Clinical Significance of Diabetes-Mellitus-Associated Antibodies in Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a canonical autoimmune disease that shares numerous risk factors with diabetes mellitus (DM). The production of autoantibodies is a characteristic feature in both diseases. To determine the frequency and specificity of DM-related antibodies (DMab) in RA patients and to study whether DMab associates with new DM cases in RA patients, we measured DMab defined as IgG against glutamic acid decarboxylase (GADA), tyrosine phosphatase (IA2-ab), and zinc transporter (ZnT8-ab) in a cohort of 290 RA patients (215 women and 75 men, median disease duration 11 years). Of those, 21 had a DM diagnosis at baseline. The development of new DM cases and mortality were traced in a 10-year prospective follow-up. Predictive analyses for DM and mortality were carried out by the Mantel-Cox regression. We found that 27 of the patients (9.3%) had DMab, equally often men and women. The presence of DMab was more frequent in patients with DM ( = 0.027. OR 4.01, 95%CI [1.20; 11.97]), suggesting their specificity for the disease. Men had more prevalent incidental DM at the baseline (12% vs. 5%, = 0.030) and among the new DM cases ( = 0.012. HR 6.08, 95%CI [1.57; 25]). New DM developed equally frequently in DMab-positive and DMab-negative patients. DM, but not DMab, significantly increased the estimated mortality rate in RA patients ( = 0.021, OR 4.38 [1.2; 13.52]). Taken together, we conclude that DMab are associated with DM in RA patients, but they are not solely enough to predict disease development or mortality in those patients.