Therapeutic use of insulin Flashcards
Outline the functions of insulin
- Prevents BG rising
- Reduces BG
- Allows the body to utilise carbohydrate in food
How does the liver increase BG levels
- Gluconeogenesis
- Glycogenolysis
Outline a normal insulin profile i.e for a non-diabetic eating 3 meals a day
- When this person isn’t eating they make a low level of background insulin all the time that stops the uncontrolled production of glucose and ketones by the liver
- Every time they eat, they make a spike of insulin that allows the body to utilise the carbs in the food without the glucose levels going up
What are we trying to mimic when we use insulin therapies in diabetic patients
- In a non-diabetic glucose levels remain very stable whether you are fasted or fed
- We are trying to mimic this narrow range
What are the differences between injectable insulin & endogenous insulin
- Injectable rather than made by the Beta cells of the pancreas
- Loss of portal:peripheral gradient… normally when the pancreas makes insulin, the portal system first takes it to the liver. This means normally the liver sees higher glucose conc compared to the rest of the body. When we inject it subcutaneously, that gradient is lost, so the liver sees similar concentrations to the rest of the body and this can affect how the insulin works on different organs
- Loss of C-peptide
- Weight gain
- Not controlled endogenously
- Narrow therapeutic index
How can C-peptide allow us to work out how much endogenous insulin is being made
-When we inject insulin we only inject the insulin molecule; so we don’t have the c-peptide that’s made along with the insulin molecule when the Beta cells of the pancreas make it. This allows us to work out how much endogenous insulin is being made
Outline the structure of proinsulin
-Comprised of an alpha chain, beta-chain and C-peptide bonded covalently
What do we use to separate the Alpha chain from C-peptide and the Beta chain from C-peptide. Thus transforming Pro insulin to soluble insulin
PC2 endopeptidase and PC3 endopeptidase respectively
Outline the different types of insulin preparation
- ) Rapid-acting insulins:
- Monomeric(rapid acting)
- Regular(short -in terms of short lived effect)(Actrapid, Humulin S)
- eg Novorapid, Humalog - ) Long-acting insulins
- Intermediate(NPH)
- ‘Peakless’ (detemir, Glargine..) - ) Mixed (biphasic) insulin: a mixture of rapid& long-acting insulin in a stated proportion
How can we make insulin last longer
By modifying it more:
eg bind it to other agents, attach to FA, change the solution it’s suspended in, make big stacks of it so that it is only released from the ends, pegylate it to make it release slowly
NOTE=soluble human insulin first exists as a hexamer
How does modifying the molecular size affect the rate of absorption of the modified insulin
- Molecular size correlates with rate of absorption
- The larger the molecular size, the longer the duration of action
How many units per ml does U100 insulin equal to?
U100 Insulin=100 units per ml
Explain the basal bolus regimen
- )Basal:
- Refers to the basic/little amount of insulin needed all the time( day& night),even between meals
- This is covered by the long-acting insulin which is administered twice(eg detemir) or once (eg glargine) daily so they either last 12-16 hours or 24 hours respectively - )Bolus:
- Insulin to cope with the rise in glucose levels after a meal
- Before each meal, a diabetic patient injects a rapid insulin to try and replace the peaks
How do we get the insulin dose needed by a patient right ?
-We ask the patient to monitor their blood glucose,preferably when the glucose is in a steady state before meals or before bed
-so multiple CPG readings are taken throughout the day, before meals and before bed
(if we monitor after meals the glucose levels may be rising or falling rapidly based on what they’ve eaten)
What are the golden rules for insulin dose adjustment
- Aim: to adjust the insulin doses to achieve target BG
- Test pre-meals & pre-bed
- Highlight the BG targets
- Look for hypos and sort out first
- Look for a pattern( except single overnight hypo cos this can be normal)
- Identify the most marked problem
- What insulin(s) are acting at the time of the problem?
- Adjust by 10-20%
- Usually make one change only (but think of knock on changes)
- If increasing pre-bed long-acting insulin, check 3am BG cos we need to ensure the BG level hasnt dipped in the night then come back up again
Link the time of hyperglycamia/hypoglycaemia increase/decrease to the insulin dose that needs to be adjusted in T1DM insulin therapies
1.) Time=pre-breakfast
insulin dose adjustment needed= pre-bed long-acting
2.)Time= pre-lunch
insulin dose adjustment needed= pre-breakfast rapid-acting or morning long-acting
3.)Time= pre-evening meal
insulin dose adjustment needed= pre-lunch rapid-acting or morning long-acting
4.) Time= pre-bed
insulin dose adjustment needed= pre-evening meal rapid-acting
Outline what DAFNE is
- Transfer of skills (from HCP to user) to replace insulin by matching it to CHO in an unrestricted diet meal-by-meal
- 5 day programme
- Adult education principles to facilitate new learning in a group setting
- Curriculum driven & quality controlled
- Emphasis on building confidence & appropriate independence
- Participants are taught how to adjust insulin to lifestyle rather than lifestyle to insulin
Explain the use of insulin pump therapy
- Continuous subcutaneous (rapid-acting) insulin infusion (CSII)
- Delivers a small amount of rapid acting insulin continuously & that can be programmed to give different amounts at different times of the day
- The person wearing the pump can tell it to give an extra amount of insulin if they’re about to eat
Why is T2DM described as a ‘progressive disease’?
- As the time from diagnosis increases, the Beta cell function decreases
- Insulin sensitivity also decreases/fluctuates
What hypothesis connecting hyperglycaemia with monotherapy has been suggested by studies
-There may be progressive hyperglycaemia with monotherapy
What insulin therapy can we use for T2DM
- ) Basal (with and without oral agents)
- Long acting insulin eg glargine once per day (usually pre-bed)
- usually continue other medications as well
- test BG pre-breakfast and dose adjust using same principles
- T2DM pts make some insulin so this offers some regulation and therefore reduces the need for as close matching as in T1DM
- This could be used in T1DM as the pt would become extremely hypoglycaemic with every administration - ) Mixed insulin pre-breakfast & pre-evening meal
- You give an injection pre-breakfast and the rapid acting component will control the BG after breakfast while the long acting component will control the BG throughout the rest of the day till the evening meal
- From the pre-evening meal injection; the rapid acting component will control the BG after the evening meal while the long -acting component will control the BG thoughout the night
- If you change the dose of this you change both components at the same time cos it’s pre-mixed at fixed proportion so both components would change amount
Link the problem to the insulin to adjust in T2DM twice daily mixed insulin therapy
1.) Problem= Pre bed AND pre breakfast BG above target
Insulin to adjust=Increase pre-evening meal mixed insulin
2.) Problem= Pre-bed AND/OR pre breakfast BG below target
Insulin to adjust=Decrease pre-evening meal mixed insulin
3.) Problem= pre lunch AND pre-evening meal BG above target
Insulin to adjust= Increase pre-breakfast mixed insulin
4.) Problem= pre lunch and/or pre evening meal BG below target
Insulin to adjust= decrease pre-breakfast mixed insulin
Outline the use of twice daily insulin therapy in T1DM
- This can come as free mixing or pre-mixed
- This is the mixed (biphasic) insulin
Which oral agents can be taken with basal insulin for T2DM patients?
-Metformin, alpha-glucosidase inhibitors (cause weight gain)
- thiazolidinediones
-sulphonyureas
etc
