Lower Renal Function Is Associated With Derangement of 11- Hydroxysteroid Dehydrogenase in Type 2 Diabetes

Christina Maria Gant, Isidor Minovic, Heleen Binnenmars, Laura de Vries, Ido Kema, André van Beek, Gerjan Navis, Stephan Bakker, Gozewijn Dirk Laverman

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Abstract

Context: Derangement of 11-β 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 T2D.

Patients: Patient with T2D [n = 373, age 64 ± 9 years, 58% men, 26% of patients estimated glomerular filtration rate (eGFR) <60 mL/min·1.73 m2] and healthy controls (n = 275, age 53 ± 11 years, 48% men).

Mean Outcome Measure: We measured cortisol, cortisone, and metabolites [tetrahydrocortisol (THF), allo-THF (aTHF), and tetrahydrocortisone (THE)] in 24-hour urine samples. Whole body 11β-HSD and 11β-HSD2 activities were calculated as the urinary (THF + aTHF)/THE and cortisol/cortisone ratios, respectively.

Results: Patients with T2D had a higher (THF + aTHF)/THE ratio [1.02 (0.84 to 1.27) vs 0.94 (0.79 to 1.0), P < 0.001] and cortisol/cortisone ratio [0.70 (0.58 to 0.83) vs 0.63 (0.54 to 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.

Original languageEnglish
Pages (from-to)609-620
Number of pages12
JournalEndocrine Connections
Volume2
Issue number7
DOIs
Publication statusPublished - 1-Jul-2018

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