Treatment of Diabetes Mellitus Flashcards
Name some rapid-acting soluble insulin and their features
- Insulin lispro,
- Insulin aspart,
- Insulin glulisine.
Rapid onset of 10-20mins and short duration 2-5 hours. Designer insulins which prevent dimer formation which increases bioavailability of active monomers.
Name an intermediate-acting insuline?
Isophane insulin (Neutral Protamine Hagedorn (NPH)). Forms precipitate suspension which slowly dissolves
Name some of the long acting insulin formulations and their features
- Insulin glargine is longer acting, decreased solubility at neutral pH allowing it to form an aggregate which slowly dissolves. (human insulin)
- Insulin detemir is long acting, binds to albumin and slowly dissociates. (designed with fatty acid)
- Insulin degludec is ultra long acting, it results in multi-hexamer formation at injection site with slow release. (designed with fatty acid)
What is a fixed dose?
- Amount of insulin is taken at each meal.
- Doesn’t offer flexibility of how much carbohydrate a patient chooses to eat.
- Doesn’t need much understanding of blood glucose
What is a flexible dose? and name examples of this type of dosing
- Gives patients ability to control what they eat as patients choose how much insulin to inject at eat meal dependant on carb quantities.
- Patients need to have a good understanding of blood glucose.
- Examples of insulin therapy type which is flexibly is basal bolus and insulin pump.
What is the main adverse affect of insulin therapy?
- Hypoglycaemia
What are the lifestyle modifications to prevent prediabetes?
- Increase exercise and dietary advice which includes; reduced intake of processed carbs, ensure carbs come from fruits, beg and whole grains, eat low fat dairy and oily fish, limit trans/saturated fats, ensure small frequent means to avoid glucose spikes, increase fibre and complex carbs and decrease alcohol consumption
What is metformin and its features
- It is an oral hypoglycaemic which is used alter glucose metabolism.
- It can potentiate residual insulin by increasing insulin sensitivity.
- Reduces gluconeogenesis in the liver
- Opposes the action og glucagon,
- Increases glucose uptake and utilisation in skeletal muscle,
- Slight delay carbohydrate absorption in the gut.
- Increases fatty acid oxidation (reducing LDL and VDLD),
- Can encourage weight loss by supressing appetite.
What is the mechanism of action of metformin
It acts on the mitochondria to change the ratio AMP to ATP. It increases AMP but decreases the ATP and this activates AMP-activated protein kinase.
- AMPK increases transcription of genes important for glucose transport, fatty oxidation and inhibits fatty acid synthesis. It also inhibits glucagon signalling and gluconeogenic pathways
What are the different insulin secretagogues?
- Sulphonylureas (older class of orally-active hypoglycaemics) and Meglitinides
Name some sulphonylureas and their mechanism of action
- Gliclazide, tolbutamide.
- They have high affinity for receptors present in beta cell membranes. They block ATP sensitive potassium channels causing beta cell depolarisation which leads to insulin secretion. ONLY works if the B cells of the pancreas are functional.
Name some examples of meglitinides and their mechanism of action
- Repaglinide and Nateglinide.
- Block potassium channels leading to more insulin release. They have a more rapid onset and a short duration of activity.
Name examples of selective sodium glucose cotransporter 2 inhibitors
- Empagliflozin, Canagliflozin and Dapagliflozin.
- 2nd line when diet/exercise is not adequate and metformin contraindicated.
- Blocks glucose reabsorption by the proximal tubule leading to theraputic glucosuria. Therefore controls glycaemia independently of insulin pathways. Doesn’t cause hypoglycaemia but is associated with increased risk of UTIs
What is the function of incretins?
- Glucagon-like peptide 1 is secreted by L cells in the gut.
- Incretins stimulate insulin biosynthesis/secretion, inhibit glucagon secretion in pancreas, delays gastric emptying and increase in brain satiety signals. Indirectly increase insulin sensitivity.
- They are rapidly degraded by an enzymes called dipeptidyl peptidase-4
Name some Incretin mimetics and their features
- Exenatide, exenatide LAR (long-acting release) and Liraglutide which are analogs of exendin-4/GLP-1.
- Exenatide is given twice daily and can cause nausea. Exenatide LAR is given weekly.
- Act by lowering blood glucose after a meal by increasing insulin secretion and supressing glucagon secretion.
