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

Arthritis Rheum. 2009 Mar;60(3):653-60. doi: 10.1002/art.24362.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Alleles
  • Antibodies / blood
  • Antibodies / immunology*
  • Arthritis, Rheumatoid / blood
  • Arthritis, Rheumatoid / genetics
  • Arthritis, Rheumatoid / immunology*
  • Autoimmune Diseases / blood
  • Autoimmune Diseases / genetics
  • Autoimmune Diseases / immunology
  • Case-Control Studies
  • Diabetes Mellitus, Type 1 / genetics
  • Diabetes Mellitus, Type 1 / immunology*
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / genetics
  • Diabetes Mellitus, Type 2 / immunology
  • Female
  • Genetic Predisposition to Disease
  • Health Surveys
  • Humans
  • Interviews as Topic
  • Male
  • Middle Aged
  • Peptides, Cyclic / immunology*
  • Protein Tyrosine Phosphatase, Non-Receptor Type 22 / genetics
  • Rheumatoid Factor / blood
  • Rheumatoid Factor / immunology
  • Sweden
  • Young Adult


  • Antibodies
  • Peptides, Cyclic
  • cyclic citrullinated peptide
  • Rheumatoid Factor
  • PTPN22 protein, human
  • Protein Tyrosine Phosphatase, Non-Receptor Type 22