Incidence, prevalence and seasonal onset variation of Addison’s disease among persons with type 1 diabetes mellitus: nationwide, matched cohort studies

Chantzichristos, Dimitrios; Persson, Anders; Eliasson, Björn; Miftaraj, Mervete; Franzén, Stefan; Svensson, Ann‐Marie; Johannsson, Gudmundur

doi:10.1530/eje-17-0751

Cited by 16 publications

(10 citation statements)

References 32 publications

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“…In our study, Addison disease clustered most often with thyroid ADs in accordance with a recent Swedish nationwide observational cohort study (33). Unlike in another Swedish study (34) where persons with T1D developed Addison disease at a younger age, no association with age at diabetes diagnosis, duration of diabetes, or age was detected in the Finnish cohort.…”

Section: Addison Diseasesupporting

confidence: 91%

Every Fifth Individual With Type 1 Diabetes Suffers From an Additional Autoimmune Disease: A Finnish Nationwide Study

et al. 2020

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The aim of this study was to quantify the excess risk of autoimmune hypothyroidism and hyperthyroidism, Addison disease, celiac disease, and atrophic gastritis in adults with type 1 diabetes (T1D) compared with nondiabetic individuals in Finland. RESEARCH DESIGN AND METHODSThe study included 4,758 individuals with T1D from the Finnish Diabetic Nephropathy (FinnDiane) Study and 12,710 nondiabetic control individuals. The autoimmune diseases (ADs) were identified by linking the data with the Finnish nationwide health registries from 1970 to 2015. RESULTSThe median age of the FinnDiane individuals at the end of follow-up in 2015 was 51.4 (interquartile range 42.6-60.1) years, and the median duration of diabetes was 35.5 (26.5-44.0) years. Of individuals with T1D, 22.8% had at least one additional AD, which included 31.6% of women and 14.9% of men. The odds ratios for hypothyroidism, hyperthyroidism, celiac disease, Addison disease, and atrophic gastritis were 3.43 (95% CI 3.09-3.81), 2.98 (2.27-3.90), 4.64 (3.71-5.81), 24.13 (5.60-104.03), and 5.08 (3.15-8.18), respectively, in the individuals with T1D compared with the control individuals. The corresponding ORs for women compared with men were 2.96 (2.53-3.47), 2.83 (1.87-4.28), 1.52 (1.15-2.02), 2.22 (0.83-5.91), and 1.36 (0.77-2.39), respectively, in individuals with T1D. Late onset of T1D and aging increased the risk of hypothyroidism, whereas young age at onset of T1D increased the risk of celiac disease. CONCLUSIONSThis is one of the largest studies quantifying the risk of coexisting AD in adult individuals with T1D in the country with the highest incidence of T1D in the world. The results highlight the importance of continuous screening for other ADs in individuals with T1D.Autoimmune diseases (ADs) comprise a range of chronic diseases in which the immune response to self-antigens results in damage or dysfunction of the target organs. As the pathogenesis of various ADs share common genetic factors and immunologic processes, these diseases often coexist within the same individual and families (1). Among the over 80 different ADs, celiac disease and hypothyroidism are the most frequently observed additional ADs in type 1 diabetes (T1D), followed by

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Section: Addison Diseasesupporting

confidence: 91%

Every Fifth Individual With Type 1 Diabetes Suffers From an Additional Autoimmune Disease: A Finnish Nationwide Study

et al. 2020

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“…As a large proportion of patients with type 1 diabetes (T1D), Hashimoto's thyroiditis (HT), Graves' disease (GD), and autoimmune Addison's disease (AD) develop polyautoimmunity or Autoimmune Polyendocrine Syndrome (2)(3)(4)(5), it can be expected that patients with these diseases have similar immunological deviations. Autoantibodies produced by B cells are the most evident immunological feature in patients with T1D, HT, GD and AD, which can directly cause symptoms and modulate the function of other immune cells (6)(7)(8).…”

Section: Introductionmentioning

confidence: 99%

Mass Cytometry Studies of Patients With Autoimmune Endocrine Diseases Reveal Distinct Disease-Specific Alterations in Immune Cell Subsets

et al. 2020

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Although there is evidence that autoimmune diseases share similar immunogenetic mechanisms, studies comparing peripheral CD45 + cells from patients with autoimmune endocrine diseases in parallel are limited. In this study, we applied high-dimensional single-cell mass cytometry to phenotypically characterize PBMC from patients with new-onset (N-T1D) and long-standing type 1 diabetes, Hashimoto's thyroiditis (HT), Graves' disease and autoimmune Addison's disease (AD), as well as healthy controls. The frequency of CD20 lo CD27 hi CD38 hi HLA-DR int plasmablasts, CD86 + CD14 lo CD16 + non-classical monocytes and two subsets of CD56 dim HLA-DR + IFN-γ + NK cells were increased in patients with HT. Subsets of CD56 dim CD69 + HLA-DR − NK cells and CD8 + TEMRA cells, both expressing IFN-γ, were expanded and reduced, respectively, in the N-T1D group. In addition, patients with AD were characterized by an increased percentage of central memory CD8 + T cells that expressed CCR4, GATA3, and IL-2. We demonstrate that patients with N-T1D, HT, and AD had altered frequencies of distinct subsets within antigen-presenting and cytotoxic cell lineages. Previously unreported alterations of specific cell subsets were identified in samples from patients with HT and AD. Our study might contribute to a better understanding of shared and diverging immunological features between autoimmune endocrine diseases.

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“…Organ-specific autoantibodies in T1DM endocrine organs, such as systemic lupus erythematosus (SLE), vitiligo, and CD [18,19]. Previous studies have found that 15-30% of T1DM patients have comorbid autoimmune thyroid diseases, 0.97-16.7%, celiac disease; and 0.5-1%, Addison's disease [20], as evidenced by the presence of autoantibodies such as TPOA, TGA, tTGA and 21-OHA. A substantial proportion of T1DM patients seropositive for other organ-specific autoantibodies will progress to a clinical condition more complex and intractable than T1DM alone, so it is critical to identify subclinical comorbidities as early as possible by autoantibody screening [21].…”

Section: Discussionmentioning

confidence: 99%

Organ-specific autoantibodies in Chinese patients newly diagnosed with type 1 diabetes mellitus

Pan

Shi

et al. 2020

Endocr J

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This study aims to investigate the prevalence of islet autoantibodies and other organ-specific autoantibodies in type 1 diabetes mellitus (T1DM) patients and characterize their clinical features. Glutamic acid decarboxylase antibody (GADA), insulinoma antigen 2 antibody (IA-2A), zinc transporter 8 antibody (ZnT8A) and tetraspanin7 antibody (TSPAN7A) were assayed by radioligand or luciferase immunoprecipitation system assays in 205 newly diagnosed acute-onset T1DM patients and 170 healthy controls. Other organ-specific autoantibodies, including thyroid peroxidase antibody (TPOA), thyroglobulin antibody (TGA), tissue transglutaminase antibody (tTGA) and 21-hydroxylase antibody (21-OHA), were also measured. The prevalence of GADA, IA-2A, ZnT8A, TSPAN7A, TPOA, TGA and 21-OHA was higher in T1DM patients than in healthy controls. The combinational assay of various islet autoantibodies could increase the frequency of autoantibody positivity in T1DM to 85.4%. GADA+ IA-2A+ T1DM patients preferentially had TPOA and TGA, while IA-2A+ patients often had tTGA. Patients positive for two or more islet autoantibodies often had TPOA and TGA. BMI of multiple islet autoantibodypositive patients was lower than that of patients with single or no islet autoantibodies, and there were no significant differences in C-peptide and glycated hemoglobin between patients positive for islet autoantibodies combined with other organ-specific antibodies and noncombined patients. Younger female patients who were islet autoantibody positive were more likely to have TPOA and TGA. The frequency of Graves' disease was much higher in T1DM patients than in healthy controls. T1DM usually occurs together with other organ-specific autoantibodies. Measuring of other organ-specific autoantibodies will be beneficial for T1DM patients.

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Incidence, prevalence and seasonal onset variation of Addison’s disease among persons with type 1 diabetes mellitus: nationwide, matched cohort studies

Abstract: The risk to develop AD among persons with T1DM is more than 10 times higher than in persons without T1DM. Persons with T1DM develop AD at a younger age. The incidence of AD may have a seasonal pattern.

Cited by 16 publications

References 32 publications

Every Fifth Individual With Type 1 Diabetes Suffers From an Additional Autoimmune Disease: A Finnish Nationwide Study

Every Fifth Individual With Type 1 Diabetes Suffers From an Additional Autoimmune Disease: A Finnish Nationwide Study

Mass Cytometry Studies of Patients With Autoimmune Endocrine Diseases Reveal Distinct Disease-Specific Alterations in Immune Cell Subsets

Organ-specific autoantibodies in Chinese patients newly diagnosed with type 1 diabetes mellitus

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