Diabetes mellitus type 1 causes

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

There are no established causes for type 1 DM. Studies have found that cause of Type 1 DM is the result of interactions of genetic, environmental, and immunologic factors.

Causes

The exact cause of type 1 DM remains unknown. Studies have found that cause of Type 1 DM is the result of interactions of genetic, environmental, and immunologic factors:

[1][2][3][4][5][6][7][8]

Type 1 Diabetes causes
Genes associated with Type 1 DM Candidate genes assoicated with type 1 diabetes are:

PTPN22, IL10, AFF3, IFIH1, STAT4, CTLA4, CCR5, IL21, IL2, IL7R, BACH2, TNFAIP3, TAGAP, IKZF1, GLIS3, IL2RA, PRKCQ, NRP1, INS, BAD, CD69, ITGB7, ERBB3, CYP27B1, SH2B3, GPR183, DLK1, RASGRP1, CTSH, CLEC16A, IL27, ORMDL3, PTPN2, CD226, TYK2, FUT2, and UBASK3A

Envirnomental triggers associated with Type 1 DM
  • Congenital rubella
  • Maternal entero-viral infection
  • Cesarean section
  • Higher birth weight
  • Older maternal age
  • Low maternal intake of vegetables
  • Enteroviral infection
  • Frequent respiratory or enteric infections
  • Abnormal microbiome
  • Early exposure to cereals, root vegetables, eggs and cow's milk
  • Infant weight gain
  • Serious life events
  • Persistent or recurrent entero-viral infections
  • Overweight or increased height velocity
  • High glycemic load, fructose intake
  • Dietary nitrates or nitrosamines
  • Puberty
  • Steroid treatment
  • Insulin resistance
  • Psychological stress
Immunologic factors associated with Type 1 DM
  • Islet cell autoantibodies
  • Activated lymphocytes in the islets, peripancreatic lymph nodes, and systemic circulation
  • T lymphocytes that proliferate when stimulated with islet proteins
  • Release of cytokines within the insulitis

References

  1. Pociot F, Lernmark Å (2016). "Genetic risk factors for type 1 diabetes". Lancet. 387 (10035): 2331–9. doi:10.1016/S0140-6736(16)30582-7. PMID 27302272.
  2. Safari-Alighiarloo N, Taghizadeh M, Tabatabaei SM, Shahsavari S, Namaki S, Khodakarim S; et al. (2016). "Identification of new key genes for type 1 diabetes through construction and analysis of protein-protein interaction networks based on blood and pancreatic islet transcriptomes". J Diabetes. doi:10.1111/1753-0407.12483. PMID 27625010.
  3. Brorsson CA, Pociot F, Type 1 Diabetes Genetics Consortium. Shared genetic basis for type 1 diabetes, islet autoantibodies, and autoantibodies associated with other immune-mediated diseases in families with type 1 diabetes. Diabetes Care 2015; 38 (suppl 3): S8–13.
  4. Ahlqvist E, van Zuydam NR, Groop LC, McCarthy MI. The genetics of diabetic complications. Nat Rev Nephrol 2015; 11: 277–87.
  5. Parkes M, Cortes A, van Heel DA, Brown MA. Genetic insights into common pathways and complex relationships among immune-mediated diseases. Nat Rev Genet 2013; 14: 661–73.
  6. Butalia S, Kaplan GG, Khokhar B, Rabi DM (2016). "Environmental Risk Factors and Type 1 Diabetes: Past, Present, and Future". Can J Diabetes. 40 (6): 586–593. doi:10.1016/j.jcjd.2016.05.002. PMID 27545597.
  7. Jaberi-Douraki M, Pietropaolo M, Khadra A (2015). "Continuum model of T-cell avidity: Understanding autoreactive and regulatory T-cell responses in type 1 diabetes". J Theor Biol. 383: 93–105. doi:10.1016/j.jtbi.2015.07.032. PMC 4567915. PMID 26271890.
  8. Rydén A, Ludvigsson J, Fredrikson M, Faresjö M (2014). "General immune dampening is associated with disturbed metabolism at diagnosis of type 1 diabetes". Pediatr Res. 75 (1–1): 45–50. doi:10.1038/pr.2013.167. PMID 24105410.

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