达格列净对预混胰岛素治疗血糖控制不达标的2型糖尿病患者的疗效和安全性研究

目的评估达格列净对预混胰岛素治疗血糖控制不达标的T2DM患者的疗效和安全性。方法选取96例门冬胰岛素30与二甲双胍和阿卡波糖联合治疗血糖控制不达标的T2DM患者,随机分为达格列净组(Dap)和对照组(Con),Dap组在服用二甲双胍和阿卡波糖的基础上口服达格列净,Con组仅口服二甲双胍和阿卡波糖。两组根据血糖水平调整胰岛素剂量,治疗和随访共16周。主要终点为HbA1c降幅,次要终点为HbA1c7.0%达标率、体重变化、低血糖事件等。结果治疗16周后,Dap组和Con组HbA1c较基线下降(1.3±1.0)%和(1.4±0.8)%,HbA1c7.0%达标率分别为56.8%和59.1%,差异均无统计学意义(P0.05);体重较基线变化值为-2.0(-4.0,0.0)kg和0.5(-0.8,3.6)kg;低血糖发生率分别为4.5%和22.7%;胰岛素剂量较基线变化幅度为(-9.9±15.4)U/d和(17.2±14.2)U/d,差异均有统计学意义(P0.05或P0.01)。结论在预混胰岛素与二甲双胍和阿卡波糖联合治疗血糖控制不佳的T2DM患者中,与Con组相比,Dap组降糖疗效相近,但减轻体重、减少低血糖风险更有效。     

西格列汀联合二甲双胍治疗老年2型糖尿病疗效分析

目的探讨单服二甲双胍(metformin)治疗未达标的老年2型糖尿病患者(T2DM)加用西格列汀(sitagliptin)的有效性及安全性。方法入选2015年5月至2016年9月中关村医院内分泌科单服二甲双胍控制不佳的老年T2DM患者52例,其中男性30例,女性22例,年龄65~78(68.0±8.0)岁。随机分成西格列汀组和阿卡波糖(acarbose)组,每组26例(男性15例,女性11例)。西格列汀组患者口服西格列汀100 mg/次,1次/d,阿卡波糖组患者口服阿卡波糖50 mg/次,3次/d,两组患者同时口服二甲双胍500 mg/次,3次/d,连续治疗12周。观察两组患者服药12周后空腹血糖(FPG)、餐后2h血糖(2hPG)、糖化血红蛋白(HbA1c)等指标变化,并记录低血糖、胃肠道不良反应的发生情况。结果两组患者治疗前FPG、2hPG和HbA1c差异均无统计学意义(P0.05);治疗12周后,两组患者FPG、2hPG和HbA1c较治疗前均明显降低,并且西格列汀组较阿卡波糖组2hPG和HbA1c下降更显著,差异有统计学意义(P0.05)。治疗期间两组患者无低血糖发生,阿卡波糖组4例发生腹胀,排气增加,两组患者不良反应发生差异无统计学意义(P0.05)。结论西格列汀与二甲双胍联用治疗T2DM患者疗效显著且安全。     

那格列奈用于老年2型糖尿病患者的临床优势

目的 观察那格列奈治疗老年2型糖尿病患者的有效性和安全性.方法 48例老年2型糖尿病患者分为新诊断糖尿病组26例,原有糖尿病组22例,新诊断组采用那格列奈控制血糖,既往组由原来应用阿卡波糖改为那格列奈控制血糖.治疗前后测定两组的空腹血糖(FPG)、餐后2 h血糖(2 h PG)、糖化血红蛋白(HbA1c),观察两组低血糖及其他严重不良反应的发生次数.结果治疗后新诊断组的FPG、2 h PG及HbA1c均较治疗前有明显下降(P＜0.05);既往组的FPG、2 h PG及HbA1c较治疗前有所下降,但差异无显著性(P＞0.05);两组均未见严重不良反应,低血糖事件两组比较差异无显著性.结论 那格列奈片治疗老年2型糖尿病降糖效果好,不良反应轻微,是一种有效安全的降糖药.     

地特胰岛素联合低剂量二甲双胍、阿卡波糖治疗老年2型糖尿病超重与肥胖患者疗效及安全性的观察

目的探讨老年T2DM超重、肥胖患者在口服降糖药基础上加用每日一次地特胰岛素(Det)治疗的临床疗效及安全性。方法 93例老年T2DM超重、肥胖患者随机分为A、B组。A组口服二甲双胍+阿卡波糖(Met+Acarbose);B组二甲双胍+阿卡波糖+Det(Met+Acarbose+Det),疗程24周。观察两组治疗前后FPG、2hPG、BMI、HbA1c及低血糖发生率等情况。结果 24周后,B组FPG、2hPG、HbA1c、BMI较基线及A组降低(P0.05),且无夜间低血糖发生。结论 Det联合低剂量二甲双胍+阿卡波糖可有效控制老年T2DM超重、肥胖患者血糖,优于单纯口服给药,并能控制体重,且无夜间低血糖发生。     

沙格列汀联合二甲双胍治疗维吾尔族老年2型糖尿病的疗效

目的观察单用二甲双胍血糖控制不佳的维吾尔族新诊断老年2型糖尿病(T2DM)患者加用沙格列汀的有效性。方法 160例单用二甲双胍12 w,血糖不达标的维族新诊断老年T2DM患者,随机分为沙格列汀组82例和阿卡波糖组78例,进行12 w的随访,对比空腹血糖(FBG)、餐后2 h血糖(2 h PG)、糖化血红蛋白(HbA1c)、血清脂联素(APN)、稳态模型评估-胰岛素抵抗指数(HOMA-IR)、体重指数(BMI)等指标的变化。结果治疗12 w后,沙格列汀组与阿卡波糖组FBG、2 h PG和HbA1c水平较治疗前明显降低,且沙格列汀组均较阿卡波糖组下降幅度大(P<0.05),HbA1c达标率明显高于阿卡波糖组(P<0.05),沙格列汀组与阿卡波糖组HOMA-IR均较治疗前明显下降而APN水平明显升高(P<0.05),沙格列汀组HOMA-IR、APN的改善优于阿卡波糖组(P<0.05),两组治疗前后BMI水平无统计学差异(P>0.05)。结论沙格列汀与二甲双胍联用治疗维吾尔族新诊断的老年T2DM患者治疗效果好。     

早期2型糖尿病患者的血小板CD62P表达及阿卡波糖的干预作用

目的 探讨早期2型糖尿病(T2DM)患者血小板CD62P表达及阿卡波糖治疗对CD62P的影响.方法 选择新诊断的早期T2DM患者83例,随机将其分为基础治疗组和阿卡波糖治疗组.两组均接受糖尿病教育、饮食控制,并进行适当的运动锻炼;阿卡波糖治疗组每日加服阿卡波糖控制血糖,共治疗16周.治疗前后,测量两组BMI、血压、空腹血糖(FPG)、餐后2h血糖(2 h PG)、血脂及血小板CD62P表达.另选40例体检健康者作为对照组,于查体时进行上述检测.结果 与对照组比较,T2DM组的FPG、2hPG与血小板CD62P表达阳性率明显升高(P均＜0.05).基础治疗组治疗前后各检测指标无明显变化(P均＞0.05);阿卡波糖治疗组治疗后FPG、2 h PG与血小板CD62P表达阳性率明显降低,且明显低于基础治疗组(P均＜0.05).多元回归分析表明,2 hPG与血小板CD62P表达率显著相关(β=0.525,P＜0.05).结论 阿卡波糖可通过降低餐后血糖,抑制早期T2DM患者的血小板CD62P表达.     

血清C肽与糖化血红蛋白联合检验对糖尿病诊断的临床意义

目的探讨血清C肽(CP)与糖化血红蛋白(HbA1c)联合检验对糖尿病(DM)诊断的临床意义。方法选取该院2016年3月—2018年3月收治的48例DM患者作为观察组,选取同期健康体检者48名作为对照组,全部患者均行空腹血糖(FPG)、餐后2 h的血糖(2 h PG)、CP、Hb A1c水平检查。比较两组受检者的检测结果,分析HbA1c与与上述各项指标的相关性。结果观察组的FPG(10.79±3.23)mmol/L、2 h PG(13.76±3.42)mmol/L及HbA1c(11.95±2.36)%均明显高于对照组的(3.12±0.59)mmol/L、(3.69±0.29)mmol/L和(5.03±0.47)%(P0.05),CP水平(0.89±0.08)μg/L明显低于对照组的(1.42±0.66)μg/L(P0.05);HbA1c与CP呈负相关关系(r=-6.653,P=0.041),与FPG呈正相关关系(r=0.445,P=0.037)。结论 CP与HbA1c联合检验可为可为医师诊断DM提供可靠的参考依据,具有积极的临床应用意义。     

GA、GA/HbA1c、CysC与老年2型糖尿病并发颈动脉粥样硬化的相关性

目的探讨老年2型糖尿病(T2DM)患者糖化白蛋白(GA)、GA/糖化血红蛋白(HbA1c)、血清胱抑素(Cys)C水平与颈动脉粥样硬化的关系。方法老年T2DM患者428例,依据有无颈动脉粥样硬化分为单纯T2DM组219例,T2DM合并颈动脉粥样硬化组209例。比较一般资料、生化指标、C肽水平、GA、HbA1c、GA/HbA1c比值及CysC水平,分析各指标与T2DM颈动脉粥样硬化病变之间的关系。结果糖尿病病程、收缩压(SBP)、体重指数(BMI)、低密度脂蛋白胆固醇(LDL-C)、空腹血糖(FPG)、餐后2 h血糖(2 h PG)、GA、GA/HbA1c、CysC水平在T2DM合并颈动脉粥样硬化组显著高于单纯T2DM组(P0.05)。GA和2 h PG、HbA1c之间存在正相关,与BMI及空腹C肽呈负相关,相关系数分别为r=0.667、0.658、-0.381、-0.321,均P0.05。GA/HbA1c与GA、年龄、糖尿病病程呈正相关,与HbA1c呈负相关,相关系数分别为(r=0.546、0.196、0.228、-0.180,均P0.05)。Logistic回归分析结果:GA、GA/HbA1c、CysC与T2DM颈动脉粥样硬化独立相关。结论 GA、GA/HbA1c、CysC水平变化与T2DM颈动脉粥样硬化的发生密切相关。     

米格列奈对比阿卡波糖治疗2型糖尿病有效性和安全性的多中心、开放、随机对照临床研究

目的比较阿卡波糖和米格列奈治疗T2DM的有效性和安全性。方法在该项多中心、开放、随机对照研究中,T2DM病程5年以下的患者被随机分为米格列奈组或阿卡波糖组,分别接受米格列奈钙片治疗10mg/次或阿卡波糖片治疗50 mg/次,3次/d,疗程均为12周。观察12周后HbA_1c、FBG、餐后血糖(PBG)的变化,以及安全性。结果本研究共入组患者248例,可进行疗效评价分析237例,其中米格列奈组118例,阿卡波糖组119例。治疗后,两组HbA_1c、FBG、PBG水平与基线比较均降低(P0.0001)。12周时,HbA_1c治疗前后下降值,米格列奈组(1.27±1.04)%,阿卡波糖组(1.00±1.30)%,两组差值(0.27±1.19)%,两组比较差异有统计学意义(P0.05)。治疗8周,米格列奈组FBG下降(1.31±1.29)mmol/L,阿卡波糖组(0.86±1.68)mmol/L,两组差值(0.45±1.51)mmol/L,两组比较,差异有统计学意义(P0.05)。治疗12周,FBG和PBG下降值两组相当(P0.05)。阿卡波糖组不良事件发生率为14.66%,米格列奈组为6.54%(P=0.0508);阿卡波糖组腹胀发生率高于米格列奈组(P=0.0055)。结论米格列奈和阿卡波糖均有降低HbA_1c、FBG及PBG的作用,且疗效相当,米格列奈较阿卡波糖有较少的胃肠道反应。     

沙格列汀治疗单用二甲双胍治疗血糖控制不佳2型糖尿病患者疗效及安全性研究

目的探索沙格列汀对二甲双胍单药治疗血糖控制不佳2型糖尿病患者的安全性及有效性。方法选择2015年1月—2016年12月在该院内分泌科门诊及住院的糖尿病患者252例。将入选患者按照1:1的比例随机分配至沙格列汀组或者阿卡波糖组。两组患者均继续维持二甲双胍治疗,沙格列汀组患者在原降糖方案的基础上加用沙格列汀片5 mg/d,1次/d;阿卡波糖组加用阿卡波糖50 mg,3次/d。随访观察期24周。每4周随访1次。观察两组患者治疗前后的FPG、2 h PG、Hb A1c的变化,并记录随访期间药物相关不良事件发生情况。比较上述指标的在两组的变化。结果 (1)沙格列汀组与阿卡波糖组治疗后FPG、2 h PG较该组治疗前均有明显降低(P0.05);与阿卡波糖组治疗后相比,沙格列汀组2 h PG显著下降,差异有统计学意义(P0.05);(2)干预24周后,沙格列汀组与阿卡波糖组各组Hb Alc均有降低(P0.05);与阿卡波糖组相比,沙格列汀组Hb Alc下降幅度更大(P0.05);沙格列汀组Hb A1c达标率为48.82%显著高于阿卡波糖组的35.20%,差异有统计学意义(P0.05)。(3)随访期间,阿卡波糖组胃肠道异常发生率高于沙格列汀组(16.80%vs 3.94%,P0.05);沙格列汀组与阿卡波糖组的低血糖事件和因不良事件而终止者相比较差异无统计学意义(7.09%vs 6.40%、5.51%vs 4.80%,P0.05)。结论对于二甲双胍单药治疗血糖不达标的2型糖尿病患者,加用沙格列汀可有效降糖,提高糖化血红蛋白达标率,且不增加低血糖和胃肠道反应风险。     

Efficacy and safety of mitiglinide versus nateglinide in newly diagnose patients with type 2 diabetes mellitus: a randomized double blind trial

This study was performed to examine the efficacy and safety of mitiglinide in type 2 diabetes patients (T2DM). Enrolled patients had received treatment with diet and exercise in the previous 3 months with glycosylated haemoglobin (HbA1c) 7-10%, and were randomized to receive mitiglinide (n = 111, 5-20 mg/meal) or nateglinide (n = 114,60-120 mg/meal) for 16 weeks. Primary and secondary efficacy endpoints were assessed by the changes in HbA1c, fasting blood glucose (FBG) and postprandial glucose (PBG) levels. The baseline HbA1c value was 8.2 and 8.3% in both groups. At the end of study, the reduction of HbA1c values from baseline by mitiglinide was slightly more than that by nateglinide (-1.11% vs. -0.76%), but not statically significant (p = 0.06). Final FBG and PBG were comparable for the two treatments. There were 2.8% subjects treated with nateglinide who had hypoglycaemic episodes, but none in the mitiglinide treatment group. The results indicate that mitiglinide and nateglinide had similar effects on FBG, PBG and HbA1c in T2DM patients after the 16-week treatments.     

Nateglinide, alone or in combination with metformin, is effective and well tolerated in treatment-naïve elderly patients with type 2 diabetes

Aim: The aim of this work was to assess the efficacy and tolerability of nateglinide alone or in combination with metformin in elderly patients with type 2 diabetes (T2DM). Methods: Study 1 was a 12‐week, multicentre, randomized, double blind and placebo‐controlled study of nateglinide monotherapy (120 mg, before meals) in 66 drug‐naïve patients with T2DM aged ≥65 years. Study 2 was a 104‐week, multicentre, randomized, double blind and active‐controlled study of nateglinide (120 mg, before meals) or glyburide (up to 5 mg bid) in combination with metformin (up to 1000 mg bid) in 69 treatment‐naïve patients with T2DM aged ≥65 years. HbA_1c, fasting and postprandial glucose levels, and safety assessments were made. Results: In Study 1, nateglinide significantly reduced HbA_1c from baseline (7.6 ± 0.1% to 6.9 ± 0.1%; Δ = ?0.7 ± 0.1%, p < 0.001) and compared with placebo (between‐group difference = ?0.5%, p = 0.004 vs. nateglinide). No hypoglycaemia was reported. In Study 2, combination therapy with nateglinide/metformin significantly reduced HbA_1c from baseline (7.8 ± 0.2% to 6.6 ± 0.1%; Δ = ?1.2 ± 0.2%, p < 0.001), as did glyburide/metformin (7.7 ± 0.1% to 6.5 ± 0.1%; Δ = ?1.2 ± 0.1%, p < 0.001). There was no difference between treatments (p = 0.310). One nateglinide/metformin‐treated patient experienced a mild hypoglycaemic episode compared with eight episodes in eight patients on glyburide/metformin; one severe episode led to discontinuation. Target HbA_1c (<7.0%) was achieved by 60% of patients receiving nateglinide (Study 1) and 70% of nateglinide/metformin‐treated patients (Study 2). Conclusion: Initial drug treatment with nateglinide, alone or in combination with metformin, is well tolerated and produces clinically meaningful improvements in glycaemic control in elderly patients with T2DM.     

沙格列汀联合二甲双胍对新诊断2型糖尿病患者的疗效及安全性

目的观察单用二甲双胍血糖控制不佳的新诊断2型糖尿病患者加用沙格列汀降糖的有效性及安全性。方法2011年11至2012年9月选取180例新诊断的2型糖尿病患者（均为单用二甲双胍12周而血糖尚不达标）,按随机数字表法分为沙格列汀联合治疗（90例）与阿卡波糖联合治疗（90例）,随访12周,观察各项血糖指标变化,并记录不良反应发生情况。组间比较采用t检验,定性资料组间比较采用疋。检验。结果治疗12周后,沙格列汀组与阿卡波糖组空腹血糖（FPG）、餐后2h血糖（2hPG）和糖化血红蛋白（HbAlC）较治疗前明显降低（t值分别为1．401、1．321、1．574、1．510、1．421、1．601,均P〈0．05）。沙格列汀组2hPG及HbAlC较阿卡波糖组下降幅度大（t值分别为－2．711、－2．600,均P〈0．05）,且HbAlc达标率（83．33％）高于阿卡波糖组（67．78％）（ｘ２=5．870,P〈0．05）。沙格列汀组与阿卡波糖组空腹胰岛素水平较治疗前升高{分别为（9．24±1．21）比（8．17±0．25）U／L,（8．62±1．20）比（8．15±0．24）U／L,t值分别为1．563、1．620,均P〈0．05};HOMA－IR指数较治疗前明显下降（分别为2．60±0．21比3．02±0．39,2．76±0．40比3．01±0．38,t值分别为1．431、1．459,均P〈0．05）;沙格列汀组空腹胰岛素水平及HOMA—IR指数的改善优于阿卡波糖组（t值分别为3．451、－3．359,均P〈0．05）;阿卡波糖组胃肠道副反应发生率高于沙格列汀组;沙格列汀组患者服药依从性优于阿卡波糖组（矿=8．760,P〈0．05）。结论沙格列汀与二甲双胍联用治疗新诊断的2型糖尿病患者降糖效果比较明显,不增加体重,低血糖发生风险及胃肠道反应低,患者依从性好。     

Acarbose improves glycemic control in insulin-treated Asian type 2 diabetic patients: results from a multinational,placebo-controlled study

The purpose of the study was to determine the efficacy and tolerability of acarbose in Asian type 2 diabetic patients insufficiently controlled by insulin. Asian type 2 diabetic patients on stable insulin dosages were enrolled into a multinational, double-blind, placebo-controlled parallel arm study. After a 2-week screening phase, patients were randomly assigned to 50 mg acarbose t.i.d. or matching placebo for 6 weeks, followed by 100 mg acarbose t.i.d. or placebo for 12 weeks. The primary efficacy parameter was change from baseline in HbA(1c); secondary variables included the changes in fasting and postprandial blood glucose. After 18 weeks of treatment there was a difference in HbA(1c) levels between the two treatment groups (-0.69%, 95% CI (-1.18; -0.2), P=0.008) in favour of acarbose. Reductions in 1-h postprandial glucose levels from baseline to endpoint were observed with acarbose treatment (P=0.029). There were no differences in fasting blood glucose, total triglyceride and cholesterol between the two groups. Safety profiles were similar for both treatment arms except for the higher incidence of flatulence in the acarbose group (28.6% vs. 16.4% for placebo). Adjunctive acarbose therapy offers an efficacious and safe means for improvement of glycemic control in Asian type 2 diabetic patients insufficiently controlled by insulin.     

阿卡波糖对2型糖尿病患者慢性炎症相关因子水平的影响

目的 观察2型糖尿病患者阿卡波糖治疗4周前后血中炎症因子水平的变化.方法 随机选取符合入选标准的2型糖尿病患者118例.患者按照随机数字表法进入A组(糖尿病阿卡波糖治疗组)58例,给予阿卡波糖150mg/d;进入B组(糖尿病对照组)60例,不服用阿卡波糖,其余治疗与A组相似,为实现血糖达标,调节除阿卡波糖之外的降糖药及胰岛素用量;57名健康个体作为C组(健康人群对照组).A、B 2组糖尿病患者均采集入组时和干预治疗4周后的空腹血清,C组采集一次空腹血清,于-80℃冰箱保存待测(排除不合格血清标本,如溶血、样本量不足等,最终进入A组实际检测人数为57例,B组为59例).监测3餐前、餐后2 h末梢血糖,测定生化指标,用ELISA法测定血清单核细胞趋化蛋白-1(MCP-1)、肿瘤坏死因子-α(TNF-α)、超敏C反应蛋白(hs-CRP)、血浆纤溶酶原激活物抑制物-1(PAI-1)、脂多糖水平,用荧光光谱法测定晚期糖基化指数(AGI)水平来表示晚期糖基化终末产物(AGEs)的相对含量.结果 干预治疗后,两组糖尿病患者的空腹血糖、HbA1C均显著降低(P＜0.05).A组治疗后各炎症因子水平MCP-1、脂多糖、AGI、hs-CRP、TNF-α均显著降低(P＜0.05),而PAI-1无显著下降(P=0.163).B组治疗后MCP-1、脂多糖、AGI、TNF-α和PAI-1水平均升高,hs-CRP水平下降(P＜0.05).与B组比较,A组MCP-1、脂多糖、PAI-1、TNF-α、AGI治疗前后水平下降趋势更明显.A、B两组的hs-CRP在干预前后的变化趋势差异无统计学意义(P＞0.05).结论 糖尿病患者炎症因子水平高于健康人群,阿卡波糖干预治疗可显著降低其部分炎症因子的水平.

Abstract：

Objective To evaluate the effect of acarbose on the circulating concentration of inflammatory factors in patients with type 2 diabetes mellitus(T2DM). Methods Total 118 patients with T2DM who did not take acarbose before enrollment within 4 weeks were recruited by a randomizing formula into 2 groups ( group A and B). 57 healthy subjects were included into group C as control. After excluding those of inadequate samples, 57 patients with T2DM were enrolled into group A in which acarbose was prescribed 50 mg three times a day, 59 patients with T2DM were enrolled into group B in which acarbose was not given and other hypoglycemic approaches were similar to group A. Serum samples at the time of enrollment and at the end of 4 weeks intervention were collected and stored in refrigerator at -80℃ until analysis. Analysis of biochemical indexes was performed in central lab of the institution,inflammatory factors were determined with commercial ELISA kits. Results (1) The metabolic indexes were significantly decreased after intervention in two diabetic groups. (2) The baseline levels of monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-α( TNF-α), prothrombin activator inhibitor-1 (PAI-1), lipopolysaccharide (LPS), high sensitive C reactive protein ( hs-CRP), and advanced glycation index (AGI) in diabetic patients were significantly higher than in group C MCP-1 [( 463.4± 187.1 vs 267.1 ± 158.3 ) pg/ml, TNF-α( 12.07 ± 19.59 vs 4.18 ±3.03 ) pg/ml, PAI-1 ( 2.47 ± 1.87 vs 1.38 ± 2.37 )ng/ ml, LPS ( 130.6 ± 128.5 vs 29.39 ± 17.93 ) pg/ml, hsCRP(4.25 ±2.29 vs 2.11 ± 1.07 ) μg/ml, AGI (3.78 ± 2.61 vs 0. 74 ± 0. 15 ) AU, all P ＜ 0. 05]. (3) Repeated measurement ANOVA analysis showed that after four weeks of intervention, MCP-1 [F( 1,106 ) = 19. 830, P＜0.001],LPS[F(1,106)=7.815, P＜0.01], PAI-1 [F(1,106)= 7.792, P＜0.01], TNF-α[F(1,106=24. 656, P=0.001 )] ,AGI[F( 1,106)= 12. 971 ,P=0. 01] decreased significantly in group A than in group B. Although hsCRP decreased in both group A and group B, but the trend was not different [F( 1,102 )= 0. 915, P = 0. 342].Conclusion The levels of inflammatory factors were elevated in patients with type 2 diabetes mellitus, which could be mostly reduced by acarbose.     

二甲双胍与格列喹酮或阿卡波糖联合治疗2型糖尿病的临床疗效和安全性比较:多中心、随机、开放、平行分组对照研究

目的 对用单药和(或)联合口服降糖药物后血糖控制不佳的2型糖尿病患者,比较二甲双胍缓释片分别联合格列喹酮或阿卡波糖治疗的疗效和安全性.方法 选取符合研究方案的2型糖尿病患者140例,男74例,女66例,平均年龄(56±10)岁,随机分为二甲双胍(1500 mg/d)+格列喹酮(初始剂量为30 mg,2次/d)组70例和二甲双胍(1500 mg/d)+阿卡波糖(初始剂量为50mg,2次/d)组70例,维持治疗14周.在基线和治疗结束时分别进行各项生化指标和胰岛素反应等检查.以糖化血红蛋白(HbA1c)是否达标为因变量,调整年龄、性别、糖尿病病程、基线时β胰岛功能和体重指数、治疗分组后,进行Logistic多元逐步回归分析.结果 (1)经14周治疗后,两组HbA1c均较治疗前显著下降,格列喹酮组为(7.4±1.1)%,阿卡波糖组为(7.8±1.1)%,格列喹酮组下降幅度更大,平均HbA1c下降1.7%(t=-4.404,P=0.0001),差异有统计学意义.HbA1c<6.5%的达标率在格列喹酮组有高于阿卡波糖组趋势(25.71%比12.86%,χ2=3.72,P=0.054).(2)两组胰岛素抵抗指数均较各自治疗前显著下降,但两组间比较无显著差异.二甲双胍+格列喹酮组在治疗过程中无严重低血糖事件或其他严重不良事件发生,患者耐受件良好.结论 格列喹酮在单药和(或)联合治疗失败的2型糖尿病中与二甲双胍联合治疗能有效降低2型糖尿病患者血糖,在HbA1c达标率较高的同时安全性较好.     

Efficacy and safety of acarbose in the treatment of Type 1 diabetes mellitus: a placebo-controlled, double-blind, multicentre study.

AIMS: The aim of the study was to evaluate the efficacy and safety of acarbose in patients with Type 1 diabetes mellitus (DM). METHODS: A multicentre double-blind, randomized, placebo-controlled study was performed. After a 6-week run-in, 121 patients were randomized to acarbose or placebo and to high- or low-fibre diet for 24 weeks. Acarbose dose was 50 mg t.d.s. for the first 2 weeks and 100 mg t.d.s. for the subsequent weeks. RESULTS: At the end of 24 weeks of treatment the intention to treat analysis showed that acarbose compared with placebo decreased 2 h postprandial plasma glucose levels (12.23 +/- 0.83 vs. 14.93 +/- 0.87 mmol/l; F = 6.1, P < 0.02) (least square means +/- SEM). No significant effect of acarbose was recorded on HbA1c or on the number of hypoglycaemic episodes. The effect of acarbose on blood glucose control was not influenced by the amount of carbohydrate and/or fibre intake. The incidence of adverse events were 75% and 39% in acarbose and placebo groups, respectively; they were mild and confined to the gastrointestinal tract. CONCLUSIONS: The use of acarbose in combination with insulin reduces postprandial plasma glucose levels in Type 1 diabetic patients who are not satisfactorily controlled with insulin alone but without significant effect on HbA1c.     

老年2型糖尿病患者动态血糖监测分析

目的 探讨老年2型糖尿病患者的动态血糖波动特点.方法 对老年2型糖尿病患者(老年组)92例和中青年2型糖尿病患者(中青年组)58例进行动态血糖监测,对比分析两组患者血糖谱特征及老年不同糖化血红蛋白(HbA1c)水平糖尿病患者的血糖谱特征.结果 (1)老年组与中青年组比较,血糖波动系数(BGFC)增大[(2.68±1.00)mmol/L对(2.12±0.74) mmol/L,t=-3.691,P＜0.001];餐后血糖漂移幅度(PPGE)增大,早餐后分别为 ( 5.96±2.47) mmol/L对(5.11±2.44) mmol/L(t=-2.058,P＜0.05),晚餐后分别为(5.17±2.15) mmol/L对 (4.16±2.28) mmol/L(t=-2.730,P＜0.01);餐后血糖达峰时间延长,早餐后(112.5±29.7) min对(97.0±27.2) min(t=-3.225,P＜0.01),中餐后(140.0±39.7)min对 (118.1±42.6) min(t=-3.195,P＜0.01);低血糖发生频率增加(26.3%对5.5%,P＜0.05);最大血糖漂移幅度(LAGE)增大,分别为(9.66±2.48) mmol/L对(8.40±3.13) mmol/L(t=-2.720,P＜0.01);(2)老年组患者随HbA1c下降,低血糖发生率增加(P＜0.05);随 HbA1c升高,血糖波动幅度增大;(3)HbA1c与空腹血糖(FBG)、日平均血糖(MBG)、高血糖时间比(PT7.8、PT11.1)、最低血糖(LBG)、最高血糖(HBG)、BGFC、PPGE、LAGE均正相关(r=0.899～0.289,均P＜0.001);逐步回归分析显示,MBG、FBG、PT7.8与HbA1c独立相关(校正的R2=0.807,P＜0.05).结论 老年2型糖尿病患者血糖波动幅度大,易发生餐后高血糖和夜间低血糖,动态血糖监测能较详细地显示患者的血糖水平及波动特征.

Abstract：

Objective To investigate the characteristics of the blood glucose fluctuation in elderly patients with type 2 diabetes mellitus (T2DM). Methods The 92 elderly patients with T2DM (the elderly group) and 58 young and middle-aged patients with T2DM (the non-elderly group) were monitored using the continuous glucose monitoring system(CGMS). The characteristics of glucose profiles of the two different age groups, and of the different glycosylated hemoglobin (HbA1c) level groups in the elderly were comparatively analyzed. Results (1)There was no significant difference in HbA1c level between the elderly group and the non-elderly group. Compared with the non-elderly group, the elderly group showed the increases in blood glucose fluctuant coefficient [BGFC, (2.68±1.00) mmol/L vs. (2.12±0.74) mmol/L, t=-3.691, P＜0.001], in postprandial glucose excursion (PPGE) of breakfast and supper [(5.96±2.47) mmol/L vs. (5.11±2.44) mmol/L, t=-2.058, P＜0.05; (5.17±2.15) mmol/L vs. (4.16±2.28) mmol/L, t=-2.730, P＜0.01], in the time to postprandial glucose peak of breakfast and lunch [(112.5±29.7) min vs. (97.0±27.2) min, t=-3.225, P＜0.01; (140.0±39.7) min vs. (118.1±42.6) min, t=-3.195, P＜0.01], in the frequency of hypoglycemia (26.3% vs. 5.5%, P＜0.05), and showed the largest amplitude of glycemic excursions [LAGE, (9.66±2.48) mmol/L vs.(8.40±3.13) mmol/L, t=-2.720, P＜0.01]. (2)In the elderly, along with decreased HbA1c, the incidence of hypoglycaemia increased (P＜0.05); And along with increased HbA1c, the amplitude of blood glucose fluctuation increased. There were significant differences in BGFC, PPGE of breakfast and lunch, and LAGE among different HbA1c level groups (P＜0.01, P＜0.05, P＜0.05, P＜0.001). (3)HbA1c was positively correlated with FBG, mean blood glucose (MBG), percentage of time at glycemia (PT7.8, PT11.1), the lowest blood glucose (LBG), the highest blood glucose (HBG), BGFC, PPGE and LAGE (r=0.899-0.289, all P＜0.001). Multiple stepwise regression analysis indicated that MBG, FBG and PT7.8 was the independent influential factor of HbA1c (adjusted R2=0.807, P＜0.05). Conclusions The elderly patients with T2DM are at a particularly high risk for postprandial hyperglycemia and nocturnal hypoglycemic episodes, CGMS could show glucose fluctuation characters of T2DM patients diurnally, and provide a clinical basis for reasonable therapy.     

阿卡波糖治疗在日常临床工作中的有效性、安全性和被接受程度——对中国2型糖尿病患者的阿卡波糖上市后监测

此项上市后监测的目的是为了评价中国的2型糖尿病患者日常实际使用阿卡波糖的有效性、安全性和接受程度。中国共有231位临床医师招募了2480例2型糖尿病患者参加了本次开放性、前瞻性，非对照、非随机的多中心研究。主要的疗效参数是阿卡波糖治疗后空腹和餐后血糖水平的变化以及HbA1c水平的变化。大部分患者入组之前曾接受其他口服降糖药或胰岛素的治疗，并且在平均为13．5周的观察期内接受了降糖药物联合治疗。大部分患者阿卡波糖的起始剂量为50mg，3次／日。在整个研究期间，阿卡波糖使空腹血糖浓度下降了56．1mg／d（18mg／d葡萄糖=1mmol／L葡萄糖），餐后2h血糖下降了111．3mg／d，HbA。c下降了1．9％，体重下降0．9kg。研究期间出现了76次阿卡波糖相关的不良事件，两例患者出现严重不良事件。主治医师对90．1％的患者做出“非常好”或“较好”的评价，患者对阿卡波糖的耐受性为89．1％，接受程度为87．1％。无论作为单药治疗还是和其他降糖药物合用，每天常规使用阿卡波糖对于中国的2型糖尿病患者是有效、安全和接受程度较好的。     

Effect of dapagliflozin in patients with type 2 diabetes who have inadequate glycaemic control with glimepiride: a randomized, 24-week, double-blind, placebo-controlled trial

Aims: Progressive deterioration of glycaemic control in type 2 diabetes mellitus (T2DM) often requires treatment intensification. Dapagliflozin increases urinary glucose excretion by selective inhibition of renal sodium‐glucose cotransporter 2 (SGLT2). We assessed the efficacy, safety and tolerability of dapagliflozin added to glimepiride in patients with uncontrolled T2DM. Methods: This 24‐week, randomized, double‐blind, placebo‐controlled, parallel‐group, international, multicentre trial (ClinicalTrials.gov NCT00680745) enrolled patients with uncontrolled T2DM [haemoglobin A1c (HbA1c) 7–10%] receiving sulphonylurea monotherapy. Adult patients (n = 597) were randomly assigned to placebo or dapagliflozin (2.5, 5 or 10 mg/day) added to open‐label glimepiride 4 mg/day for 24 weeks. Primary endpoint was HbA1c mean change from baseline at 24 weeks. Secondary endpoints included change in body weight and other glycaemic parameters. Results: At 24 weeks, HbA1c adjusted mean changes from baseline for placebo versus dapagliflozin 2.5/5/10 mg groups were ?0.13 versus ?0.58, ?0.63, ?0.82%, respectively (all p < 0.0001 vs. placebo by Dunnett's procedure). Corresponding body weight and fasting plasma glucose values were ?0.72, ?1.18, ?1.56, ?2.26 kg and ?0.11, ?0.93, ?1.18, ?1.58 mmol/l, respectively. In placebo versus dapagliflozin groups, serious adverse events were 4.8 versus 6.0–7.1%; hypoglycaemic events 4.8 versus 7.1–7.9%; events suggestive of genital infection 0.7 versus 3.9–6.6%; and events suggestive of urinary tract infection 6.2 versus 3.9–6.9%. No kidney infections were reported. Conclusions: Dapagliflozin added to glimepiride in patients with T2DM uncontrolled on sulphonylurea monotherapy significantly improved HbA1c, reduced weight and was generally well tolerated, although events suggestive of genital infections were reported more often in patients receiving dapagliflozin.