No Increased Risk of Diabetes Seen With RA

Patients with rheumatoid arthritis (RA) were not at increased risk for developing type 2 diabetes, a large population-based cohort study found.

The hazard ratio for incident type 2 diabetes among RA patients was 0.72 (95% CI 0.66-0.78) compared with the general non-RA population, according to Seoyoung C. Kim, MD, ScD, and colleagues from Brigham and Women’s Hospital in Boston.

Additionally, the likelihood of developing type 2 diabetes was 24% to 35% lower among RA patients compared with patients with hypertension, osteoarthritis, and psoriatic arthritis, the researchers reported in Arthritis Care & Research.

Patients with RA have a well-recognized elevated risk of cardiovascular disease (CVD), which is only partly explained by traditional cardiovascular risk factors, but which also may relate to systemic inflammation.

Pro-inflammatory cytokines such as tumor necrosis factor-α and interleukin-6 are involved in the pathogenesis and progression of RA, and also disrupt insulin-signaling pathways that can lead to insulin resistance. “Therefore, the risk of type 2 diabetes mellitus, which is a traditional CVD risk factor, may be increased in RA and could be a target for intervention to reduce CVD-related mortality,” Kim and colleagues wrote.

Previous studies looking at the incidence of diabetes among RA patients have had conflicting results, with a U.S. study finding a lower risk, a U.K. study showing no difference, and a Canadian report indicating a higher risk. These differences may relate to the type of comparator group used for analysis, with some matching patients and controls only by age and sex, but others excluding patients with any other underlying inflammatory diseases.

Therefore, to examine the risk of diabetes in RA compared with the general population, as well as other patient populations that share risk factors, Kim’s group analyzed data from Optum Clinformatics Data Mart, a large commercial health claims database, for the years 2005 to 2017. They hypothesized that the risk for developing type 2 diabetes among RA patients would be higher than in a general non-RA population and among individuals with osteoarthritis, but similar to or lower than in patients with psoriatic arthritis or hypertension.

The analysis included 108,568 patients with RA, matched with the same number each for general non-RA patients and patients with hypertension and osteoarthritis. All 15,055 with psoriatic arthritis identified in the database were also included. The mean age was 55.6 years in all groups, except the psoriatic arthritis group, in which the mean age was 48.6 years. More than three-quarters were women in all groups, again with the exception of the psoriatic arthritis group, which included similar numbers of men and women.

Comorbidities and medication use differed across the groups, with RA patients having the highest comorbidity scores, and obesity and other cardiovascular comorbidities being highest in the hypertension group. Glucocorticoids were more commonly used by patients with RA and psoriatic arthritis, while nonsteroidal anti-inflammatory drugs and statins were more commonly used by the osteoarthritis group and the hypertension group, respectively.

During median follow-up times ranging from 1.4 to 1.8 years, diabetes diagnoses were reported in 2,091 of the RA group, 1,828 of the general non-RA group, 3,012 of the hypertension group, 1,802 of the osteoarthritis group, and 366 of the psoriatic arthritis group. Crude incidence rates were highest in the hypertension and psoriatic arthritis groups, at 12.3 and 9.9 per 1,000 person-years, respectively, and lowest among RA patients, at 7 per 1,000 person-years.

After adjustment for baseline demographics, comorbidities, and medication use, the risk of developing type 2 diabetes in the RA group was lower when compared with patients with other underlying conditions:

• RA vs hypertension, HR 0.65 (95% CI 0.60-0.71)
• RA vs osteoarthritis, HR 0.75 (95% CI 0.69-0.81)
• RA vs psoriatic arthritis, HR 0.76 (95% CI 0.67-0.86)

The authors offered several explanations for the differences in risks among the groups. For example, the lower risk in RA patients may relate to the widespread use of biologic therapies, which have been shown to reduce the likelihood of diabetes when compared with non-biologic treatments such as methotrexate. The reduced risk compared with osteoarthritis may reflect the frequency of obesity in that group of patients, and the lower risk compared with hypertension and psoriatic arthritis could result from metabolic dysregulation commonly associated with those disorders.

“While systemic inflammation in RA is thought to increase the risk of CVD and cardiovascular risk factors such as diabetes mellitus, our findings suggest that having RA itself does not confer an increased risk of type 2 diabetes mellitus,” the researchers concluded.

Further research should consider whether inadequately treated RA influences risk, they suggested.

A limitation of the study was its reliance on claims data.