Skip to main content
SpringerLink
Log in

Effects of medication-treated diabetes on incidence and progression of knee osteoarthritis: a longitudinal analysis of the Osteoarthritis Initiative data

  • Observational Research
  • Published:
Rheumatology International Aims and scope Submit manuscript

Abstract

Diabetes has been proposed as a factor involved in the pathogenesis of osteoarthritis (OA). Currently, there is a lack of research evaluating the prospective impact of diabetes on OA structural outcomes. In this study, we assessed the effects of medication-treated diabetes on incidence and progression of knee OA. We analysed longitudinal data from the multi-center, longitudinal, prospective observational Osteoarthritis Initiative (OAI) study. The main outcomes were radiographic OA incidence (development of Kellgren–Lawrence grade 2 with joint space narrowing, JSN) and progression (increase in semiquantitative JSN or a new knee replacement). For the study of incidence, we selected participants with KL <2 or /KL = 2 without JSN at baseline (incidence sample). To evaluate progression, we selected participants with baseline JSN <3 (progression sample). We used generalized estimating equations (GEE) logistic regression with adjustment for potential confounders to evaluate the effects of medication-treated diabetes on knee OA incidence and progression. We studied 3725 knees (3498 non-diabetic and 228 diabetic) in the incidence sample and 3594 knees (3335 non-diabetic and 259 diabetic) in the progression sample. Medication-treated diabetes did not have an effect on knee OA incidence (odds ratio, OR 0.53, 95% confidence interval, CI 0.23–1.5). There was an independent association between medication-treated diabetes and reduced progression of knee OA [OR 0.66, 95% CI (0.44–0.98)]. Medication-treated diabetes has no effect on knee OA incidence but reduces knee OA progression. The role of diabetes and anti-diabetic drugs in knee OA progression needs further exploration.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

  1. Kadam UT, Croft PR (2007) Clinical comorbidity in osteoarthritis: associations with physical function in older patients in family practice. J Rheumatol 34:1899–1904

    PubMed  Google Scholar 

  2. Zullig LL, Bosworth HB, Jeffreys AS, Corsino L, Coffman CJ, Oddone EZ, Yancy WS Jr, Allen KD (2014) The association of comorbid conditions with patient-reported outcomes in Veterans with hip and knee osteoarthritis. Clin Rheumatol

  3. Berenbaum F (2011) Diabetes-induced osteoarthritis: from a new paradigm to a new phenotype. Ann Rheum Dis 70:1354–1356

    Article  PubMed  Google Scholar 

  4. Louati K, Vidal C, Berenbaum F, Sellam J (2015) Association between diabetes mellitus and osteoarthritis: systematic literature review and meta-analysis. RMD Open 1:e000077

    Article  PubMed  PubMed Central  Google Scholar 

  5. Schett G, Kleyer A, Perricone C, Sahinbegovic E, Iagnocco A, Zwerina J, Lorenzini R, Aschenbrenner F, Berenbaum F, D’Agostino MA, Willeit J, Kiechl S (2013) Diabetes is an independent predictor for severe osteoarthritis: results from a longitudinal cohort study. Diabetes Care 36:403–409

    Article  PubMed  PubMed Central  Google Scholar 

  6. Altman RD, Abadie E, Avouac B, Bouvenot G, Branco J, Bruyere O, Calvo G, Devogelaer JP, Dreiser RL, Herrero-Beaumont G, Kahan A, Kreutz G, Laslop A, Lemmel EM, Menkes CJ, Pavelka K, Van De Putte L, Vanhaelst L, Reginster JY (2005) Total joint replacement of hip or knee as an outcome measure for structure modifying trials in osteoarthritis. Osteoarthr Cartil 13:13–19

    Article  CAS  PubMed  Google Scholar 

  7. Gossec L, Paternotte S, Maillefert JF, Combescure C, Conaghan PG, Davis AM, Gunther K-P, Hawker G, Hochberg M, Katz JN (2011) The role of pain and functional impairment in the decision to recommend total joint replacement in hip and knee osteoarthritis: an international cross-sectional study of 1909 patients. Report of the OARSI-OMERACT Task Force on total joint replacement. Osteoarthr Cartil 19:147–154

    Article  CAS  PubMed  Google Scholar 

  8. Eymard F, Parsons C, Edwards MH, Petit-Dop F, Reginster JY, Bruyere O, Richette P, Cooper C, Chevalier X (2015) Diabetes is a risk factor for knee osteoarthritis progression. Osteoarthr Cartil 23:851–859

    Article  CAS  PubMed  Google Scholar 

  9. Kobayashi T, Notoya K, Naito T, Unno S, Nakamura A, Martel-Pelletier J, Pelletier JP (2005) Pioglitazone, a peroxisome proliferator-activated receptor gamma agonist, reduces the progression of experimental osteoarthritis in guinea pigs. Arthritis Rheum 52:479–487

    Article  CAS  PubMed  Google Scholar 

  10. Cai L, Okumu FW, Cleland JL, Beresini M, Hogue D, Lin Z, Filvaroff EH (2002) A slow release formulation of insulin as a treatment for osteoarthritis. Osteoarthr Cartil 10:692–706

    Article  CAS  PubMed  Google Scholar 

  11. Centers for Disease Control and Prevention. Age-adjusted percentage of adults with diabetes using diabetes medication, by type of medication, United States, 1997–2011. In: 2012.

  12. Margolis KL, Lihong Q, Brzyski R, Bonds DE, Howard BV, Kempainen S, Simin L, Robinson JG, Safford MM, Tinker LT, Phillips LS (2008) Validity of diabetes self-reports in the Women’s Health Initiative: comparison with medication inventories and fasting glucose measurements. Clin Trials 5:240–247

    Article  PubMed  PubMed Central  Google Scholar 

  13. Schneider AL, Pankow JS, Heiss G, Selvin E (2012) Validity and reliability of self-reported diabetes in the atherosclerosis risk in communities study. Am J Epidemiol 176:738–743

    Article  PubMed  PubMed Central  Google Scholar 

  14. Pahor M, Chrischilles EA, Guralnik JM, Brown SL, Wallace RB, Carbonin P (1994) Drug data coding and analysis in epidemiologic studies. Eur J Epidemiol 10:405–411

    Article  CAS  PubMed  Google Scholar 

  15. Bellamy N, Buchanan WW, Goldsmith CH, Campbell J, Stitt LW (1988) Validation study of WOMAC: a health status instrument for measuring clinically important patient relevant outcomes to antirheumatic drug therapy in patients with osteoarthritis of the hip or knee. J Rheumatol 15:1833–1840

    CAS  PubMed  Google Scholar 

  16. Felson DT, Niu J, Guermazi A, Sack B, Aliabadi P (2011) Defining radiographic incidence and progression of knee osteoarthritis: suggested modifications of the Kellgren and Lawrence scale. Ann Rheum Dis 70:1884–1886

    Article  PubMed  PubMed Central  Google Scholar 

  17. Lydersen S (2015) Statistical review: frequently given comments. Ann Rheum Dis 74:323–325

    Article  PubMed  Google Scholar 

  18. Glymour MM, Weuve J, Berkman LF, Kawachi I, Robins JM (2005) When is baseline adjustment useful in analyses of change? An example with education and cognitive change. Am J Epidemiol 162:267–278

    Article  PubMed  Google Scholar 

  19. Twisk J, de Vente W (2002) Attrition in longitudinal studies. How to deal with missing data. J Clin Epidemiol 55:329–337

    Article  PubMed  Google Scholar 

  20. Carey VJ Generalized Estimation Equation Solver. R package version 4.13–19.. In: 2015

  21. Nathan DM, Buse JB, Davidson MB, Ferrannini E, Holman RR, Sherwin R, Zinman B (2009) Medical management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy: a consensus statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care 32:193–203

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Home PD (2008) Impact of the UKPDS—an overview. Diabet Med 25(Suppl 2):2–8

    Article  PubMed  Google Scholar 

  23. Centers for Disease Control and Prevention (2014) National diabetes statistics report: estimates of diabetes and its burden in the United States. US Department of Health and Human Services, Atlanta

    Google Scholar 

  24. Cameron AR, Morrison VL, Levin D, Mohan M, Forteath C, Beall C, McNeilly AD, Balfour DJ, Savinko T, Wong AK, Viollet B, Sakamoto K, Fagerholm SC, Foretz M, Lang CC, Rena G (2016) Anti-inflammatory effects of metformin irrespective of diabetes status. Circ Res 119:652–665

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Heliovaara MK, Herz M, Teppo AM, Leinonen E, Ebeling P (2007) Pioglitazone has anti-inflammatory effects in patients with Type 2 diabetes. J Endocrinol Invest 30:292–297

    Article  CAS  PubMed  Google Scholar 

  26. Son HJ, Lee J, Lee SY, Kim EK, Park MJ, Kim KW, Park SH, Cho ML (2014) Metformin attenuates experimental autoimmune arthritis through reciprocal regulation of Th17/Treg balance and osteoclastogenesis. Mediat Inflamm 973–986

  27. Leung YY, Allen JC, Ang LW, Yuan JM, Koh WP (2017) Diabetes mellitus and the risk of total knee replacement among Chinese in Singapore, the Singapore Chinese Health Study. Sci Rep 7:40671

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Shin D (2014) Association between metabolic syndrome, radiographic knee osteoarthritis, and intensity of knee pain: results of a national survey. J Clin Endocrinol Metab 99:3177–3183

    Article  CAS  PubMed  Google Scholar 

  29. Engstrom G, Gerhardsson de Verdier M, Rollof J, Nilsson PM, Lohmander LS (2009) C-reactive protein, metabolic syndrome and incidence of severe hip and knee osteoarthritis. A population-based cohort study. Osteoarthr Cartil 17:168–173

    Article  CAS  PubMed  Google Scholar 

  30. Tuomi T, Santoro N, Caprio S, Cai M, Weng J, Groop L (2014) The many faces of diabetes: a disease with increasing heterogeneity. Lancet 383:1084–1094

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

The OAI is a public–private partnership comprised of five contracts (N01-AR-2-2258; N01-AR-2-2259; N01-AR-2-2260; N01-AR-2-2261; N01-AR-2-2262) funded by the National Institutes of Health, a branch of the Department of Health and Human Services, and conducted by the OAI Study Investigators. Private funding partners include Merck Research Laboratories; Novartis Pharmaceuticals Corporation, GlaxoSmithKline; and Pfizer, Inc. Private sector funding for the OAI is managed by the Foundation for the National Institutes of Health. This manuscript was prepared using an OAI public use data set and does not necessarily reflect the opinions or views of the OAI investigators, the NIH, or the private funding partners. We would like to acknowledge Jonathan McFarland for editing the manuscript.

Author contributions

All authors have made substantial contributions to all of the following: (1) the conception and design of the study, or acquisition of data, or analysis and interpretation of data (2) drafting the article or revising it critically for important intellectual content (3) final approval of the version to be submitted. Ivan Shirinsky takes responsibility for the integrity of the work as a whole, from inception to finished article.

Author information

Authors and Affiliations

  1. Laboratory of Clinical Immunopharmacology, Research Institute of Fundamental and Clinical Immunology, 6 Zalesskogo Str., 630099, Novosibirsk, Russia

    Ivan V. Shirinsky & Valery S. Shirinsky

Authors
  1. Ivan V. Shirinsky
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Valery S. Shirinsky
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ivan V. Shirinsky.

Ethics declarations

Funding

The analysis presented in this paper had no funding.

Conflict of interest

The authors have no conflict of interest to disclose.

Ethical approval

All procedures performed in studies involving human participants 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.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 26 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Shirinsky, I.V., Shirinsky, V.S. Effects of medication-treated diabetes on incidence and progression of knee osteoarthritis: a longitudinal analysis of the Osteoarthritis Initiative data. Rheumatol Int 37, 983–991 (2017). https://doi.org/10.1007/s00296-017-3676-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00296-017-3676-7

Keywords

Search

Navigation