A Systematic Review and Meta-analysis of Association Between Brain-derived Neurotrophic Factor and Type 2 Diabetes and Glycemic Profile

Several epidemiologic studies have evaluated the relation between serum/plasma brain-derived neurotrophic factor (BDNF) levels and glycemic parameters, but the findings were conflicting. We performed a systematic review and meta-analysis to compare circulating BDNF levels in individuals with type 2 diabetes (T2D) or other glycemic disorders with healthy controls and to evaluate correlation between BDNF concentrations with glycemic profile. A systematic search up to July 2020 was conducted in reliable electronic databases (MEDLINE (Pubmed), EMBASE, Scopus) and Google scholar. Sixteen observational studies compared serum/plasma BDNF levels in diabetic patients (or individuals with glycemic disorders) vs. healthy controls or reported correlations between serum BDNF levels and glycemic parameters in adults were included in the review. Overall weighted mean difference (WMD) of circulating BDNF levels in 1306 patients with T2D (or other glycemic disorders) was 1.12 ng/mL lower than 1250 healthy subjects (WMD: - 1.12; 95%CI - 1.37, - 0.88, I = 98.7%, P < 0.001). Subgroup analysis revealed that both diabetic patients and subjects with other glycemic disorders had lower serum/plasma BDNF levels than healthy controls (WMD: - 1.74; 95%CI - 2.15, - 1.33 and WMD: - 0.49; 95%CI - 0.82, - 0.16, respectively). No significant correlation was found between BDNF levels and glycemic parameters [fasting blood glucose (FBG) (Fisher's Z = 0.05; 95%CI - 0.21, 0.11; n = 1400), homeostatic model assessment for insulin resistance (HOMA-IR) (Fisher's Z = 0.12; 95%CI - 0.20, 0.44; n = 732) and glycosylated hemoglobin (HbA1c) (Fisher's Z = 0.04; 95%CI - 0.05, 0.12; n = 2222)]. We found that diabetic patients and subjects with glycemic disorders had lower circulating BDNF levels than healthy controls. However, there was no significant correlation between BDNF concentrations and glycemic parameters including FBG, HOMA-IR and HbA1c. Further prospective investigations are required to confirm these findings.