Response to the dipeptidyl peptidase‐4 inhibitors in J apanese patients with type 2 diabetes might be associated with a diplotype of two single nucleotide polymorphisms on the interleukin‐6 promoter region under a certain level of physical activity

Aims/Introduction Muscle‐derived interleukin‐6 ( IL ‐6) has been reported to promote glucagon‐like peptide‐1 ( GLP ‐1) secretion, and we explored the association of single nucleotide polymorphisms ( SNP s) in the human IL ‐6 promoter region with the responsiveness to dipeptidyl peptidase‐4 inhibitors ( DPP ‐4Is), drugs that increase circulating GLP ‐1. Materials and Methods The present observational study enrolled Japanese patients with type 2 diabetes who took a DPP ‐4I over 3 months, and most of the clinical information was collected retrospectively. We defined non‐responders as those having less than a 0.2% decrease of the glycated hemoglobin level at 3 or 4 months after starting DPP ‐4I treatment. Physical activity was retrospectively estimated by the Japanese short version of I nternational P hysical A ctivity Q uestionnaire. Results We studied 316 patients whose physical activity corresponding to the season of the DPP ‐4I administration was estimated. The non‐responder rate was 29.7%. We analyzed rs1800796 and rs2097677, both are suggested to be functional in Japanese. Multivariate analysis for all patients showed that the adjusted odds ratio for the non‐responder risk of the diplotype rs1800796 G/*–rs2097677 A/* against C/C‐G/G ( OR _G*A*) was 0.445 ( P  = 0.068). When patients were stratified by the I nternational P hysical A ctivity Q uestionnaire into low ( n  = 149) and moderate/high ( n  = 167) activity groups, however, OR _G*A* in each group was 1.58 ( P  = 0.615) and 0.153 ( P  = 0.003), respectively. Conclusions The diplotype rs1800796 G/*–rs2097677 A/* might contribute to responsiveness to DPP ‐4Is in J apanese patients with type 2 diabetes under a certain level of physical activity. However, further investigation is warranted to confirm this.