Association Between Exercise and Brain-Derived Neurotrophic Factor (BDNF) Levels in Diabetes Mellitus: A Systematic Review and Meta-Analysis.

Abstract

Background: Diabetes mellitus (DM) is a metabolic disorder characterized by a consistently elevated blood sugar level. DM poses a major risk factor for many neurodegenerative diseases, causing a decline in cognitive function. BDNF (brain-derived neurotrophic factor) is a neurotrophin in the central and peripheral nervous systems that plays a crucial role in the development of brain circuits. Hence, disturbance in levels of BDNF is linked to the occurrence of neurodegenerative diseases and cognitive decline in diabetic patients. Physical exercise has emerged as a nonpharmacological intervention in elevating BDNF levels. Our systematic review and meta-analysis evaluate the relationship between a globally affecting metabolic disorder, diabetes, with decreased BDNF levels, and explore exercise as a promising potential intervention.

Methods: After screening 37 articles, 4 studies have been included in the systematic review and meta-analysis, out of which 3 of them are randomized controlled trials (RCTs), and 1 is a crossover trial. The search was conducted on PubMed (MEDLINE), ScienceDirect, Embase, Scopus, and Cochrane Central databases from inception to June 2025. PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines were followed to conduct a systematic review. Cochrane risk-of-bias tool was used to assess the quality of the studies. Data were pooled using a random effect model. The protocol for this systematic review was registered in PROSPERO.

Results: A total of 37 articles were screened, 3 RCTs and 1 crossover trial with 131 participants were included in the meta-analysis. Serum BDNF levels were higher in the exercise group compared with controls (MD = 73.50; p = 0.05). A small reduction in body fat percentage in the exercise group compared with the control was found (MD = -1.24%; p = 0.17), which was not statistically significant. Body weight and fasting blood glucose (FBG) showed no statistically significant differences between the exercise and control groups (MD = 0.97; p = 0.65), (MD = -27.20; p = 0.31). Moderate to high heterogeneity was noticed across the data analyzed.

Conclusion: This meta-analysis overall concludes that regular exercise positively affects serum BDNF levels in diabetics. However, the small number of trials and small sample sizes has limited the conclusions. Further large-scale RCTs are required to determine the long-term neurological effects of exercise in diabetics.