Elevated autoantibodies against dipeptidyl peptidase-4 are associated with poor prognosis in patients with type 2 diabetes
Abstract
Dipeptidyl peptidase-4 (DPP4) is involved in immune regulation and metabolic homeostasis. Although DPP4 inhibitors are widely used in type 2 diabetes, the clinical relevance of autoantibodies against DPP4 (DPP4-Ab) remains unclear. In this study, we aimed to investigate the association between circulating DPP4-Ab levels and mortality in 274 patients with type 2 diabetes (mean age, 63 years). Serum DPP4-Ab levels were measured using amplified luminescent proximity homogeneous assay-linked immunosorbent assay (AlphaLISA), and survival was assessed using Kaplan-Meier analysis and Cox proportional hazards regression analysis. During a mean follow-up of approximately 5 years, 32 deaths had occurred. Patients with elevated DPP4-Ab titers (>1,676.8 alpha counts) had a higher mortality rate than those with low titers (22.2% vs. 9.3%, p = 0.0177). In Cox proportional hazards regression analysis, DPP4-Ab titers showed a trend toward association with all-cause mortality when analyzed as a continuous variable per 100 alpha counts (a.c.) increase (hazard ratio [HR], 1.042; 95% confidence interval [CI], 0.996-1.090; p = 0.071). When patients were stratified using the predefined cutoff value of 1,676.8 a.c., the high DPP4-Ab group showed significantly higher mortality risk than the low DPP4-Ab group (HR, 2.30; 95% CI, 1.09-4.84; p = 0.028). Addition of DPP4-Ab to an age-based model only slightly improved predictive discrimination. These findings suggest that elevated DPP4-Ab titers may be associated with mortality risk; however, this association should be interpreted cautiously and warrants further investigation as a potential adjunctive immunometabolic biomarker in type 2 diabetes.
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BibTeX
@article{yagihashi2026elevated,
title = {{Elevated autoantibodies against dipeptidyl peptidase-4 are associated with poor prognosis in patients with type 2 diabetes}},
author = {Takeshi Yagihashi and Takahide Hashimoto and Naoki Ohtake and Tokiko Okamoto and Bo-Shi Zhang and Yoichi Yoshida and Masaya Yamaga and Tomohiko Yoshida and Amika Kajiyama and Rikako Furukawa and Takaki Hiwasa and Minoru Takemoto},
journal = {Endocrine Journal},
year = {2026},
month = jul,
doi = {10.1507/endocrj.ej26-0170},
url = {https://www.jstage.jst.go.jp/article/endocrj/advpub/0/advpub_EJ26-0170/_article},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Elevated autoantibodies against dipeptidyl peptidase-4 are associated with poor prognosis in patients with type 2 diabetes
AU - Takeshi Yagihashi
AU - Takahide Hashimoto
AU - Naoki Ohtake
AU - Tokiko Okamoto
AU - Bo-Shi Zhang
AU - Yoichi Yoshida
AU - Masaya Yamaga
AU - Tomohiko Yoshida
AU - Amika Kajiyama
AU - Rikako Furukawa
AU - Takaki Hiwasa
AU - Minoru Takemoto
PY - 2026
DA - 2026/07/22
JO - Endocrine Journal
DO - 10.1507/endocrj.ej26-0170
UR - https://www.jstage.jst.go.jp/article/endocrj/advpub/0/advpub_EJ26-0170/_article
AB - Dipeptidyl peptidase-4 (DPP4) is involved in immune regulation and metabolic homeostasis. Although DPP4 inhibitors are widely used in type 2 diabetes, the clinical relevance of autoantibodies against DPP4 (DPP4-Ab) remains unclear. In this study, we aimed to investigate the association between circulating DPP4-Ab levels and mortality in 274 patients with type 2 diabetes (mean age, 63 years). Serum DPP4-Ab levels were measured using amplified luminescent proximity homogeneous assay-linked immunosorbent assay (AlphaLISA), and survival was assessed using Kaplan-Meier analysis and Cox proportional hazards regression analysis. During a mean follow-up of approximately 5 years, 32 deaths had occurred. Patients with elevated DPP4-Ab titers (>1,676.8 alpha counts) had a higher mortality rate than those with low titers (22.2% vs. 9.3%, p = 0.0177). In Cox proportional hazards regression analysis, DPP4-Ab titers showed a trend toward association with all-cause mortality when analyzed as a continuous variable per 100 alpha counts (a.c.) increase (hazard ratio [HR], 1.042; 95% confidence interval [CI], 0.996-1.090; p = 0.071). When patients were stratified using the predefined cutoff value of 1,676.8 a.c., the high DPP4-Ab group showed significantly higher mortality risk than the low DPP4-Ab group (HR, 2.30; 95% CI, 1.09-4.84; p = 0.028). Addition of DPP4-Ab to an age-based model only slightly improved predictive discrimination. These findings suggest that elevated DPP4-Ab titers may be associated with mortality risk; however, this association should be interpreted cautiously and warrants further investigation as a potential adjunctive immunometabolic biomarker in type 2 diabetes.
SN - 1348-4540
SN - 0918-8959
ER -