Clinical and serological differences associated with type 2 diabetes mellitus in Sjögren’s disease: a real-world multicenter analysis

Type 2 diabetes mellitus (DM) is a common metabolic comorbidity in patients with Sjögren’s disease (SjD), but their clinical and serologic profile remain incompletely characterized. We retrospectively compared SjD patients with and without DM and explored factors associated with a history of cardiovascular (CV) events. Patients with DM were compared with individually age- and sex-matched non-diabetic comparators. Group comparisons used appropriate parametric or non-parametric tests. Associations with DM were examined using logistic regression adjusted for age and disease duration and, in sensitivity analyses accounting for the matched design, conditional logistic regression stratified by reconstructed matched sets. A clinically prespecified Firth logistic model fitted to the original observed data evaluated factors associated with a history of CV events. Among 245 patients (95% female; mean age 70 ± 12 years), 100 had DM. Compared with non-diabetic patients, those with DM had higher BMI and more hypertension, hypercholesterolemia and hypertriglyceridemia. Disease activity was similar but ESSDAI was available for only 54% of patients. After adjustment for age and disease duration, DM was associated with lower odds of anti-SSB/La positivity (OR 0.48, 95% CI 0.25–0.88) and low C3 (OR 0.30, 95% CI 0.10–0.76); estimates were similar in conditional analyses accounting for matched sets (OR 0.48, 95% CI 0.25–0.91, and OR 0.27, 95% CI 0.09–0.80, respectively). Thirty-one patients had a history of CV events. In the primary Firth model (n = 239), age (OR 1.07, 95% CI 1.02–1.12; p = 0.005) and hypertension (OR 3.21, 95% CI 1.27–9.54; p = 0.012) were associated with CV history. Anti-SSB/La, smoking and current HCQ use were not significantly associated with CV history. Multiple-imputation results were consistent. Adjusted metformin analyses showed no statistically significant associations. Type 2 DM was associated with a clinical and serologic profile characterized by greater metabolic burden and lower prevalence of serological markers associated with B-cell activity. In the exploratory CV analysis, age and hypertension were associated with a history of CV events. These observational findings, in particular the serological associations, were identified at nominal significance without correction for multiple testing and require independent and prospective validation.