Clinicians are aware that diabetes mellitus (DM) and osteoarthritis (OA) often co-exist, but they may be unaware that the link is not necessarily through body weight. Although OA and DM are each highly prevalent and share certain risk factors, new research adds weight to the evidence that DM alone is an independent risk factor for osteoarthritis (OA) knee pain as well as for the declines in physical and mental health seen in patients with osteoarthritis.
Osteoarthritis affects more than 30 million adults in the United States. Radiographically defined knee OA increases dramatically with age, affecting 14% of adults aged over 25 years and 37% of those over the age of 60 years.
Individuals with diabetes mellitus experience greater rates of OA compared with those without DM and have higher rates of joint replacement. Pain intensity is also higher in OA joints of individuals with DM.
Obesity occurs in the majority of people with DM and is thought to be a risk factor for OA because of the increased mechanical stress placed on weight-bearing joints. In addition, the release of proinflammatory cytokines by adipose tissue may contribute to the structural pathology of osteoarthritis. Obesity and radiographic evidence of OA severity are often related to OA pain. However, because pain intensity is not always aligned with radiographic severity, the source of pain can be difficult to identify.
Annett Eitner, PhD, at the Clinic of Traumatology and Orthopedic Surgery, Friedrich Schiller University, in Jena, Germany and her colleagues dug into this issue. They sought to examine whether greater pain reported by individuals with OA and DM was due to greater BMI and radiographic OA severity of those with DM, or whether DM induced a particular phenotype of OA, in which other pain mechanisms were at play.
They evaluated data from 202 patients with both osteoarthritis and diabetes mellitus and 2,270 patients with osteoarthritis alone. Participants were pulled from the Osteoarthritis Initiative database. The Osteoarthritis Initiative is an NIH sponsored, 10-year, multicenter observational study in the United States that enrolled 4796 participants with or at risk of knee OA to investigate the impact of knee OA over time and to better understand prevention and treatment strategies.
Dr. Eitner and colleagues found that participants with both knee OA and DM reported worse knee pain as well as a higher incidence of physical and mental issues compared with those without DM. The knee pain, which was evaluated using the Knee Injury and Osteoarthritis Outcome Score (KOOS), a self-administered assessment of short- and long-term knee injury, and a numerical rating scale of non-activity related pain was found to occur independently of body mass index (BMI), OA severity as shown radiographically, age, and gender.
In addition, the negative influence of DM was apparent in results indicating worse physical and mental health on standardized tests, including the Medical Outcomes Study Short Form 12 (SF-12 physical, SF-12 mental) and the Center for Epidemiological Studies – Depression Scale (CES-D).
"Given that previous studies into the relationship between DM and OA pain were of moderate sample size only and did not adjust for radiographic OA severity, the current study used a large observational cohort to test the hypothesis that OA pain sensation in individuals with DM is stronger than in non-DM controls, independently of BMI and radiographic disease status,” Dr. Eitner and colleagues wrote.
Pain intensity may be greater in patients with OA and DM because of increased systemic and local inflammation, microvascular changes, and pain sensitization alterations. In addition, hyperglycemia may contribute to mitochondrial dysfunction, hypoxia, and release of reactive oxygen species in peripheral tissues, possibly leading to abnormal nociception and peripheral neuropathy.
These factors, along with psychosocial factors, may cause the presence of DM to result in greater knee pain, independent of elevated BMI and radiographic OA status, concluded the investigators, and should be further investigated.
In another recently published study using data from the Osteoarthritis Initiative, Alenazi and colleagues examined the association between DM and knee pain in individuals with OA and explored the association between DM and knee pain distribution (unilateral or bilateral versus no pain) in those with knee OA. They found that DM was also significantly associated with OA knee pain severity, and participants with knee OA and DM had a 2.5 times greater likelihood of having unilateral and bilateral knee pain than those without DM and without knee pain. These results occurred even after controlling for age, gender, BMI, race, depression symptoms, composite OA score, pain medications, and knee injections. Pain severity was examined over 7 days and over 30 days, and DM had a negative influence on both.
The authors had hypothesized that participants with DM would be more likely to have bilateral knee pain than those without DM, because DM, as a systemic disease, could affect both knees in individuals with knee OA. “However, since both unilateral and bilateral joint pain were significantly associated with DM, it could be that DM contributes to pain in knees that are otherwise compromised, rather than causing symptomatic knee OA,” wrote the authors. They proposed that the results could be explained by recent research showing that DM was associated with accelerated cartilage degeneration that might affect one or both knees.
Investigators from the same group (Alenazi) examined the association between type 2 diabetes (T2D) and pain severity, and explored the association between glycemic control, measured by hemoglobin A1c (HbA1c) level, and pain severity in those with localized OA and T2D. Using data from 819 patients at a tertiary medical center, they found that T2D was associated with increased pain severity in those with localized OA, even after controlling for age, gender, BMI; diagnoses of depression, hypertension, dyslipidemia; OA locations; and medications.
Furthermore, poor glycemic control in patients with T2D was significantly associated with higher pain severity, after controlling for age, gender, BMI, medications, and OA locations. “Clinicians should emphasize that better HbA1c control might help with pain management in people with T2D and OA,” concluded the investigators.“
“Everyone is well aware of the association of diabetes with obesity but these new studies, as well as a recent review, demonstrate that this association is not just related to increased weight-bearing load but is multifactorial,” said PPM editorial board member Don L. Goldenberg, MD.
“I don’t believe that rheumatologists or primary care providers are that aware of the association of type 2 diabetes with OA, independent of BMI,” he added. “Therefore, although I’m sure every clinician asks about important health issues, particularly diabetes, they should make patients aware that diabetes, independent of obesity, has a negative effect on pain and osteoarthritis and is another reason to keep blood glucose under control.”