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New-onset diabetes mellitus risk associated with concurrent autonomous cortisol secretion in patients with primary aldosteronism

Abstract

Concurrent autonomous cortisol secretion (ACS) in patients with primary aldosteronism (PA patients) is not uncommon. This work aimed to determine the effect of cortisol levels on incident new-onset type 2 diabetes mellitus (NODM) in PA patients. Using the prospectively designed observational TAIPAI cohort, the PA patients were grouped by cortisol level after an overnight low-dose dexamethasone suppression test (1-mg DST). Of the 476 PA patients, 387 (43.7% men; mean age 52.8 years) did not have baseline DM. After a mean follow-up of 4.3 ± 2.9 years, 32 patients (8.3%) developed NODM. The cutoff value obtained via a generalized additive model showed that a serum cortisol level ≥ 2.65 µg/dL after 1-mg DST was a risk factor for developing NODM (HR, 3.5, p = 0.031) by Cox proportional- hazards model.. In PA patients with a higher body mass index (>25 kg/m2; HR, 3.16), lower estimated glomerular filtration rate (<90 ml/min/1.73 m2; HR, 3.18), longer hypertension duration (>7 years; HR, 3.34), and higher waist-to-hip ratio (>0.9; HR, 3.07), a concomitant cortisol level ≥ 2.65 μg/dL after 1-mg DST were more likely to develop NODM. The high-cortisol group of patients with aldosterone-producing adenoma (APA) using mineralocorticoid receptor antagonist (MRA) was associated with an increased risk of NODM (HR, 5.72). Our results showed that PA patients with a concomitant cortisol level ≥ 2.65 µg/dL after 1-mg DST, independent of the aldosterone level, had a higher incidence of NODM. Such PA patients should be carefully evaluated and managed to achieve better glucose control and prevent metabolic syndrome.

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Acknowledgements

We would like to thank the National Taiwan University Hospital, Taiwan’s National Health Research Institutes, and Taiwan’s Ministry of Science and Technology. We thank the Members of the Taiwan Primary Aldosteronism Investigation (TAIPAI) Study Group.

TAIPAI group

Tai-Shuan Lai7, Shih-Chieh Jeff Chueh7, Shao-Yu Yang7, Kao-Lang Liu7, Chin-Chen Chang7, Bo-Chiag Lee7, Shuo-Meng Wang7, Kuo-How Huang7, Po-Chih Lin7, Yen-Hung Lin7, Lian-Yu Lin7, Shih-Cheng Liao7, Ruoh-Fang Yen7, Ching-Chu Lu7, Chieh-Kai Chan2, Leay-Kiaw Er8, Ya-Hui Hu8, Chia-Hui Chang8, Che-Hsiung Wu8, Yao-Chou Tsai8, Chen-Hsun Ho9, Wei-Chieh Huang10, Ying-Ying Chen11, Vin-Cent Wu12

Funding

This study was supported by the Ministry of Science and Technology (MOST) of the Republic of China (Taiwan) [grant number, MOST 107–2314-B-002-026-MY3, 108-2314-B-002-058, 110-2314-B-002-241, 110-2314-B-002-239], National Science and Technology Council (NSTC) [grant number, NSTC 109-2314-B-002-174-MY3, 110-2314-B-002-124-MY3, 111-2314-B-002-046, 111-2314-B-002-058], National Health Research Institutes [PH-102-SP-09], National Taiwan University Hospital [109-S4634, PC-1246, PC-1309, VN109-09, UN109-041, UN110-030, 111-FTN0011] Grant MOHW 110-TDU-B-212-124005 and Mrs. Hsiu-Chin Lee Kidney Research Fund.

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Correspondence to Shuo-Meng Wang.

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Wu, VC., Chan, CK., Wu, WC. et al. New-onset diabetes mellitus risk associated with concurrent autonomous cortisol secretion in patients with primary aldosteronism. Hypertens Res 46, 445–455 (2023). https://doi.org/10.1038/s41440-022-01086-w

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  • DOI: https://doi.org/10.1038/s41440-022-01086-w

Keywords

  • Primary aldosteronism
  • Autonomous cortisol secretion
  • Incident
  • New-onset diabetes
  • TAIPAI

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