Associations of stress hormones, autonomic function, and endothelial function in patients with diabetes

Abstract

Endothelial dysfunction is an early feature of diabetic vascular injury. Stress-induced activation of the hypothalamic–pituitary–adrenal (HPA) axis, together with autonomic imbalance, may contribute to endothelial dysfunction. However, its clinical relevance in diabetes remains to be fully elucidated. We retrospectively analyzed 60 patients with diabetes who underwent both flow-mediated dilation (FMD) of the brachial artery and the coefficient of variation of the R–R interval (CVRR) measurements. The primary objective was to examine the association between FMD and stress-related hormones, including adrenocorticotropic hormone (ACTH) and cortisol. The secondary objective was to evaluate the association with autonomic function (CVRR) and other clinical variables. Mean FMD was 5.10 ± 2.32%. FMD correlated inversely with ACTH (r = –0.41, p = 0.0015) and cortisol (r = –0.39, p = 0.0024), and positively with CVRR (r = 0.49, p < 0.001). These relationships were stronger in patients with BMI ≥27 kg/m2, among whom the correlation between FMD and ACTH was particularly pronounced (r = –0.68, p = 0.0007). No significant associations were found between FMD and hemoglobin A1c or other lipid parameters. Given the cross-sectional design, these findings indicated associations rather than causality. Our results suggest that the HPA axis activity and autonomic function may be associated with endothelial dysfunction in diabetes, particularly in individuals with a higher BMI. This study was registered in the UMIN Clinical Trials Registry (UMIN-CTR; UMIN000060540).

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BibTeX RIS

BibTeX

@article{saheki2026associations,
  title = {{Associations of stress hormones, autonomic function, and endothelial function in patients with diabetes}},
  author = {Takanobu Saheki and Keisuke Takahashi and Eri Harada and Takafumi Yoshimura and Toshihiro Kobayashi and Kensaku Fukunaga and Hitomi Imachi and Koji Murao},
  journal = {Endocrine Journal},
  year = {2026},
  month = oct,
  doi = {10.1507/endocrj.ej26-0067},
  url = {https://www.jstage.jst.go.jp/article/endocrj/73/10/73_EJ26-0067/_article},
  note = {CC BY-NC-ND},
}

RIS

TY  - JOUR
TI  - Associations of stress hormones, autonomic function, and endothelial function in patients with diabetes
AU  - Takanobu Saheki
AU  - Keisuke Takahashi
AU  - Eri Harada
AU  - Takafumi Yoshimura
AU  - Toshihiro Kobayashi
AU  - Kensaku Fukunaga
AU  - Hitomi Imachi
AU  - Koji Murao
PY  - 2026
DA  - 2026/10/01
JO  - Endocrine Journal
DO  - 10.1507/endocrj.ej26-0067
UR  - https://www.jstage.jst.go.jp/article/endocrj/73/10/73_EJ26-0067/_article
AB  - Endothelial dysfunction is an early feature of diabetic vascular injury. Stress-induced activation of the hypothalamic–pituitary–adrenal (HPA) axis, together with autonomic imbalance, may contribute to endothelial dysfunction. However, its clinical relevance in diabetes remains to be fully elucidated. We retrospectively analyzed 60 patients with diabetes who underwent both flow-mediated dilation (FMD) of the brachial artery and the coefficient of variation of the R–R interval (CVRR) measurements. The primary objective was to examine the association between FMD and stress-related hormones, including adrenocorticotropic hormone (ACTH) and cortisol. The secondary objective was to evaluate the association with autonomic function (CVRR) and other clinical variables. Mean FMD was 5.10 ± 2.32%. FMD correlated inversely with ACTH (r = –0.41, p = 0.0015) and cortisol (r = –0.39, p = 0.0024), and positively with CVRR (r = 0.49, p < 0.001). These relationships were stronger in patients with BMI ≥27 kg/m2, among whom the correlation between FMD and ACTH was particularly pronounced (r = –0.68, p = 0.0007). No significant associations were found between FMD and hemoglobin A1c or other lipid parameters. Given the cross-sectional design, these findings indicated associations rather than causality. Our results suggest that the HPA axis activity and autonomic function may be associated with endothelial dysfunction in diabetes, particularly in individuals with a higher BMI. This study was registered in the UMIN Clinical Trials Registry (UMIN-CTR; UMIN000060540).
SN  - 1348-4540
SN  - 0918-8959
ER  -

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