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Leptin as an obesity marker in rheumatoid arthritis

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Abstract

The determination of excess of body fat mass provides a more suitable determinant of obesity in rheumatoid arthritis patients; however, body mass index (BMI) may not be accurate for the quantification of adiposity. To identify a marker of excess adiposity in women with rheumatoid arthritis (RA) using different methods for fat mass evaluation. A cross-sectional study was conducted in adult female patients with RA. Disease activity was assessed by DAS28-ESR, and obesity was determined by waist circumference (WC), BMI and dual-energy X-ray absorptiometry (DXA). The Human Bone Metabolism kit (Merck Millipore, Darmstadt, Alemanha) was used to determine the plasma levels of leptin, TNF-α, IL-6, and IL-1β by quantification of serum proteins by technical microspheres (LUMINEX, TX, USA). Adiponectin was measured by enzyme-linked immunosorbent assay sandwich kit (R&D Systems, Minneapolis, MN, USA). Eighty-nine female patients, median age of 55.4 (± 11.6) years, and median disease duration of 16.4 (± 14.9) years were included. The frequency of obesity was 33.7% according to BMI, 89.9% with WC, and 56.1% with DXA. The median serum leptin concentration was the only marker that correlated with body fat percentage according to the three methods. This correlation was positive and not influenced by DAS28, C-reactive protein, erythrocyte sedimentation rate, or inflammatory cytokines levels (IL-6, TNF-α, IL-1β). Analysis of ROC curves determined the cut-off point of 10.3 ng/mL of leptin as an obesity marker, with a sensitivity of 96.43% and a specificity of 23.81%. Serum leptin correlates positively with fat mass and is potentially useful in excess fat mass determination in clinical practice.

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References

  1. Scarno A, Perrotta FM, Cardini F, Carboni A, Annibali G, Lubrano E et al (2014) Beyond the joint: subclinical atherosclerosis in rheumatoid arthritis. World J Orthop 5(3):328–335

    Article  PubMed  PubMed Central  Google Scholar 

  2. Wallberg-Jonsson S, Ohman ML, Dahlqvist SR (1997) Cardiovascular morbidity and mortality in patients with seropositive rheumatoid arthritis in Northern Sweden. J Rheumatol 24(3):445–451

    PubMed  CAS  Google Scholar 

  3. Myasoedova E, Gabriel SE (2010) Cardiovascular disease in rheumatoid arthritis: a step forward. Curr Opin Rheumatol 22(3):342–347

    Article  PubMed  Google Scholar 

  4. Abella V, Scotece M, Conde J, López V, Lazzaro V, Pino J et al (2014) Adipokines, metabolic syndrome and rheumatic diseases. J Immunol Res 2014:343746. https://doi.org/10.1155/2014/343746

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  5. Kremers HM, Nicola PJ, Crowson CS, Ballman KV, Gabriel SE (2004) Prognostic importance of low body mass index in relation to cardiovascular mortality in rheumatoid arthritis. Arthritis Rheum 50(11):3450–3457

    Article  PubMed  Google Scholar 

  6. Lecker SH, Solomon V, Mitch WE, Goldberg AL (1999) Muscle protein breakdown and the critical role of the ubiquitin-proteasome pathway in normal and disease states. J Nutr 129(1S Suppl):227S–237S

    Article  PubMed  CAS  Google Scholar 

  7. Fantuzzi G (2005) Adipose tissue, adipokines, and inflammation. J Allergy Clin Immunol 115(5):911–919 (quiz 920)

    Article  PubMed  CAS  Google Scholar 

  8. Lago F, Dieguez C, Gómez-Reino J, Gualillo O (2007) Adipokines as emerging mediators of immune response and inflammation. Nat Clin Pract Rheumatol 3(12):716–724

    Article  PubMed  CAS  Google Scholar 

  9. Jéquier E (2002) Leptin signaling, adiposity, and energy balance. Ann NY Acad Sci 967:379–388

    Article  PubMed  Google Scholar 

  10. Scotece M, Conde J, Gómez R, López V, Lago F, Gómez-Reino JJ et al (2011) Beyond fat mass: exploring the role of adipokines in rheumatic diseases. Sci World J 11:1932–1947

    Article  CAS  Google Scholar 

  11. Martin SS, Qasim A, Reilly MP (2008) Leptin resistance: a possible interface of inflammation and metabolism in obesity-related cardiovascular disease. J Am Coll Cardiol 52(15):1201–1210

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  12. Schäffler A, Ehling A, Neumann E, Herfarth H, Tarner I, Schölmerich J et al (2003) Adipocytokines in synovial fluid. JAMA 290(13):1709–1710

    Article  PubMed  Google Scholar 

  13. Ku IA, Imboden JB, Hsue PY, Ganz P (2009) Rheumatoid arthritis: model of systemic inflammation driving atherosclerosis. Circ J 73(6):977–985

    Article  PubMed  CAS  Google Scholar 

  14. Gómez-Ambrosi J, Silva C, Galofré JC, Escalada J, Santos S, Millán D et al (2012) Body mass index classification misses subjects with increased cardiometabolic risk factors related to elevated adiposity. Int J Obes (Lond) 36(2):286–294

    Article  CAS  Google Scholar 

  15. Katz PP, Yazdany J, Trupin L, Schmajuk G, Margaretten M, Barton J et al (2013) Sex differences in assessment of obesity in rheumatoid arthritis. Arthritis Care Res (Hoboken) 65(1):62–70

    Article  Google Scholar 

  16. Summers GD, Deighton CM, Rennie MJ, Booth AH (2008) Rheumatoid cachexia: a clinical perspective. Rheumatology 47(8):1124–1131

    Article  PubMed  CAS  Google Scholar 

  17. Hunter HL, Nagy TR (2002) Body composition in a seasonal model of obesity: longitudinal measures and validation of DXA. Obes Res 10(11):1180–1187

    Article  PubMed  Google Scholar 

  18. Xia Y, Ergun DL, Wacker WK, Wang X, Davis CE, Kaul S (2014) Relationship between dual-energy X-ray absorptiometry volumetric assessment and X-ray computed tomography-derived single-slice measurement of visceral fat. J Clin Densitom 17(1):78–83

    Article  PubMed  Google Scholar 

  19. Snijder MB, Visser M, Dekker JM, Seidell JC, Fuerst T, Tylavsky F et al (2002) The prediction of visceral fat by dual-energy X-ray absorptiometry in the elderly: a comparison with computed tomography and anthropometry. Int J Obes Relat Metab Disord 26(7):984–993

    Article  PubMed  CAS  Google Scholar 

  20. Kaul S, Rothney MP, Peters DM, Wacker WK, Davis CE, Shapiro MD et al (2012) Dual-energy X-ray absorptiometry for quantification of visceral fat. Obesity (Silver Spring) 20(6):1313–1318

    Article  Google Scholar 

  21. Dao HH, Do QT, Sakamoto J (2011) Abnormal body composition phenotypes in Vietnamese women with early rheumatoid arthritis. Rheumatology 50(7):1250–1258

    Article  PubMed  Google Scholar 

  22. Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS et al (1988) The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 31(3):315–324

    Article  PubMed  CAS  Google Scholar 

  23. Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham CO et al (2010) 2010 rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum 62(9):2569–2581

    Article  PubMed  Google Scholar 

  24. Prevoo ML, van ‘t Hof MA, Kuper HH, van Leeuwen MA, van de Putte LB, van Riel PL (1995) Modified disease activity scores that include twenty-eight-joint counts. Development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. Arthritis Rheum 38(1):44–48

    Article  PubMed  CAS  Google Scholar 

  25. (1995) Physical status: the use and interpretation of anthropometry. Report of a WHO Expert Committee. World Health Organ Tech Rep Ser 854:1–452

  26. Alberti KG, Zimmet P, Shaw J (2006) Metabolic syndrome—a new world-wide definition. A consensus statement from the International Diabetes Federation. Diabet Med 23(5):469–480

    Article  PubMed  CAS  Google Scholar 

  27. Bray G (2003) Contemporary diagnosis and management of obesity and the metabolic syndrome, 3rd edn. Handbooks in Health Care, Newtown

    Google Scholar 

  28. Alberti KG, Zimmet P, Shaw J (2006) Metabolic syndrome—a new world-wide definition. A consensus statement from the International Diabetes Federation. Diabet Med 23:469–480

    Article  PubMed  CAS  Google Scholar 

  29. Ramsey PH (1989) Critical values for Spearman’s rank order correlation. J Educ Stat 14(3):245–253

    Google Scholar 

  30. Mulaka MM (2012) A guide to appropriate use of correlation coefficient in medical research. Malawi Med J 24(3):69–71

    Google Scholar 

  31. Considine RV, Sinha MK, Heiman ML, Kriauciunas A, Stephens TW, Nyce MR et al (1996) Serum immunoreactive-leptin concentrations in normal-weight and obese humans. N Engl J Med 334(5):292–295

    Article  PubMed  CAS  Google Scholar 

  32. Nishiya K, Nishiyama M, Chang A, Shinto A, Hashimoto K (2002) Serum leptin levels in patients with rheumatoid arthritis are correlated with body mass index. Rinsho Byori 50(5):524–527

    PubMed  CAS  Google Scholar 

  33. Rho YH, Solus J, Sokka T, Oeser A, Chung CP, Gebretsadik T et al (2009) Adipocytokines are associated with radiographic joint damage in rheumatoid arthritis. Arthritis Rheum 60(7):1906–1914

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  34. Hayashi H, Satoi K, Sato-Mito N, Kaburagi T, Yoshino H, Higaki M et al (2012) Nutritional status in relation to adipokines and oxidative stress is associated with disease activity in patients with rheumatoid arthritis. Nutrition 28(11–12):1109–1114

    Article  PubMed  CAS  Google Scholar 

  35. Mirfeizi Z, Noubakht Z, Rezaie AE, Jokar MH, Sarabi ZS (2014) Plasma levels of leptin and visfatin in rheumatoid arthritis patients; is there any relationship with joint damage? Iran J Basic Med Sci 17(9):662–666

    PubMed  PubMed Central  Google Scholar 

  36. Oner SY, Volkan O, Oner C, Mengi A, Direskeneli H, Tasan DA (2015) Serum leptin levels do not correlate with disease activity in rheumatoid arthritis. Acta Reumatol Port 40(1):50–54

    PubMed  Google Scholar 

  37. Kopec-Medrek M, Kotulska A, Widuchowska M, Adamczak M, Więcek A, Kucharz EJ (2012) Plasma leptin and neuropeptide Y concentrations in patients with rheumatoid arthritis treated with infliximab, a TNF-α antagonist. Rheumatol Int 32(11):3383–3389

    Article  PubMed  CAS  Google Scholar 

  38. Gautron L, Elmquist JK (2011) Sixteen years and counting: an update on leptin in energy balance. J Clin Invest 121(6):2087–2093

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  39. Tian G, Liang JN, Pan HF, Zhou D (2014) Increased leptin levels in patients with rheumatoid arthritis: a meta-analysis. Ir J Med Sci 183(4):659–666

    Article  PubMed  CAS  Google Scholar 

  40. Gannagé-Yared MH, Khalife S, Semaan M, Fares F, Jambart S, Halaby G (2006) Serum adiponectin and leptin levels in relation to the metabolic syndrome, androgenic profile and somatotropic axis in healthy non-diabetic elderly men. Eur J Endocrinol 155(1):167–176

    Article  PubMed  CAS  Google Scholar 

  41. Maury E, Brichard SM (2010) Adipokine dysregulation, adipose tissue inflammation and metabolic syndrome. Mol Cell Endocrinol 314(1):1–16

    Article  PubMed  CAS  Google Scholar 

  42. Xibillé-Friedmann DX, Ortiz-Panozo E, Bustos Rivera-Bahena C, Sandoval-Ríos M, Hernández-Góngora SE, Dominguez-Hernandez L et al (2015) Leptin and adiponectin as predictors of disease activity in rheumatoid arthritis. Clin Exp Rheumatol 33(4):471–477

    PubMed  Google Scholar 

  43. Otero M, Lago R, Gomez R, Lago F, Dieguez C, Gómez-Reino JJ et al (2006) Changes in plasma levels of fat-derived hormones adiponectin, leptin, resistin and visfatin in patients with rheumatoid arthritis. Ann Rheum Dis 65(9):1198–1201

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  44. Lee SW, Park MC, Park YB, Lee SK (2007) Measurement of the serum leptin level could assist disease activity monitoring in rheumatoid arthritis. Rheumatol Int 27(6):537–540

    Article  PubMed  CAS  Google Scholar 

  45. Yoshino T, Kusunoki N, Tanaka N, Kaneko K, Kusunoki Y, Endo H et al (2011) Elevated serum levels of resistin, leptin, and adiponectin are associated with C-reactive protein and also other clinical conditions in rheumatoid arthritis. Intern Med 50(4):269–275

    Article  PubMed  CAS  Google Scholar 

  46. Hizmetli S, Kisa M, Gokalp N, Bakici MZ (2007) Are plasma and synovial fluid leptin levels correlated with disease activity in rheumatoid arthritis? Rheumatol Int 27(4):335–338

    Article  PubMed  CAS  Google Scholar 

  47. Tian G, Liang JN, Wang ZY, Zhou D (2014) Emerging role of leptin in rheumatoid arthritis. Clin Exp Immunol 177(3):557–570

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  48. Cao H, Lin J, Chen W, Xu G, Sun C (2016) Baseline adiponectin and leptin levels in predicting an increased risk of disease activity in rheumatoid arthritis: a meta-analysis and systematic review. Autoimmunity 49(8):547–553

    Article  PubMed  CAS  Google Scholar 

  49. Kahn R, Buse J, Ferrannini E, Stern M, Association AD, Diabetes EAftSo (2005) The metabolic syndrome: time for a critical appraisal: joint statement from the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care 28(9):2289–2304

    Article  PubMed  Google Scholar 

  50. Van Gaal LF, Mertens IL, De Block CE (2006) Mechanisms linking obesity with cardiovascular disease. Nature 444(7121):875–880

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

Adriana Maria Kakehasi received grants from the Fundos de Apoio à Pesquisa da Sociedade Brasileira de Reumatologia.

Funding

Fundos Remanescentes da Sociedade Brasileira de Reumatologia.

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Contributions

All authors were involved in drafting the article or revising it critically for important intellectual content, and all authors approved the final version to be submitted for publication. MFBRG had full access to all study data and takes responsibility for the integrity of the data. Study conception and design: AMK, MFBRG, and MVMA. Acquisition of data: MFBRG and MRCP. Analysis and interpretation of data: CJM, ELMV, ALTJ, and MFBRG.

Corresponding author

Correspondence to Maria Fernanda Brandão de Resende Guimarães.

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Conflict of interest

The authors declare they have no conflicts of interest regarding the publication of this paper.

Ethical standards

We declare that this study was approved by the Research Ethics Committee of Universidade Federal de Minas Gerais (UFMG) on January 10, 2012 (CAAE-0547.0.203.000-11) and was, therefore, conducted in accordance with the ethical standards set forth in the 1964 Declaration of Helsinki and its subsequent amendments.

Informed consent

All patients gave their informed consent prior to their inclusion in the study. Details that may reveal the identity of the subjects under study have been omitted.

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Guimarães, M.F.B.R., de Andrade, M.V.M., Machado, C.J. et al. Leptin as an obesity marker in rheumatoid arthritis. Rheumatol Int 38, 1671–1677 (2018). https://doi.org/10.1007/s00296-018-4082-5

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  • DOI: https://doi.org/10.1007/s00296-018-4082-5

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