Diabetes Flashcards
What causes production and inhibition of insulin? What is it’s role?
Secreted in response to: Glucose Incretins(GLP-1, GIP) Glucagon Parasympathetic activity
Inhibited:
Low glucose
Cortisol
Sympathetic activity
Role:
Decreased hepatic glucose output via inhibition of gluconeogenesis, inhibits glycogenolysis, promotes uptake of fats
Which drugs increase your risk of developing type 2 diabetes?
Thiazides/ thiazide- like, glucocorticoids, beta blockers
How far back does HbA1c predict the percentage of red blood cells with sugar coating?
Reflects average blood sugar over last 10-12 weeks mmol/ mol or %
Types of therapeutic insulins
Bovine - human (3aa)
Porcine - human (1aa)
Immunogenicity
Human insulin - recombinant DNA or enzymatic modification of porcine
Protein - must given parenterally to avoid gut digestion
Usually 100 U/ mL
Pharmacokinetics of insulin
Routine delivery by injection (upper arms, thighs, buttocks, abdomen)
I.v. For emergency treatment
t1/2 5 mins (plasma, renal, hepatic metabolism and elimination)
Plasma conc greatest after 2-3hrs - dose 15-30mins prior to meals
Protamine &/ or zinc used to modify absorption
Site of administration route - lipodystophy
Why do diabetics need to rotate the injection site of insulin?
Can get lipodystrophy - hypertrophy of lipids around injection site can affect vasculature
List some different insulin profiles, the onset of action, peak, duration and class
Insulin aspart - 10- mins onset, 40-50mins peak, 3-5hrs duration, rapid class
Soluble insulin (Humulin S, Actrapid) - 30-60mins onset, 2-12hrs peak, 5-8hrs duration, short class
Isophane insulin (NPH) - 60-120mins onset, 4-12hrs peak, 18-24hrs duration, intermediate class
Insulin glargine- 60-90mins, plateau between 2-20hrs, 20-24hrs duration, long class
What are potential risks of insulin therapy and what other drugs should you be cautious of prescribing simultaneously?
❌hypoglycaemia, lipohypertrophy, lipoatrophy, renal impairment -> hypoglycaemic risk
Increased dose if taking steroids, caution with other hypoglycaemic agents
What is meant by basal-bolus dosing?
Can take a bolus dose which is rapid acting after meals e.g. aspart
Basal dose is long acting and taken first thing in the morning e.g. glargine
Normal ppl have basal level of insulin which increases after meals
When would you suspect a diabetic ketoacidosis, how would you treat?
Blood glucose _>11mmol/ L (not always) and:
Infection Stress/ trauma Poor insulin adherence ADRs Ketosis Can have low blood ketones
✅fluids priority then insulin, then glucose and K+ if needed
(Total K+ levels in body quite low but measurements of blood may suggest higher as acidosis)
How does type 2 diabetes occur?
Slow progression of disease
Cellular resistance to insulin associated with obesity
- resistance initially overcome by increased pancreatic secretions
Decreased insulin receptors, decreased GLP-1 secretion in response to oral glucose and reduced beta cell response
What is the NIcE guidance for type 2 diabetes glucose lowering therapy if they can take metformin?
If HbA1c rises to 48mmol/mol on lifestyle interventions ->
standard release metformin, aim for HbA1c 48. If rises to 58->
Consider dual therapy metformin and DPP-4i/ pioglitazone/ SU/ SGLT-2i. Aim for 53. If rises to 58 ->
Consider triple therapy metformin and: DPP-4i + SU OR pioglitazone + SU OR pioglitazone/ SU + SGLT-2i. Consider insulin based. Aim for 53.
(Is standard release metformin not tolerated e.g. GI upset consider trial of modified release)
What is the NIcE guidance for type 2 diabetes glucose lowering therapy if metformin contraindicated or not tolerated?
HbA1c rises to 48 mmol/mol on lifestyle interventions ->
Consider one: DPP-4i/ pioglitazone/ SU/ SGLT-2i. Aim for 48 or 53 if on SU. If rises to 58->
Consider dual therapy: DPP-4i + pioglitazone, DPP-4i + SU, pioglitazone + SU. Aim for 53. If reaches 58 ->
Consider insulin based treatment. Aim for 53.
Slide 14
What type of drug is metformin and how does it work? Side effects and drug cautions
Biguanide
- Decrease hepatic glucose output (gluconeogenesis, glycogenolysis)
- Increase glucose utilisation in skeletal muscle
- suppress appetite
Typically first drug offered can be taken concomitantly with other options
❌GI upset - nausea, vomiting, diarrhoea, lactic acidosis STOP if eGFR <30mL/ min
Drug cautions: ACEi, diuretics, NSAIDS (any drugs that may impair renal function) thiazide- like diuretics increase glucose so can reduce action
Give an example of a sulfonylurea, how do they work, side effects, drug cautions?
Gliclazide, stimulate beta cell pancreatic insulin secretion blocking ATP dependent K+ channels, need residual pancreatic function
Typically in combo with other agents or a first line option if metformin contraindicated
❌ mild GI upset, hypoglycaemia, rare hypersensitivity reactions, weight gain through anabolic insulin effects
Drug cautions: other hypoglycaemic agents, hepatic impairment, renal impairment thiazide like diuretics increase glucose so can reduce action
