Diabetes Pathogenesis Type 1 Flashcards
What is the blood glucose with diabetes?
> 7mM
(normally between 5-7)
What are the acute symptoms of hypoglycaemia?
(decreased sugar = brain has less glucose)
Nervous
Shakey
Dizzy
Confused
Headache
Hunger
Cold clammy skin
Tachycardia
Irritability
What are the acute symptoms of hyperglycaemia?
(increased sugar but cells can’t take it in)
Weak
Tired
Frequent urination
Increased thirst
Decreased appetite
Blurry vision
Itchy skin
Breath smells fruity
Describe pathogenesis of Type 1
Beta cells destroyed by cytotoxic CD8 T cells
= reactive to peptides complexed with MHC molecules from the beta cell
Describe overall Type 1
Failure of insulin secretion
Sudden onset
Childhood onset
What is gestational diabetes?
High blood glucose during pregnancy that disappears after birth
= beta cells cannot produce enough insulin to meet extra need
What are the possible consequences of gestational diabetes?
Baby grows larger than usual
Premature birth
Jaundice
Pre-eclampsia
What are the symptoms of Type 1?
Weight loss
Glucose in urine
Excessive urine
Thirst
Why is there weight loss in Type 1?
No insulin
= no glucose utilised at metabolic fuel
= proteins + FAs used
= weight loss
Why is there glucose in the urine, dehydration, excessive urine + thirst in Type 1?
High glucose enters glomerular filtrate
= overwhelms glucose capacity of proximal convoluted tubule
= increased fluid osmolarity
= more water secreted
= reabsorption reduced
= increased urine flow
What is the aim of insulin therapy?
Artificially regulate blood glucose
What are the problems with repeatedly injecting insulin?
Fat deposition
Promote deposition of fate
Cells close to site receive high amounts of insulin
Same site used frequently = lipohypertrophy
= important to change site frequently
What is the problem with repeatedly injecting insulin?
Absorption
lead to unpredictable rate of insulin absorption
= poor glycaemic control
= important to change site frequently
What are the forms of insulin used?
Animal - STOPPED
Human
Human analogues
What is soluble human insulin?
Rapid + short lived
= intravenous emergency
What is isophane human insulin?
Intermediate acting
What is human insulin zinc suspension?
Long acting
What is insulin Lispro (Humalog)?
Analogue
Modified insulin = switch lysine to proline residue at end of B chain
= very rapid + short-lived = emergency
When is insulin Lispro taken?
Before a meal
What is insulin glargine?
Analogue
Mutating Asn-12 in Gly + adding 2 Arg to end of B chain
= long acting + slowly absorbed
When is insulin glargine taken?
Before a meal in combination with short-acting form
What is the first choice for daily treatment for Type 1?
Multiple daily injections
= 1 or more separate daily injections of intermediate/long-acting insulin
= multiple injections of short-acting before meals
What are the other options for daily treatment of Type 1?
- Multiple injections per day pf short-acting mixed with intermediate
- Insulin pump
Who is the insulin pump only available to?
Suffering from hypos + hypers without warning
OR glycosylated haemoglobin >69mmol/mol
Describe the insulin pump
Pre-programmed doses of insulin
= programmed to fit the patten needed for insulin with activity level
What are the advantages of an insulin pump?
Allows for mealtime boluses to be delivered over a period of time
Insulin action matches carbohydrate absorption
Can deliver very small volumes (0.01-0.05 units)
What are the disadvantages of an insulin pump?
Worn all the time
Rapid risk of diabetic ketoacidosis if technical failure
Expensive
What does insulin pumps allow?
Insulin delivery to be closely + conveniently matched to insulin requirement
What is a hybrid closed loop technology?
Takes readings from a continuous glucose monitor + uses an algorithm to tell an insulin pump how much to deliver
Who is the hybrid closed loop technology recommended for?
HbA1c of 58mmol/mol or more
OR have disabling hypoglycaemia
What is Teplizumab?
Ab that blocks CD3 = no signalling = beta cell NOT killed
NEED CD3 to send signal to T cell so it can bind
