利格列汀对老年2型糖尿病患者轻度认知功能障碍的影响及机制研究

Effect and its mechanism of Linagliptin on mild cognitive impairment in elderly type 2 diabetes mellitus patients

目的探讨利格列汀对2型糖尿病（T2DM）患者轻度认知功能障碍（MCI）的影响及可能机制。方法前瞻性研究，应用蒙特利尔认知评估量表（MoCA）对2016年12月至2017年6月就诊于我院的T2DM患者进行认知功能筛查，选取98例老年T2DMMCI患者，随机数字表法分为利格列汀药物组（利格列汀±二甲双胍）50例和非利格列汀药物组（格列奇特±二甲双胍）48例，于用药前和用药24周后分别比较MoCA评分、空腹血糖、糖化血红蛋白、血脂、血清β淀粉样蛋白（Aβ）1—42含量，稳态模型评估胰岛素抵抗指数（HOMA—IR）。结果利格列汀组干预24周后与治疗前比较，空腹血糖[（7．29±1．00）mmol／L比（9．16±1．60）mmol／L，P〈0．05]，糖化血红蛋白[（7．19±0．99）％比（9．36±1．07）％，P〈0．05]、HOMA-IR[（3．05±1．12）比（4．05±1．30），P〈0．05]、Aβ1—42[（0．463±0．093）g／L比（0．528±0．110）g／L，P〈0．05]均降低；MoCA评分[（24．48±1．18）分比（23．22±1．37）分，P〈0．05]提高。非利格列汀组干预24周后与治疗前比较，空腹血糖、糖化血红蛋白均降低（P〈0．05）；HOMA—IR、Aβ1～42差异无统计学意义（P〉0．05）。利格列汀组干预24周后与非利格列汀组干预24周后比较，HOMA-IR、Aβ1—42降低（P〈0．05），MoCA评分提高，差异有统计学意义（P〈0．05）。结论利格列汀可改善老年T2DM患者认知功能，可能与其降低血清AB含量及改善胰岛素抵抗有关。DDP-4酶抑制剂可能是将来治疗糖尿病患者认知功能障碍的理想药物。

Objective To investigate the effect and its underlying mechanism of Linagliptin on mild cognitive impairment（MCI）in elderly type 2 diabetes mellitus （T2DM） patients. Methods Montreal Cognitive Assessment （MoCA）scale was used to prospectively screen T2DM patients for MCI in our hospital from December 2016 to June 2017,and a total of 98 elderly T2DM patients with MCI were recruited. They were randomly divided into the linagliptin group（Linagliptin ＋ metformin, n=50）and the non-linagliptin group （gliclazide ＋ metformin, n = 48）. Serum fasting plasma glucose （FPG）, glycosylated hemoglobin（ HbAle）, blood lipids and amyloid Q-protein 1-42 （Aβ1-42）levels were determined, and MoCA score and homeostasis model assessment of insulin resistance（HOMA-IR）were calculated,and were compared between the two groups before and after 24 weeks of treatment. Results In the linagliptin group, serum FPG, HbAlc, HOMA-IR, Aβ1-42 levels were significantly decreased and MoCA score was increased after 24 weeks of treatment as compared with pre-treatment [（7.29±1.00）mmol/Lvs. （9.16±1.60）mmol/L,（7.19±0.99）% vs. （9.36±1.07）%,（3.05± 1.12） vs. （4. 05±1.30） ,（0. 463±0. 093）g/L vs. （0. 528±0. 110）g/L, （24.48±1.18） vs. （23.22± 1.37） ,all P〈0.05]. In the non-linagliptin group as control, FPG and HbAlc levels were decreased after 24 weeks of treatment as compared with pre-treatment[（7.23 ± 1.09）mmol/L vs. （9.20± 1.75） mmol/L,（7.23± 1.03）M vs. （9.69±1.18）],both P〈0. 05],while there was no significant difference in HOMA-IR,Aβ1-42 level and MoCA score[（3. 95± 1.00） vs. （4. 19± 1.13）, （0. 517± 0. 113）g/L vs. （0. 526±0. 119）g/L,（23.21±1.18） vs. （23. 00±1.32）,all P〉0.05]. It is worth to pay close attention to the key discovery of this paper that HOMA-IR and Aβ1-42 levels were significantly lower and MoCA score was significantly higher in the linagliptin group than in the non-linagliptin group after 24 weeks of treatment（all P〈0.05）. Conclusions Linagliptin as one of DPP- 4 enzyme inhibitors can improve the cognitive function in elderly patients with T2DM,which might be relevant to reducing serum Aβ level and improving HOMA-IR. DPP-4 enzyme inhibitor may be a good option for treatment of mild cognitive dysfunction in T2DM patients in the future.