Autoimmune Insulin Dependent Diabetes Flashcards
Is the trigger for coeliac disease endogenous or exogenous?
Exogenous
How is type 2 diabetes often picked up?
Not by clinical symptoms but by screening
What is C peptide?
Part of proinsulin
Cleaved off in beta cell and secreted with insulin
Why is C peptide measured?
Measure of endogenous insulin production
How much more common is type 2 diabetes than type 1?
10x
How is the incidence of type 1 diabetes changing?
Increasing
Is type 1 diabetes present at birth?
No
Why is there a significant burden of disease in type 1 diabetes?
Obligate use of exogenous insulin
How is type 1 diabetes treated?
Short- or long-acting insulin
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
What causes the disease process in type 1 diabetes?
Inflammatory infiltrate
- T cells
- B cells
- Macrophages
- DCs
Why are islets in type 1 diabetes called pseudo-atrophic?
Still have alpha cells and produce glucagon
What do CD8 T cells release to destroy beta cells in type 1 diabetes?
Perforin
Granzymes
What are the clinical features of type 1 diabetes?
Symptoms - Polyuria - Polydipsia - Polyphagia Weight loss Ketoacidosis Insulin requirement
Do people with type 1 diabetes have autoantibodies?
Yes
What proportion of people with type 2 diabetes develop autoantibodies, and what does this mean?
10%
Progressing to T1D slowly
What are some of the autoantibodies that can be detected in type 1 diabetes?
Insulin autoAbs
GAD autoAbs
IA-2 autoAbs
What is the key self-antigen in the development of type 1 diabetes?
Insulin
Are all the self-antigens recognised by autoantibodies in type 1 diabetes specific to beta pancreatic cells?
No - some are, some aren’t
Does everyone with type 1 diabetes have all autoantibodies?
Not everyone has each autoAb but almost everyone does have them
Why are autoantibodies in type 1 diabetes diagnostic of, but not disease causing?
Because Ags recognised intracellular > Abs can’t bind and block function
How can babies get congenital autoimmunity?
Possibility of crossing placenta if mother has autoAbs
Wanes with half life of maternal Abs
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
Is there an age limit to developing type 1 diabetes?
No, but most common in childhood
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
What is the rate of loss of function in type 1 diabetes?
Unknown
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
What is APS-I syndrome?
Loss of thymic tolerance to peripheral Ags
Because of mutations in AIRE gene
Multiple autoimmune disorders
- 18% have T1D
What is immune dysfunction, polyendocrinopathy, enteropathy, X-linked (IPEX)?
Mutation of FoxP3 gene
80% of children develop T1D
What can reverse IPEX?
Bone marrow transplant
Which gene associations are the strongest with type 1 diabetes?
HLA
Insulin - polymorphic expression in thymus
Which two HLA are strongly associated with type 1 diabetes?
HLA-DQ2 and -DQ8
What is the pathogenesis of type 1 diabetes?
- Proinsulin-reactive T cells escape negative selection
- Become activated due to high concentration/altererd Ag
- Recognition of beta cells
- CD8 T cell dominant destruction
- Spreading to other specifications
What are possible environmental triggers for autoimmunity?
UV Diet Drugs - not for T1D Hygiene hypothesis Infection
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
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
What are some possible avenues of correcting autoimmunity?
Immunosuppression Immunomodulatory drugs Anti-inflammatory biologicals Ag specific Cell therapy
Can hypoglycaemia unawareness be treated with islet transplantation?
Yes, with associated freedom from severe hypoglycaemic events
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
