Lower Renal Function is Associated with Derangement of 11Beta Hydroxysteroid Dehydrogenase in Type 2 Diabetes

Lower Renal Function is Associated with Derangement of 11Beta Hydroxysteroid Dehydrogenase in... Abstract Context Derangement of 11-beta hydroxysteroid dehydrogenase type 1 and type 2 (11β-HSD1 and 11β-HSD2), which regulate intracellular cortisol production, has been suggested in both type 2 diabetes (T2D) and chronic kidney disease (CKD). However, activity of 11β-HSD enzymes in patients with T2D and CKD has never been assessed. Objectives To compare 11β-HSD activities between patients with T2D and healthy controls, and assess whether in T2D, renal function is associated with 11β-HSD activities. Design Cross-sectional analysis in the DIAbetes and LifEstyle Cohort Twente (DIALECT-1). Setting Referral center for type 2 diabetes. Patients Patient with type 2 diabetes (n=373, age 64 ± 9 years, 58% men, 26% of patients eGFR <60 ml/min•1.73m2) and healthy controls (n=275, age 53 ± 11 years, 48% men). Mean outcome measure We measured cortisol, cortisone and metabolites (tetrahydrocortisol (THF), alloTHF (aTHF) and tetrahydrocortisone (THE)) in 24h urine samples. Whole body 11β-HSD and 11β-HSD2 activities were calculated as the urinary (THF+aTHF)/THE and cortisol/cortisone ratio respectively. Results Patient with T2D had a higher (THF+aTHF)/THE ratio (1.02 [0.84-1.27] vs 0.94 [0.79-1.0], P<0.001) and cortisol/cortisone ratio (0.70 [0.58-0.83] vs 0.63 [0.54-0.74], P<0.001) than healthy controls. In T2D, lower eGFR was associated with a higher (THF+aTHF)/THE ratio (β=-0.35, P<0.001), and a higher cortisol/cortisone ratio (β=-0.16, P=0.001). Conclusions In this real life secondary care setting of patients with T2D, 11β-HSD enzymes activities were shifted to higher intracellular cortisol production in T2D, which was further aggravated in patients with CKD. Prospective analyses are warranted to investigate causality of these associations. Copyright © 2018 Endocrine Society This article has been published under the terms of the Creative Commons Attribution Non-Commercial, No-Derivatives License (CC BY-NC-ND; https://creativecommons.org/licenses/by-nc-nd/4.0/). http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal of the Endocrine Society Oxford University Press

Lower Renal Function is Associated with Derangement of 11Beta Hydroxysteroid Dehydrogenase in Type 2 Diabetes

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Publisher
Endocrine Society
Copyright
Copyright © 2018 Endocrine Society
eISSN
2472-1972
D.O.I.
10.1210/js.2018-00088
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Abstract

Abstract Context Derangement of 11-beta hydroxysteroid dehydrogenase type 1 and type 2 (11β-HSD1 and 11β-HSD2), which regulate intracellular cortisol production, has been suggested in both type 2 diabetes (T2D) and chronic kidney disease (CKD). However, activity of 11β-HSD enzymes in patients with T2D and CKD has never been assessed. Objectives To compare 11β-HSD activities between patients with T2D and healthy controls, and assess whether in T2D, renal function is associated with 11β-HSD activities. Design Cross-sectional analysis in the DIAbetes and LifEstyle Cohort Twente (DIALECT-1). Setting Referral center for type 2 diabetes. Patients Patient with type 2 diabetes (n=373, age 64 ± 9 years, 58% men, 26% of patients eGFR <60 ml/min•1.73m2) and healthy controls (n=275, age 53 ± 11 years, 48% men). Mean outcome measure We measured cortisol, cortisone and metabolites (tetrahydrocortisol (THF), alloTHF (aTHF) and tetrahydrocortisone (THE)) in 24h urine samples. Whole body 11β-HSD and 11β-HSD2 activities were calculated as the urinary (THF+aTHF)/THE and cortisol/cortisone ratio respectively. Results Patient with T2D had a higher (THF+aTHF)/THE ratio (1.02 [0.84-1.27] vs 0.94 [0.79-1.0], P<0.001) and cortisol/cortisone ratio (0.70 [0.58-0.83] vs 0.63 [0.54-0.74], P<0.001) than healthy controls. In T2D, lower eGFR was associated with a higher (THF+aTHF)/THE ratio (β=-0.35, P<0.001), and a higher cortisol/cortisone ratio (β=-0.16, P=0.001). Conclusions In this real life secondary care setting of patients with T2D, 11β-HSD enzymes activities were shifted to higher intracellular cortisol production in T2D, which was further aggravated in patients with CKD. Prospective analyses are warranted to investigate causality of these associations. Copyright © 2018 Endocrine Society This article has been published under the terms of the Creative Commons Attribution Non-Commercial, No-Derivatives License (CC BY-NC-ND; https://creativecommons.org/licenses/by-nc-nd/4.0/).

Journal

Journal of the Endocrine SocietyOxford University Press

Published: May 22, 2018

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