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
What type of dietary advice and insight is given to T1D px?
dose adjustment for carb content
Carb counting
Refine carb substitute…
What is a closed loop / artifical pancreas?
Real time continuous glucose sensor after change in glucose and pump can calculate and deliver insulin
- issue of eating and the lag of 15 mins, due to time taken to sense glucose so when eating the px will have to tell pump to intervene for the time being
What is a closed loop / artifical pancreas?
Real time continuous glucose sensor after change in glucose and pump can calculate and deliver insulin
- issue of eating and the lag of 15 mins, due to time taken to sense glucose so when eating the px will have to tell pump to intervene for the time being
Islet cell transplantas?
- Isolate human islets from donor and inject into hepatic portal vein
require life long immunosuppression
What is simultaenous pancreas and kidney transplants?
Better survical of pancreas graft when transplanted …
Why is glycated haemoglobin important?
HbA1c:
reflects 4 months of glycaemia
Glucose will stick to N-terimal valine residue Beta chain
Linear relationship with high glucose and high hbA1c
Irreversible reaction
Why is hbA1c not a perfect measure?
Many things can affect red blood cell turnover e.g. anaemia, CKD
When can acute diabettic ketoacidosis?
- inadequate long acting insulin dos
- missed doses
- acute illness
or as a presenting feature of new onset T1D
What is the issue with frequent hypoglycaemia?
1-2 episodes a week is common but frequent can cause the symptoms or awareness decrease / nocturnal hypoglycaemia
if cannot detect and left untreated = seizure, coma, death, cognition impact
What are the risk factors for hypoglycaemia?
People with Diabetes
- exercise
- missed meals
- wrong insulin
- alcohol
- lower HbA1c
How to manage hypoglycaemia acutely If they are alert and orientated?
- oral carbs
- rapid acting juice/sweets
- longer acting sandwich
How to manage hypoglycaemia acutely If they are drowsy/confused but swallow intact?
- Buccal glucose
- Hypostop / glucogel
- Complex carb
How to manage hypoglycaemia acutely If they are unconscious or concerned about swallow?
IV access
20% glucose IV
