RESUMEN
CONTEXT: Derangement of 11-ß hydroxysteroid dehydrogenase type 1 and type 2 (11ß-HSD1 and 11ß-HSD2), which regulate intracellular cortisol production, has been suggested in both type 2 diabetes (T2D) and chronic kidney disease (CKD). However, activity of 11ß-HSD enzymes in patients with T2D and CKD has never been assessed. OBJECTIVES: To compare 11ß-HSD activities between patients with T2D and healthy controls, and assess whether in T2D, renal function is associated with 11ß-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 11ß-HSD and 11ß-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 (ß = -0.35, P < 0.001), and a higher cortisol/cortisone ratio (ß = -0.16, P = 0.001). CONCLUSIONS: In this real-life secondary care setting of patients with T2D, 11ß-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.
RESUMEN
BACKGROUND: Renal function decline in diabetic kidney disease is accompanied by calcium and phosphate metabolism alterations. Whereas strontium (Sr2+ ) has many similarities with calcium, little is known about Sr2+ in this respect. We studied the association of plasma Sr2+ concentration and parameters associated with an altered calcium and phosphate metabolism in diabetic kidney disease. MATERIALS AND METHODS: Plasma Sr2+ concentration was measured in 450 patients included in the DIAbetes and LifEstyle Cohort Twente-1. Patients were classified based on chronic kidney disease (CKD) stages: stages 1-2, stage 3 and stages 4-5 (estimated glomerular filtration rate of ≥60 mL·min-1 ·1.73 m-2 , 30-59 mL·min-1 ·1.73 m-2 and ≤29 mL·min-1 ·1.73 m-2 , respectively). The associations between log-transformed plasma Sr2+ concentration and parameters of calcium and phosphate metabolism were studied using multivariate linear regression analysis. RESULTS: Overall, median plasma Sr2+ concentration was in normal range, 269 nmol/L, but was progressively higher in patients with lower renal function, that is 246 nmol/L (CKD 1-2), 347 nmol/L (CKD 3) and 419 nmol/L (CKD 4-5). In multivariate analysis, independent associations were found between plasma Sr2+ concentration and both eGFR (ß = -0.401, P < 0.001) and plasma fibroblast growth factor 23 (FGF23) concentration (ß = 0.087, P = 0.04). CONCLUSIONS: We found an independent inverse association between eGFR and plasma Sr2+ concentration and an independent association between plasma Sr2+ concentration and plasma FGF23 concentration, a marker of deranged calcium and phosphate metabolism. Further research is needed to determine the mechanisms behind these associations and the impact of an elevation in plasma Sr2+ concentration on bone mineralization and calcification.
