Study Finds Rheumatoid Arthritis Associated With Lower T2D Risk

Results from a large population-based cohort study, published in Arthritis Care & Research, found individuals with rheumatoid arthritis (RA) had a lower rate of incident type 2 diabetes (T2D) compared with the general non-RA population and cohorts with hypertension, osteoarthritis (OA), and psoriatic arthritis (PsA).

“Proinflammatory cytokines such as tumor-necrosis factor alpha (TNFα) and interleukin-6 (IL-6) play critical roles in RA pathogenesis and simultaneously interfere with insulin-signaling mechanisms which are associated with insulin resistance and T2D,” authors write. Because of this, the risk of T2D, a traditional cardiovascular disease (CVD) risk factor, “may be increased in RA and could be a target for intervention to reduce CVD related mortality.”

Patients with OA also tend to exhibit known risk factors for T2D such advanced age and obesity, while prior studies have found PsA to be associated with increased risk of diabetes compared with the general population. In addition, both hypertension and PsA are associated with metabolic dysregulation and increase the risk of diabetes.

As previous epidemiologic studies have yielded inconsistent relative risk estimates for the relationship between T2D in RA, researchers set out to examine this risk using a large US commercial database, which amassed information from 449,327 patients. The risk of incident T2D in RA patients was compared with 4 different non-RA groups: general non-RA patients, those with hypertension, those with OA, and those with PsA.

The Optum Clinformatics Data Mart (Optum) is a commercial health insurance claims database which includes data from January 2005 through December of 2017. Optum also provides information on demographics, hospital admissions, emergency room visits, outpatient visits and other metrics throughout all 50 US states.

Patients with RA were matched to the general non-RA, hypertension, and OA patients based on age, sex, and index date with a 1:1:1:1 ratio. Because of a substantially smaller PsA cohort, matching was not conducted with this population. Researchers also collected all covariates during the 365-day baseline period prior to and on the index date.

In total, 108,568 matched patients in the RA, general non-RA, hypertension, and OA cohorts were included in the study. Average age among these cohorts was around 56 while the majority (77.3%) were female. In the PsA cohort, patients had an average age of around 47 and 48.3% were female.

Analyses found:

• During the median of 1.6 (range, 0.6-3.3) years of follow-up, the incidence rate (IR) of T2D was the lowest in the RA cohort (7.0 per 1000 person-years) and highest (12.3 per 1000 person-years) in the hypertension cohort
• Crude IRs of T2D per 1000 person-years was 7.4 in the general non-RA cohort, 7.8 in the OA cohort, and 9.9 in the PsA cohort
• After adjusting for over 40 baseline covariates, RA was associated with a 24% to 35% lower risk of incident T2D compared with the 4 comparison groups
• Prevalence of obesity was the highest in hypertension cohort (14.8%), followed by OA (14.4%), PsA (10.7%), RA (8.9%), and the general non-RA cohorts (7.4%)
• Cardiovascular comorbidities were generally more prevalent in the hypertension cohort than other cohorts
• A higher risk of hip fracture in the RA cohort was found compared with the general non-RA cohort and the hypertension cohort

“While systemic inflammation in RA increases the risk of CVD, our findings unexpectedly show that having RA itself does not confer an increased risk of T2D compared with 4 different comparator groups,” said Seoyoung C. Kim, MD, a lead author of the study.

As the study mainly used diagnosis codes and pharmacy dispensing records in claims data, potential misclassification of cohorts and covariates may exist, marking a limitation to the study. Baseline obesity also tends to be underreported and may not have been accurately captured in claims data, while residual confounding may exist due to unmeasured covariates such as body mass index, diet, and physical activity.

“Since all RA patients included in our study were treated with at least 1 disease-modifying antirheumatic drug, our study is unable to test the association between no treatment or undertreatment for RA and risk of T2D,” Kim said.

Future studies are warranted to determine whether untreated or undertreated RA is associated with a greater risk of developing T2D, authors conclude.

Reference

Jin Y, Chen SK, Liu J and Kim SC. Risk of incident type 2 diabetes among patients with rheumatoid arthritis: a population-based cohort study. Arthritis Care Res. Published online August 4, 2020. doi:10.1002/acr.24343