Published online Nov 15, 2020. doi: 10.4239/wjd.v11.i11.527
Peer-review started: June 25, 2020
First decision: August 22, 2020
Revised: August 27, 2020
Accepted: October 13, 2020
Article in press: October 13, 2020
Published online: November 15, 2020
Autoimmune diseases (AID) tend to occur together in the same subjects and cluster in families. Type 1 diabetes (T1D) is caused by an autoimmune-induced inflammatory destruction of the pancreatic tissue and clusters with several other AID.
To obtain a better understanding of the clustering of several autoimmune diseases in the same subject and related families.
With this longitudinal, long-term observational study, we aimed to compare the demographic, clinical, and serological features of patients with single T1D vs those with T1D and associated AID and to analyze the frequency of other AID in T1D.
From October 1999 to February 2020, the medical records of a total of 665 patients with T1D and their first-degree relatives were evaluated. All patients and relatives were screened for signs and symptoms of suspected AID. Diseases were diagnosed and characterized according to an interview regarding their medical history, agreed-upon definition, typical clinical presentation and specific serology. The Johannes Gutenberg University Central Laboratory reference ranges were set as cut-offs, while for data acquisition, standardized clinical and laboratory diagnostic criteria were used. Only patients with confirmed T1D were included in the analysis.
A total of 665 patients with T1D and their first-degree relatives were evaluated. Compared to patients with T1D only, the female to male ratio was approximately two-fold greater in patients with T1D + AID. The mean age of patients with T1D was 33 (± 16) years and 56 (± 16) years for patients with T1D + AID. Average disease duration of T1D was similar in both groups. More importantly, the average time interval between T1D onset and the onset of a second glandular AID was markedly shorter (13 ± 12 years) than the time interval between T1D and the occurrence of a non-endocrine AID (19 ± 15 years).
On average, we observed two associated AID, with a minimum of zero and a maximum of five. We found slightly more T1D relatives were also affected by AID (58.1%) when compared to T1D + AID (44.3%) relatives. The prevalence of autoantibodies (Ab) against various other tissues was found to be higher in patients with T1D + AID. In the relatives of patients with T1D, nearly all subjects with positive diabetes Ab titers had diagnosed T1D (> 90%), and in the relatives of patients with T1D + AID, approximately 35% of Ab-positive subjects had no AID. The prevalence of Ab against various other tissues was found to be higher in relatives of patients with isolated T1D.
As expected we found that T1D often clusters with several other AID. Gastrointestinal AID such as type A gastritis and celiac disease are often prevalent in patients with T1D + AID, while Hashimoto’s thyroiditis (HT) is the most frequent autoimmune thyroid disease (AITD). Therefore, at the onset of T1D, whether as a monoglandular disease or in combination with another AID, serological and subsequent functional screening for additional glandular and non-glandular AID are recommended. The significantly different sex profile in patients with isolated T1D vs those in the combined group may be explained by the fact that AITD, such as HT and Graves‘ disease occur significantly more often in females. High Ab titers in the combination group (T1D + AID) might be explained by the later disease onset of diabetes in patients with T1D + AID. On average not as much time since onset of disease might have passed when Ab were measured.
In this study, we compared patients with isolated T1D to patients with T1D + AID. We found that approximately one third of T1D patients will develop thyroid-Ab and thyroid dysfunction; therefore, general organ-specific Ab screening and functional testing in patients with either monoglandular T1D or monoglandular Addison disease, will help identify subjects at risk of developing polyglandular autoimmunity, and management of T1D associated with other AID requires care by specialized centers for endocrine and metabolic AID. We also recommend serological screening of first-degree relatives of T1D patients.