Endocrine Abstracts

Introduction: Corticosteroids are amongst the most prescribed drugs and their use has been linked to cardiometabolic adverse events including weight gain and abdominal adiposity. We previously showed that users were also more likely to have the metabolic syndrome (MetS). Since an essential role in the pathway of glucocorticoid (GC) action is reserved for the glucocorticoid receptor (GR), it could be proposed that GC sensitivity altering polymorphisms could affect the vulnerability for these adverse effects. We therefore assessed the relationships between functional GR polymorphisms with anthropometric measurements and MetS in users of corticosteroids.

Methods: We included 10,619 adult participants in the population-based Lifelines cohort study. Subjects were evaluated for drug use, body mass index (BMI), waist circumference (WC), blood pressure, and fasting metabolic parameters. Genotyping was performed for GR polymorphisms associated with a relatively increased (BclI and N363S) or decreased (ER22/23EK and 9β) GC sensitivity. All included subjects had complete information on MetS components, and were classified as wild type (WT) (2 wild type alleles), GC hypersensitive (1 or 2 copies BclI and/or N363S), or GC resistants (1 or 2 copies ER22/23EK and/or 9β). Analyses were performed between nonusers (genotypes combined) and users (specified) and were adjusted for various covariates.

Results: Overall corticosteroids use was associated with a significantly higher BMI and WC in GC hypersensitive (BMI: mean difference +0.67 kg/m² (95% CI, 0.32–1.02); WC: +2.09 cm (1.16–3.02), both P<0.001), and WT users (BMI: +0.57 kg/m² (0.04–1.11), P=0.04; WC: +1.90 cm (0.48–3.31), P<0.01) but not in GC resistant users. In particular, the use of inhaled corticosteroids was associated with similar findings in GC hypersensitive (BMI: +1.68 kg/m² (1.15–2.20); WC: +4.72 cm (3.33–6.10), both P<0.001), and WT users (BMI: +1.07 kg/m² (0.25–1.89), P=0.01; WC: +3.53 cm (1.35–5.70), P<0.01). In regard to MetS, again only GC hypersensitive (odds ratio (OR) 1.23 (95% CI, 1.01–1.50)) and WT users (OR 1.43 (1.06–1.93)) were more likely to have MetS in comparison to nonusers. This was predominantly found in users of only inhaled corticosteroids (GC hypersensitive users, OR 1.44 (1.08–1.91); WT users, OR 1.64 (1.05–2.54)).

Conclusion: Corticosteroid users, in particular of inhaled corticosteroids, have an increased BMI, WC and more often MetS in comparison to nonusers. These relationships are significantly evident in carriers of GR genotypes associated with GC hypersensitivity or the wild type genotype, but not in users harboring GC resistant polymorphisms.