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Symmetric dimethylarginine (SDMA) serum levels in rheumatoid arthritis: correlations with insulin resistance and disease activity scores

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Abstract

Vascular abnormalities predisposing to atherosclerosis are present in patients with rheumatoid arthritis (RA) and associate with excess cardiovascular risk. Symmetric dimethylarginine (SDMA), an endogenous inhibitor of nitric oxide (NO) synthase activity, has been recognised as novel risk factor for endothelial dysfunction and cardiovascular disease. We aimed to compare SDMA levels in RA patients and controls and to investigate whether they are influenced by demographic, inflammatory or metabolic factors. Serum SDMA levels were measured in 197 RA individuals [median age: 67 years (quartiles: 59–3), 153 (78 %) females] and 82 controls [median age: 44 years [quartiles: 33–55, 50 (61 %) females]. Routine biochemistry tests, lipid profile, glycemic profile [glucose, insulin, homeostasis model assessment (HOMA-IR), quantitative insulin sensitivity check index (QUICKI)], as well as inflammatory markers were measured in all patients. Paired analysis was employed for the comparison of SDMA in two groups and multivariable regression models were performed to identify predictors of SDMA in the RA cohort. SDMA was significantly lower in RA than control patients in both unpaired and paired analyses (P < 0.001 and P = 0.005, respectively), with the magnitude of the difference being similar in both models. QUICKI (P = 0.005) and disease activity score-28 (P = 0.007) were positively related to SDMA in the RA cohort, whilst a negative correlation with renal function (eGFR) was detected (P = 0.005). The molecular explanation of lower serum SDMA is unclear, but the established relationships with indices of disease activity and insulin resistance, may underline the pathogenetic role of the l-arginine/NO pathway dysregulation in the development of atherosclerosis in RA. The biological and clinical importance of SDMA in RA remains to be evaluated in clinical and experimental studies.

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Abbreviations

ADMA:

Asymmetric dimethylarginine

AGXT2:

Alanine-glyoxylate aminotranaferase2

CRP:

C-reactive protein

CV:

Cardiovascular

DAS 28:

Disease activity score 28

DDAH:

Dimethylamine dimethylaminohydrolase

eGFR:

Estimated glomerular filtration rate

ESR:

Estimated sedimentation rate

HAQ:

Health assessment questionnaire

HOMA-IR:

Homeostasis model assessment of insulin resistance

NO:

Nitric oxide

QUICKI:

Quantitative insulin sensitivity check index

RA:

Rheumatoid arthritis

SDMA:

Symmetric dimethylarginine

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Conflict of interest

The authors declare that they have no conflict of interest.

Research involving human participants

The study received approval from the Black Country Research Ethics Committee. All procedures performed in the study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study according to the Declaration of Helsinki.

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Authors and Affiliations

  1. Department of Rheumatology, Dudley Group of Hospitals NHS Trust, Russells Hall Hospital, Dudley, DY1 2HQ, UK

    Theodoros Dimitroulas, Aamer Sandoo, Jacqueline Smith & George D. Kitas

  2. Wolfson Computer Laboratory, University Hospital Birmingham NHS Foundation Trust, Queen Elizabeth Hospital Birmingham, Mindelsohn Way, Birmingham, B15 2WB, UK

    James Hodson

  3. School of Sport, Health and Exercise Sciences, Bangor University, George Building, Bangor, Gwynedd, LL57 2PZ, Wales, UK

    Aamer Sandoo

  4. Arthritis Research UK Epidemiology Unit, University of Manchester, Oxford Road, Manchester, M13 9PT, UK

    George D. Kitas

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  1. Theodoros Dimitroulas
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  2. James Hodson
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  3. Aamer Sandoo
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  4. Jacqueline Smith
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Correspondence to Theodoros Dimitroulas.

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Dimitroulas, T., Hodson, J., Sandoo, A. et al. Symmetric dimethylarginine (SDMA) serum levels in rheumatoid arthritis: correlations with insulin resistance and disease activity scores. Amino Acids 47, 1995–2004 (2015). https://doi.org/10.1007/s00726-015-1953-x

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