title: Response to the dipeptidyl peptidase-4 inhibitors in Japanese 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.
abstract: OBJECTIVE
  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 (SNPs) in the human IL-6 promoter region with the responsiveness to dipeptidyl peptidase-4 inhibitors (DPP-4Is), drugs that increase circulating GLP-1.
  
  
  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 International Physical Activity Questionnaire.
  
  
  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 International Physical Activity Questionnaire 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 Japanese patients with type 2 diabetes under a certain level of physical activity. However, further investigation is warranted to confirm this.
authors: Division of Diabetes and Metabolism, Department of Internal Medicine, Iwate Medical University Morioka, Japan.
authors: Mizue
authors: M
authors: Matsui
authors: Division of Diabetes and Metabolism, Department of Internal Medicine, Iwate Medical University Morioka, Japan.
authors: Yoshihiko
authors: Y
authors: Takahashi
authors: Division of Diabetes and Metabolism, Department of Internal Medicine, Iwate Medical University Morioka, Japan.
authors: Noriko
authors: N
authors: Takebe
authors: Division of Diabetes and Metabolism, Department of Internal Medicine, Iwate Medical University Morioka, Japan.
authors: Kazuma
authors: K
authors: Takahashi
authors: Division of Diabetes and Metabolism, Department of Internal Medicine, Iwate Medical University Morioka, Japan.
authors: Kan
authors: K
authors: Nagasawa
authors: Division of Diabetes and Metabolism, Department of Internal Medicine, Iwate Medical University Morioka, Japan.
authors: Hiroyuki
authors: H
authors: Honma
authors: Division of Diabetes and Metabolism, Department of Internal Medicine, Iwate Medical University Morioka, Japan.
authors: Tomoyasu
authors: T
authors: Oda
authors: Division of Diabetes and Metabolism, Department of Internal Medicine, Iwate Medical University Morioka, Japan.
authors: Mitsutaka
authors: M
authors: Ono
authors: Division of Diabetes and Metabolism, Department of Internal Medicine, Iwate Medical University Morioka, Japan.
authors: Riyuki
authors: R
authors: Nakagawa
authors: Division of Diabetes and Metabolism, Department of Internal Medicine, Iwate Medical University Morioka, Japan.
authors: Takayoshi
authors: T
authors: Sasai
authors: Division of Diabetes and Metabolism, Department of Internal Medicine, Iwate Medical University Morioka, Japan.
authors: Hirobumi
authors: H
authors: Togashi
authors: Division of Diabetes and Metabolism, Department of Internal Medicine, Iwate Medical University Morioka, Japan.
authors: Mari
authors: M
authors: Hangai
authors: Division of Diabetes and Metabolism, Department of Internal Medicine, Iwate Medical University Morioka, Japan.
authors: Takashi
authors: T
authors: Kajiwara
authors: Division of Diabetes and Metabolism, Department of Internal Medicine, Iwate Medical University Morioka, Japan.
authors: Haruhito
authors: H
authors: Taneichi
authors: Division of Diabetes and Metabolism, Department of Internal Medicine, Iwate Medical University Morioka, Japan.
authors: Yasushi
authors: Y
authors: Ishigaki
authors: Division of Diabetes and Metabolism, Department of Internal Medicine, Iwate Medical University Morioka, Japan.
authors: Jo
authors: J
authors: Satoh
keywords: Glucagon-like peptide-1; Interleukin-6; Single nucleotide polymorphism