Plasma levels of leptin and visfatin in rheumatoid arthritis patients; is there any relationship with joint damage?

Document Type: Original Article


1 Rheumatic Diseases Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

2 Medical Research Assistant, University of Toronto, Toronto, ON, CA


Objective (s):Rheumatoid arthritis (RA) is a chronic systemic inflammatory disorder, primarily targeting the synovium and articular cartilage that leads to joint damage. Recent reports have suggested the role of adipocytokines in mediating joint damage; however it still is a matter of debate. The purpose of this study was to evaluate the association between serum values of adiopocytokines (leptin, visfatin) and radiographic joint damage in patients with RA.
Materials and Methods:Fifty-four patients diagnosed with RA, based on Revised ACR Criteria 2010, with 1-5 year disease duration since diagnosis, were enrolled. Twenty-nine of patients had erosion in radiographic studies and 25patients had no erosion. Radiographic joint damages were defined according to Larsen Score. Additionally, serum levels of adipocytokines were measured and cross-sectional associations with radiographic damage were explored, adjusting for pertinent confounders.
Results:The serum level of visfatin were significantly higher in patients with radiographic joint damage compared with patients with no joint damage (P=0.013). This difference remained significant after adjustment for C-reactive protein levels (P=0.008), but not after adjustment for disease duration (P=0.247). The mean leptin serum levels were not different between these two groups (P=0.903). There was a positive correlation between leptin levels and BMI (r=0.494, P<0.001). However, after adjustment for BMI, leptin levels had no difference between two groups (P=0.508).
Conclusion:This study revealed that visfatin levels were significantly higher in patients with radiographic joint damage dependently to disease duration. Therefore, it seems that adipocytokine may be a valuable factor in therapeutic targets in the future.


  1. Scotece M, Conde J, Gَmez R, Lَpez V, Lago F, Gَmez-Reino J, et al. Beyond fat mass: exploring the Role of adipokines in rheumatic diseases. Sci World J 2011; 11:1932-1947.
  2. Barbosa V, Rego J, Da Silva N. Possible role of adipokines in systemic lupus erythematosus and rheumatoid arthritis. Rev Bras Reumatol 2012; 52:271-287.
  3. Bokarewa M, Bokarew D, Hultgren O, Tarkowski A. Leptin consumption in  the inflamed Joints of patients with rheumatoid arthritis. Ann Rheum Dis 2003; 62:952-956.
  4. Lee SW, Park MC, Park YB, Lee SK.  Measurement of the serum leptin level could assist Disease activity monitoring in rheumatoid arthritis. Rheumatol Int 2007; 27:537-540.
  5. Targonska-Stepniak B, Majdan M, Dryglewska M. Leptin serum levels in rheumatoid arthritis Patients: relation to disease duration and activity. Rheumatol Int 2008; 28:585-591.
  6. Seven  A, Guzel S, Aslan  M, Hamuryudan  V. Serum  and  synovial fluid  leptin levels and Markers of inflammation in rheumatoid arthritis. Rheumatol Int 2009; 29:743-747.
  7. Otero M, Lago R, Gomez R, Lago F, Dieguez C, Gomez-Reino JJ, et al. Changes in plasma levels of fat-derived hormones adiponectin, leptin, resistin and visfatin  in  patients   with rheumatoid arthritis. Ann Rheum Dis 2006; 651198-1201.
  8. Gunaydin R, Kaya T, Atay A, Olmez N, Hur A, Koseoglu M. Serum leptin levels in rheumatoid Arthritis and relationship with disease activity. South Med J 2006; 99:1078-1083.
  9. Salazar-Paramo M, Gonzalez-Ortiz M, Gonzalez-Lopez L, Sanchez-Ortiz A, Valera-Gonzalez IC, Martinez-Abundis E, et al. Serum leptin levels in patients with rheumatoid arthritis. J Clin Rheumatol 2001; 7:57-59.
10. Anders HJ, Rihl M, Heufelder A, Loch O, Schattenkirchner M. Leptin serum levels are not corelated  with  disease  activity  in  patients  with  rheumatoid arthritis. Metabolism 1999; 48:745-748.

11. Wislowska M, Rok M, Jaszczyk B, Stepień K, Cicha M. Serum leptin in rheumatoid arthritis. Rheumatol Int 2007; 27:947-954.

12. Hizmetli S, Kisa M, Gokalp N, Bakici MZ. Are plasma and synovial fluid leptin levels corelated with disease activity in rheumatoid arthritis? Rheumatol Int 2007; 27:335-338.

13. Rho YH, Solus J, Sokka T. Adipocytokines are associated with radiographic joint damage in rheumatoid arthritis. Arthritis Rheum 2009; 60:1906-1914.

14. Giles JT, Allison M, Bingham CO 3rd, Scott WM Jr, Bathon JM. Adiponection is a mediator of the  inverse  association  of  adiposity  with  radiographic  damage  in  rheumatoid  arthritis. Arthritis Rheum 2009; 61:1248-1256.

15. Sokka T. Radioqraphic Scoring in Rheumatoid arthritis: a short introduction to the methods.  Ball Hosp Jt Dis 2008; 66:166-168.

16. Pagano C, Pilon C, Olivieri M, Mason P, Fabris R, Serra R, et al. Reduced plasma visfatin/pre-B cell colony-enhancing factor in obesity is not related to insulin resistance in humans. J Clin Endocrinol Metab 2006; 91:3165-3170.

17. Chen CC, Li TC, Li CI, Liu CS, Lin WY, Wu MT, et al. The relationship between visfatin levels and
anthropometric and metabolic parameters:  association with cholesterol levels woman. Metabolism 2007; 56:1216-1220.

18. Tilg H, Moschen Ar. Adipocytokines: mediators linking adipose tissue, inflammation and immunity. Nat Rev Immunol 2006; 6:772-783.

19. Luk T, Malam Z, Marshall JC. Pre-B cell colony-enhancing factor (PBEF)/visfatin: a novel mediator of innate immunity. J Leukoc Biol 2008; 83:804-16.

20. Brentano F, Schorr O, Ospelt C, Stanczyk J, Gay RE, Gay S, et al. Pre-B cell colony-enhancing  factor/visfatin, a new marker of inflammation in rheumatoid arthritis with proinflammatory and matrix- degrading activities. Arthritis Rheum 2007; 56:2829-2839.

21. Busso N, Karababa M, Nobile M, Rolaz A, Van Gool F, Galli M, et al. Pharmacological inhibition of nicotinamide phospharibosyltranferase/visfatin enzymatic activity identifies a new inflammatory pathway linked to NAD. PLoS One 2008; 3:e2267.

22. Westhoff G, Rau R, Zink A. Radiographic joint damage in early rheumatoid arthritis is highly dependent on body mass index. Arthritis Rheum 2007; 56:3575-3582.

23. Kaufmann J, Kielstein V, Kilian S, Stein G, Hein G. Relation between body mass index and radiological progression in patients with rheumatoid arthritis. J Rheumatol 2003; 30:2350-2355.

24. Van der Helm-van Mil AH, Van der Kooij SM, Allaart CF, Toes RE, Huizinga TW. A high body mass index has a protective effect on the amount of joint destruction in small joints in early rheumatoid arthritis. Ann Rheum Dis 2008; 67:769-774.