Diabetes and Osteoarthritis: A Vicious Cycle

Type 2 diabetes mellitus (T2DM) and osteoarthritis (OA) often come together. Higher frequencies of other conditions often linked to diabetes, such as obesity, hypertension, and dyslipidemia, also have been associated with OA.¹ While the relationship is complex, OA and T2DM may feed into each other in a vicious cycle-with progression of T2DM contributing to worsening OA, and vice versa.

Which Comes First?

Body mass index (BMI) and age are well-known risk factors for both T2DM and OA, but there may be more here than meets the eye. Injury and mechanical wear and tear on the joints and cartilage over time might not be enough to explain the increased risk of OA in patients with T2DM.

Some researchers are beginning to suspect that diabetes itself could be an independent risk factor for OA and have proposed a “diabetes-induced phenotype.”² Chronic, low-grade inflammation is common in both OA and metabolic disorders. Studies suggest that lipid irregularities, hyperglycemia, and advanced glycosylation end products can be deleterious to cartilage homeostasis. Adipokines, inflammatory mediators released from adipose tissue, could also play a role.³

Moreover, treatment for T2DM could affect bone metabolism, with specific effects varying by type of agent. While thiazolidinediones can promote bone loss, metformin could stimulate bone formation through differentiation of osteoblasts.⁴ Some patients with T2DM already tend to have higher bone density, possibly linked to hyperinsulinemia and the anabolic action of insulin on bone.⁴

T2DM and OA: 1 + 1 = 3

While scientists debate which comes first, it is fair to say that concomitant OA and T2DM increases the risk for other comorbidities. People with OA are at increased risk for depression and lower quality of life in general.⁵ Having multiple co-morbidities, such as the triad of diabetes, osteoarthritis, and cardiovascular disease, is associated with even lower levels of emotional well-being.⁵

Having T2DM may also increase the risk of having more severe OA and the need for subsequent arthroplasty. In a Scottish population-based cohort study, researchers looked at 927 men and women aged 40 to 80 years. After approximately 20 years of follow-up (from 1990 to 2010), the rate of knee arthroplasty in patients with T2DM was more than three times the rate of those without T2DM (17.7  [95% CI 9.4 to 30.2] and 5.3 [95% CI 4.1 to 6.6] per 1,000 person-years, respectively, p<.001). After adjusting for age, BMI, and other OA risk factors, having T2DM was an independent predictor for knee arthroplasty, and the probability increased along with longer diabetes duration.⁶ Other studies have suggested that patients with T2DM who require arthroplasty also have worse outcomes.⁷

The physical disability that accompanies osteoarthritis affects other body systems also impacted by T2DM, particularly the cardiovascular system. Osteoarthritis of the hand and knee joints has been independently linked to atherosclerosis.⁸ Cardiovascular disease has been found to be more prevalent in patients with inflammatory arthritis, T2DM, and osteoarthritis, compared with people without these conditions.⁹ After controlling for age, gender, hypertension, and hypercholesterolemia, the association with cardiovascular disease remained for inflammatory arthritis and diabetes, but dropped out for OA, which could suggest a larger role for lifestyle factors such as physical inactivity in the case of osteoarthritis.⁹

Osteoarthritis has also been linked to higher risk for death. In a study of 1163 patients over age 35 years who were seen at general practices in England, those with OA had higher all-cause mortality than the general population (standardized mortality ratio [SMR] 1.55, 95% CI 1.41 to 1.70). These rates increased among those with a self-reported history of diabetes (SMR, 1.95, 95% CI 1.31 to 2.90), cardiovascular disease (SMR, 1.38, 95% CI 1.12 to 1.71), and walking disability (SMR 1.48, 95% CI 1.17 to 1.86). The risk of death increased along with severity of walking disability (P for trend <.001).¹⁰

Keep Trucking

Early identification of walking disabilities and other functional limitations that interfere with diabetes self-care (eg, hand arthritis that impedes insulin injections) could help break, or at least modify, the vicious cycle between T2DM and OA. Personalized exercise programs that are tailored to specific comorbidities and that make the most of individual abilities also could play a vital role.

References:

• Marshall M, Peat G, Nicholls E, van der Windt D, Myers H, Dziedzic K. Subsets of symptomatic hand osteoarthritis in community-dwelling older adults in the United Kingdom: prevalence, inter-relationships, risk factor profiles and clinical characteristics at baseline and 3-years. Osteoarthritis Cartilage. 2013;21:1674-1684. doi: 10.1016/j.joca.2013.08.004. Epub 2013 Aug 13.
• Berenbaum F. Diabetes-induced osteoarthritis: from a new paradigm to a new phenotype. Postgrad Med J. 2012;88:240-242. doi: 10.1136/pgmj.2010.146399rep.
• Sellam J, Berenbaum F. Is osteoarthritis a metabolic disease? Joint Bone Spine. 2013;80:568-573. doi: 10.1016/j.jbspin.2013.09.007. Epub 2013 Oct 29.
• Yan W, Li X. Impact of diabetes and its treatments on skeletal diseases. Front Med. 2013;7:81-90. doi: 10.1007/s11684-013-0243-9. Epub 2013 Feb 2.
• Wikman A, Wardle J, Steptoe A. Quality of life and affective well-being in middle-aged and older people with chronic medical illnesses: a cross-sectional population based study. PLoS One. 201129;6:e18952. doi: 10.1371/journal.pone.0018952.
• Schett G, Kleyer A, Perricone C, et al. Diabetes is an independent predictor for severe osteoarthritis: results from a longitudinal cohort study. Diabetes Care. 2013;36:403-409. doi: 10.2337/dc12-0924. Epub 2012 Sep 21.
• Robertson F, Geddes J, Ridley D, McLeod G, Cheng K. Patients with type 2 diabetes mellitus have a worse functional outcome post knee arthroplasty: a matched cohort study. Knee. 2012;19:286-289. doi: 10.1016/j.knee.2011.06.001. Epub 2011 Jun 28.
• Hoeven TA, Kavousi M, Clockaerts S, et al. Association of atherosclerosis with presence and progression of osteoarthritis: the Rotterdam Study. Ann Rheum Dis. 2013;72:646-651. doi: 10.1136/annrheumdis-2011-201178. Epub 2012 May 6.
• Nielen MM, van Sijl AM, Peters MJ, Verheij RA, Schellevis FG, Nurmohamed MT. Cardiovascular disease prevalence in patients with inflammatory arthritis, diabetes mellitus and osteoarthritis: a cross-sectional study in primary care. BMC Musculoskelet Disord. 2012;13:150. doi: 10.1186/1471-2474-13-150.
• Nüesch E, Dieppe P, Reichenbach S, Williams S, Iff S, Jüni P. All cause and disease specific mortality in patients with knee or hip osteoarthritis: population based cohort study. BMJ. 2011;8;342:d1165. doi: 10.1136/bmj.d1165.