甘精胰岛素联合阿卡波糖治疗2型糖尿病效果观察

目的探讨甘精胰岛素联合阿卡波糖治疗2型糖尿病的临床效果。方法将86例2型糖尿病患者随机分为两组,各43例。对照组给予诺和锐30联合阿卡波糖治疗,观察组给予甘精胰岛素联合阿卡波糖治疗。治疗3个月后,观察两组临床疗效及低血糖事件发生率,治疗前后空腹血糖（FBG）、餐后2 h血糖（2 h PG）、糖化血红蛋白（Hb A1c）及超敏C反应蛋白（hs-CRP）指标。结果观察组患者有效率为88.37%,对照组为83.72%,两组有效率比较差异无统计学意义（P〉0.05）;观察组低血糖事件发生率为2.33%,低于对照组的18.60%（P〈0.05）。治疗前两组FBG、2 h PG、Hb A1c及hs-CRP比较差异均无统计学意义（P〉0.05）;治疗3个月后,除对照组hs-CRP外,两组上述指标均有明显下降;两组治疗后比较,观察组FBG低于对照组（P〈0.01）,其他指标两组差异均无统计学意义（P〉0.05）。结论甘精胰岛素联合阿卡波糖治疗2型糖尿病效果显著,可有效降低低血糖事件发生率,平稳降糖,值得临床推广应用。     

益生菌对T2DM 患者肠道菌群和脂联素的影响

目的 探讨益生菌辅助口服降糖药物治疗2 型糖尿病（T2DM）疗效及对患者肠道菌群和脂联 素水平的影响。方法 选取2015 年1 月-2015 年12 月于西南医科大学附属医院就诊的120 例T2DM 患者 作为研究对象,按照随机数字表法分为对照组和观察组。常规治疗基础上,对照组患者给予口服降糖药物（二 甲双胍＋阿卡波糖）治疗,观察组患者在对照组基础上给予益生菌（双歧杆菌乳杆菌三联活菌片）治疗。比 较两组患者血糖指标、肠道菌群、血浆脂联素水平及不良反应发生情况。结果 治疗后,与对照组相比,观 察组患者空腹血糖、餐后2 h 血糖、糖化血红蛋白A1c 水平降低,粪便中革兰阳性杆菌、革兰阴性杆菌数量 增多（P <0.05）,而两组革兰阳性球菌、革兰阴性球菌数量比较无差异（P >0.05）。脂联素水平检测显示,观 察组患者治疗后血浆脂联素水平高于对照组（P <0.05）。治疗过程中,均未出现低血糖反应。观察组和对照 组不良反应发生率分别为11.7% 和8.3%,两组比较无差异（P >0.05）。结论 益生菌辅助口服降糖药物在 T2DM 中应用效果良好,能够改善血糖,调节肠道菌群,升高血浆脂联素水平,且不良反应轻微,临床上值得 应用。     

Production of a highly potent epoxide through the microbial metabolism of 3β-acetoxyurs-11-en-13β,28-olide by Aspergillus niger culture

Context 3β-Acetoxyurs-11-en-13β,28-olide (I), a triterpenoid, is found in most plant species. Pharmacologically triterpenes are very effective compounds with potent anticancer, anti-HIV and antimicrobial activities.

Objectives Microbial transformation of 3β-acetoxyurs-11-en-13β,28-olide (I) was performed in order to obtain derivatives with improved pharmacological potential.

Materials and methods Compound (I, 100?mg) was incubated with Aspergillus niger culture for 12 d. The metabolite formed was purified through column chromatography. Structure elucidation was performed through extensive spectroscopy (IR, MS and NMR). In vitro α- and β-glucosidase inhibitory, and antiglycation potentials of both substrate and metabolite were evaluated.

Results Structure of metabolite II was characterized as 3β-acetoxyurs-11,12-epoxy-13β,28-olide (II). Metabolite II was found to be an oxidized product of compound I. In vitro α- and β-glucosidases revealed that metabolite II was a potent and selective inhibitor of α-glucosidase (IC₅₀ value?=?3.56?±?0.38?μM), showing that the inhibitory effect of metabolite II was far better than compound I (IC₅₀ value?=?14.7?±?1.3?μM) as well as acarbose (IC₅₀ value?=?545?±?7.9?μM). Antiglycation potential of compound II was also high with 82.51?±?1.2% inhibition. Thus, through oxidation, the biological potential of the substrate molecule can be enhanced.

Conclusion Biotransformation can be used as a potential tool for the production of biologically potent molecules.     

European study on dose-response relationship of acarbose as a first-line drug in non-insulin-dependent diabetes mellitus: efficacy and safety of low and high doses

The aim of this double-blind, placebo-controlled, multinational, five-arm study was to investigate the dose-response relationship of acarbose as a first-line drug in the treatment of type 2 diabetes (non-insulin dependent) over a range of minimal and maximal doses according to the European recommendations. The study included 495 patients from 7 countries who were insufficiently controlled with diet alone (glycosylated haemoglobin HbA_1C 6.5%–9%). Acarbose, 25, 50, 100 or 200 mg t.i.d., or placebo t.i.d. was given for 24 weeks. Even a low dosage of 25 mg t.i.d. acarbose reduced fasting and postprandial blood glucose levels (1 h postprandial –11.6%; 2 h postprandial –11.3%). Acarbose in a dosage of 200 mg t.i.d. had the greatest effect on these parameters. In the placebo group the mean 2 h postprandial area under the curve (AUC) value for blood glucose was 22.6 mmol/l after 24 weeks' therapy. The mean 2 h postprandial AUC values in the patients given acarbose at doses of 25, 50, 100 and 200 mg t.i.d. were found to be 21.2, 19.6, 20.3 and 18.5 mmol/l, respectively. The corresponding HbA_1C values for the placebo and acarbose groups were 7.83%, 7.37%, 7.08%, 6.98% and 6.79%. Interestingly, there was a plateau of blood glucose level at a dosage of 50–100 mg t.i.d. The frequency of flatulence decreased with the duration of drug therapy, but we could not find a linear relationship between doses of acarbose and the gastrointestinal side effects. Less than 3% of patients stopped tablet intake due to adverse events. Received: 18 March 1997 / Accepted in revised form: 14 November 1997     

拜唐苹联合其他口服降糖药治疗2型糖尿病的有效性和安全性临床研究——多中心、非随机、开放性、自身对照研究

目的 评价已用其他口服降精药物治疗血糖不能达标的2型糖尿病患者,联合拜唐苹后的有效性和安全性.方法 全国17个中心的493例糖尿病患者参加了本次多中心、非随机、开放性、自身对照的临床研究,在患者已用其他口服降糖药物基础上加用拜唐苹治疗后观察12周,主要的疗效参数是空腹血糖(FBG)和餐后2 h血糖(PBG)水平的变化及糖化血红蛋白(Hb)A1c水平的变化.结果 联合拜唐苹治疗后总体FBG下降1.3 mmol/L,早餐PBG下降3.3 mmol/L,午餐PBG下降3.2mmol/L,晚餐PBG下降3.44 mmol/L,HbA1c降低了0.90%,P均＜0.001.拜唐苹联合非胰岛素促泌剂组、磺脲类组和格列奈类组的FBG分别下降1.24 mmol/L、1.30 mmol/L和1.13 mmol/L;早餐PBG分别下降3.36 mmol/L、3.35 mmol/L和2.25 mmol/L;午餐PBG分别下降3.57 mmol/L、3.61 mmol/L和3.15 mmol/L,晚餐PBG分别下降3.65 mmol/L、3.48 mmol/L和3.09 mmol/L;HbA1c分别降低了0.99%、1.06%和1.01%;P均＜0.001.联合拜唐苹治疗后无严重低血糖反应,体重无增加,消化道不良反应发生率为3.60%,多为腹胀和(或)排气,但可耐受.结论 当2型糖尿病患者使用一种或多种口服降糖药治疗血糖不能达标时,联用拜唐苹可使血糖控制获得明显改善,达标率显著提高,且有良好的安全性和耐受性.     

阿卡波糖(拜唐苹(R))在中国临床应用经验回顾及展望

作为第一个主要针对餐后血糖控制的降糖药,阿卡波糖(拜唐苹)在中国上市十几年来,得到医生和患者普遍认可,并且已经逐渐成为临床应用最广泛的口服降糖药之一.这与西方国家情况似有不同,是偶然因素还是另有原因?     

Comparison of Acarbose and Gliclazide as First-line Agents in Patients with Type 2 Diabetes

Summary

Aim: To compare the effect of acarbose and gliclazide on clinical findings, biochemical parameters and safety in type 2 diabetic patients insufficiently controlled with medical nutrition therapy (MNT).

Methods: Seventy-two patients (age 35–70 years, BMI ≤ 35 kg/m²), who had not taken any oral antidiabetic drug previously, were randomised into two groups after a four-week placebo period, and treated for 24 weeks with acarbose (100 mg two to three times daily) and gliclazide (40–80 mg twice daily). The study was open and 57 patients (33 males and 24 females) completed it. MNT was provided for each patient based on personal requirements as defined by a dietitian. The effect of treatment was evaluated by fasting and postprandial (PP) metabolic parameters (blood glucose, insulin and C peptide levels), HbA1C and plasma lipid levels. In addition, side-effects were recorded and clinical examinations performed.

Results: Both drugs were effective in reducing of HbA1C, fasting and PP blood glucose levels. However, PP serum insulin levels in the gliclazide group increased more than those in the group treated with acarbose (p = 0.007). Moreover, a small weight reduction was obtained with acarbose treatment but not with gliclazide. Lipid levels were favourably affected by both drugs. Total cholesterol levels decreased in both groups, the decrease only reaching significance in the acarbose group (p = 0.013). However, serum levels of LDL cholesterol decreased in both groups (acarbose and gliclazide, p = 0.033 and p = 0.023, respectively), but the ratio of HDL to LDL cholesterol increased in the acarbose group only (p = 0.045). Both treatments were generally well tolerated. Common complaints in the acarbose group were flatulence and meteorism (29.6%). However, 10.0% of the patients in the gliclazide group reported at least one mild hypoglycaemic episode.

Conclusions: The results of the study demonstrate that acarbose and gliclazide were reasonably effective in improving metabolic control in patients insufficiently controlled with diet alone, and both treatments were well tolerated. Because of its effects on weight reduction and PP hyperinsulinaemia, acarbose may be preferred as a firstline drug, particularly in the treatment of overweight type 2 diabetic patients.     

Metabolic effect of repaglinide or acarbose when added to a double oral antidiabetic treatment with sulphonylureas and metformin: a double-blind,cross-over,clinical trial

ABSTRACT

Objective: To compare the metabolic effects of acarbose and repaglinide in type 2 diabetic patients who are being treated with a sulphonylurea–metformin combination therapy. The primary endpoint of the study was to evaluate which add-on treatment between acarbose and repaglinide is more efficacious in reducing PPG. The second endpoint was to evaluate which of these two treatment is more efficacious in the global management of glucose homeostasis in the enrolled patients.

Research design and methods: After a 4-week run-in period with a suplonylurea–metformin combination, 103 patients were randomised to receive in addition either repaglinide, up to 6?mg/day (2?mg three times a day) or acarbose, up to 300?mg/day (100?mg three times a day) with forced titration (independently of their glycaemic control, unless side-effects developed due to the drug dosage) for 15 weeks. The treatment was then crossed-over for further 12 weeks until the 27th week. We assessed body mass index (BMI), glycosylated haemoglobin (HbA_1c), fasting plasma glucoe (FPG), postprandial plasma glucose (PPG), fasting plasma insulin (FPI), postprandial plasma insulin (PPI), homeostatic model assesssment (HOMA) index, systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides (Tg), at baseline and at 1, 2, 15 and 27 weeks of treatment.

Results: Seven patients did not complete the study, comprising one patient who was lost to follow-up and a further six through side-effects (two in week 1, one in week 15 and three after cross-over) Side-effects were classified as nausea (one in acarbose group), gastrointestinal events (four in acarbose group), and hypoglycaemia (one in repaglinide group). After 15 weeks of therapy, the repaglinide-treated patients experienced a significant decrease in HbA_1c (?1.1%, p?<?0.05), FPG (?9.5%, p?<?0.05), and PPG (?14.9%, p?<?0.05), when compared to the baseline values. However, the same treatment was associated with a significant increase in body weight (+2.3%, p?<?0.05), BMI (+3.3%, p?<?0.05) and FPI (+22.5%, p?<?0.05); The increase was reversed during the cross-over phase. After 15 weeks of therapy, the acarbose-treated patients experienced a significant decrease in body weight (?1.9%, p?<?0.05), BMI (?4.1%, p?<?0.05), HbA_1c (?1.4%, p?<?0.05), FPG (?10.7%, p?<?0.05), PPG (?16.2%, p?<?0.05), FPI (?16.1%, p?<?0.05), PPI (?26.9%, p?<?0.05), HOMA index (?30.1%, p?<?0.05), when compared to the baseline values. All these changes were reversed during the cross-over study phase, except those relating to HbA_1c, FPG and PPG. The only changes that significantly differed when directly comparing acarbose- and repaglinide-treated patients were those relating to FPI (?16.1% vs. +22.5%, respectively, p?<?0.05) and HOMA index (?30.1% vs. +2.7%, p?<?0.05).

Conclusion: In addition from having a similar effect to repaglinide on PPG, acarbose appeared to have a more comprehensive positive effect on glucose metabolism compared to repaglinide in this relatively small sample of type 2 diabetic patients when used as add-on therapy to sulphonylureas and metformin.     

HPLC测定阿卡波糖胶囊的含量及有关物质

目的　建立测定阿卡波糖胶囊含量及有关物质的方法。方法　采用HPLC法 ,LichrospherNH2 色谱柱 (4 .6mm× 2 5 0mm ,5 μm) ,以乙腈 -磷酸盐缓冲液 (72∶2 8)为流动相 ,流速 1.3ml·min-1,检测波长 2 10nm。结果　阿卡波糖在浓度为 0 .6～1.2mg·ml-1范围内线性关系良好 (r=0 .9999) ,平均回收率为 10 0 .6 3% ,样品溶液在 2 4h内稳定 ,最低检测限为 0 .0 8μg。 结论　所用方法简便、重复性好 ,结果准确。     

罗格列酮联合阿卡波糖治疗2型糖尿病的临床疗效研究

目的 探讨罗格列酮联合阿卡波糖治疗2型糖尿病的有效性和安全性.方法 选取2010-2011年来我院门诊内分泌科治疗的符合标准的2型糖尿病患者96例,给予罗格列酮片和阿卡波糖片,定期检测患者空腹血糖、餐后2h血糖和糖化血红蛋白,比较治疗前后变化情况.结果 采用罗格列酮联合阿卡波糖治疗2型糖尿病12周之后,空腹血糖、餐后2h血糖及糖化血红蛋白等指标相对治疗前均有下降,差异有统计学意义（P＜0.05）.其他各项指标均正常,未发生严重不良反应.结论 罗格列酮联合阿卡波糖治疗2型糖尿病安全有效,不良反应少,具有较大的临床意义.