Specific association of type 1 diabetes mellitus with anti–cyclic citrullinated peptide–positive rheumatoid arthritis

Abstract

Objective The co‐occurrence of autoimmune diseases such as rheumatoid arthritis (RA) and type 1 diabetes mellitus (DM) has been reported in individuals and families. In this study, the strength and nature of this association were investigated at the population level in a Swedish case–control cohort. Methods For this case–control study, 1,419 patients with incident RA diagnosed between 1996 and 2003 were recruited from university, public, and private rheumatology units throughout Sweden; 1,674 matched control subjects were recruited from the Swedish national population registry. Sera from the subjects were tested for the presence of antibodies to cyclic citrullinated peptide (anti‐CCP), rheumatoid factor (RF), and the 620W PTPN22 allele. Information on a history of diabetes was obtained by questionnaire, telephone interview, and/or medical record review. The prevalence of type 1 DM and type 2 DM was compared between patients with incident RA and control subjects and further stratified for the presence of anti‐CCP, RF, and the PTPN22 risk allele. Results Type 1 DM was associated with an increased risk of RA (odds ratio [OR] 4.9, 95% confidence interval [95% CI] 1.8–13.1), and this association was specific for anti‐CCP–positive RA (OR 7.3, 95% CI 2.7–20.0), but not anti‐CCP–negative RA. Further adjustment for the presence of PTPN22 attenuated the risk of anti‐CCP–positive RA in patients with type 1 DM to an OR of 5.3 (95% CI 1.5–18.7). No association between RA and type 2 DM was observed. Conclusion The association between type 1 DM and RA is specific for a particular RA subset, anti‐CCP–positive RA. The risk of developing RA later in life in patients with type 1 DM may be attributed, in part, to the presence of the 620W PTPN22 allele, suggesting that this risk factor may represent a common pathway for the pathogenesis of these 2 diseases.