Causes of Type 1 diabetes

Question 1

when would primary prevention of type 1 diabetes occur

Answer 1

• genetic predisposition, before beta cells are lost
• can screen for haplotypes

Question 2

what are HLA molecules and what are their classes

Answer 2

1. HLA antigens are glycoproteins found on the cell surface that are involved in the immune process
2. 2 classes: class I and class II which differ in structure

Question 3

where are class I HLA molecules found

Answer 3

found on all nucleated cells

Question 4

where are class II HLA molecules found

Answer 4

only found on antigen presenting cells
- eg macrophages

Question 5

what is the role of class II HLA molecules

Answer 5

• bind to foreign antigen peptides and present them to T helper lymphocytes
• 3 types (DP, DQ and DR)

Question 6

is there an association between HLA and type 1 diabetes

Answer 6

• recent genome-wide studies have confirmed strong association between T1D and HLA genes
• but there are at least 47 non HLA genetic factors thought to contribute

Question 7

what are the environmental triggers of type 1 diabetes

Answer 7

1. chemicals- N nitro compounds
   - streptozoticin
2. viruses- mumps, rubella, enterovirus
3. vaccination
4. bacteria- streptomyces
5. psychological stress- child/parent separation, difficult adaptation
6. food components- short breastfeeding, cereals, vitamin d deficiency
7. energy intake- high energy intake and weight gain
   - increased insulin resistance
   - puberty

Question 8

how do viruses contribute to killing beta cells

Answer 8

1. cytolysis- causing cell death
2. molecular mimicry- mimic autoantigen to provoke an immune response
3. T cell activation- auto reactive T cell activation
   - beta cell killing
4. overproduction of interferon- inhibition of insulin production and loss of beta cell function

Question 9

which virus is most commonly associated with contributing to the development of type 1 diabetes

Answer 9

enteroviruses
- specifically Coxsackie B virus
- 30% of newly diagnosed diabetic patients have IgM antibodies to coxsackie B virus

Question 10

what are the 4 islet cell autoantibodies involved in the pathogenesis of type 1 diabetes

Answer 10

1. GAD65
2. islet antigen 2
3. insulin
4. ZnT8 transporter
   - markers for chance of developing type 1 diabetes and speed of developing type 1 diabetes
   - risk increases if you have more than 1 autoantibody

Question 11

what are the preventative therapies for type 1 diabetes

Answer 11

1. immune system- conventional non specific immunosuppression (ciclosporin)
   - targeted or selective immunotherapy
2. pancreatic islet- B cell defence/repair and growth promoters