利拉鲁肽和门冬胰岛素30对超重和肥胖2型糖尿病患者的疗效和安全性比较

目的比较人胰高糖素样肽-1（GLP-1）类似物利拉鲁肽和门冬胰岛素30与二甲双胍联合应用对超重和肥胖2型糖尿病患者的疗效和安全性。方法选取2012年3月1013至2012年6月2013住院的体质指数（BMI）〉25kg／m^2的2型糖尿病患者109例,按随机数字表法分为利拉鲁肽治疗组和门冬胰岛素30治疗组。其中利拉鲁肽治疗组52例,给予利拉鲁肽联合二甲双胍治疗,门冬胰岛素30治疗组57例,给予门冬胰岛素30联合二甲双胍治疗共24周,于用药前、用药4、12、24周后分别测定患者的空腹血糖（FPG）、餐后2h血糖（PPG）、糖化血红蛋白（HbAlc）、体重、腰围、血压、甘油三酯（TG）、总胆固醇（TC）、高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇（LDL-C）、肝功能、肾功能、C反应蛋白（CRP）、24h尿微量白蛋白（UMA）,记录用药期间低血糖发生情况和其他不良反应。采用t检验和重复测量资料方差分析进行数据分析。结果两组患者治疗3d后血糖均开始下降,24周后利拉鲁肽组和门冬胰岛素30组FPG分别下降（2．9±1．3）、（3．5±1．2）mmol／L（t=-3．2,P〈0．01）;PPG分别下降（4．2±3．7）、（4．5±2．8）mmol／L（t=-0．83,P〉0．05）;HbAlC分别下降（1．7±0．6）％、（1．9±0．8）％（t=-0．6,P〉0．05）。利拉鲁肽组体重下降（4．2±2．7）kg,门冬胰岛素30组体重增加（1．2±1．7）kg（t=-3．7,P〈0．05）。两组收缩压分别下降（5．2±4．4）、（1．8±2．3）mmHg（1mmHg=0．133kPa）（t=4．9,P〈0．01）。两组间舒张压差异无统计学意义。两组患者均出现TG、TC、LDL．C降低和HDL-C升高,但是组问差异均无统计学意义（均P〉0．05）。利拉鲁肽组比门冬胰岛素30组低血糖发生率低,但是两组间差异无统计学意义（3．8％比14．0％,t=-1．51,P〉0．05）。利拉鲁肽组患者的胃肠道不良反应多于门冬胰岛素30组,差异具有统计学意义（46．2％比1．8％,t=2．00,P〈0．05）。结论对超重和肥胖2型糖尿病患者,利拉鲁肽联合二甲双胍与门冬胰岛素30联合二甲双胍降糖效果相当,而利拉鲁肽能够更有效地降低患者体重和血压,同时具有良好的安全性。     

利拉鲁肽治疗肥胖2型糖尿病患者临床观察

目的应用利拉鲁肽治疗肥胖T2DM患者,观察有效性及安全性。方法应用二甲双胍或二甲双胍＋胰岛素血糖仍控制不佳的肥胖T2DM患者,加用利拉鲁肽0．6～1．2mg／d,观察3个月,比较治疗前后FPG、2hPG、HBAlC-、BMI、C肽的变化。观察并记录不良反应。结果治疗后患者上述指标均比治疗前有所下降,C肽水平有所恢复,对比差异有统计学意义（P〈0．01）,应用胰岛素的患者胰岛素用量均有不同程度减少,部分患者停用胰岛素。部分患者出现一过性恶心症状。无严重低血糖发生。结论胰岛功能轻度受损的肥胖T2DM患者应用利拉鲁肽治疗不仅可以良好的控制血糖、减少血糖的波动、减少胰岛素用量,而且能够改善患者BMI。     

荷芪散治疗痰瘀互结证2型糖尿病合并冠心病的临床疗效及对血清TMAO水平的影响

[目的]观察荷芪散治疗痰瘀互结证2型糖尿病(T2DM)合并冠心病(CHD)的临床疗效及其对血清氧化三甲胺(TMAO)水平的影响.[方法]将40例痰瘀互结证T2DM合并CHD患者随机分为观察组和对照组,每组各20例.2组患者均给予降压、调脂及抗血小板聚集等西医基础治疗,在此基础上,对照组给予利拉鲁肽治疗,观察组在对照组的...     

胰高血糖素样肽-1类似物药物的研究进展

目的介绍胰高血糖素样肽-1（GLP-1）及其类似物药物在2型糖尿病治疗中的应用。方法通过归纳总结近年来国内外相关文献,介绍了GLP-1的序列结构及其生理功能,并对其类似物药物（如Exendin-4,Liraglutide等）的临床应用或研发进展,以及它们目前在临床应用上的缺陷及相应的修饰或改造途径进行了阐述。结果与结论与现有药物比较,GLP-1及其类似物药物对2型糖尿病有着显著的疗效,在糖尿病治疗领域有广泛的应用前景。     

Extrinsic compression of pancreactic duct by intragastric balloon treatment and its potential to cause acute pancreatitis: two case reports and clinical discussion

We describe two cases of increased pancreatic enzyme levels after intragastric balloon (IGB) placement possibly related to extrinsic pancreatic duct compression, followed by a short review of the literature.Case 1 is the first, to our knowledge, of a patient with asymptomatic increase of pancreatic enzymes due to pancreatic duct compression, with unknown clinical significance. We hypothesize that this finding maybe can be relatively common in IGB users and almost certainly an important risk factor for the development of acute pancreatitis (AP). On the other hand, case 2 reports an AP that occurred one day after IGB placement, presented with nausea and vomiting, making AP a differential diagnosis of initial IGB intolerance.     

利拉鲁肽应用于2型糖尿病合并非酒精性脂肪肝患者的疗效及安全性分析

目的 观察利拉鲁肽治疗2型糖尿病合并非酒精性脂肪肝患者的疗效和安全性.方法 随机选择40例符合诊断标准的2型糖尿病合并NAFLD患者,口服二甲双胍,每天2次,每次1g,疗程12周,同时给予利拉鲁肽,初始剂量0.6mg,1次/d,睡前皮下注射,疗程12周.第2周调整剂量为1.2 mg/d,第3周调整为1.8 mg/d,若不能耐受则维持0.6 mg/d,症状缓解再按上述原则加量.若为非初诊治疗的患者,在纳入前停服其他药物(二甲双胍除外).比较治疗前后体重、体质指数(BMI)、空腹血糖(FPG)、餐后2h血糖(2hPG)、糖化血红蛋白(HbA1c),以及肝功指标:谷丙转氨酶(ALT)、谷草转氨酶(AST)、谷氨酰转肽酶(GGT),脂代谢及其他指标:总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C),高密度脂蛋白胆固醇(HDL-C),血尿酸(UA),同时观察用药期间有无不良反应.结果 患者体重、BMI、FPG、2hPG、HbA1c均较治疗前下降(P ＜0.05);ALT、AST、GGT及SUA均较治疗前下降(P＜0.05);治疗后血脂水平(低密度脂蛋白、甘油三酯、总胆固醇)较治疗前降低,差异有统计学意义(P＜0.05).治疗过程中无低血糖及其他严重的不良反应.结论 利拉鲁肽治疗2型糖尿病合并NAFLD患者,可有效安全降糖,改善肝功能,同时调脂并降低体重.     

Protective effects of liraglutide on renal tissues and related mechanism in diabetic rats

Objective To explore the effects of glucagon-like peptide-1 (GLP-1) analogues liraglutide on renal tissues of diabetic rats and its mechanism. Methods Forty male SD rats were randomly divided into four groups: normal control rats (NC group), normal control rats with liraglutide treatment (NCL group), diabetic rats (DM group) and diabetic rats with liraglutide treatment. The body weight, glycosylated hemoglobin (HbA1c), albuminuria/creatinine (A/C), kidney index (KI, kidney mass/body mass) were detected after 8 weeks treatment. The gene expression of tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6), interleukin-1β (IL-1β), monocyte chemotactic protein-1 (MCP-1), type IV collagen, and transforming growth factor-β1 (TGF-β1) were measured by real time PCR. The protein expression of COL-Ⅳ, NF-κB, GLP-1R and phosphorylation levels of ERK, JNK and p38MAPK were evaluated by Western blotting. Results Compared to NC group, the body weight in DM group was reduced, and HbA1c, KI, A/C levels were significantly increased (P＜0.05). The gene expression of TNF-α, IL-6, IL-1β, MCP-1, TGF-β1 and COL- IV was increased (P＜0.05). Moreover, the protein expression of NF-κB in the nucleus of the kidney tissues and the phosphorylation levels of ERK, JNK and p38MAPK were significantly increased in DM group, accompanied by the decline of GLP-1R protein level (P＜0.05). After 8 weeks of liraglutide treatment, the urinary protein excretion was reduced, and the gene expressions of TNF-α, IL-6, IL-1β, MCP-1, TGF-β1, COL-IV were inhibited. Importantly, the phosphorylation levels of ERK and JNK were significantly inhibited and the expression of NF-κB protein in the nucleus of the kidney tissue was reduced (P＜0.05). These changes may be associated with the increased expression of GLP-1R after liraglutide treatment. However, blood glucose and the body weight in DML group rats had no significant changes after liraglutide treatment. Conclusion Liraglutide has a protective effect on renal tissues through inhibiting ERK and JNK phosphorylation and related inflammation in diabetic rats.     

利拉鲁肽早期干预对高脂饮食大鼠代谢的影响

目的观察利拉鲁肽早期干预对高脂喂养大鼠代谢的影响。方法雄性SD大鼠18只,随机均分为普通饲料（ND组）,高脂饲料（HFD组）,高脂+利拉鲁肽（Lira组）,Lira组高脂喂养同时给予利拉鲁肽200滋g/kg皮下注射18周。记录体重、进食量、葡萄糖耐量实验AUC、胰岛素钳夹实验葡萄糖输注率（GIR）,酶联免疫吸附法测血清TG、TC、胰高血糖素样肽-1（GLP-1）,染色观察肝脏病理、骨骼肌毛细血管密度。结果与ND组大鼠相比,HFD组大鼠体重、脂体比、AUC、TG、TC显著升高（均P＜0.05）,GIR、骨骼肌血管密度显著下降（均P＜0.05）,肝脂肪变明显;Lira组比HFD组摄食少且食物利用率低,血清GLP-1显著增加（均P＜0.05）;Lira组大鼠与ND组相比,体重、脂体比、血清TG、TC、AUC、GIR、骨骼肌血管密度均无统计学差异（均P＞0.05）。结论利拉鲁肽干预减少高脂喂养大鼠摄食量,降低食物利用率,控制体重,改善血脂代谢及肝细胞脂肪变性,保留高脂喂养大鼠的毛细血管密度,维持胰岛素敏感性且无低血糖等不良反应。