Celiac disease, Addison's, and Autoimmune Gastritis in T1D patients: ISPAD guidelines

M3 India Newsdesk Jun 25, 2019

The ISPAD Clinical Practice Consensus Guidelines 2018 Compendium provides:

  • Recommendations for management of primary adrenal insufficiency, collagen vascular diseases, and other gastrointestinal issues associated with T1D
  • Updates on the revised recommendations for the screening of celiac disease for T1D patients

This guideline, based on the International Society for Paediatric and Adolescent Diabetes (ISPAD) Clinical Practice Consensus Guidelines 2018 Compendium, elaborates on the common autoimmune conditions that arise in children and adolescents with type 1 diabetes (T1D).

Autoimmune conditions

Celiac disease is the second most common of the various other conditions associated with T1D patients. Screening for the typically asymptomatic disease is also recommended once diabetes is diagnosed and then again during the second and the fifth year. If the test is positive and if the patient has a first-degree relative with celiac disease, the screening may have to be conducted more frequently.

Other common autoimmune conditions include primary adrenal insufficiency, collagen vascular diseases namely, rheumatoid arthritis, lupus, psoriasis and scleroderma, and other gastrointestinal diseases like Crohn’s disease, ulcerative colitis, autoimmune hepatitis and autoimmune gastritis.

Lab tests are imperative for diagnosis and it is important that the clinician has knowledge of the symptoms of common comorbid autoimmune diseases so as to advise specific tests for clinical symptom- or suspicion-related diseases associated to autoimmune conditions in patients with T1D. It is also important that the clinician thinks of possibilities outside of the recommended tests. However, in case lab-based tests are not available or seem expensive to the patient’s family, the clinician must carefully monitor each symptom and linear growth alongside.

Celiac Disease

Any T1D child showing signs of gastrointestinal problems, such as chronic or intermittent diarrhoea and/or constipation, chronic abdominal pain/distention, flatulence, anorexia, dyspeptic symptoms as well as anaemia, unexplained poor growth, weight loss, or recurrent aphthous ulceration, should be evaluated for celiac disease.


Celiac disease can be asymptomatic and not necessarily linked to poor growth, deterioration in glycemic control or hypoglycaemia. However, an exclusion should be made in such situations.

Tests for celiac disease are based on the detection of IgA antibodies (tissue transglutaminase (tTG-A) and/or endomysial (EmA)).

  • As per the recent guidelines, it is recommended that HLA-DQ2 and HLA-DQ8 tests be conducted as celiac disease may not test positive if both haplotypes are negative
  • Some guidelines also recommend a routine measurement of the total IgA to exclude IgA deficiency
  • Alternatively, measuring IgA only if the initial screening test conducted using tTG-A and/or EmA is negative, is also a common practice
  • If the child is IgA-deficient, IgG-specific antibody tests (tTG or EmA IgG, or both) should be used for screening as celiac disease may be more common in those with IgA deficiency than in the general population
  • If an elevated antibody level is detected, a small bowel biopsy should be conducted to confirm the presence of celiac disease by demonstrating subtotal villus atrophy, as outlined in the Marsh Classification
  • Multiple biopsy samples should be taken from different intestinal sites, including the duodenal bulb, as this disease can show up with variable biopsy findings
  • Screening for IgA deficiency should be performed at the same time when the patient tests positive for diabetes
  • For patients with confirmed IgA deficiency, tests for celiac disease should be performed using IgG-specific antibody tests (tTG or EmA IgG, or both)
  • Measurement of HLA-DQ2 and HLA-DQ8 is not always helpful to exclude celiac disease in patients with T1D and definitely not recommended as a screening test

Treatment: Children with T1D and with celiac disease during a routine screening, should be referred to a paediatric gastroenterologist as well. This is because testing for serologic alone in patients without the typical symptoms does not prove effective in children. Patients of celiac disease and their families should be provided educational support from an experienced paediatric dietitian.


  • Putting the patient on a gluten-free diet may help normalise the bowel mucosa and even lead to the disappearance of antibodies, but not necessarily positively impact glycemic control
  • Gluten-free diet also reduces the risk of a possible, subsequent gastrointestinal malignancy and other conditions associated with subclinical malabsorption, such as osteoporosis, iron deficiency, and growth failure
  • Long-standing celiac disease in T1D patients can be linked to an increased risk of retinopathy, while not following a gluten-free diet may increase the risk of albuminuria

Additional recommendations

  1. The possibility of the presence of celiac disease is high among first-degree relatives of children patients with T1D, especially in mothers. Hence, family members of the child patient, newly diagnosed with celiac disease should also be screened for tTG.
  2. Clinical laboratories reporting celiac disease-specific antibody test results for diagnostic use must continuously participate in quality control programs at a national or an international level.

Addison’s Disease

Primary adrenal insufficiency, also known as the Addison’s disease is characterised by frequent hypoglycaemia, nausea, salt cravings, unexplained decrease in insulin requirements, increased skin pigmentation and mucosa, lassitude, postural hypotension, weight loss, hyponatraemia and hyperkalaemia.


  • Addison's disease can be confirmed based on a low cortisol response to an ACTH stimulation test and positive anti-adrenal (21-hydroxylase) antibodies
  • In asymptomatic children patients of T1D with positive adrenal antibodies identified on routine screening, a 10 rising ACTH level suggests a failing adrenal cortex and the development of primary adrenal insufficiency

Treatment: Treatment is with a glucocorticoid; while it is urgent, it is also lifelong. For some patient cases, the therapy may also have to be supplemented with a mineralocorticoid such as fludrocortisone.

Additional recommendation: Diabetes care providers should watch out for the symptoms of adrenal insufficiency (a result of Addison’s disease) in children and adolescents patients with T1D, even though its occurrence is rare.

Autoimmune Gastritis

As per the ISPAD Clinical Practice Consensus Guidelines 2018 Compendium, Type 1 diabetes is linked to an increased risk of parietal cell antibody positivity. Parietal cell antibodies are the principal immunological markers of autoimmune gastritis and react against the H+ /K+ ATPase of the gastric parietal cells. Parietal cell antibodies may also inhibit intrinsic factor secretion, resulting in vitamin B12 deficiency and pernicious anaemia.


  1. Physicians or clinicians should know that parietal cell antibodies can be present in children and adolescent patients of T1D diabetes in cases where unclear anaemia (microcytic as well as macrocytic) or gastrointestinal symptoms were identified. However, only a routine screening is not recommended.
  2. Alongside parietal cell autoantibodies (APCA), blood counts, vitamin B12, ferritin and gastrin should also be tested.

Systemic Autoimmune Diseases: Sarcoidosis and Sjogren Syndrome

Juvenile idiopathic rheumatoid arthritis (JIA), Sjogren syndrome and sarcoidosis are some non-organic-specific or systemic autoimmune diseases besides organ-specific autoimmune diseases that often show up in patients of T1D.

Combined Autoimmune Conditions: Autoimmune Polyglandular Syndrome and APECED

Autoimmune Polyglandular Syndrome (APS) is identified as the presence of at least two endocrine gland insufficiencies. The simultaneous occurrence of vitiligo and other autoimmune conditions are signs that the patient should be checked for autoimmune polyglandular syndrome (APS).

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare autosomal recessive disease caused by mutations of the AutoImmune REgulator gene. APS 1, also known as autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) mostly occurs during childhood and can be identified if the diagnosis presents the development of adrenal insufficiency, chronic mucocutaneous candidiasis and hypoparathyroidism. APS-2 is a more common condition than APS1 and usually presents itself later in life.

  • APS1 is identified by the combination of at least two of the following three diseases in the same patient: adrenal insufficiency, T1D and autoimmune thyroid disease
  • APS-2 Syndrome may be related to IgA deficiency, Graves’ disease, primary hypothyroidism, hypogonadism, hypopituitarism, Parkinson’s disease, myasthenia gravis, celiac disease, vitiligo, alopecia, pernicious anemia and stiff-man syndrome

Diagnosis for APECED

  • The disease can be detected if at least two components of the classic triad including, chronic mucocoutaneous candidiasis (CMC), chronic hypoparathyroidism (CH), Addison's disease (AD) seem present
  • Other common features of the disease are hypergonadotropic hypogonadism, alopecia, vitiligo, autoimmune hepatitis, type 1 diabetes, gastrointestinal dysfunction

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