Prevalence of Type 1 Diabetes Mellitus across Antinuclear Antibody Patterns and Their Distribution in a Taiwanese Cohort

Background Type 1 Diabetes Mellitus (T1DM) is an autoimmune disease characterized by pancreatic β-cell destruction. While islet-specific autoantibodies are key markers, Antinuclear Antibodies (ANA) are also observed, but their relationship with specific ANA patterns, classified by the International Consensus on ANA Patterns (ICAP), in T1DM, especially in diverse populations like Taiwan, needs more investigation. This study aimed to determine the prevalence of T1DM across various pure ANA patterns and describe the distribution of these patterns among T1DM patients in a large Taiwanese cohort. Methods This cross-sectional study utilized de-identified data from the Chang Gung Research Database (CGRD) from January 2019 to September 2021. Patients undergoing ANA testing by indirect immunofluorescence (IIF) on HEp-2 cells were included. Individuals with inconsistent or mixed ANA patterns were excluded. T1DM diagnosis was based on International Classification of Diseases (ICD)-9-CM/ICD-10-CM codes, validated by endocrinologist records and further confirmed by catastrophic illness certificate (CIC) data for T1DM from Taiwan's National Health Insurance system. The prevalence of T1DM was calculated for each pure ANA pattern (AC-1 to AC-29), using the ANA-negative group (AC-0) as the reference. Odds ratios (ORs) with 95% confidence intervals (CIs) and Fisher’s exact test were used for statistical comparisons. Results From 38,572 initial patients, 35,763 with pure ANA patterns were analyzed (31,151 AC-0; 4,612 ANA-positive). The overall T1DM prevalence in the AC-0 group was 0.11% (34/31,151). Among ANA-positive patterns, only the AC-4 (Speckled) pattern (n = 670) showed a significantly higher T1DM prevalence (0.60%, 4 cases; OR 5.50, 95% CI [1.75–17.26], p = 0.0082) compared to the AC-0 group. Other patterns such as AC-1 (Homogeneous, 0.18%), AC-3 (Centromere, 0.16%), and AC-5 (Fine speckled, 0.19%) also had T1DM cases, but these associations were not statistically significant. The overall ANA positivity rate was not significantly different between T1DM patients (19.05%, 8/42) and non-T1DM individuals (12.91%, 4612/35721) in this pure pattern cohort (p = 0.2360). Among the 8 ANA-positive T1DM patients, Speckled patterns (AC-4/AC-5) were predominant (6/8, 75.00%), followed by AC-1 (Homogeneous; 1/8, 12.50%) and AC-3 (Centromere; 1/8, 12.50%). All identified patterns in T1DM patients were nuclear. Conclusion In this large Taiwanese cohort, while overall ANA positivity was not significantly increased in T1DM patients, the pure AC-4 Speckled ANA pattern was associated with a significantly higher prevalence of T1DM compared to ANA-negative individuals. Speckled patterns were the most common ANA patterns observed among ANA-positive T1DM patients. These findings suggest a potential specific link between certain ANA patterns, particularly AC-4, and T1DM autoimmunity, warranting further investigation into the specific antigens involved and the clinical implications in diverse populations.