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The link between gluten, celiac disease and type I diabetes

Celiac disease is thought to affect 0.5 to 1% of the population. Depending on the literature, type I diabetics carry a risk of between 1.7 and 10%, with most studies assuming around 5% (Amin et al. 2002; Abid et al. 2011). So there is clearly a connection between type I diabetes and celiac disease.


Studies in animal models have shown that the pathogenesis – i.e. the development of the disease – is related to nutrition. In non-diabetic mice, a gluten-free diet largely prevents the development of diabetes, while a gluten-rich or grain-based diet appears to favor the development of diabetes. The amount, timing, and manner of introducing grains into an infant's diet affect gluten's diabetogenic potential. Recent research provides evidence that a gluten-free diet can preserve beta cell function (cells responsible for insulin production) (Antvorskov et al. 2014).

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According to Antvorskov et al. Grain proteins (e.g. gluten), cow's milk proteins, low vitamin D levels, enteroviruses, changes in the composition of the intestinal bacteria and stressful life events have an influence on the development of diabetes.


What is celiac disease?

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Celiac disease is an inflammatory bowel disease with autoimmune features that is triggered by exposure to gluten and related grain proteins. The proteins trigger an inflammatory immune response in the gut, which leads to symptoms such as flatulence or diarrhea.

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The formation is triggered when gluten peptides penetrate the intestinal mucosa. The peptides can be deamidated by the enzyme tissue transglutaminase (tTG). Deamidation introduces a negative charge into the gluten peptides, increasing their binding affinity to HLA-DQ2 or HLA-DQ8 on antigen presenting cells (APCs). This increases the possibility of reaching the threshold required to activate gluten-reactive T cells.

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How is diabetes related to this?

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The genetic background of the two diseases diabetes and celiac disease is very similar. Both diseases appear to be associated with a high susceptibility to the HLA-DQ2/DQ8 genotype.

For example, an association was also found between early exposure to cow's milk and late exposure to gluten (after 6 months of age). There is also strong evidence that omitting gluten from the diet (especially during the first three months of life) has a protective effect on the development of possible diabetes (Serena et al. 2015).


Does a gluten-free diet help?


The study situation on the gluten-free diet (GFD) in connection with diabetes is still uncertain. Passali et al. (2020) were able to prove that GFD significantly increases glucose tolerance and insulin sensitivity in people at risk of diabetes (type I).

In 2012, a Danish case report drew attention, showing that GFD introduced 2-3 weeks after diagnosis of type I diabetes could have prolonged remission in a five-year-old boy without celiac disease. Both his HbA1c and his fasting blood sugar stabilized without insulin therapy. Twenty months after diagnosis, he was still without the need for daily insulin therapy (Sildorf et al. 2012).


The case report prompted a pilot study which found that GFD improved HbA1C by 21% and resulted in partial remission of diabetes. Positive effects on HbA1C were also observed in other studies (Amin et al. 2002). In addition, GFD also resulted in much less hypoglycaemia (Abid et al. 2011).


What does that mean now?


Type I diabetes will not be cured by GFD. If GFD starts early, however, the development of diabetes can be slowed down or even stopped. However, this will require more studies in the future and the balance between the innate and the "learned" immune system must also be examined more closely.


credentials


  • Sildorf SM, Fredheim S, Svensson J, Buschard K. Remission without insulin therapy on gluten-free diet in a 6-year old boy with type 1 diabetes mellitus. BMJ Case Rep. 2012 Jun 21;2012:bcr0220125878. doi: 10.1136/bcr.02.2012.5878. PMID: 22729336; PMCID: PMC3387460.

  • Svensson J, Sildorf SM, Pipper CB, Kyvsgaard JN, Bøjstrup J, Pociot FM, Mortensen HB, Buschard K. Potential beneficial effects of a gluten-free diet in newly diagnosed children with type 1 diabetes: a pilot study. knight plus. 2016 Jul 7;5(1):994. doi: 10.1186/s40064-016-2641-3. PMID: 27398272; PMCID: PMC4936999.

  • Abid N, McGlone O, Cardwell C, McCallion W, Carson D. Clinical and metabolic effects of gluten free diet in children with type 1 diabetes and celiac disease. Pediatric Diabetes. 2011 Jun;12(4 Pt 1):322-5. doi: 10.1111/j.1399-5448.2010.00700.x. Epub 2011 Mar 29. PMID: 21615651.

  • Amine R, Murphy N, Edge J, Ahmed ML, Acerini CL, Dunger DB. A longitudinal study of the effects of a gluten-free diet on glycemic control and weight gain in subjects with type 1 diabetes and celiac disease. Diabetes Care. 2002 Jul;25(7):1117-22. doi: 10.2337/diacare.25.7.1117. PMID: 12087007.

  • Antvorskov JC, Josefsen K, Engkilde K, Funda DP, Buschard K. Dietary gluten and the development of type 1 diabetes. diabetology. 2014 Sep;57(9):1770-80. doi: 10.1007/s00125-014-3265-1. Epub 2014 May 29. PMID: 24871322; PMCID: PMC4119241.

  • Serena G, Camhi S, Sturgeon C, Yan S, Fasano A. The Role of Gluten in Celiac Disease and Type 1 Diabetes. nutrients. 2015 Aug 26;7(9):7143-62. doi: 10.3390/nu7095329. PMID: 26343710; PMCID: PMC4586524.

  • Passali M, Josefsen K, Frederiksen JL, Antvorskov JC. Current Evidence on the Efficacy of Gluten-Free Diets in Multiple Sclerosis, Psoriasis, Type 1 Diabetes and Autoimmune Thyroid Diseases. nutrients. 2020 Aug 1;12(8):2316. doi: 10.3390/nu12082316. PMID: 32752175; PMCID: PMC7468712.

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