The effects of ingestion time of gliclazide in relationship to meals on plasma glucose,insulin and c-peptide levels

Summary The effect of altering the timing of gliclazide administration in relation to a meal was studied in ten type 2 (non-insulin dependent) chronically treated diabetics. Gliclazide was given 30 min before, at the start of and 30 min after breakfast or omitted altogether. Plasma gliclazide was present at greater than 2 mg/l throughout the study periods. Administration at 30 min after the meal significantly delayed the time to peak for plasma gliclazide. No significant difference was noted in plasma glucose, insulin or c-peptide patterns with any protocol. It is concluded that, in clinical practice, with chronically treated diabetics the timing of gliclazide ingestion in relation to meals is not critical.     

2型糖尿病患者糖耐量试验与胰岛素释放试验相关性分析

目的 通过对糖耐量试验与胰岛素释放试验相关性研究,探讨其对2型糖尿病的诊断与治疗的临床意义.方法 对248例糖病病患者入院治疗前按其空腹胰岛素水平分为空腹低值组(A组)、空腹低值有峰组(B组)、空腹中值组(C组)、空腹高值组(D组)及44例正常对照组(E组),分别采用Backman LX20已糖激酶法测定空腹、糖耐量试验1、2、3 h的血糖和用美国Backman Asscey化学发光仪测定相应的胰岛素水平.结果 糖尿病患者各组胰岛素水平较正常人群组差异有显著性意义(P＜0.05)或非常显著意义(P＜0.01),A组、B组、C组、E组其血糖水平与相应的胰岛素水平具有正相关性,D组血糖水平与相应的胰岛素水平无相关性.结论 2型糖尿病患者在治疗前做糖耐量试验(OGTT)与胰岛素释放试验对其诊断治疗与预后有很重要临床意义.     

新型2型糖尿病治疗药那格列奈

那格列奈是一种新型口服降血糖药 ,它通过刺激胰岛素释放而降低血糖 ,与磺酰脲类药物相比 ,本品降血糖作用起效快 ,维持时间短 ,可有效降低餐后血糖水平。本文综述了那格列奈的药理学、毒理学、药动学和临床应用方面的研究进展     

前列地尔对非胰岛素依赖型糖尿病病人胰岛素及血小板聚集率的影响

目的：探讨前列地尔对非胰岛素依赖型糖尿病（ＮＩＤＤＭ）病人胰岛素及血小板聚集率的影响。方法：应用前列地尔２００μｇ加入０．９％氯化钠注射液５００ｍＬ中静脉滴注，ｑｄ×１０ｄ，治疗５０例ＮＩＤ ＤＭ病人（男性２３例，女性２７例，年龄５８±ｓ１０ａ）。治疗前后测定空腹胰岛素、餐后２ｈ胰岛素及血小板聚集率。结果：前列地尔刺激胰岛素分泌增加和降低血小板聚集率。治疗后的餐后２ｈ胰岛素显著增加（Ｐ＜０．０１），血小板聚集率显著下降（Ｐ＜０．０１，Ｐ＜０．０５）。结论：前列地尔增加ＮＩＤＤＭ病人的胰岛素分泌，降低血小板聚集率     

人胰岛素30R联合阿卡波糖与门冬胰岛素30对2型糖尿病患者餐后血糖的疗效比较

目的:比较人胰岛素30R联合阿卡波糖与门冬胰岛素30治疗2型糖尿病的有效性和安全性。方法:选择60例使用人胰岛素30R且餐后2 h血糖(PBG)控制不佳的2型糖尿病患者,随机配对法分为两组。人胰岛素30R+阿卡波糖组以人胰岛素30R餐前半小时皮下注射,bid,起始剂量同原方案;阿卡波糖50 mg,tid,餐前即刻吞服。门冬胰岛素30组用门冬胰岛素30餐前15 min皮下注射,bid,起始剂量同原方案。疗程3个月,比较治疗后两组患者的空腹血糖(FBG)、PBG、糖化血红蛋白(HbA1c)和胰岛素剂量,并记录低血糖发生率。结果:两组患者治疗后FBG和HbA1c无显著性差异(P>0.05)。两组患者所用的胰岛素剂量相当。与人胰岛素30R+阿卡波糖组相比,门冬胰岛素30组患者PBG下降更明显[(12.4±0.8)vs(11.0±0.6)mmol/L,P<0.01],低血糖发生率更低(40.0%vs16.7%,P<0.05)。结论:对使用预混人胰岛素治疗的PBG控制较差的2型糖尿病患者,应用门冬胰岛素30疗效更好,并且低血糖发生率更低。     

Dose-response relationships of tolbutamide and glibenclamide in diabetes mellitus

Summary Using a new procedure to study the dose-response relationships of sulphonylureas, the effects of tolbutamide and glibenclamide on blood sugar and serum insulin have been examined in 9 diabetic patients. Particular changes sought in serum insulin were alteration in the two initial peaks, elevation of basal levels and augmentation of the response to glucose infusions. In general, both sulphonylureas had identical effects and glibenclamide was not superior to tolbutamide. In 3 or 4 obese patients the first of the two initial insulin peaks was as high as in healthy volunteers, whereas the second peak was diminished; both initial peaks were greatly reduced in non-obses patients. The basal level of insulin was elevated in only one patient after glibenclamide. The response of insulin levels to glucose infusions was not increased in any patient and was actually inhibited by glibenclamide in one case. Tolbutamide produced its maximal effects after a dose of 1.0 g, glibenclamide after 1 mg. Blood sugar levels declined more rapidly in patients with latent diabetes than in those with the overt disease. In two of the latter, the fall in blood sugar was not associated with a corresponding increase in serum insulin.Dedicated to Prof. Dr. h. c. Hedwig Langecker on her 80th birthday.     

两种胰岛素注射液治疗2型糖尿病的疗效比较

目的比较门冬胰岛素30注射液和精蛋白锌重组人胰岛素混合注射液治疗2型糖尿病的临床疗效和安全性。方法68例经口服降糖药正规治疗后血糖控制不良的2型糖尿病患者随机分为门冬胰岛素30注射液治疗组和精蛋白锌重组人胰岛素混合注射液对照组，每组34例。比较治疗前后两组在血糖控制、糖化血红蛋白水平、日胰岛素剂量、低血糖发生率等方面的差异。结果两组空腹血糖控制均较理想，差异无统计学意义（P〉0．05）；餐后血糖控制治疗组显著低于对照组（P〈0．01），低血糖发生总次数，治疗组较对照组明显减少（P〈0．05）；糖化血红蛋白水平治疗组较对照组明显降低（P〈0．01）；两组胰岛素每日总剂量无统计学差异。结论门冬胰岛素30注射液治疗2型糖尿病，与精蛋白锌重组人胰岛素混合注射液同样可以很好控制血糖，但对餐后血糖控制更佳。     

格列喹酮治疗非胰岛素依赖型糖尿病35例

格列喹酮——一种新的第二代磺脲类口服降糖药物,治疗35例非胰岛素依赖型糖尿病患者作临床前瞻性研究,该药是降糖药中唯一不受肾功能影响的药物。以格列本脲作为对照药物。格列喹酮平均剂量94±30mg/d,分1-3次口服,共服药4-4.5mo。研究结果表明格列喹酮降糖作用肯定,其疗效与格列本脲相当,并有改善周围组织胰岛素敏感性的作用,无明显毒副作用。该药是一种安全、有效的口服降糖药物,值得临床推广使用。     

芬氟拉明单用对非胰岛素依赖型糖尿病45例的降糖效果

为了研究芬氟拉明的降糖效果,45例非胰岛素依赖型糖尿病患者(男12例,女33例,年龄58±8yr)在停用各种药物1-2wk后先服安慰剂1wk,继而单服芬氟拉明2-3mo,结果发现从wk1(第1周)起血糖即有降低,嗣后逐周降低,与服安慰剂时比较,有非常显著差异(P<0.001)。降糖程度与体重减轻之间无明显相关性(P>0.05)。     

阿卡波糖对2型糖尿病病人胰岛素抵抗的影响

目的 :探讨阿卡波糖对 2型糖尿病病人胰岛素抵抗的影响。方法 :16 0例 2型糖尿病病人随机分为 2组 ,治疗组 80例口服阿卡波糖治疗 ,前 2wk ,5 0mg ,po ,tid ,2wk后 ,10 0mg ,po ,tid ;安慰剂组 80例口服安慰剂 ,方法同治疗组 ,疗程为 2 4wk。同时观察空腹及餐后 2h血糖、血清胰岛素水平、体重指数、糖化血红蛋白、空腹时的红细胞胰岛素受体和红细胞膜流动性治疗前后变化。结果 :(1)wk 4时 ,阿卡波糖明显降低病人的空腹血糖、餐后 2h血糖、糖化血红蛋白 ,下降值分别为 :(2 .9±s 0 .8)mmol·L- 1,(4.0± 1.8)mmol·L- 1,(1.2± 2 .1) % ,P<0 .0 1;(2 ) 2 4wk后 ,阿卡波糖降低病人的体重、空腹血清胰岛素、餐后 2h血清胰岛素 ,下降值分别为 :(6± 4 )kg·m- 2 ,(10± 6 )MIU·L- 1,(14± 10 )MIU·L- 1,增加红细胞胰岛素受体 ,升高值为 :(80± 71)sites·RBC- 1,降低膜流动性 ,下降值为 :(1.5± 1.3) ,P <0 .0 1。结论 :阿卡波糖能改善 2型糖尿病病人的胰岛素抵抗     

血清脂联素水平与2型糖尿病胰岛素抵抗的关系

目的阐明脂联素与2型糖尿病胰岛素抵抗的相关性。方法2型糖尿病患者66例,根据1999年WHO诊断标准确诊,同期正常人30例年龄、性别与糖尿病足匹配。测定所有观察对象的空腹血清脂联素,体质指数、血糖、胰岛素、胰岛素抵抗指数及尿白蛋白排泄率等相关指标。用稳态模式胰岛素抵抗指数(Homa-IR)评估胰岛素抵抗。结果2型糖尿病组血清脂联素水平均低于正常对照组。Homa-IR2型糖尿病组高于正常对照组(P<0.05),脂联素水平超重肥胖者低于非肥胖者(P<0.01);相同WHR间脂联素水平2型糖尿病者较正常人低。脂联素与WHR、Homa-IR独立负相关(P<0.01)。结论血清脂联素与糖尿病、胰岛素抵抗之间存在着密切的相关性,在2型糖尿病的发生发展中发挥重要作用。     

葛根素对2型糖尿病病人胰岛素抵抗的影响

目的 :观察葛根素对 2型糖尿病病人胰岛素抵抗的影响。方法 :将 88例控制不良的 2型糖尿病病人随机分为 2组 ,葛根素组 4 8例在常规治疗基础上加用葛根素 5 0 0mg加入氯化钠注射液 2 5 0mL中静脉滴注 ,qd× 6 0d。另外 4 0例单用常规治疗 6 0d为对照组。观察葛根素对 2型糖尿病病人空腹、餐后血糖、胰岛素及血压、血脂、血液流变学、胰岛素敏感性指数 (ISI)的影响。结果 :葛根素组治疗后空腹、餐后 2h血糖、胰岛素、糖化血红蛋白等指标明显下降 ,分别为 (2 .2±s 0 .6 )mmol·L- 1,(6 .4±0 .8)mmol·L- 1,(7.2± 1.7)mU·L- 1,(1.6±0 .4 ) % ;胰岛素敏感性指数明显升高 ,差异均有显著意义 ,均P <0 .0 5 ,与对照组比较差异有显著意义 ,P <0 .0 5。结论 :葛根素具有改善 2型糖尿病病人胰岛素抵抗的作用。     

Effect of doxazosin on insulin sensitivity in hypertensive non-insulin dependent diabetic patients

Summary The effect of doxazosin, an a,-adrenoceptor blocking drug, on blood pressure, sensitivity to insulin and serum lipids has been evaluated in 14 hypertensive, non-insulin dependent diabetic patients. The dose was titrated individually upwards from 1 mg until the diastolic blood pressure was below 90 mm Hg, side-effects precluded further dosage increase or the maximum daily dose of 16 mg was achieved.After 12 weeks of treatment (mean doxazosin dose 5.6 ± 5.1 mg daily), the supine and standing diastolic blood pressure of the patients had declined by about 7 mmHg, whereas their systolic blood pressure and heart rate were not significantly changed. The metabolic clearance rate of glucose increased from 2.35 to 3.37 ml - min^–1 - kg^–1 during treatment, suggesting improved sensitivity to insulin. Fasting plasma glucose was 11.9 mmol·1^–1 before and 10.9 mmol·l^–1 after doxazosin therapy (NS). Serum electrolytes and lipids did not change significantly but serum uric acid decreased from 305 to 281 mol · 1^–1 Doxazosin may be a useful alternative for the treatment of hypertension in NIDDM patients.     

糖尿病患者泪糖浓度与血糖浓度的相关性

目的探讨正常人和糖尿病患者泪糖浓度和血糖浓度的相关性。方法 2型糖尿病(T2DM)患者75例85只眼(A组)和正常对照组28例28只眼(B组),以微量血糖仪测定两组空腹血糖,随即以微量采血管采集非刺激性泪液20μl并以高效液相色谱质谱联用法(HPLC-MS)测定泪糖。结果 A组泪糖明显高于B组[(0.460±0.204)mmol/L vs.(0.081±0.027)mmol/L](P<0.01)。A组泪糖与血糖呈直线正相关(r=0.870,P<0.01);B组泪糖与血糖无直线相关(r=0.229,P>0.05)。结论在糖尿病患者中,泪糖浓度可以作为一个反映血糖浓度的良好指标。     

白藜芦醇衍生物改善2型糖尿病大鼠血糖及胰岛素抵抗作用的研究

目的探讨白藜芦醇衍生物BTM-0512对2型糖尿病大鼠血糖及胰岛素抵抗作用的影响。方法单次腹腔注射链脲佐菌素（STZ,35mg·kg^-1）结合高脂饮食建立2型糖尿病大鼠模型。糖尿病大鼠分为3组（模型组、BTM-0512低剂量组、BTM-0512高剂量组）,药物灌胃3周。检测空腹血糖（FBG）、糖基化血红蛋白（HblAC）、空腹血清胰岛素（Fins）和口服糖耐量（OGTT）;计算HOME．IR、胰岛素敏感指数（1AD、胰岛素分泌指数（IS）,以此评价胰岛素抵抗（IR）。结果BTM-0512能剂量依赖性降低2型糖尿病大鼠FBG和HblAC,改善HOME．IR和IAI,但对OGTT与IS没有影响。结论BTM0512可以降低2型糖尿病大鼠血糖并改善IR。     

Understanding bolus insulin dose timing: the characteristics and experiences of people with diabetes who take bolus insulin

Objective: Despite the increased popularity of newer, fast-acting bolus insulin treatment options that allow for more flexibility in the timing of bolus insulin dosing in recent years, relatively little is known about people with diabetes who administer bolus insulin at differing times in relation to their meals. The purpose of this study was to investigate bolus insulin dose timing in relation to meals among people with type 1 (T1D) and type 2 (T2D) diabetes, as well as to better understand the characteristics and experiences of people who bolus dose at differing times.

Methods: A web-based survey of adults with T1D and T2D treated with bolus insulin therapy in Germany, the UK, and USA was conducted.

Results: A total of 906 respondents completed the survey (39% T1D; 61% T2D). A majority of respondents reported bolus dosing before meals in the previous week (57.0%), followed by after meals (18.9%), with meals (12.7%), and at varying times (11.5%). Compared to respondents who dosed with or after meals, those who dosed before meals were significantly less likely to experience hypoglycemia (before, 55.7%; with, 72.8%; after, 68.7%; p?p?Conclusion: Results show that many people with T1D and T2D dose their bolus insulin with or after meals. Key limitations of all self-report surveys include potential bias in responses and generalizability of findings. However, the study was designed to help mitigate these limitations. The findings have implications for clinicians and suggest opportunities for improving diabetes education and care.     

胰岛素注射相关皮下脂肪增生对糖尿病患者短期血糖波动的影响

目的 探讨胰岛素注射相关的皮下脂肪增生（LH）对糖尿病患者短期胰岛素泵治疗期间血糖波动的影响。方法 回顾性分析同时接受短期胰岛素泵治疗和动态血糖监测的住院糖尿病患者232例,其中1型糖尿病（T1DM）52例,2型糖尿病（T2DM）180例。统计不同类型糖尿病患者胰岛素注射相关LH的发生率,比较LH患者和无LH患者短期血糖波动指标的差异。分析平均葡萄糖波动幅度（MAGE）与临床指标的关系。采用二元Logistic回归分析血糖波动的影响因素。结果 232例患者总体LH的发生率为61.2%,其中T1DM和T2DM患者LH的发生率分别为57.7%(30/52)和62.2%(112/180)。T1DM患者中LH组仅MAGE高于无LH组,T2DM患者中LH组的短期血糖波动指标均高于无LH组（P<0.01）。在T1DM和T2DM患者中,MAGE与LH均呈正相关,与BMI、胰岛素使用年限、糖尿病病程均呈负相关（均P<0.05）。多因素Logistic分析结果显示,LH升高是T1DM(OR=4.665,95%CI:1.134～19.200)和T2DM(OR=6.659,95%CI:3.248...     

格列齐特治疗非胰岛素依赖性糖尿病的疗效

本文对国产和进口格列齐特各治疗８１和７６例非胰岛素依赖性糖尿病进行为期３－４ｍｏ的疗效对比。结果：２组的空腹和餐后血糖、ＨｂＡ１及血清三酰甘油（甘油三酯）明显降低，但空腹和餐后血清胰岛素和血清胆固醇没有明显变化。国产格列齐特的有效剂量明显低于进口格列齐特（Ｐ＜０．０５）。本文证明两者的疗效没有明显差别。     

Mechanism-based population modelling of the effects of vildagliptin on GLP-1, glucose and insulin in patients with type 2 diabetes

AIM

To build a mechanism-based population pharmacodynamic model to describe and predict the time course of active GLP-1, glucose and insulin in type 2 diabetic patients after treatment with various doses of vildagliptin.

METHODS

Vildagliptin concentrations, DPP-4 activity, active GLP-1, glucose and insulin concentrations from 13 type 2 diabetic patients after oral vildagliptin doses of 10, 25 or 100 mg and placebo twice daily for 28 days were co-modelled. The population PK/PD model was developed utilizing the MC-PEM algorithm in parallelized S-ADAPT version 1.56.

RESULTS

In the PD model, active GLP-1 production was stimulated by gastrointestinal intake of nutrients. Active GLP-1 was primarily metabolized by DPP-4 and an additional non-saturable pathway. Increased plasma glucose stimulated secretion of insulin which stimulated utilization of glucose. Active GLP-1 stimulated both glucose-dependent insulin secretion and insulin-dependent glucose utilization. Complete inhibition of DPP-4 resulted in an approximately 2.5-fold increase of active GLP-1 half-life.

CONCLUSIONS

The effects of vildagliptin in patients with type 2 diabetes on several PD endpoints were successfully described by the proposed model. The mechanisms of vildagliptin on glycaemic control could be evaluated from a variety of aspects such as effects of DPP-4 on GLP-1, effects of GLP-1 on insulin secretion and effects on hepatic and peripheral insulin sensitivity. The present model can be used to predict the effects of other dosage regimens of vildagliptin on DPP-4 inhibition, active GLP-1, glucose and insulin concentrations, or can be modified and applied to other incretin-related anti-diabetes therapies.