Does your patient have an existing autoimmune condition? Check for type 1 diabetes!

Key Takeaway

Concomitant autoimmune conditions may represent additional burden and complications in patients with T1D¹

In the US, prevalence of autoimmune diseases is higher in Caucasians and women and tends to rise with advancing age⁷

T1D confers an increased risk of autoimmune diseases in first-degree relatives¹

Shared genetic risk factors and immune system dysregulation are potentially implicated both in polyautoimmunity* and family autoimmunity† among individuals with T1D³

Screening for T1D should be advised in individuals with other associated autoimmune diseases^4-6,10

*Polyautoimmunity is the occurrence of ≥2 autoimmune diseases in a single patient; †Family autoimmunity presence of ≥2 autoimmune diseases in members of a nuclear family

Could autoantibodies serve as markers for autoimmunity in T1D?

In some patients, T1D is associated with the presence of additional autoimmune diseases, such as autoimmune thyroid disease, coeliac disease, and Addison’s disease, which could lead to the production of organ-specific autoantibodies.¹

Autoantibodies such as insulin autoantibodies (IAA), glutamic acid decarboxylase-65 (GAD-65), islet cell antigen 2 (IA-2), and islet cells autoantibodies (ICA), may be present for years prior to the diagnosis of T1D and could serve as markers of T1D.¹

Do other associated autoimmune diseases frequently coexist with T1D?

Concomitant autoimmune conditions may represent additional burden and complications in patients with T1D.^3,7 In the US, the prevalence of autoimmune diseases is higher in Caucasians and women and tends to rise with advancing age.⁷

Please refer to the below figure to know more about the prevalence of other associated autoimmune diseases linked with T1D.

Prevalence of other associated autoimmune diseases linked with T1D^1,2

^aRatio between observed and expected disease frequency; ^bPresence of thyroid antibodies among new onset T1D patients is a frequent occurrence; ^cIndividuals with T1D may require a repeat screening as the first screen is not positive for autoantibodies in a significant proportion; ^d15% of such individuals may develop it within a relatively short follow-up time. SIR>1: Greater than expected disease frequency

21-OH, 21-hydroxylase; AITD, autoimmune thyroid disease; EMA, endomysial; SIR, Standardised incidence ratio; TG, thyroglobulin; T1D, type 1 diabetes; TPO, thyroid peroxidase; TTG, transglutaminase

Is there a familial association between T1D and other associated autoimmune diseases?

A familial association of T1D with other associated autoimmune diseases has been observed. Several genes linked to T1D risk also increase the chance of other associated autoimmune diseases.⁸

The inheritance pattern of autoimmune diseases is complex and involves multiple factors, including the consolidated impact of genotype and environmental triggers.²

Risk for T1D

T1D puts first-degree relatives of patients at 1.6-times increased risk. A significant association for singleton siblings was found for T1D (SIR = 2.14).²

Autoantibodies may develop sequentially. First-degree relatives expressing autoantibodies to IAA, GAD-65, and IA-2 had a 75% 5-year risk of diabetes vs 25% 5-year risk in relatives expressing only one of those autoantibodies.¹ People diagnosed with Stage 2 T1D have a near 100% lifetime chance of progression to Stage 3 T1D, with 75% of them progressing within five years.⁹

Risk for other associated autoimmune diseases

Family autoimmunity is characterised by presence of ≥2 autoimmune diseases in members of a nuclear family.2 T1D also confers an increased risk of autoimmune diseases in first-degree relatives, with 8% and <6% developing autoimmune thyroid disease and coeliac disease, respectively.¹

In a first population-level study that assessed the familial risks for T1D and a large number of other associated autoimmune diseases using MigMed database found that:⁸

T1D in offspring was associated with the following diseases in parents:

Individuals with a first-degree relative with T1D have approximately 15-fold increased relative risk of developing T1D¹

Do common genetic risk factors overlap for the autoimmune diseases?

Shared genetic risk factors and immune system dysregulation are potentially implicated both in polyautoimmunity and family autoimmunity among individuals with T1D.2 Human leukocyte antigen (HLA) genotypes, PTPN22 gene, and cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) — all contribute to the complex interplay of genetic factors in autoimmune diseases that overlap with T1D, as depicted in the below figure.¹

Genotype	Disease association	Additional information
HLA DR3-DQ2 & DR4-DQ8	Highest risk of T1D DR3-DQ2 is also strongly associated with coeliac disease DR3-DQ2 expression is also reported in members of family with autoimmune thyroid disease and T1D	By the age of 15 years, 5% of individuals with this genotype expression develop T1D
MHC class I chain related gene A Polymorphism of MIC-A (especially alleles 5 and 5.1)	Strongly associated with T1D and coeliac disease (alleles 4 and 5.1)	Homozygous MIC-A 5.1 allele expression along with positivity for 21-OH enzyme is known to predispose individuals with T1D to Addison's disease
Polymorphism of PTPN22 gene, encoding LYP	Associated with T1D, Grave's disease, rheumatoid arthritis, systemic lupus erythematosus and Addison's disease	N/A
CTLA-4	Linked to autoimmune thyroid disease and Addison's disease	More strongly linked to patients affected with Addison's disease in association with T1D and autoimmune thyroid disease vs Addison's disease alone

ADA guideline recommendations for screening of autoimmune diseases in T1D

Individuals with an existing autoimmune disease are more prone to develop other associated autoimmune diseases.^4-6,10

The 2024 ADA guidelines on Comprehensive Medical Evaluation and Assessment of Comorbidities recommend screening for autoimmune thyroid disease soon after a T1D diagnosis and periodically, thereafter. Additionally, screening for coeliac disease is recommended in the presence of gastrointestinal symptoms, signs, laboratory manifestations, or suspicion of coeliac disease.¹⁰

Learn more about screening for autoantibodies to identify individuals at risk for T1D in this article.

Screening for T1D should be advised in individuals with other associated autoimmune diseases, given their higher risk than general population^4‑6

21-OH, 21-hydroxylase; AITD, autoimmune thyroid disease; CTLA-4, cytotoxic T lymphocyte-associated antigen-4; EMA, endomysial; GAD-65, glutamic acid decarboxylase-65; HLA, human leukocyte antigen; IA-2, islet cell antigen 2; IAA, insulin autoantibodies; ICA, islet cells autoantibodies; LYP, lymphoid tyrosine phosphatase; MIC-A, MHC-I related gene; SIR, Standardised incidence ratio; T1D, type 1 diabetes; TG, thyroglobulin; TPO, thyroid peroxidase; TTG, transglutaminase

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