Therapeutic use of insulin

Question 1

Outline the functions of insulin

Answer 1

• Prevents BG rising
• Reduces BG
• Allows the body to utilise carbohydrate in food

Question 2

How does the liver increase BG levels

Answer 2

• Gluconeogenesis

- Glycogenolysis

Question 3

Outline a normal insulin profile i.e for a non-diabetic eating 3 meals a day

Answer 3

• 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

Question 4

What are we trying to mimic when we use insulin therapies in diabetic patients

Answer 4

• In a non-diabetic glucose levels remain very stable whether you are fasted or fed
• We are trying to mimic this narrow range

Question 5

What are the differences between injectable insulin & endogenous insulin

Answer 5

• 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

Question 6

How can C-peptide allow us to work out how much endogenous insulin is being made

Answer 6

-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

Question 7

Outline the structure of proinsulin

Answer 7

-Comprised of an alpha chain, beta-chain and C-peptide bonded covalently

Question 8

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

Answer 8

PC2 endopeptidase and PC3 endopeptidase respectively

Question 9

Outline the different types of insulin preparation

Answer 9

1. ) Rapid-acting insulins:
   - Monomeric(rapid acting)
   - Regular(short -in terms of short lived effect)(Actrapid, Humulin S)
   - eg Novorapid, Humalog
2. ) Long-acting insulins
   - Intermediate(NPH)
   - ‘Peakless’ (detemir, Glargine..)
3. ) Mixed (biphasic) insulin: a mixture of rapid& long-acting insulin in a stated proportion

Question 10

How can we make insulin last longer

Answer 10

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

Question 11

How does modifying the molecular size affect the rate of absorption of the modified insulin

Answer 11

• Molecular size correlates with rate of absorption

- The larger the molecular size, the longer the duration of action

Question 12

How many units per ml does U100 insulin equal to?

Answer 12

U100 Insulin=100 units per ml

Question 13

Explain the basal bolus regimen

Answer 13

1. )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
2. )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

Question 14

How do we get the insulin dose needed by a patient right ?

Answer 14

-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)

Question 15

What are the golden rules for insulin dose adjustment

Answer 15

• 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

Question 16

Link the time of hyperglycamia/hypoglycaemia increase/decrease to the insulin dose that needs to be adjusted in T1DM insulin therapies

Answer 16

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

Question 17

Outline what DAFNE is

Answer 17

• 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

Question 18

Explain the use of insulin pump therapy

Answer 18

• 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

Question 19

Why is T2DM described as a ‘progressive disease’?

Answer 19

• As the time from diagnosis increases, the Beta cell function decreases
• Insulin sensitivity also decreases/fluctuates

Question 20

What hypothesis connecting hyperglycaemia with monotherapy has been suggested by studies

Answer 20

-There may be progressive hyperglycaemia with monotherapy

Question 21

What insulin therapy can we use for T2DM

Answer 21

1. ) 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
2. ) 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

Question 22

Link the problem to the insulin to adjust in T2DM twice daily mixed insulin therapy

Answer 22

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

Question 23

Outline the use of twice daily insulin therapy in T1DM

Answer 23

• This can come as free mixing or pre-mixed

- This is the mixed (biphasic) insulin

Question 24

Which oral agents can be taken with basal insulin for T2DM patients?

Answer 24

-Metformin, alpha-glucosidase inhibitors (cause weight gain)
- thiazolidinediones
-sulphonyureas
etc