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

Abstract

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(HbAlc), blood lipids and amyloid β-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, HbA1c, 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/L vs.(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]. 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. Key words: Diabetes mellitus, type 2; Cognitive impairment; Linagliptin; Amyloid β-protein