APS Screening in Adults with Type 1 Diabetes Often Missed
Key Takeaways
- At a tertiary diabetes center in Trieste, Italy, 31% of adults with T1DM met clinical APS criteria, but only 8.6% had APS formally documented in the medical record.
- Broader screening found previously unknown autoantibody positivity in 39% of tested patients.
- Follow-up evaluation confirmed new autoimmune disease in 11.5%, with chronic autoimmune gastritis the most frequent new diagnosis.
- After newly identified and previously recorded conditions were combined, 32% of the 139 APS patients who underwent extended screening had at least three autoimmune diseases.
- Female sex and CSII use were associated with APS, while glycemic control did not differ materially between patients with and without APS.
Investigators conducted a real-world cross-sectional study of 639 adults older than 18 years with T1DM identified through electronic records at the ASUGI Diabetes Center in Trieste, Italy. Patients with concomitant autoimmune thyroid disease (AITD) and/or celiac disease met the study's clinical APS criteria, and records were reviewed for diabetes characteristics, prior APS documentation, and coexisting autoimmune disease. Of the 198 eligible patients, 139 consented to an extended screening workup that included thyroid and celiac antibodies, gastric and adrenal antibodies, antinuclear antibodies, rheumatoid factor, immunoglobulin A, vitamin B12, serum protein electrophoresis, and routine laboratory parameters, followed by condition-specific confirmatory evaluation when screening was positive.
Formal APS labeling often lagged behind the underlying clinical picture in this adult T1DM cohort. APS was independently associated with female sex and with continuous subcutaneous insulin infusion (CSII) use, while age, diabetes duration, glycated hemoglobin, microvascular complications, and cardiovascular disease did not differ significantly between patients with and without APS.
In APS screening yield and association results in adult T1DM, previously unknown autoantibody positivity was found in 39% of screened patients, new autoimmune diseases were confirmed after additional evaluation in 11.5%, and 32% of the 139 APS patients who underwent extended screening ultimately had at least three autoimmune diseases after newly identified and previously recorded conditions were combined. Chronic autoimmune gastritis was the most frequent new diagnosis, with smaller numbers of newly identified thyroid disease, celiac disease, Addison's disease, rheumatic disease, systemic lupus erythematosus, and autoimmune hepatitis. Antinuclear antibodies and anti-parietal cell antibodies were the most frequent previously unrecognized serologic findings.
Because the study was cross-sectional, it could not determine whether newly detected autoantibodies would progress to overt autoimmune disease over time. About 30% of eligible patients declined the extended workup, which may introduce selection bias, and the primarily antibody-based strategy could miss seronegative conditions. Positive antibodies also did not always correspond to overt disease at the time of screening. The findings come from a single adult tertiary center in Trieste, Italy; for U.S. clinicians, the study underscores a question that extends beyond routine thyroid and celiac surveillance in T1DM, but it does not establish how broadly this screening approach applies outside that setting.
The authors concluded that APS in adult T1DM was frequently under-recognized and that identifying AITD or celiac disease may represent only one stage in a broader autoimmune profile.
Clinician Questions
How did this analysis define and classify autoimmune polyendocrine syndrome in adults with type 1 diabetes?
Adults in this study met the clinical APS definition when type 1 diabetes coexisted with autoimmune thyroid disease and/or celiac disease. The authors classified APS-2 as Addison's disease with AITD and/or T1DM, APS-3 as T1DM with AITD in the absence of Addison's disease, and APS-4 as T1DM or AITD with another organ-specific autoimmune disease, again excluding Addison's disease.
What did the extended autoimmune screening workup include for adults with type 1 diabetes and APS features?
The extended workup included thyroid peroxidase antibodies, thyroglobulin antibodies, thyroid-stimulating hormone receptor antibodies, tissue transglutaminase antibodies, total immunoglobulin A, anti-parietal cell antibodies, 21-hydroxylase antibodies, antinuclear antibodies, rheumatoid factor, serum protein electrophoresis, vitamin B12, and general laboratory parameters. Positive screening findings were followed by confirmatory evaluation such as gastroscopy, morning cortisol and adrenocorticotropic hormone testing, or specialist assessment with condition-specific testing.
Which autoimmune diseases were newly uncovered after additional evaluation in adults with type 1 diabetes and APS features?
Chronic autoimmune gastritis was the most frequent newly identified autoimmune disease after follow-up evaluation. Smaller numbers of patients were newly found to have autoimmune thyroid disease, celiac disease, Addison's disease, rheumatoid arthritis, systemic lupus erythematosus, and autoimmune hepatitis, and low vitamin B12 was also identified in two patients. The authors noted that autoantibody positivity did not always translate into confirmed overt autoimmune disease.
What can this Italian APS screening study tell us about progression from autoantibody positivity to overt autoimmune disease?
This Italian study used a cross-sectional design with one-time extended screening, so it cannot determine the rate or timing of progression from newly detected autoantibodies to overt autoimmune disease in adults with type 1 diabetes. The authors interpreted antibody positivity as potentially preceding disease in some cases, while also noting that an antibody-based strategy may miss seronegative autoimmune conditions.