Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Overview
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:
Type 1 Diabetes causes
|
Genes associated with Type 1 DM
|
Genes important to type 1 diabetes pathogenesis
|
Region
|
Odds ratio
|
Gene funtion
|
PTPN22
|
1p13.2
|
1·89
|
Regulation of innate immune response, T-cell activation, and natural killer cell proliferation
|
IL10
|
1q32.1
|
0·86
|
Cytokines and inflammatory response
|
AFF3
|
2q11.2
|
1·11
|
Regulation of transcription
|
IFIH1
|
2q24.2
|
0·85
0·85
0·59
|
Innate immune system NF-κB activation
|
STAT4
|
2q32.3
|
1·10§
|
Cytokine-mediated signalling pathway
|
CTLA4
|
2q33.2
|
0·82
0·84
|
T-cell activation
|
CCR5
|
3p21.31
|
0·85
|
Th1 cell development and chemokine-mediated signalling pathway
|
IL21, IL2
|
4q27
|
1·13
1·12
1·14
1·15
|
Cytokines and inflammatory response and Th1 or Th2 cell differentiation
|
IL7R
|
5p13.2
|
1·11
|
T-cell-mediated cytotoxicity, immunoglobulin production, and antigen binding
|
BACH2
|
6q15
|
1·10
0·88
1·20
|
Transcription
|
TNFAIP3
|
6q23.3
|
1·12
|
Inflammatory response
|
TAGAP
|
6q25.3
|
0·92
|
Signal transduction
|
IKZF1
|
7p12.2
|
0·89
|
Immune-cell regulation
|
GLIS3
|
9p24.2
|
1·12
1·12
0·90
|
Regulation of transcription
|
IL2RA
|
10p15.1
|
1·20
0·73
0·52
0·62
0·82
|
Alternative mRNA splicing Th1 or Th2 cell differentiation
|
PRKCQ
|
10p15.1
|
0·69
|
Apoptotic process, inflammatory response, innate immune response, and T-cell-receptor signalling pathway
|
NRP1
|
10p11.22
|
1·11
|
Signal transduction
|
INS
|
11p15.5
|
0·42
0·63
0·63
|
Insulin signalling pathway
|
BAD
|
11q13.1
|
0·92
|
Apoptosis
|
CD69
|
12p13.31
|
0·87
1·10
|
Signal transduction
|
ITGB7
|
12q13.13
|
1·19
|
Response to virus and regulation of immune response
|
ERBB3
|
12q13.2
|
1·25
|
Regulation of transcription, innate immune response, and lipid metabolism
|
CYP27B1
|
12q14.1
|
0·82
|
Metabolism of lipids, lipoproteins, steroid hormones, and vitamin D
|
SH2B3
|
12q24.12
|
1·24
0·76
0·76
|
Signal transduction
|
GPR183
|
13q32.3
|
1·12
|
Humoral immune response
|
DLK1
|
14q32.2
|
0·88
0·90
|
Regulation of gene expression
|
RASGRP1
|
15q14
|
0·85
1·15
|
Inflammatory response to antigenic stimulus and cytokine production
|
CTSH
|
15q25.1
|
0·81
0·78
0·90
|
Immune response-regulating signalling pathway T-cell-mediated cytotoxicity adaptive immune response
|
CLEC16A
|
16p13.13
|
0·83
0·82
1·14
|
Unknown
|
IL27
|
16p11.2
|
1·19
0·90
1·24
|
Inflammatory response and regulation of defence response to virus
|
ORMDL3
|
17q12
|
0·90
|
Protein binding
|
PTPN2
|
18p11.21
|
1·20
|
Cytokine signalling and B-cell and T-cell differentiation
|
CD226
|
18q22.2
|
1·13
|
Immunoregulation and adaptive immune system
|
TYK2
|
19p13.2
|
0·82
0·87
0·67
|
Cytokine-mediated signalling pathway, intracellular signal transduction, and type I interferon signalling pathway
|
FUT2
|
19q13.33
|
0·87
0·75
0·87
|
Metabolic pathways
|
UBASH3A
|
21q22.3
|
1·16
|
Regulation of cytokine production
Regulation of T-cell receptor signalling pathway
|
C1QTNF6
|
22q12.3
|
1·11
|
B-cell receptor signalling pathway, chemokine signalling pathway, and natural killer cell-mediated cytotoxicity
|
|
|
|
Envirnomental triggers associated with Type 1DM
|
- 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
|
|
|
The exact cause is unknown, but most likely there is a viral or environmental trigger in genetically susceptible people that causes an immune reaction. The body's white blood cells mistakenly attack the insulin-producing pancreatic beta cells. There are several forms of diabetes. Type 1 diabetes is called juvenile or insulin-dependent diabetes. Type 1 diabetes can occur at any age, but it is most often diagnosed in children, adolescents, or young adults.
Insulin is a hormone produced by special cells, called beta cells, in the pancreas. Insulin is needed to move blood sugar (glucose) into cells, where it is stored and later used for energy. In type 1 diabetes, these cells produce little or no insulin. Without enough insulin, glucose builds up in the bloodstream instead of going into the cells. The body is unable to use this glucose for energy. This leads to the symptoms of type 1 diabetes. Within 5 - 10 years, the insulin-producing beta cells of the pancreas are completely destroyed and the body can no longer produce insulin.
References
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