Tianpeng Zheng1, Hongbo Liu2, Linyuan Qin3, Bo Chen4, Xiaoxi Zhang5, Xueping Hu6, Liuping Xiao6, Shenghua Qin7. 1. Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Guilin Medical University, Guilin, Guangxi, PR China; Center of Diabetic Systems Medicine, Guilin Medical University, Guilin, Guangxi, PR China. Electronic address: w19831120@126.com. 2. Department of laboratory medicine, The Second Affiliated Hospital of Guilin Medical University, Guilin, Guangxi, PR China. 3. Department of Epidemiology and Health Statistics, Guilin Medical University, Guilin, Guangxi, PR China. 4. Research Center of Combined Traditional Chinese and Western Medicine, Affiliated Traditional Medicine Hospital of Southwest Medical University, Luzhou, Sichuan, PR China; Department of Human Anatomy, Southwest Medical University, Luzhou, Sichuan, PR China. 5. Center of Diabetic Systems Medicine, Guilin Medical University, Guilin, Guangxi, PR China. 6. Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Guilin Medical University, Guilin, Guangxi, PR China. 7. Medical Examination Center, Affiliated Hospital of Guilin Medical University, Guilin, Guangxi, PR China.
Abstract
OBJECTIVE: Increased dipeptidyl peptidase-4 (DPP4) activity and reduced brain-derived neurotrophic factor (BDNF) in peripheral circulation are both associated with a high risk of mild cognitive impairment (MCI) in the elderly. Hence, we aimed to investigate the association between plasma DPP4 activity to BDNF ratio (DBR) and MCI in elderly patients with type 2 diabetes. DESIGN AND METHODS: We measured plasma DPP4 activity, BDNF levels, oxidative stress parameters, inflammatory markers and calculated DBR in 1833 elderly type 2 diabetic patients aged 60 years or older. MCI was diagnosed according to the National Institute on Aging-Alzheimer's Association workgroups criteria. Further, mediation analysis was performed to estimate the mediator role of oxidative stress on the relationship between DPP4 activity and BDNF. RESULTS: DPP4 activity was negatively associated with BDNF (r = -0.408, P < 0.001). Oxidative stress, particularly in male participants, acted as a partial mediator in the relationship between DPP4 activity and BDNF. Participants in the highest quartile of DBR had higher nitrotyrosine, 8-isoPGF2a, interleukin-6, C-reactive protein and lower Montreal Cognitive Assessment score compared with those in the lowest quartile. The odds ratio (5.15, 95% CI 3.64-7.30) for MCI in the highest DBR quartile was significantly higher than in the lowest quartile. The risk for MCI increased with higher levels of DPP4 activity and lower levels of BDNF. CONCLUSIONS: Oxidative stress partially mediates the inverse relationship between DPP4 and BDNF. Our data provide evidence for a strong link between DBR and MCI, suggesting DBR to be a new biomarker for MCI in type 2 diabetic patients.
OBJECTIVE: Increased dipeptidyl peptidase-4 (DPP4) activity and reduced brain-derived neurotrophic factor (BDNF) in peripheral circulation are both associated with a high risk of mild cognitive impairment (MCI) in the elderly. Hence, we aimed to investigate the association between plasma DPP4 activity to BDNF ratio (DBR) and MCI in elderly patients with type 2 diabetes. DESIGN AND METHODS: We measured plasma DPP4 activity, BDNF levels, oxidative stress parameters, inflammatory markers and calculated DBR in 1833 elderly type 2 diabeticpatients aged 60 years or older. MCI was diagnosed according to the National Institute on Aging-Alzheimer's Association workgroups criteria. Further, mediation analysis was performed to estimate the mediator role of oxidative stress on the relationship between DPP4 activity and BDNF. RESULTS:DPP4 activity was negatively associated with BDNF (r = -0.408, P < 0.001). Oxidative stress, particularly in male participants, acted as a partial mediator in the relationship between DPP4 activity and BDNF. Participants in the highest quartile of DBR had higher nitrotyrosine, 8-isoPGF2a, interleukin-6, C-reactive protein and lower Montreal Cognitive Assessment score compared with those in the lowest quartile. The odds ratio (5.15, 95% CI 3.64-7.30) for MCI in the highest DBR quartile was significantly higher than in the lowest quartile. The risk for MCI increased with higher levels of DPP4 activity and lower levels of BDNF. CONCLUSIONS: Oxidative stress partially mediates the inverse relationship between DPP4 and BDNF. Our data provide evidence for a strong link between DBR and MCI, suggesting DBR to be a new biomarker for MCI in type 2 diabeticpatients.