Why don’t autoantibodies play an important role in pathogenesis for type 1 diabetes?
Because the ag is intracellular
How do you diagnose type 1 diabetes?
Presenting symptoms: Weight loss, polyuria, polyphagia, polydipsia, fatigue, pain
Autoantibodies
Glucose tolerance test
HbA1c
When are autoantibdoies found in diabetes development?
Long before the onset of symptoms
Do you get polyuria because of polydipsia or vice versa?
Vice versa - polydipsia because of polyuria
Which tissues are preferentially damaged in diabetes?
The retina
The nerves
The kidney
When is glargine taken?
At bedtime - to control overnight blood glucose
What are the consequences of neuropathy?
Sensory disturbance:
Numb feet (+ poor circulation) + injury > gangrene > Amputation
Autonomic:
Gastric stasis
Impotence
What type of insulin therapy is determir?
Long acting
What does a fructosamine test tell you?
The level of glycosylation of amines - similar to HbA1c
- may be indicated if there is blood loss
What is an example of an open loop system?
Insulin pump
What type of insulin therapy is isophane?
Long acting
Below what blood glucose level is hypoglycaemia an emergency?
4mmol/L
What type of insulin therapy is glulisine?
Short acting
High postprandal glucose but low HbA1c is indicative of what?
Unrecognised blood loss
How do we know type 1 diabetes is an autoimmune disease?
- demonstrate presence of antibody to normal tissue
- establish the molecular identity of antigen
- induce/identify similar antibodies and pathology in animal model
- benefit of immunosuppression,
Why is it thought that determir causes weight lose?
It can cross the BBB (due to the addition of a FA) allowing it to act on the hypothalamus to suppress apeptite
What type of insulin therapy is glargine?
Long acting
What are the two limitations of islet cell transplantation?
- Availability of Islet cells to donate
- Chronic immunosuppression
What are some new treatments indevelopment?
Transplantation, regeneration of islets
Correct autoimmunity - avoid reccurrence
Artificial pancreas
Describe the therapy regimen called basal bolus?
One long acting insulin given at bedtime - typically glargine or determir
One short acting prior to meals - Apart, glulisine or lispro
How do you test for nephropathy? How often do you test for it?
Protein in urine
Annually
What percentage of risk is accounted for by genetics?
30-40%
Why do you get polyuria?
Because of the diuretic effect of glucose
Whis is APS-1 syndrome?
Loss of thymic tolerance due to mutations of AIRE gene
What is the effect of genetically modifying short acting insulin variants?
Speed up their subcutaneous absorption
What MHC is most strongly associated with type I diabetes?
HLA-DQ8
Which part of the insulin protein do most T cells recognise?
The C-peptide in the context of HLA-DQ8
What does insulin deficiency do to protein and lipid homeostasis?
Increase lipolysis and protein degradation for energy
How do you test for retinopathy and how often do you test for it?
Examine the retina
Annually
How can a hypoglycaemic event cause AMI?
Hypoglycaemia > Stim. of sympathetic NS > Tachycardia > Silent angina > AMI
How can you tell if autoimmunity is antibody mediated?
If there a neonatal syndromes - mother passing autoantibodies to children
What is the ideal HbA1c level to reduce complications?
7%
How long does it take for ketoacidosis to occur in a long term T1DM patient who is without insulin?
1 day
What are the three components required for an artificial pancreas?
Glucose sensor
Glucagon pump
Insulin pump
Why must potassium be administered in the treatment of ketoacidosis?
Because insulin causes it to enter cells
