Insulin Flashcards
What does insulin do?
Stimulates uptake of glucose into liver, muscle and adipose tissue.
Decreases hepatic glucose output via inhibition of gluconeogenesis
Inhibits glyconeogenesis
Promotes uptake of fats
Ideal insulin treatment would be to reinstate the normal daily insulin profile to prevent both hyperglycaemia and hypoglycaemia.
What are the types if insulin available?
Animal (porcine and bovine)
Human insulin (made from recombinant DNA technology) Human short acting insulins Human rapid acting insulin analogues Isophane intermediate acting insulin Long acting basal analogue insulins Very long acting basal analogue insulins
How has recombinant DNA technology changed insulin?
Has allowed for the development and production of analogues - the insulin molecule structure is modified to alter the pharmacokinetic properties, primarily affecting the absorption of the drug from subcutaneous tissue.
B26-30 region altered.
What are the 6 main insulin categories?
Ultrafast acting
Rapid acting - rapid onset of action 5-15mins. Inject just before eating. Peak at 60 mins. Duraring 4-6hours
Short acting - Starts to work 30-60mins. Need to inject at least 15-30mins before earning several times a day to cover meals. Peak at 2-3 hours. Duration 8-10hours.
Intermediate acting - Slower onset 2-4hours. Peaks 4-8 hours. duration 12-20 hours (used over night to keep insulin normal)
Long acting - slow onset 2-6 hours, duration up to 24hours,
Very long acting -up to 50+ hours (DEGLUDEC insulin)
Can get fixed combinations too.
The formulation affects the rate of absorption but, once they are in the blood stream they all act the same.
What is Insulin pump therapy and why is ti good?
When a person has a pump and wiring attached to them which injects rapid acting insulin into their blood constantly. They can turn up or down the rate of insulin to mirrow daily routine.
What are the ADRs of insulin?
Hypoglycaemia
Hypeglycaemia
Lipodystophy - lipohypertrophy or lipoatrophy (lumps from injecting into the same place - leads to destabilisation of diabetes)
Painful injections
Insulin allergies (usually allergic to preservatives and not actual insulin)
Safer administration of insulin
In UK 4-5% of population has diabetes
30 to 40% treated with insulin
Insulin errors are very common in UK with approximately prescribing errors in 20% cases.
Why does blood glucose rise?
Inability to produce insulin due to beta cell failure or
Insulin production adequate but insulin resistance prevents insulin working effectively.
How do we treat type 2 diabetes?
Type 2:
Lifestyle plus non-insulin therapies.
Biguanides (metformin), sulphonylureas, thiazolidinediones, DPP4 inhibitors, a-Glucosidase inhibitors, SGLT2s, GLP1 analogues and insulin
Plus non pharmacological methods via bariatric surgery an very low calorie diets
Also patient education and ability to monitor results of therapy.
What are the key challenges for patients with type 2 diabetes?
Weight gain (or fear of) and risk (or perceived risk) of hypoglycaemia = poor adherence to therapy.
What are the NICE targets in type 2 diabetes?
HbA1c target is 6.5-7.5%
Metformin
Lowers insulin resistance so more sensitive.
Reduces hepatic gluconeogenesis
Weight neutral (not promote weight gain)
Well tolerated
Decrease CVS events
Can combine with lots of other tablets.
ADRs = wind, nausea (GI symptoms)
If diarrhoea and loose stools then stop
B12 deficiency (rare)
Not pescribed if CKD as risk of lactic acidosis associated with AKI.
Cheap
Suphonylureas
Cheap
Stimulate B cells to release insulin
Extensice experience decreasing microvascular risk
ADRs:
Weight gain
Hypoglycaemia
Metabolised by liver so can be used in CKD.
E.g. Gliclazide, Glimepiride
What is acarbose?
A glucosidase inhibitor.
Not really prescribed int he UK anymore
Inhibits the breakdown of carbohydrates to glucose by blocking action of the enzyme s glucosidase.
Side effects = wind, loose stools, diarrhoea
Only modest reduction in HbA1c(0.5%)
What are Glitazones (pioglitazone)?
Increase insulin sensitively in muscle and adipose tissue and decrease hepatic glucose output.
They bind to and activate one or more peroxisome proliferator-activated receptors (PPARs)
Can be used in combination
CV concerns with Rosiglitazone
But, lots of side effects - MI angina, weight gain, HF, bone metabolism effects (as inhibit osteoblasts), increase bladder cancer risk
Rarely used now
