Endocrine Abstracts

Background

2–3% of the general population is chronically treated with glucocorticoids (GCs). Modification of the structure and/or function of the glucocorticoid receptor (GR) due to its polymorphisms may result in increased (GC – S – bclI, N363S) or decreased (GC – I – A3669G, ER22/23EK) sensitivity to GCs. To date, whether such modulation of cell’s response to GCs can be associated with presence or absence of the side effects of GCs treatment has not been studied.

Objective

The aim of the study was to investigate the association between GR polymorphisms (bclI, N363S, A3669G and ER22/23EK) and adverse events of GC treatment in patients diagnosed with rheumatic disease during chronic glucocorticoid treatment.

Material and methods

150 patients were enrolled into the study. Based on five-point (0’–120’) oral glucose tolerance test (OGTT) glucose and insulin areas under the curve (AUC) as well as indicators of insulin resistance were calculated. Data regarding BMI and waist circumference were gathered and body composition was measured using dual energy X-ray absorptiometry. High Resolution Melting method was used for genotyping.

Results

OGTT was performed in 125 females and 25 males of mean age of 56.8 years. Mean current dose of GCs was 7 mg. 21 carriers of GC – I variants (excluding GC – S carriers) had lower glucose concentrations 2 h after OGTT compared to 55 carriers of the ’wild type’ of all four polymorphisms (98.9 mg/dl vs 128.4 mg/dl, P = 0.01). There was also a trend towards higher cumulative dose of GCs (31.9 g vs 12.55 g, P = 0.06) and longer treatment duration in GC – I carriers (139.1 months vs 80 months, P = 0.09). There was no difference between groups in age, current dose of GCs, cholesterol concentrations, BMI, waist circumference, body or trunk fat percentage, HOMA-IR, HbA1c, Matsuda Index, AUCs, glucose or insulin concentrations in other time points of OGTT. 53 carriers of N363S and/or heterozygous bclI variants (excluding GC – I carriers) were compared to 50 ’wild type’ carriers. There was no difference between groups in age, current, cumulative dose of GCs, treatment duration, cholesterol concentrations, BMI, waist circumference, body or trunk fat percentage, HOMA-IR, HbA1c, Matsuda Index, AUCs, glucose or insulin concentrations in OGTT.

Conclusion

Polymorphisms of GR that decrease sensitivity to GCs (A3669G and ER22/23EK) are associated with lower glucose concentrations after 2 h of OGTT. Whether this could lead to decrease risk of diabetes in carriers is open for future studies.