Miglitol,a new α-glucosidase inhibitor

Miglitol (Bay m 1099, Bayer) is a second generation α-glucosidase inhibitor. It is a derivative of 1-desoxynojirimycin, and binds reversibly to the brushborder α-glucosidase enzymes. In contrast to its parent drug (acarbose, Bay g 5421, Bayer), miglitol is almost completely absorbed in the small intestine. It has to be taken with each main meal, and through its effect on carbohydrate digestion it blunts the postprandial blood glucose increase. Miglitol has no or a very small effect on fasting blood glucose levels. The blood-glucose lowering effects of miglitol in patients with Type 2 diabetes are lower than those of the frequently-used sulphonylurea compounds. Long-term studies show that a moderate average reduction of HbA1c of 0.3 - 0.7% point from baseline can be achieved. An advantage over sulphonylurea is the effect on serum insulin levels: miglitol therapy leads to slightly lower postprandial levels of serum insulin, whereas chronic sulphonylurea treatment usually increases serum insulin levels. This insulin-sparing effect may, in theory, lead to a lesser weight gain or even no weight gain and reduced risk of hypoglycaemia during chronic treatment. Long-term experience in Type 1 diabetic patients is limited. Similarly, miglitol may lead to reduced postprandial glucose excursions, slightly reduced insulin requirements and perhaps, as a consequence, a lower risk of hypoglycaemia. More long-term data are needed to fully assess to the clinical use of miglitol in these patients.     

阿卡波糖和伏格列波糖治疗2型糖尿病的比较

目的：对两种α－糖苷酶抑制剂的疗效与安全性进行评价比较。方法：按1997年ADA标准诊断的2型糖尿病人60例,按1：1分为阿卡波糖组和伏格列波糖组,经2周筛选,8周治疗并比较,结果：与治疗前相比,阿波卡糖组和伏格列波糖组治疗4周和8周后,餐后1h和2h血糖有明显下降（P＜0．05）,但空腹血糖下降不明显（P＞0．05）,阿卡波糖组在治疗8周后,餐后2h血糖下降较伏格列波糖组明显（P＜0．05）,两组HbAlc治疗后较治疗前明显降低（P＜0．01）,组间比较鞠显著性（P＞0．05）,伏格列波糖组治疗前后的空腹,餐后胰岛素水平无明显变化（P＞0．05）, 卡波糖组治疗后空腹,餐后胰岛纱均明显降低（P＜0．01）,两组病人治疗前后血脂无显著变化（P＞0．05）,两组间治疗期间无低血糖,肝,肾功能损害发生,治疗之初常见胃肠道副作用,但可以耐受,组间比较差异无显著性。结论：阿卡波糖和伏格列波糖均为有效降低餐后血糖和HbA1c的药物,阿卡波糖与伏格列波糖对控制空腹血糖及餐后血糖疗效相同,阿卡波糖降低餐后2h血糖和胰岛素水平较伏格列波糖明显,阿卡波糖和伏格列波糖均用药安全,耐受性好。αααααα     

荞麦种子提取物对α-糖苷酶及餐后血糖影响的实验研究

目的：研究荞麦种子提取物（EBR）对大鼠小肠α-葡萄糖苷酶的抑制作用及对餐后血糖水平的影响,探讨荞麦降血糖的可能机制。方法：提取大鼠小肠α-葡萄糖苷酶,测定EBR体外对α-葡萄糖苷酶活性的抑制作用;一次性灌胃麦芽糖（2g·kg^-1）,同时灌EBR（50、100mg·kg^-1）,测定60min后血糖水平的变化;以阿卡波糖（acar-bose,ACAR）作为阳性对照药物。结果：随着EBR和阿卡波糖浓度（0.001,0.01,0.1,1,10mg·ml^-1）的增加,对α-葡萄糖苷酶的抑制作用逐渐增强,有明显的浓度-效应关系,其中阿卡波糖作用强于ΕΒR,但当EBR浓度达到10mg·ml^-1时,其对α-葡萄糖苷酶的抑制率已达80%,相当于浓度1mg·ml^-1的ACAR的作用。体内餐后血糖实验结果显示,EBR可显著抑制大鼠一次性灌胃麦芽糖60min后血糖水平的升高（P〈0.05,P〈0.01）,与对照组比较,低、高剂量的EBR和ACAR对餐后血糖的抑制率分别为（40.85±7.43）%、（57.48±9.28）%和（76.39±7.94）%,但高剂量EBR和ACAR对大鼠空腹灌胃麦芽糖后血糖水平的升高没有差异（P〉0.05）。结论：EBR体内外对α-葡萄糖苷酶活性均有明显抑制作用,其降低血糖作用机制之一是抑制小肠α-葡萄糖苷酶活性实现的。     

一种用微孔板筛选alpha-葡萄糖苷酶抑制剂的方法

目的：建立敏感的微孔板方法检测alpha-葡萄糖苷酶抑制活性，以进行抑制剂体外高通量筛选。方法：调整酶和底物适当配比，通过标准曲线、波长扫描、动力学分析以及最佳反应条件的研究，用阿卡波糖验证所建方法。结果：确定反应步骤，96孔板，160μl体系含2．5mmol·L~(-1)PNPG和0．2U·ml~(-1)alpha-葡萄糖苷酶，37℃，pH7．0反应15min，400 nm检测，此法正确、可靠。结论：本文所述用小体积样品筛选得到大量抑制剂的方法，利于从天然产物中开发改善餐后血糖的糖尿病及其并发症治疗药物。     

α-葡萄糖苷酶抑制剂的研究及应用

概述α-葡萄糖苷酶抑制剂的化学结构特点、作用机制、制备途径与临床应用情况。临床上常用的降糖药阿卡波糖、伏格列波糖、米格列醇为一类微生物来源的α-葡萄糖苷酶抑制剂,其与寡糖结构类似,因此可竞争性地与α-葡萄糖苷酶结合,阻滞寡糖水解成单糖,从而降低餐后血糖峰值。并且某些α-葡萄糖苷酶抑制剂还具有抗HIV活性。     

阿卡波糖对糖耐量减低人群干预治疗的临床观察

目的:观察应用阿卡波糖干预治疗糖耐量减低(IGT)患者的临床疗效,协助临床控制糖耐量以减低患者向2型糖尿病的转变。方法:对120例糖耐量减低患者随机分为治疗组和对照组各60例,两组均予饮食和运动干预,治疗组加用阿卡波糖,12个月后比较两组患者糖尿病发生率以及体质量指数(BMI)、腰臀比(WHR)、空腹血糖(FPG)、葡萄糖耐量试验(OGTT)2 h后血糖(2HPG)、空腹胰岛素(FINS)和OGTT 2 h后胰岛素(PINS)、胰岛素抵抗指数(IRI)和胰岛素敏感指数(ISI)等指标。结果:干预治疗1年后,对照组患者糖尿病的发病率为8.3%,阿卡波糖组的发病率为5.0%;治疗组BMI、WHR、FPG、2HPG、FINS、PINS以及IRI值均明显低于对照组,而ISI显著高于对照组,差异有统计学意义。结论:阿卡波糖能够降低IGT人群糖尿病的发病率,明显改善IGT患者的代谢紊乱因素。     

阿卡波糖对2型糖尿病患者胰高血糖素的影响

目的探讨阿卡波糖对新诊断2型糖尿病患者胰高血糖素水平的影响。方法正常对照组12例和糖尿病组13例进食混合餐,分别于空腹和餐后15、30、60、90和120分钟测量血糖、胰岛素及胰高血糖素。1周后,糖尿病组进食混合餐＋阿卡波糖（100mg）,再次测量以上指标进行比较。结果干预前糖尿病组与正常对照组相比,餐后30分钟和90分钟胰高血糖素明显升高,胰高血糖素曲线下面积升高显著（P〈0．05）。干预后糖尿病组胰高血糖素15分钟有明显下降,胰高血糖素曲线下面积下降显著（P〈0．05）。结论阿卡波糖干预可降低2型糖尿病患者混合餐餐后血糖,同时降低胰高血糖素分泌。     

尼莫地平联合阿卡波糖治疗糖尿病周围神经病变的临床研究

目的观察尼莫地平联合阿卡波糖治疗糖尿病周围神经病变的临床疗效及对神经传导速度与神经相关生长因子的影响。方法将我院收治的76例糖尿病周围神经病变患者,随机分为试验组和对照组,每组38例。对照组给予尼莫地平40 mg,每天3次;试验组在对照组的基础上给予阿卡波糖50 mg,每天3次。所有患者均连续治疗1个月。比较2组患者的临床疗效、神经传导速度、神经相关生长因子和药物不良反应发生情况。结果治疗后,试验组的临床总有效率为89.47%(34例/38例),对照组为60.53%(23例/38例),差异有统计学意义(P<0.05)。治疗后,试验组腓总神经、正中神经运动神经传导速度(MCV)和感觉神经传导速度(SCV)分别为(45.88±4.06),(51.69±4.56),(44.12±4.09),(46.29±5.71)m·s^-1;对照组分别为(41.16±3.83),(44.98±4.46),(39.52±3.19),(43.13±4.46)m·s^-1,差异均有统计学意义(均P<0.05)。试验组的游离脂肪酸(FFA)、肿瘤坏死因子-α(TNF-α)、人磷髓脂碱性蛋白(MBP)水平分别为(471.45±44.28)μmol·L^-1,(11.15±1.18)pg·mL^-1,(1.90±0.14)μg·L^-1;对照组分别为(542.79±46.68)μmol·L^-1,(18.21±1.92)pg·mL^-1,(3.41±0.38)μg·L^-1(均P<0.05)。试验组血管内皮生长因子(VEGF)、人脑源性神经营养因子(BDNF)水平分别为(943.39±97.85),(4.87±0.58)ng·L^-1;对照组分别为(755.94±70.11),(3.09±0.26)ng·L^-1,差异均有统计学意义(均P<0.05)。试验组出现腹泻1例,腹胀3例,药物不良反应发生率为10.53%(4例/38例);对照组出现轻度头晕1例,消化道反应2例,腹胀和轻度腹部不适2例,药物不良反应发生率为13.16%(5例/38例),差异无统计学意义(P>0.05)。结论尼莫地平联合阿卡波糖治疗糖尿病周围神经病变,能有效改善患者神经传导速度与神经相关生长因子,临床疗效良好,安全性高。     

Acarbose and metabolic control in patients with type 2 diabetes with newly initiated insulin therapy

AIM: This study was designed to investigate the effect of acarbose in patients with type 2 diabetes with newly initiated insulin treatment who had previously been insufficiently controlled with oral antihyperglycaemic agents [haemoglobin A(1c) (HbA(1c)) >/= 8%]. METHODS: In this 20-week double-blind, placebo-controlled study, 163 patients were randomized to receive acarbose up to 100 mg three times a day or matching placebo. Both the groups were newly initiated with insulin, which was adjusted according to blood glucose values. Primary efficacy parameter was the change in HbA(1c) from baseline; changes in daily insulin doses were also assessed. RESULTS: Mean HbA(1c) was significantly reduced by acarbose compared with placebo (2.31 vs. 1.81%, p = 0.033). Insulin doses were comparable at the end of the study. There was no difference in blood glucose and triglyceride levels between the treatment groups. Postprandial serum insulin levels increased in both treatment arms owing to insulin administration but less so under acarbose. In contrast to the placebo group, an increase in body mass index was prevented for acarbose-treated patients. CONCLUSION: As adjunct administration to newly initiated insulin therapy, acarbose enhances the optimization of blood glucose control in patients with type 2 diabetes.     

Influence of treatment with acarbose or glibenclamide on insulin sensitivity in type 2 diabetic patients

Aim: The aim of our double-blind, placebo-controlled study was to compare the effect of acarbose and glibenclamide on the insulin sensitivity in type 2 diabetes.
Methods: We investigated 77 patients (mean age 58.7 years, mean BMI 27.3 kg/m²), treated by diet alone for at least 4 weeks. The subjects were randomized into three treatment groups for 16 weeks: 100 mg t.i.d. acarbose ( n  = 25) or 1 mg t.i.d. glibenclamide ( n  = 27) or one t.i.d. placebo ( n  = 25). Before and after therapy, the levels of fasting plasma glucose, glycosylated haemoglobin, fasting insulin, plasma glucose and insulin 1 h after a standardized breakfast were measured and insulin sensitivity determined by euglycaemic hyperinsulinaemic clamp test.
Results: After the treatment period, BMI in the acarbose and placebo group decreased significantly, whereas in the glibenclamide group a significant increase was observed. Fasting plasma glucose was only significant reduced under glibenclamide. The postprandial glucose decreased significantly after acarbose (13.8 vs. 11.4 mmol/l, p < 0.05) and glibenclamide treatment (14.6 vs. 11.4 mmol/l, p < 0.05) and was unchanged under placebo (13.8 vs. 13.7 mmol/l). The fasting insulin levels remained unchanged in all three groups, whereas postprandial insulin values increased significantly under glibenclamide. Neither acarbose nor glibenclamide significantly changed insulin sensitivity [acarbose: glucose disposal rate before treatment 2.3 mg/kg body weight/min/insulin, after treatment 3.2; glibenclamide 2.2 vs. 2.1; placebo 2.6 vs. 3.0].
Conclusions: Our results show a more substantial improvement of glucose control under glibenclamide than under acarbose which, however, was not associated with an increase of insulin sensitivity.