eISSN: 2083-8441
ISSN: 2081-237X
Pediatric Endocrinology Diabetes and Metabolism
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vol. 29
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Lidia Groele
1, 2
Agnieszka Szypowska
1, 2

Department of Paediatrics, Medical University of Warsaw, Poland
Department of Paediatric Diabetology and Paediatrics, University Clinical Centre of Warsaw Medical University, Poland
Pediatr Endocrinol Diabetes Metab 2023; 29 (4): 209-213
Data publikacji online: 2024/01/11
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Type 1 diabetes mellitus (T1DM) is a chronic autoimmune disease leading to immune-mediated destruction of pancreatic b cells, resulting in the need for insulin therapy. A genetic susceptibility to the development of islet autoimmunity and type 1 diabetes is well documented, and an environmental influence and impaired function of the immune system is assumed.

Genetic background

Polymorphisms of multiple genes of the human DNA can increase the risk of the disease. Approximately 50% of the genetic risk is associated with the HLA-DR and HLA-DQ HLA haplotypes, located in the major region of the tissue compatibility complex – MHC, which are responsible for antigen presentation to CD4 T lymphocytes by b cells, dendritic cells, and macrophages. HLA risk genes are responsible for the abnormal presentation of pancreatic islet antigens and the subsequent survival and expansion of b-cell reactive T cells, leading to pancreatic b-cell destruction. Most non-HLA genes are related to immune function and regulation (protein tyrosine phosphatase, PTPN22, IL2RA, CTLA4, Ins) [1].
Gene polymorphisms involved in sphingolipid metabolism and Vitamin D metabolism that contribute to the genetic predisposition to T1DM were also identified [2, 3].

Environmental factors

Environmental factors that increase the risk of developing T1DM include:
  • Viral infections (Coxsackie B virus, rubella viruses, enteroviruses, rotaviruses, CMV, retroviruses) through a mimicry mechanism [4].
  • Vitamin deficiency, mainly D and C through immunomodulatory effect [5, 6].
  • Factors that can affect the intestinal immune system, immune system, including diet (cow’s milk, gluten, toxins and chemical compounds, sweetened beverages) and hygiene. Some studies showed that early (< 4 months) and late (≥ 6 months) introduction of solid foods increased risk for development of isled antibodies in children at increased genetic risk, whereas breastfeeding had a protective effect [7, 8].
  • Changes in the gut microbiota. The intestinal flora is involved in the maturation of the innate and acquired immune system in early human life and in the formation of the intestinal barrier. The diversity of species depends on the type of birth, breastfeeding, and diet in early life. The use of antibiotics or improper nutrition lead to a disruption of the normal composition of the intestinal bacterium, the so-called dysbacteriosis, which, due to a...

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