| Avtor/Urednik | Perdan-Pirkmajer, Katja; Pirkmajer, Sergej; Praprotnik, Sonja; Hočevar, Alojzija; Rotar, Žiga; Gašperšič, Nataša; Sodin-Šemrl, Snežna; Žibert, Janez; Omersel, Jasna; Tomšič, Matija; Ambrožič, Aleš | |
| Naslov | Methotrexate reduces HbA1c concentration but does not produce chronic accumulation of ZMP in patients with rheumatoid or psoriatic arthritis | |
| Tip | članek | |
| Vol. in št. | , št. 1 | |
| Leto izdaje | 2016 | |
| ISSN | 0300-9742 - Scandinavian journal of rheumatology | |
| Jezik | eng | |
| Abstrakt | Objectives: The mechanism by which methotrexate (MTX) improves glucose homeostasis in patients with rheumatoid (RA) and psoriatic arthritis (PsA) remains undetermined. Animal studies indicate a role for intracellular accumulation of 5-aminoimidazole-4-carboxamide-1-beta-d-ribofuranosyl 5-monophosphate (ZMP) but this has not been directly demonstrated in humans. We explored whether accumulation of ZMP is associated with improvements in glucose homeostasis during MTX therapy. Method: MTX-naïve, non-diabetic RA (n = 16) and PsA (n = 10) patients received uninterrupted MTX treatment for 6 months. To evaluate whether ZMP accumulated during MTX therapy, we measured the concentration of ZMP in erythrocytes and the concentration of its dephosphorylated derivative 5-aminoimidazole-4-carboxamide-1-beta-d-ribofuranoside (AICAR) in urine using liquid chromatography mass spectrometry (LC-MS/MS). To assess glucose homeostasis, we determined the concentration of glycated haemoglobin (HbA1c) and homeostasis model assessment of insulin resistance [HOMA-IR: fasting glucose (mmol/L) x fasting insulin (microU/mL)/22.5]. Results: Erythrocyte ZMP and urinary AICAR concentrations did not increase during 6 months of MTX therapy. HbA1c concentration was reduced from 5.80 +- 0.29% at baseline to 5.51 +- 0.32% at 6 months (p < 0.001), while HOMA-IR remained unaltered. Reduction in HbA1c concentration was not associated with increased ZMP or AICAR concentrations. Conclusions: MTX therapy probably does not produce a chronic increase in erythrocyte ZMP or urinary AICAR concentrations. Collectively, our data do not support the hypothesis that MTX improves glucose homeostasis through chronic accumulation of ZMP. | |
| Proste vsebinske oznake | methotrexate HbA1c concentration arthritis metotreksatom koncentracija HbA1c artritis |