Pharmacology of diabetes 1 Flashcards
Define diabetes
Metabolic disorder characterised by chronic hyperglycaemia with disturbances in carbohydrate, fat and protein metabolism resulting from defects in insulin secretion or action
What are the three types of diabetic complications?
Microvascular (retinopathy, nephropathy)
Macrovascular (atherosclerosis)
Neuropathy
What is the difference between type 1 and 2 Diabetes Mellitus?
1) Insulin-dependant
- pancreatic beta cells destroyed and no insulin made
2) non-insulin dependant
- insulin stops working at target tissue
- insulin resistant or insufficient insulin
What is the age of onset for type one and two?
1) childhood/puberty
2) middle age > 35
What is the nutritional status of type one and two diabetes?
1) Frequently malnourished
2) usually obese
What is the prevalence of type 1 and 2 diabetes?
1) 10-20% of all cases
2) 80-90% of cases
What is the genetic predisposition to type 1 and 2?
1) moderate
2) very strong
When is insulin prescribed?
- All patients with type 1 diabetes
- Emergency treatment of ketoacidosis
- In type 2 for improving control of diabetes and for intercurrent events
- during pregnancy
- emergency treatment of hyperkalaemia to lower extracellular potassium
What test is used to measure insulin?
C-peptide ELISA
- measures C-chain peptide released in the final step of insulin synthesis proinsulin > insulin
- means test only measures active form insulin
What are the phases in insulin release?
Phase 1) rapid, triggered by increase glucose levels
Phase 2) Slow, sustained, newly formed vesicles triggered independently of glucose
What is the half life of insulin?
5-6 mins, most removed through liver by first pass
Which transporters take up Glucose?
GLUT 2
What are the steps of insulin secretion within the beta cells?
- Glucose in cell metabolised to form ATP
- ATP inhibits ATP-sensitive potassium channels preventing potassium from leaving the cell
- causes cell depolarisation
- results in voltage gated calcium channels to open and calcium enters
- calcium required to release insulin from storage granules
What enzyme is needed to metabolise glucose?
Glucokinase phosphorylises glucose into glucose-6-phosphate
What times would you measure fasting and peak glucose?
Fasting: 5 am
Peak: 8-9 am (breakfast)
peak after every meal
How does insulin stimulate glucose uptake?
- insulin binds to insulin receptor
- signal transducer by activated receptor
- triggers glucose uptake by GLUT4 (found in liver, muscle and fat)
Why do glucose transporters in brain and heart differ from the liver, muscles and fat?
Don’t want insulin to affect glucose uptake in brain and heart as want to always keep uptake high as very metabolically active
What is the insulin receptor on cells called?
Insulin receptor tyrosine kinase
What four organs does insulin affect?
Liver
Muscle
Adipose tissue
Brain (stimulates hunger in the brain)
What are effects of insulin in the liver?
- increase glucose uptake
- increased glycolysis (conversion of glucose > energy)
- increased glycogenesis
- decreased gluconeogenesis
- decreased glycogenolysis (doesn’t need the energy)
What are effects of insulin in the Muscles?
- increase glucose uptake
- increase glycogenesis
- increased glycolysis (muscle want the energy)
- increased amino acid uptake and protein synthesis (to build muscle)
What are effects of insulin in the Fat?
- increase glucose uptake
- increase triglyceride formation
- overall increased fat deposition (create storage of fat in form of glycogen)
How do we manufacture insulin?
Recombinant human protein in bacteria
Why can we not use oral insulin and what do we do instead?
Broken down by GI so injected subcutaneously
what machine is used to check blood glucose?
- Glucometer is manual machine to check where need to take finger prick blood
- Can also use transdermal sensor for glucose which is attached to the arm
What types of insulin can be injected?
1) Short acting (Insulin Pen)
- before every meal
- e.g. Novorapid
2) Intermediate acting
- insulin zinc suspension which extends half life
- twice daily
3) Long-acting
- insulin zinc suspension
- once/twice daily
Give an example of long-acting insulin?
Insulin Glargine (Lantus = brand)
- provides constant basal insulin supply and prolonged absorption from injection site
- useful in preventing hypoglycaemia at night
What is the best form of insulin to be taking as treatment for type 1 diabetes?
Short acting before meals and long acting via insulin pump
Where on the body can insulin be injected?
abdomen, arm, buttock and thighs
What factors affect the absorption of the insulin after injection?
- site of injection
- exercise
- depth of injection
- concentration of dose
- insulin degrading activity in subcutaneous tissue
What are the side effects of injection too much insulin?
1) hypoglycaemia - sweating, shaky, irritable and dizzy (treat by drinking sugary drink)
2) allergic reactions
3) lipodystrophy (excessive fat breakdown)
4) lipohypertrophy (fat accumulation at site of infection)
How does insulin affect serum potassium?
- Insulin decreases serum potassium
- stimulates potassium uptake into cells via activation of Na/K ATPase pump
- potassium leaves blood all intracellular
How is hypoglycaemia treated?
1) If patient is conscious given sugary drink or quick acting carb
2) If conscious but not cooperating give oral glucose gel or glucagon
3) if unconscious give IV glucose or IM glucagon
Why are there insulin specific syringes?
Use micro litres unlike millilitres in the syringes
What are the symptoms of ketoacidosis?
- unconscious
- alcoholic breath
- dehydrated
- blood glucose + ketones high
- vomiting
- excessive thirst
- fruity smelling breath
What is ketoacidosis?
- Type 1 patient doesn’t take their insulin
- body compensates by starting to breakdown fat as energy source
- fat breakdown generates ketones (acids)
- Lowers PH of blood and patient goes into diabetic ketoacidosis
How is DKA (diabetic ketoacidosis) treated?
- Need to get blood glucose down and resolve venous ketones
- Give saline
- and IV infusion of insulin
- Need to check serum potassium to ensure no hypokalaemia
