**11. Associativity between T1D and autoimmune diseases. Polyglandular autoimmune syndromes**

T1D is often concomitant with local or systemic autoimmune disturbances, which further progress to complex autoimmune diseases or polyglandular syndromes via the crossreactivity mechanism. By illustration, in many patients T1D is associated with autoimmune thyroiditis (24.5%/autoAbs vs 47.5%), celiac disease (1.4%/autoAbs to gliadin and IgA to tissue transglutaminase vs 18.7%), MS (0.5-2%/autoAbs vs 7%), Addison's disease (1.4%/adrenal cortex autoAbs vs 0.7%), autoimmune gastritis (6.9-7.2%/parietal cell autoAbs vs 20.9%), etc. (Somers et al., 2009; Villano et al., 2009; De Block et al., 2006)

Secondary autoimmune disorders associated with later steps of T1D have a number of specific features. Thus, autoimmune thyroiditis (AIT) (autoimmune polyglandular syndrome 3A version (APS3Av)) is diagnosed in 12-15% of T1D patients; its clinical manifestations correlate positively with age, gender (AIT is more frequent in females (8.6%) than in males (3.4%)), duration of T1D (mean age of AIT patients varies between 5 and 15 years), serum levels of the thyroid-stimulating hormone (TSH), etc. Both diseases have a common familial hereditary background, but can also be present in a single individual suggesting a crucial role of genetic predisposition in the development of polyglandular syndromes. Furthermore, high incidence of AIT among first-degree relatives of T1D patients points to a significant contribution of genetic factors to immune system failures (see above). (Severinski et al., 2003; Hunger-Battefeld et al., 2009)

Noteworthy, the predominant form of AIT in patients of both sexes is hypothyroidism (8.1%), but in males with anti-thyroid Abs AIT is prevalent (85.7% vs 37.5% in females). the total incidence of hypothyroidism in T1D patients with anti-thyroid Abs is 52.2%. The interval between the onset of T1D and the appearance of first clinical manifestations of AIT varies from one year to 5–6 years, while the first thyroid autoAbs appear in the period between 6 months and 5–3 years before the onset of the disease. Blood sera of patients with APS3Av (AIT and T1D) (Hunger-Battefeld et al., 2009) contain circulating anti-thyroid peroxidase and anti-thyroglobulin Abs emerging soon after emergence of GADA (10% and 8% of cases, respectively); more than 6% of such patients contain both types of autoAbs. As mentioned earlier in this chapter, MS is also associated with T1D. In this case, morbidity from MS among male patients exceeds that in females nearly fourfold (2% vs. 0.5%). According to statistic reports, non-diabetic sisters run five times higher risks for MS than other cohorts of the general population. Consequently, adult females with T1D can be assigned to the highest risk group for associated autoimmune disorders (e.g., MS). (Bussone et al., 2009; Otto-Buczkowska et al., 2009)

The association between T1D and RA is not so apparent as in the case of T1D and MS. In depth studies established that about 13% of patients whose first-degree relatives suffer from T1D have clinical signs of RA. According to other authors, no such linkage does not exist. (Hakala et al., 1992)

Based on these findings, we can state with assurance that T1D increases the risk for autoimmune disorders through triggering the formation of autoimmune clusters and polyglandular autoimmune syndromes. As a rule, circulating autoAbs begin to appear in the blood serum as early as several years before the development of severe secondary disorders and absolute clinical manifestations of the disease. The genetic data provide the physician with a broad spectrum of autoimmune diseases that are likely to develop in patients with T1D. Time-lapse monitoring of patients' blood sera not only affords reliable dynamic control over disease progression, but also enables the physician to estimate the efficiency of ongoing therapy, to search for early-stage biomarkers for diagnosing secondary autoimmune disorders and, last but not least, to implement adequate preventive and curative treatment.
