Autoimmune Insulin Dependent Diabetes Flashcards Preview

MD1 Metabolism > Autoimmune Insulin Dependent Diabetes > Flashcards

Flashcards in Autoimmune Insulin Dependent Diabetes Deck (39):
1

Is the trigger for coeliac disease endogenous or exogenous?

Exogenous

2

How is type 2 diabetes often picked up?

Not by clinical symptoms but by screening

3

What is C peptide?

Part of proinsulin
Cleaved off in beta cell and secreted with insulin

4

Why is C peptide measured?

Measure of endogenous insulin production

5

How much more common is type 2 diabetes than type 1?

10x

6

How is the incidence of type 1 diabetes changing?

Increasing

7

Is type 1 diabetes present at birth?

No

8

Why is there a significant burden of disease in type 1 diabetes?

Obligate use of exogenous insulin

9

How is type 1 diabetes treated?

Short- or long-acting insulin

10

What is the pattern of destruction of beta cells in the pancreas in type 1 diabetes?

From normal beta cell function to none at all
Not uniform destruction

11

What causes the disease process in type 1 diabetes?

Inflammatory infiltrate
- T cells
- B cells
- Macrophages
- DCs

12

Why are islets in type 1 diabetes called pseudo-atrophic?

Still have alpha cells and produce glucagon

13

What do CD8 T cells release to destroy beta cells in type 1 diabetes?

Perforin
Granzymes

14

What are the clinical features of type 1 diabetes?

Symptoms
- Polyuria
- Polydipsia
- Polyphagia
Weight loss
Ketoacidosis
Insulin requirement

15

Do people with type 1 diabetes have autoantibodies?

Yes

16

What proportion of people with type 2 diabetes develop autoantibodies, and what does this mean?

10%
Progressing to T1D slowly

17

What are some of the autoantibodies that can be detected in type 1 diabetes?

Insulin autoAbs
GAD autoAbs
IA-2 autoAbs

18

What is the key self-antigen in the development of type 1 diabetes?

Insulin

19

Are all the self-antigens recognised by autoantibodies in type 1 diabetes specific to beta pancreatic cells?

No - some are, some aren't

20

Does everyone with type 1 diabetes have all autoantibodies?

Not everyone has each autoAb but almost everyone does have them

21

Why are autoantibodies in type 1 diabetes diagnostic of, but not disease causing?

Because Ags recognised intracellular > Abs can't bind and block function

22

How can babies get congenital autoimmunity?

Possibility of crossing placenta if mother has autoAbs
Wanes with half life of maternal Abs

23

What is the relationship between the time course and disease process in type 1 diabetes?

Quite well > get sick very suddenly, but disease process going on for a long time

24

Is there an age limit to developing type 1 diabetes?

No, but most common in childhood

25

What is the risk of developing type 1 diabetes in monozygotic twins, where one sibling develops it in childhood?

In non-diabetic twin at start
- Develop autoAbs
- Increased risk of developing type 1 diabetes later in life

26

What is the rate of loss of function in type 1 diabetes?

Unknown

27

What are the stages proposed for type 1 diabetes?

Variable genetic and environmental risk
Stage 1 - pre-symptomatic T1D
- Beta cell autoimmunity
- Normoglycaemia
Stage 2 - pre-symptomatic T1D
- Beta cell autoimmunity
- Dysglycaemia
- No symptoms
Stage 3 - symptomatic T1D
- Beta cell autoimmunity
- Dysglycaemia
- Symptoms

28

What is APS-I syndrome?

Loss of thymic tolerance to peripheral Ags
Because of mutations in AIRE gene
Multiple autoimmune disorders
- 18% have T1D

29

What is immune dysfunction, polyendocrinopathy, enteropathy, X-linked (IPEX)?

Mutation of FoxP3 gene
80% of children develop T1D

30

What can reverse IPEX?

Bone marrow transplant

31

Which gene associations are the strongest with type 1 diabetes?

HLA
Insulin - polymorphic expression in thymus

32

Which two HLA are strongly associated with type 1 diabetes?

HLA-DQ2 and -DQ8

33

What is the pathogenesis of type 1 diabetes?

1. Proinsulin-reactive T cells escape negative selection
2. Become activated due to high concentration/altererd Ag
3. Recognition of beta cells
4. CD8 T cell dominant destruction
5. Spreading to other specifications

34

What are possible environmental triggers for autoimmunity?

UV
Diet
Drugs - not for T1D
Hygiene hypothesis
Infection

35

What is wrong with the current treatment of type 1 diabetes?

Incapable of mimicking physiological glucose control > can't prevent complications
Multiple injections per day

36

What are the possible future therapies for type 1 diabetes?

Restore insulin production
- Transplant/regenerate
Abolish disease recurrence
- Correct autoimmunity
In meantime
- Islet transplantation
- Artificial pancreas

37

What are some possible avenues of correcting autoimmunity?

Immunosuppression
Immunomodulatory drugs
Anti-inflammatory biologicals
Ag specific
Cell therapy

38

Can hypoglycaemia unawareness be treated with islet transplantation?

Yes, with associated freedom from severe hypoglycaemic events

39

What are the problems with islet transplantation?

Availability of organ doners
Viability and function of islets
Immunosuppression - needed for
- Rejection
- Recurrence of T1D
Longevity of graft
All-sensitisation
Cost