组不良反应发生率比较,差异无统计学意义(P>0.05)。结论格列美脲联合二甲双胍治疗老年糖尿病效果确切,可有效改善血糖和血脂,且无明显不良反应,安全性高。     

HPLC测定复方盐酸二甲双胍格列美脲胶囊中的格列美脲

目的用HPLC法测定复方盐酸二甲双胍格列美脲胶囊中格列美脲的含量。方法采用Diamonsil C18色谱柱(250mm×4.6 mm,5μm),流动相为0.05 mol·L-1甲酸铵缓冲液(pH4)-乙腈(40∶60),检测波长228 nm,流速1.0 mL·min-1。结果 1.014～20.280μg·mL-1格列美脲与峰面积呈良好的线性关系(r=0.9999),平均回收率为99.5%,RSD=1.0%。结论所用方法简便、准确性高、专属性强,且盐酸二甲双胍对格列美脲的测定无干扰,可用于该类复方制剂的质量控制。     

格列美脲治疗2型糖尿病42例的临床观察

目的 观察口服格列美脲治疗2型糖尿病的临床疗效.方法 选择符合诊断标准的42例2型糖尿病患者,给予格列美脲治疗,观察空腹血糖、餐后2 h血糖、糖化血红蛋白的变化及不良反应,治疗前后进行比较.结果 治疗后空腹、餐后2 h血糖、糖化血红蛋白水平均较治疗前明显下降（P〈0.01）,不良反应较少.结论 格列美脲是比较理想的治疗2型糖尿病新型磺脲类药物.     

甘精胰岛素联合格列美脲片治疗2型糖尿病的疗效观察

目的探讨甘精胰岛素联用格列美脲片治疗磺脲类药物继发性失效的2型糖尿病患者的疗效及安全性。方法60例口服磺脲类降糖药血糖控制不理想的2型糖尿病患者随机分为甘精胰岛素治疗组（GL组）和中性鱼精蛋白锌胰岛素（NPH）组,予睡前皮下注射胰岛素联合口服格列美脲治疗12周,观察12周前后空腹血糖、餐后2h血糖、糖化血红蛋白、空腹C肽、餐后C肽的变化。结果GL组治疗后FPG（6．3±1．41mmol／L,2hPG（8．7±1．4）mmol／L,HbAlc（6．7±0．6）％;NPH组治疗后FPG（6．4±1．0）mmol／L,2hPG（8．8±1．2）mmol／L,HbAlc（6．6±0．7）％,较治疗前差异有极显著性（P〈0．01）;但GL组的低血糖事件明显少于NPH组（P〈0．05）,且GL组治疗后C肽水平明显升高。结论甘精胰岛素联用格列美脲片治疗2型糖尿病的方案安全有效,简便易行,能减少低血糖事件的发生,且可能改善胰岛功能。     

格列美脲片治疗2型糖尿病的效果与安全性分析

目的观察格列美脲片治疗2型糖尿病的效果与安全性。方法选择本院126例2型糖尿病患者,随机分为格列美脲组66例和格列吡嗪组60例,分别给予格列美脲和格列吡嗪治疗,4周后测定空腹血糖（FPG）、餐后2h血糖（2hPG）、空腹血C肽、餐后2h血C肽和糖化血红蛋白（HbAlc）含量,检测胰岛素抵抗指数（HOMA—IR）和胰岛β细胞功能指数（HOMA—β）,记录发生低血糖反应的次数。结果治疗后两组FPG和HbAlc均显著下降,格列美脲组下降更明显;两组患者空腹血C肽、餐后2h血C肽水平都升高,格列美脲组患者血C肽升高更明显,低血糖反应次数明显减少;而且格列美脲组HOMA—IR下降明显,HOMA—β功能升高显著（P〈0．05）。结论格列美脲片治疗2型糖尿病效果较好,能减少低血糖反应,安全性好,患者用药依从性高,在改善胰岛β细胞功能方面更有优势。     

二甲双胍遗传药理学研究进展

遗传药理学研究发现药物代谢酶、受体和转运体基因遗传多态性是药物作用个体差异的重要决定因素。二甲双胍是治疗2型糖尿病(type2diabetes mellitus,T2DM)的一线药物,同时还可治疗多囊卵巢综合征(polycystic ovary syn-drome,PCOS)等其他与胰岛素抵抗有关的疾病。二甲双胍在临床使用中表现出显著的药物反应个体差异,这种差异性导致药物反应性降低或药物毒副反应的发生。有机阳离子转运体(organiccation transporters,OCTS)遗传多态性对二甲双胍药物反应个体差异有重要影响。本文阐述了OCTS等多个药物相关基因的遗传多态性对二甲双胍药代动力学和药效学的影响,可为临床制定二甲双胍的个体化用药提供参考。     

国产格列美脲胶囊在治疗2型糖尿病中的作用

目的：评价国产格列美脲胶囊应用于2型糖尿病患者的有效性和安全性。方法：40例2型糖尿病患者随机分为试验组和对照组各20例，分别口服国产和进口格列美脲剂量2－8mg,qd疗程8周。治疗前后测定空腹及餐后2h血糖。结果：治疗8周后，试验组空腹血糖（FBG）下降，3．14mol/L(32．31％），餐后2h血糖（PBG）下降4．96mmol/L(37．36 %)，糖化血红蛋白（HbA1c)下降1．60％（16．98％），与对照组相比无统计学意义（P＞0．05）。试验组降低FBG与PBG的总有效率分别为85％和90％，与对照组相比（85％，80％0无统计学意义。结论：国产格列美脲胶囊能有效降低FBG和PGB，其降糖疗效与进口格列美脲相似。     

Oxidative stress and endothelium influenced by metformin in type 2 diabetes mellitus

Objective Metformin may influence atherogenesis but the mechanisms are not well understood. A pilot study was undertaken to determine whether metformin administration is associated with changes in oxidative stress and endothelial function. Methods Fifteen type 2 diabetic patients were treated for 3 months with metformin (1,700 mg daily) or with a placebo in a crossover study. Laboratory parameters of oxidative stress, fibrinolysis and endothelial function were evaluated both prior to and following the respective treatments. In addition, laser Doppler was used to determine microcirculation changes in the skin. Results Increases in serum N-acetyl-β-glucosaminidase activity (p < 0.05) and plasma malondialdehyde concentration were found following 1 month of metformin administration. Three months of treatment was accompanied by significantly increased plasma malondialdehyde (p < 0.001) and ascorbic acid (p < 0.01) concentrations as well as the alpha-tocopherol/(cholesterol + triglyceride) ratio (p < 0.001). The concentration of tissue plasminogen activator (tPA), vascular cell-adhesion molecules (VCAM) and intercellular cell-adhesion molecules (ICAM) were significantly decreased (p < 0.01) compared with placebo. Microcirculation measured by laser Doppler flowmetry was not significantly changed. Conclusions We conclude that initiation of metformin treatment in type 2 diabetic patients is associated with improved diabetes control as well as with activation of oxidative stress together with antioxidant system. The atherogenic process measured by biochemical indicators is diminished in parallel. Our results show that in short-term metformin administration in type 2 diabetes promotes endothelium effects associated with a complex of metabolic changes.     

格列美脲联合治疗单用胰岛素效果不佳2型糖尿病患者的临床观察

目的分析加用格列美脲治疗单用胰岛素效果不佳2型糖尿病患者的临床效果。方法取昆山市第二人民医院收治的单用胰岛素治疗效果不佳的2型糖尿病患者作为研究对象,分别给予格列呲嗪控释片、格列美脲进行治疗,比较两组患者接受治疗后的FBG、PBG、HbAlc水平、胰岛素用量及低血糖发生率等情况差异。结果观察组患者接受治疗后1月及3月的各项糖尿病指标均明显优于对照组患者（P〈0．05）;接受治疗后1月,观察组与对照组患者的胰岛素用量无明显差异,观察组患者的低血糖发生率明显低于对照组患者（P〈0．05）;接受治疗后3月,观察组患者的胰岛素用量明显少于对照组患者（P〈0．05）,低血糖发生率明显低于对照组患者（P〈0．05）。结论格列美脲可以有效改善患者对于胰岛素的抵抗,优化其血糖水平,同时避免低血糖的发生。     

格列美脲治疗2型糖尿病伴肥胖患者的临床效果及药理分析

目的 探讨2型糖尿病伴肥胖患者施以格列美脲治疗的临床效果,并作药理分析。方法 46例2型糖尿病伴肥胖患者,根据随机数字表法分为观察组和对照组,每组23例。对照组患者给予格列吡嗪缓释片治疗,观察组患者给予格列美脲片治疗。比较两组患者治疗前后血糖指标[空腹血糖(FPG)、餐后2 h血糖(2 h PG)、空腹胰岛素(FINS)、糖化血红蛋白(HbA1c)]、血脂[总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)]及体质量指数(BMI)。结果 治疗后,观察组患者FPG、2 h PG、FINS、HbA1c水平分别为(6.04±0.43)mmol/L、(11.12±2.52)mmol/L、(657.84±10.37)pmol/L、(6.46±0.58)%,均低于对照组的(7.45±0.27)mmol/L、(14.24±2.09)mmol/L、(704.29±11.09)pmol/L、(8.53±0.79)%,差异均具有统计学意义(P<0.05)。观察组患者TC、TG、LDL-C、BMI水平分别为(3.24±0.79)mmol/L、(1.88±0.69)mmol/L、(1.96±0.48)mmol/L、(23.05±2.55)kg/m2,均低于对照组的(4.75±0.38)mmol/L、(2.35±0.75)mmol/L、(2.95±0.66)mmol/L、(27.76±4.10)kg/m2,差异均具有统计学意义(P<0.05)。结论 以格列美脲治疗2型糖尿病伴肥胖患者,可使患者血糖及血脂水平得以有效控制,同时可减轻其肥胖程度,具较高应用价值。     

Safety and efficacy of metformin up-titration in Japanese patients with type 2 diabetes mellitus treated with vildagliptin and low-dose metformin

Background: This study investigated the safety and efficacy of metformin up-titration in Japanese patients with type 2 diabetes mellitus treated with vildagliptin (100 mg/day) and low-dose metformin (500 or 750 mg/day).

Research design and methods: Fifty patients were randomly allocated to the control group (maintaining the initial low-dose of metformin) and the dose increase group (up-titrating of metformin to 1,500–2,250 mg/day) for 24 weeks. The primary outcome was change in HbA1c from baseline to 24 weeks.

Results: Among the 25 patients allocated to the dose increase group, four patients were not able to complete the study protocol because of gastrointestinal symptoms. HbA1c in the dose increase group was significantly but modestly lower than in the control group (change in HbA1c: 0.22 ± 0.57 vs. ?0.15 ± 0.58%, group comparison, P < 0.05). The dose increase group did not gain weight during the study period, and no hypoglycemic events were reported in both groups. The rate of gastrointestinal symptoms in the dose increase group was profoundly higher than in the control group (32 vs. 0%, P < 0.01).

Conclusions: In Japanese patients with type 2 diabetes treated with vildagliptin and low-dose metformin, metformin up-titration significantly but modestly improved glycemic control without hypoglycemia and weight gain.     

Contraindications to metformin therapy among patients with type 2 diabetes mellitus

Objective The biguanide, metformin, is a commonly prescribed oral antihyperglycemic agent. However, there are several clinical conditions that are considered as contraindications to the use of metformin among patients with type 2 diabetes mellitus. The aim of this study was to investigate the presence and nature of contraindications to metformin therapy among patients with type 2 diabetes mellitus. Method A retrospective study of the medical files of diabetic patients available at Alwosta clinic, north Palestine was carried out. Information about disease and medication profile of the patients was retrieved and analyzed using SPSS during the study period in 2004/2005. Focus was on metformin users who have contraindications to metfromin therapy. Main outcome measure Presence and number of contraindications to metformin therapy. Results Two hundred and seventy-two type 2 diabetic patients were identified. One hundred and twenty four of those diabetic patients were metformin users. Approximately, 60% of patients in the metformin group had a least one contraindication. Congestive heart failure and renal impairment were the most quantitatively present contraindications. Conclusion Contraindications to metformin therapy are common among type 2 diabetic patients and mostly disregarded. Patients have to be critically assessed before starting therapy and in case of metformin prescribing; dose should be adjusted based on the presence of risk factors for metformin adverse effects.     

Comparative effects of sitagliptin and metformin in patients with type 2 diabetes mellitus: a meta-analysis

Abstract

Background:

Sitagliptin has been widely used in the treatment of type 2 diabetes mellitus (T2DM); however, the therapeutic efficacy of sitagliptin remains inconclusive in randomized controlled studies on T2DM in which metformin has served as a control.     

联合沙格列汀与二甲双胍治疗2型糖尿病的临床疗效分析

目的探讨二甲双胍联合沙格列汀治疗2型糖尿病效果。方法96例糖尿病患者随机分为二甲双胍组、联合用药组各48例,二甲双胍组给二甲双胍,0.5 g,tid,po;联合用药组另加沙格列汀片,5mg,qd,po。结果治疗6个月以后,联合用药组空腹血糖(FBG)(6.01±0.97)mol/L、餐后2 h血糖(2hPBG)(8.53±1.22)mol/L、糖化血红蛋白HbAlc(6.94±0.88)%、体重指数(BMI)(24.47±1.09)kg/m^2低于二甲双胍组的(7.42±1.04)mol/L、(9.28±1.34)mol/L、(7.14±0.97)%、(25.82±1.22)kg/m^2(P<0.05);总有效率95.83%高于二甲双胍组83.33%(P<0.05)。结论联合沙格列汀与二甲双胍治疗2型糖尿病,显著降低FBG、2hPBG、HbAlc、BMI,提高治疗总有效率。     

艾塞那肽联合二甲双胍对2型糖尿病伴肥胖患者的干预效果

目的 探讨艾塞那肽联合二甲双胍对2型糖尿病(T2DM)伴肥胖患者的干预效果.方法 选取本院2012年1月至2015年1月期间收治的T2DM伴肥胖患者78例,以随机数表法分为观察组和对照组,每组各39例.观察组给予艾塞那肽联合盐酸二甲双胍治疗,对照组给予盐酸二甲双胍口服治疗,两组治疗周期均为12周;比较治疗前后两组患者体重(BW)、腰围(W)、体重指数(BMI)、血脂总胆固醇(TC)、甘油三酯(TG)、血糖(FBG)、餐后2h血糖(2 hPBG)控制及胰岛素分泌指数(HOMA-％B)、胰岛素抵抗指数(HOMA-R)的变化,并观察和比较两组不良反应和低血糖发生情况.结果 治疗前后,观察组BW、W、BMI、TC、TG、FBG、2hPBG、HOMA-％B、HOMA-R比较差异有统计学意义(P＜0.05),对照组仅BW、TC、2hPBG、HOMA-R比较差异有统计学意义(P＜0.05);治疗后与对照组比较,观察组W(96.56±7.22) cm、BMI(25.03±2.33)kg/m、TG(3.09±0.21) mmol/L、FBG(7.09±1.07)mmol/L、2hPBG(10.04±2.12)mmol/L、HOMA-R(3.10±0.77)显著低于对照组(P＜0.05);HOMA-％B显著高于对照组(P＜0.05);观察组不良反应为10.26％显著低于对照组的33.33％(P＜0.05).结论 艾塞那肽联合二甲双胍能有效减低T2DM伴肥胖患者的血糖水平和体重指数,并有效改善血脂代谢,减轻胰岛素抵抗,是一种值得临床推广的安全方案.     

格列美脲联合二甲双胍对老年糖尿病患者血脂、凝血、血管内皮功能指标的影响

目的探索格列美脲联合二甲双胍对老年糖尿病患者血脂、凝血、血管内皮功能指标的影响。方法87例老年糖尿病患者为研究对象,依据治疗方案不同分为对照组(43例)及实验组(44例)。对照组患者服用二甲双胍治疗,实验组患者在对照组基础上结合格列美脲治疗。对比两组患者治疗前后的血脂指标[甘油三酯(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)],治疗后的凝血指标[凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)、凝血酶时间(TT)、纤维蛋白原(FIB)],治疗前后的血管内皮功能指标[血栓调节蛋白(TM)、血管性假血友病因子(vWF)]水平。结果治疗后,两组患者的TC、TG、LDL-C较本组治疗前降低,HDL-C较本组治疗前升高,且实验组患者的TC、TG、LDL-C低于对照组,HDL-C高于对照组,差异具有统计学意义(P<0.05)。实验组患者的PT、APTT、TT长于对照组,FIB低于对照组,差异具有统计学意义(P<0.05)。两组患者的vWF、TM较本组治疗前降低,且实验组患者的v WF(63.25±5.39)%、TM(15.62±3.26)ng/ml低于对照组的(79.36±6.43)%、(23.78±1.85)ng/ml,差异具有统计学意义(P<0.05)。结论采用格列美脲联合二甲双胍方案治疗老年糖尿病的效果确切,治疗后血脂、凝血、血管内皮功能指标显著改善,值得临床推广应用。     

二甲双胍和吡格列酮对2型糖尿病患者的疗效及抗氧化作用研究

目的 探讨二甲双胍或吡格列酮对2型糖尿病患者的疗效及其对超氧化物歧化酶（SOD）、丙二醛（MDA）的影响。方法 纳入北京市昌平区中西医结合医院收治的2型糖尿病患者160例,按随机数字表法平均分为二甲双胍组和吡格列酮组,分别给予盐酸二甲双胍肠溶片（1 g/次,每日2次）和盐酸吡格列酮片（30 mg/次,每日1次）,两组疗程均为4周。比较两组患者治疗前后空腹血糖（FPG）、餐后2 h血糖（PPPG）、糖化血红蛋白（HbA1c）,血脂以及两组患者SOD、MDA水平。结果 给予降糖药4周后,两组患者FPG、PPPG、HbA1c均显著下降,同组治疗前后比较差异有统计学意义（P<0.05）。治疗后,二甲双胍组患者三酰甘油（TG）、低密度脂蛋白（LDL）水平显著降低,同组治疗前后比较差异有统计学意义（P<0.05）,而吡格列酮患者则无显著性变化。吡格列酮组患者血清MDA水平下降,同组治疗前后比较差异有统计学意义（P<0.05）;二甲双胍组患者血清SOD水平显著上升（P<0.05）,且显著高于吡格列酮组（P<0.05）;吡格列酮组患者血清MDA水平显著下降（P<0.05）,且显著低于二甲双胍组（P<0.05）。结论 二甲双胍或吡格列酮均能改善胰岛素抵抗和糖尿病并发症;吡格列酮降低MDA水平效果优于二甲双胍,但增加SOD水平仅见于二甲双胍。两种药物对氧化应激的作用机制不同,有利于联合用药。     

瑞格列奈联合二甲双胍治疗2型糖尿病对血糖指标的影响分析

目的 分析瑞格列奈联合二甲双胍治疗2型糖尿病对血糖指标的影响.方法 110例2型糖尿病患者,随机分为观察组与对照组,各55例.对照组给予二甲双胍治疗,观察组给予二甲双胍联合瑞格列奈治疗.比较两组血糖恢复正常时间、治疗期间低血糖次数、治疗前后血糖生化值[空腹血糖(FPG)、餐后2 h血糖(2 h PG)、糖化血红蛋白(H...     

二甲双胍联合阿卡波糖治疗2型糖尿病的效果观察

目的观察二甲双胍联合阿卡波糖治疗2型糖尿病的临床效果。方法选取本院2011年3月~2012年7月收治的70例2型糖尿病患者,随机分为两组,各35例,对照组采用二甲双胍治疗,观察组采用二甲双胍联合阿卡波糖治疗,治疗2个月,比较两组的FPG、2hPG和HbA1c。结果两组治疗后的FPG、2hPG和HbA1c均下降,观察组下降更明显,差异有统计学意义（P〈0.05）。结论二甲双胍联合阿卡波糖治疗2型糖尿病的疗效肯定,安全性高,值得推广应用。