Type 1 Diabetes Flashcards
Why is it a challenge to diagnose differentially?
Although there are trends, type 1 can occur in later life due to genetic + environmental componants. Need to diagnose this
How does type 1 diabetes develop?
- Stage A/B = genetic predisposition
- Stage C/D/E = Beta cells start to decline
- Stage ? Once declined to a large rate and insulin is lost but glucose is normal ( overt diabetes = c-peptide present
- Then C-peptide is lost
What is happening in the immune system during type 1 diabetes development?
Genetic risk is required
- immune activation and beta cells are attacked
- immune response by developing a single autoantibody
- stage 1 : normal blood glucose
- stage 2 : Abnormal blood glucose
- stage 3 : clinical diagnosis
stage 4: long standing T1 alongside autoantibodies present
How does immune filtration look in early type 1 compared to later in life type 1 diabetes?
Lots of immune infiltration in beta cells compared to later in life where this a quintescent phase
Why is the immune basis important in type 1 diabetes?
Increased prevalance of other autoimmune disease
risk of autoimmunity in relatives
more complete destruction of B cells
autoantibodies ca be useful clinically
What defects in the innate and adaptive immune system cause diabetes?
- primary step is the presentation of auto-antigen to autoreactive CD4+ T lymphocytes
- CD4+ activate –> CD8+ T lymphocytes
- CD8+ travels to iselts and lyse beta cells which express the auto antigen
Exacerbated by pro-inflammatory cytokines
Are all beta cells destroyed by the immune process?
Some people do continue to produce small amounts of insulin
not enough to negate the need for insulin therapy * these indavituals so have fewer complications
What allele mediates genetic susceptibility?
HLA region on allele
What environmenal factors could increase incidence of T1?
enteroviral infection (Coxsackieviruses)
cows milk protein exposure
seasonal variation
changes in microbiota
What are the symptoms of type 1 Diabetes?
- Excessive urination
- Nocturia
- Polydipsia
- Blurring of vision
- Recurrent infections e.g. thrush
- Weightloss
- Fatigue
What are the sign of T1D?
Dehydration cachexia hyperventiliation small amount of ketones glycosuria ketonuria
What can be detectable in the sera of people with T1D at diagnosis?
Pancreatic auto-antibodies
Although this is not needed for diagnosis in most cases
e. g. Glutamic acid decarboxylase : widespread neurotransmitter
- Insulinoma associated - 2 autoantibodies - zinc transporter 8
What are the treatment in type 1 diabetes?
Insulin for life:
- Maintain glucose levels without excessive hypoglycaemia
- Restore a close to physiological insulin profile
- Prevent acute metabolic decompensation
- Prevent micro and macro complications
How is insulin used to recreate physiological insulin profile look like?
With meals you give short quick acting insulin:
- Human insulin, which is exact molecular replicate called actrapid
- Insulin analogue - Lispro. aspart, glulisine)
Or long acting:
- bound to zinc or protamine - Neutral protamine hagedorn
- Insulin analogue - glargine, determir, degludec
What is insulin pump therapy?
Continuous delivery of short acting insulin analogue e.g. novorapid via pump
Into subcutaneous space
