Diabetes mellitus type 1 causes

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Vishal Devarkonda, M.B.B.S [2]

Overview

There are no established causes for type 1 diabetes mellitus. Studies have found that cause of type 1 diabetes mellitus is the result of interactions of genetic, environmental, and immunologic factors. There are at least 37 genes associated with type 1 diabetes mellitus. Furthermore, certain infections, diet and some maternal related factors are known to cause type 1 diabetes mellitus.

Causes

The exact cause of type 1 diabetes mellitus remains unknown. Studies have found that cause of type 1 diabetes mellitus is the result of interactions of genetic, environmental, and immunologic factors:^[1]^[2]^[3]^[4]^[5]^[6]^[7]^[8]^[9]^[10]

Type 1 Diabetes causes
Genes associated with type 1 diabetes mellitus	Candidate genes assoicated with type 1 diabetes mellitus are: PTPN22, Interleukin 10, AFF3, IFIH1, STAT4, CTLA-4, CCR5, Interleukin 21, Interleukin 2, Interleukin 7R, BACH2, TNFAIP3, TAGAP, IKZF1, GLIS3, IL2RA, PRKCQ, NRP1, INS (insulin gene), BAD, CD69, ITGB7, ERBB3, CYP27B1, SH2B3, GPR183, DLK1, RASGRP1, CTSH, CLEC16A, Interleukin 27, ORMDL3, PTPN2, CD226, Tyrosine kinase 2, FUT2, YBX1, SRPK1, PSMA1, XRCC6, Src, PIK3R1, PLCG1, UBE2N and UBASH3A
Envirnomental triggers associated with type 1 diabetes mellitus	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 diabetes mellitus	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

↑ 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.
↑ 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.
↑ 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.
↑ Ahlqvist E, van Zuydam NR, Groop LC, McCarthy MI. The genetics of diabetic complications. Nat Rev Nephrol 2015; 11: 277–87.
↑ 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.
↑ 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.
↑ 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.
↑ 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.
↑ Chen YG, Ciecko AE, Khaja S, Grzybowski M, Geurts AM, Lieberman SM (2020). “UBASH3A deficiency accelerates type 1 diabetes development and enhances salivary gland inflammation in NOD mice”. Sci Rep. 10 (1): 12019. doi:10.1038/s41598-020-68956-6. PMC 7374577 Check |pmc= value (help). PMID 32694640 Check |pmid= value (help).
↑ Safari-Alighiarloo, Nahid; Taghizadeh, Mohammad; Tabatabaei, Seyyed Mohammad; Shahsavari, Soodeh; Namaki, Saeed; Khodakarim, Soheila; Rezaei-Tavirani, Mostafa (2017). “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”. Journal of Diabetes. 9 (8): 764–777. doi:10.1111/1753-0407.12483. ISSN 1753-0393.

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[pmid27302272-1] 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.

[pmid27625010-2] 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.

[pmid27545597-6] 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.

[pmid26271890-7] 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.

[pmid24105410-8] 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.

[pmid32694640-9] Chen YG, Ciecko AE, Khaja S, Grzybowski M, Geurts AM, Lieberman SM (2020). “UBASH3A deficiency accelerates type 1 diabetes development and enhances salivary gland inflammation in NOD mice”. Sci Rep. 10 (1): 12019. doi:10.1038/s41598-020-68956-6. PMC 7374577 Check |pmc= value (help). PMID 32694640 Check |pmid= value (help).

[Safari-AlighiarlooTaghizadeh2017-10] Safari-Alighiarloo, Nahid; Taghizadeh, Mohammad; Tabatabaei, Seyyed Mohammad; Shahsavari, Soodeh; Namaki, Saeed; Khodakarim, Soheila; Rezaei-Tavirani, Mostafa (2017). “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”. Journal of Diabetes. 9 (8): 764–777. doi:10.1111/1753-0407.12483. ISSN 1753-0393.

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