KEGG   DISEASE: Type 1 diabetes mellitus
Entry
H00408                      Disease                                
Name
Type 1 diabetes mellitus
Description
The majority of type 1 diabetes mellitus (T1DM) cases are believed to arise from an inflammatory, autoimmune attack against the beta cells in the pancreas, which consequently leads to the failure of insulin-mediated blood glucose regulation in the body. T1DM signs and symptoms can come on quickly and may include increased thirst and frequent urination, fatigue, weight loss and so on. It is recognized that both genetic and environmental determinants are important in defining disease risk. The HLA class II genes are most strongly associated with T1DM. Another plausible candidate genes are INS, CTLA4 and PTPN22. The disease may be a result of variations in several susceptibility genes, with the majority only contributing weak effects.
Category
Metabolic disease; Immune system disease; Endocrine disease
Brite
Human diseases in ICD-11 classification [BR:br08403]
 05 Endocrine, nutritional or metabolic diseases
  Endocrine diseases
   Diabetes mellitus
    5A10  Type 1 diabetes mellitus
     H00408  Type 1 diabetes mellitus
Pathway-based classification of diseases [BR:br08402]
 Endocrine system
  nt06325  Hormone/cytokine signaling
   H00408  Type 1 diabetes mellitus
Disease
pathway
hsa04940  Type I diabetes mellitus
Pathway
hsa04659  Th17 cell differentiation
hsa04658  Th1 and Th2 cell differentiation
hsa04672  Intestinal immune network for IgA production
hsa04060  Cytokine-cytokine receptor interaction
hsa04630  JAK-STAT signaling pathway
hsa04151  PI3K-Akt signaling pathway
Network
nt06325 Hormone/cytokine signaling
Gene
(T1D2) INS [HSA:3630] [KO:K04526]
(T1D5) SUMO4 [HSA:387082] [KO:K12160]
(T1D10) IL2RA [HSA:3559] [KO:K05068]
(T1D12) CTLA4 [HSA:1493] [KO:K06538]
(T1D20) HNF1A [HSA:6927] [KO:K08036]
(T1D22) CCR5 [HSA:1234] [KO:K04180]
HLA-DRB1 [HSA:3123] [KO:K06752]
HLA-DQB1 [HSA:3119] [KO:K06752]
HLA-DQA1 [HSA:3117] [KO:K06752]
PTPN22 [HSA:26191] [KO:K18024]
PTPN2 [HSA:5771] [KO:K18026]
ERBB3 [HSA:2065] [KO:K05084]
IL2 - IL21 [HSA:3558 59067] [KO:K05429 K05434]
IFIH1 [HSA:64135] [KO:K12647]
CLEC16A [HSA:23274] [KO:K19513]
BACH2 [HSA:60468] [KO:K09042]
CTSH [HSA:1512] [KO:K01366]
SH2B3 [HSA:10019] [KO:K12459]
C12orf30 [HSA:80018] [KO:K17973]
CD226 [HSA:10666] [KO:K06567]
ITPR3 [HSA:3710] [KO:K04960]
CYP27B1 [HSA:1594] [KO:K07438]
Drug
Insulin human [DR:D03230]
Insulin lispro [DR:D04477]
Insulin aspart [DR:D04475]
Insulin glulisine [DR:D04540]
Insulin glargine [DR:D03250]
Insulin detemir [DR:D04539]
Insulin degludec [DR:D09727]
Pramlintide acetate [DR:D05595]
Teplizumab [DR:D09013]
Donislecel [DR:D12634]
Dasiglucagon [DR:D11359]
Dasiglucagon hydrochloride [DR:D12314]
Other DBs
ICD-11: 5A10
MeSH: D003922
OMIM: 125852 600320 601942 601388 612520 612522 222100
Reference
PMID:19369670
  Authors
Concannon P, Rich SS, Nepom GT
  Title
Genetics of type 1A diabetes.
  Journal
N Engl J Med 360:1646-54 (2009)
DOI:10.1056/NEJMra0808284
Reference
PMID:18482868
  Authors
Ounissi-Benkalha H, Polychronakos C
  Title
The molecular genetics of type 1 diabetes: new genes and emerging mechanisms.
  Journal
Trends Mol Med 14:268-75 (2008)
DOI:10.1016/j.molmed.2008.04.002
Reference
PMID:18192540 (INS)
  Authors
Molven A, Ringdal M, Nordbo AM, Raeder H, Stoy J, Lipkind GM, Steiner DF, Philipson LH, Bergmann I, Aarskog D, Undlien DE, Joner G, Sovik O, Bell GI, Njolstad PR
  Title
Mutations in the insulin gene can cause MODY and autoantibody-negative type 1 diabetes.
  Journal
Diabetes 57:1131-5 (2008)
DOI:10.2337/db07-1467
Reference
PMID:15247916 (SUMO4)
  Authors
Guo D, Li M, Zhang Y, Yang P, Eckenrode S, Hopkins D, Zheng W, Purohit S, Podolsky RH, Muir A, Wang J, Dong Z, Brusko T, Atkinson M, Pozzilli P, Zeidler A, Raffel LJ, Jacob CO, Park Y, Serrano-Rios M, Larrad MT, Zhang Z, Garchon HJ, Bach JF, Rotter JI, She JX, Wang CY
  Title
A functional variant of SUMO4, a new I kappa B alpha modifier, is associated with type 1 diabetes.
  Journal
Nat Genet 36:837-41 (2004)
DOI:10.1038/ng1391
Reference
PMID:15776395 (IL2RA)
  Authors
Vella A, Cooper JD, Lowe CE, Walker N, Nutland S, Widmer B, Jones R, Ring SM, McArdle W, Pembrey ME, Strachan DP, Dunger DB, Twells RC, Clayton DG, Todd JA
  Title
Localization of a type 1 diabetes locus in the IL2RA/CD25 region by use of tag single-nucleotide polymorphisms.
  Journal
Am J Hum Genet 76:773-9 (2005)
DOI:10.1086/429843
Reference
PMID:8817351 (CTLA4)
  Authors
Nistico L, Buzzetti R, Pritchard LE, Van der Auwera B, Giovannini C, Bosi E, Larrad MT, Rios MS, Chow CC, Cockram CS, Jacobs K, Mijovic C, Bain SC, Barnett AH, Vandewalle CL, Schuit F, Gorus FK, Tosi R, Pozzilli P, Todd JA
  Title
The CTLA-4 gene region of chromosome 2q33 is linked to, and associated with, type 1 diabetes. Belgian Diabetes Registry.
  Journal
Hum Mol Genet 5:1075-80 (1996)
DOI:10.1093/hmg/5.7.1075
Reference
PMID:9313763 (HNF1A)
  Authors
Yamada S, Nishigori H, Onda H, Utsugi T, Yanagawa T, Maruyama T, Onigata K, Nagashima K, Nagai R, Morikawa A, Takeuchi T, Takeda J
  Title
Identification of mutations in the hepatocyte nuclear factor (HNF)-1 alpha gene in Japanese subjects with IDDM.
  Journal
Diabetes 46:1643-7 (1997)
DOI:10.2337/diacare.46.10.1643
Reference
PMID:19073967 (CCR5)
  Authors
Smyth DJ, Plagnol V, Walker NM, Cooper JD, Downes K, Yang JH, Howson JM, Stevens H, McManus R, Wijmenga C, Heap GA, Dubois PC, Clayton DG, Hunt KA, van Heel DA, Todd JA
  Title
Shared and distinct genetic variants in type 1 diabetes and celiac disease.
  Journal
N Engl J Med 359:2767-77 (2008)
DOI:10.1056/NEJMoa0807917
Reference
PMID:22106694 (HLA-DRB1 HLA-DQB1 HLA-DQA1)
  Authors
Rohana AG, Loh KC, Tin SK, Soh CH, Nazaimoon WM, Fong KY, Azmi KN, Khalid BA
  Title
HLA-DQA1, -DQB1 and -DRB1 gene polymorphism--in Malay type 1 diabetes mellitus patients and their use for risk prediction.
  Journal
Med J Malaysia 66:133-7 (2011)
Reference
PMID:25729936 (PTPN22)
  Authors
Liu HW, Xu RY, Sun RP, Wang Q, Liu JL, Ge W, Yu Z
  Title
Association of PTPN22 gene polymorphism with type 1 diabetes mellitus in Chinese children and adolescents.
  Journal
Genet Mol Res 14:63-8 (2015)
DOI:10.4238/2015.January.15.8
Reference
PMID:26344020 (PTPN2)
  Authors
Peng H, Li J, Chen X, Zhou X, Zhu W, Li F
  Title
Genetic Variants of PTPN2 Gene in Chinese Children with Type 1 Diabetes Mellitus.
  Journal
Med Sci Monit 21:2653-8 (2015)
DOI:10.12659/MSM.893607
Reference
PMID:29109006 (ERBB3)
  Authors
Lemos NE, Dieter C, Dorfman LE, Assmann TS, Duarte GCK, Canani LH, Bauer AC, Crispim D
  Title
The rs2292239 polymorphism in ERBB3 gene is associated with risk for type 1 diabetes mellitus in a Brazilian population.
  Journal
Gene 644:122-128 (2018)
DOI:10.1016/j.gene.2017.11.009
Reference
PMID:34328597 (IL2 IL21)
  Authors
Khalil RG, Abdel-Moneim A, Yousef AI, Abdel-Rahman H, Zanaty MI, El-Sayed A
  Title
Association of interleukin-2, interleukin-21 and interleukin-23 with hyperlipidemia in pediatric type 1 diabetes.
  Journal
Mol Biol Rep 48:5421-5433 (2021)
DOI:10.1007/s11033-021-06545-0
Reference
PMID:28929635 (IFIH1)
  Authors
Jermendy A, Szatmari I, Korner A, Szabo AJ, Toth-Heyn P, Hermann R
  Title
Association between interferon-induced helicase (IFIH1) rs1990760 polymorphism and seasonal variation in the onset of type 1 diabetes mellitus.
  Journal
Pediatr Diabetes 19:300-304 (2018)
DOI:10.1111/pedi.12569
Reference
PMID:31570815 (CLEC16A)
  Authors
Gingerich MA, Sidarala V, Soleimanpour SA
  Title
Clarifying the function of genes at the chromosome 16p13 locus in type 1 diabetes: CLEC16A and DEXI.
  Journal
Genes Immun 21:79-82 (2020)
DOI:10.1038/s41435-019-0087-7
Reference
PMID:32236312 (BACH2)
  Authors
Dieter C, Lemos NE, Dorfman LE, Duarte GCK, Assmann TS, Crispim D
  Title
The rs11755527 polymorphism in the BACH2 gene and type 1 diabetes mellitus: case control study in a Brazilian population.
  Journal
Arch Endocrinol Metab 64:138-143 (2020)
DOI:10.20945/2359-3997000000214
Reference
PMID:24982147 (CTSH)
  Authors
Floyel T, Brorsson C, Nielsen LB, Miani M, Bang-Berthelsen CH, Friedrichsen M, Overgaard AJ, Berchtold LA, Wiberg A, Poulsen P, Hansen L, Rosinger S, Boehm BO, Ram R, Nguyen Q, Mehta M, Morahan G, Concannon P, Bergholdt R, Nielsen JH, Reinheckel T, von Herrath M, Vaag A, Eizirik DL, Mortensen HB, Storling J, Pociot F
  Title
CTSH regulates beta-cell function and disease progression in newly diagnosed type 1 diabetes patients.
  Journal
Proc Natl Acad Sci U S A 111:10305-10 (2014)
DOI:10.1073/pnas.1402571111
Reference
PMID:20546165 (SH2B3)
  Authors
Lavrikova EY, Nikitin AG, Kuraeva TL, Peterkova VA, Tsitlidze NM, Chistiakov DA, Nosikov VV
  Title
The carriage of the type 1 diabetes-associated R262W variant of human LNK correlates with increased proliferation of peripheral blood monocytes in diabetic patients.
  Journal
Pediatr Diabetes 12:127-32 (2011)
DOI:10.1111/j.1399-5448.2010.00656.x
Reference
PMID:20089178 (PTPN22 C12orf30 CD226)
  Authors
Douroudis K, Kisand K, Nemvalts V, Rajasalu T, Uibo R
  Title
Allelic variants in the PHTF1-PTPN22, C12orf30 and CD226 regions as candidate susceptibility factors for the type 1 diabetes in the Estonian population.
  Journal
BMC Med Genet 11:11 (2010)
DOI:10.1186/1471-2350-11-11
Reference
PMID:30145014 (CD226)
  Authors
Abu El-Ella SS, Khattab ESAEH, El-Mekkawy MS, El-Shamy AA
  Title
CD226 gene polymorphism (rs763361 C>T) is associated with susceptibility to type 1 diabetes mellitus among Egyptian children.
  Journal
Arch Pediatr 25:378-382 (2018)
DOI:10.1016/j.arcped.2018.06.009
Reference
PMID:18340361 (ITPR3)
  Authors
Qu HQ, Marchand L, Szymborski A, Grabs R, Polychronakos C
  Title
The association between type 1 diabetes and the ITPR3 gene polymorphism due to linkage disequilibrium with HLA class II.
  Journal
Genes Immun 9:264-6 (2008)
DOI:10.1038/gene.2008.12
Reference
PMID:15225764 (CYP27B1)
  Authors
Lopez ER, Regulla K, Pani MA, Krause M, Usadel KH, Badenhoop K
  Title
CYP27B1 polymorphisms variants are associated with type 1 diabetes mellitus in Germans.
  Journal
J Steroid Biochem Mol Biol 89-90:155-7 (2004)
DOI:10.1016/j.jsbmb.2004.03.095

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   OMIM (7)   
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