Universität zu Köln

Perdan-Pirkmajer, K., Pirkmajer, S., Thevis, M., Thomas, A., Praprotnik, S., Hocevar, A., Rotar, Z., Gaspersic, N., Sodin-Semrl, S., Zibert, J., Omersel, J., Chibalin, A. V., Tomsic, M. and Ambrozic, A. (2016). Methotrexate reduces HbA1c concentration but does not produce chronic accumulation of ZMP in patients with rheumatoid or psoriatic arthritis. Scand. J. Rheumatol., 45 (5). S. 347 - 356. ABINGDON: TAYLOR & FRANCIS LTD. ISSN 1502-7732

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Abstract

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-naive, 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 ( U/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 HbAlc 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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Perdan-Pirkmajer, K. UNSPECIFIED UNSPECIFIED UNSPECIFIED Pirkmajer, S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Thevis, M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Thomas, A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Praprotnik, S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hocevar, A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Rotar, Z. UNSPECIFIED UNSPECIFIED UNSPECIFIED Gaspersic, N. UNSPECIFIED UNSPECIFIED UNSPECIFIED Sodin-Semrl, S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Zibert, J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Omersel, J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Chibalin, A. V. UNSPECIFIED UNSPECIFIED UNSPECIFIED Tomsic, M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Ambrozic, A. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-266020
DOI:	10.3109/03009742.2015.1105290
Journal or Publication Title:	Scand. J. Rheumatol.
Volume:	45
Number:	5
Page Range:	S. 347 - 356
Date:	2016
Publisher:	TAYLOR & FRANCIS LTD
Place of Publication:	ABINGDON
ISSN:	1502-7732
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language ACTIVATED PROTEIN-KINASE; AMINOIMIDAZOLECARBOXAMIDE EXCRETION; AICA-RIBOSIDURIA; FOLIC-ACID; ADENOSINE; ERYTHROCYTE; PHARMACOKINETICS; TRANSFORMYLASE; POLYGLUTAMATE; INHIBITION Multiple languages Rheumatology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/26602