Oxidative stress-mediated influence of plasma DPP4 activity to BDNF ratio on mild cognitive impairment in elderly type 2 diabetic patients: results from the GDMD study in 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  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.