利拉鲁肽对2型糖尿病患者认知功能的影响及可能机制

Effects of liraglutide on the cognitive function in patients with type 2 diabetes mellitus and the underlying mechanism

目的 探讨利拉鲁肽对2型糖尿病患者认知功能的影响及可能机制.方法 应用蒙特利尔认知评估量表对2012年11月至2013年5月就诊于我院的2型糖尿病患者进行认知筛查,将认知障碍者分为利拉鲁肽组和非利拉鲁肽药物组,利拉鲁肽组：每日1次早餐前皮下注射,起始剂量为0.6 mg,治疗1周后,增加至1.2 mg,最大剂量可加用至1.8 mg.非利拉鲁肽组应用胰岛素、二甲双胍、阿卡波糖、磺脲类.12周后比较两组认知能力、血清β淀粉样蛋白（Aβ）含量、血糖、血脂、体重等变化.应用x2或t检验及多因素相关分析进行统计学分析.结果 利拉鲁肽组有44.2％（19/43）的患者认知功能得到改善,总体MoCA评分由（23.0±1.9）分,提高到（25.1±2.0）分,其中有19例治疗后评分达到（27.0±0.8）分,差异有统计学意义（t =8.975,P＜0.05）.而非利拉鲁肽组却仅有2.6％ （1/39）的患者认知功能得到改善,总体MoCA评分治疗前为（23.2±1.7）分,治疗后为（23.2±1.5）分,差异无统计学意义（t=0.09,P＞0.05）.利拉鲁肽组血清Aβ含量由（266±98） ng/L降至治疗后的（256±96） ng/L,体重则由（83±12） kg降至（80±11）kg,差异有统计学意义（t值分别为-2.76、-2.89,均P＜0.01）.非利拉鲁肽组Aβ含量升高而体重变化不明显.相关分析表明认知功能改善与利拉鲁肽的应用、体重减轻及Aβ减少相关（r=0.57、-0.42、-0.28,均P＜0.05）,而与血糖、糖化血红蛋白、总胆固醇、甘油三酯、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇无相关性（r=-0.13 ～0.09,均P＞0.05）.结论 利拉鲁肽可改善2型糖尿病患者认知功能,可能与其降低血清Aβ含量及减轻体重有关.

Objective To investigate the effects of liraglutide on cognitive function in patients with type 2 diabetes mellitus and the underlying Mechanism.Methods The cognitive function of type 2 diabetics treated in our hospital from November 2012 to May 2013 was evaluated with Montreal Cognitive Assessment （MoCA score）.Subjects with cognitive dysfunction were screened out and divided into liraglutide group （LI group） or non-liraglutide group（NLI group）.Patients in LI group were received liraglutide for 12 weeks.Patients in NLI group were given non-liraglutide drugs （such as insulin,metformin,acarbose,sulfonylureas,etc） for 12 weeks.The levels of serum Aβ,fasting plasma glucose,glycosylated hemoglobin,blood lipids,body weight were measured,and the cognitive function was evaluated again.The x2 test or t text and the multiple factor correlation analysis were used for statistical analysis.Results In LI group,the cognitive function was improved in 44.2％ （19/43） of patients.The overall MoCA score of （23.0 ± 1.9） points rised up to （25.1 ±2.0） points.There were 19 cases in LI group whose post-treatment score reached （27.0 ± 0.8） points.The difference was statistically significant（t =8.975,P ＜ 0.05）.Only 2.6％ （1/39）of patients in NLI group had better cognitive function,and the overall MoCA score was （23.2 ± 1.7） points before treatment,while （23.2 ± 1.5） points after treatment （t =0.09,P ＞ 0.05）.In LI group,Serum Aβ levels reduced from （266 ±98） ng/L to （256 ±96） ng/L,the body weight reduced from （83 ± 12） kg to （80 ± 11） kg.The difference was statistically significant （t =-2.76,-2.89,all P ＜ 0.01）.While Aβ levels increased and body weight did not change significantly in NLI group.Correlation analysis showed that the improved cognitive function was relevant to the application of liraglutide （r =0.57,P ＜ 0.05）,weight loss （r =-0.42,P ＜ 0.05） and Aβ decrease （r =-0.28,P ＜ 0.05）.Conclusion Liraglutide could improve the cognitive ability of type 2 diabetes patients and its mechanism might be relevant to the reduction of serum Aβ level and body weight.