Val66Met single nucleotide polymorphism in brain-derived neurotrophic factor and physical activity might influence responsiveness to dipeptidyl peptidase-4 inhibitors in type 2 diabetes

Abstract

Exercise increases the levels of brain-derived neurotrophic factor (BDNF), which is beneficial in glucose metabolism. The combined effect of the single nucleotide polymorphism (SNP) in BDNF (rs6265; G to A, Val66Met) and physical activity (PA) on the effectiveness of dipeptidyl peptidase-4 inhibitors (DPP-4Is) was studied in 173 patients with type 2 diabetes. DPP-4I nonresponse was defined as less than 0.2% decrease in HbA1c level 3–4 months after treatment initiation. PA was retrospectively estimated using the International Physical Activity Questionnaire. In patients categorized according to the SNP status and the median PA level, the non-responder rates in the G/* with lower PA, G/^* with higher PA, A/A with lower PA, and A/A with higher PA groups were 40.0%, 26.3%, 18.2%, and 9.1%, respectively, in the entire cohort (p = 0.083), and 56.8%, 28.6%, 25.0%, and 20.0%, respectively, after the exclusion of metformin-treated patients (n = 99, p = 0.037). These findings were sustained in the multivariate model. PA seems more important for responsiveness to DPP-4Is in G/^* patients with activity-dependent BDNF secretion than in A/A patients who are expected to be defective in such secretion, but several limitations exist and further investigation is warranted to conclude this issue.