Diabetes Management Flashcards
1
Q
How is insulin released?
A
- amino acids and parasympathetic release of Ach increase intracellular calcium in beta cells through the phospholipase C-IP3 pathway and stimulate insulin release. (adrenaline on the other hand suppresses insulin release)
- increased glucose levels in the blood lead to glucose uptake by beta cells through GLUT 2 low affinity transporters (have high Km bcs of low substrate affinity). intracellular glucose leads to increased ATP and decreased ADP so this ratio causes closure of potassium channels and cell depolarization. the cell depolarization opens calcium channel which leads to insulin granule exocytosis and secretion
2
Q
How is insulin action terminated?
A
- downregulation of insulin receptors by internalisation of insulin-receptor complex and metabolisation of these complexes
- receptors are then recycled to plasma membrane
3
Q
What are the effects of insulin?
A
- increased glycolysis, glycogen synthesis, lipid and protein synthesis
- inhibited gluconeogenesis, lipolysis and protein degradation
- increased glucose uptake from blood by inducing GLUT4 transporter translocation to plasma membrane. increased triglyceride and amino acid uptake into tissues
4
Q
How is insulin cleared?
A
- 50% of endogenous insulin removed during first pass
- kidney is major site of insulin clearance from systemic circulation. exogenous insulin also mainly cleared by kidneys
5
Q
What is the difference between type 1 and type 2 diabetes?
A
- type 1 : immune mediated beta cell destruction that leads to absolute insulin deficiency
- type 2 : ranges from insulin resistance with relative insulin deficiency to a predominant secretory defect together with insulin resistance
- gestational diabetes is the onset of glucose intolerance in pregnancy
6
Q
What are some symptoms of diabetes?
A
- always being tired
- polyuria
- sudden weight loss
- wounds that don’t heal well
- sexual problems in men and vaginal infections in women
- always being hungry
- blurry vision
- numb or tingling in peripheries
- polydipsia
7
Q
How are type 1 and type 2 diabetes managed?
A
- type 1 : must receive exogenous insulin to mimic normal basal and prandial pancreatic insulin secretion
- type 2 : initially may have lifestyle modification unless they are symptomatic and severely hyperglycemic (glucose>15 mmol/L) in which case they are first given oral hypoglycemic agents but if they don’t work can supplement with exogenous insulin
8
Q
What are the different types of exogenous insulin drugs?
A
- rapid acting insulins : lispro, aspart, glulisine
- short acting insulins : recombinant human regular insulin so similar to endogenous insulin
- intermediate acting insulins : NPH (neutral protamine hagedorn)
- long acting insulins : glargine, detemir
9
Q
What are the different onset and peak features of the different endogenous insulins?
A
- rapid acting insulins : 15-30 mins onset time and 1-3 hrs peak time
- short acting insulins : 30-40 mins onset time and 2-4 hours peak time
- NPH : 1-4 hrs onset time so high risk of hypoglycemia and 4-8 hrs peak time
- long acting insulins : 1-4 hrs onset time but are peakless so are often used as basal insulin
10
Q
What is the mechanism of action of lispro, aspart, glulisine?
A
- developed by substitution/addition of amino acids that cause changes to charge/conformation of insulin molecule at physiological pH so these insulin self-associate lesser by charge repulsion
- with lesser dimer formation, there is rapid absorption of these monomers that’s why fast onset time and can be injected just before meals. dose can be adjusted according to food
- their shorter duration of action lowers hypoglycemia risk
- clear appearance
11
Q
What is the mechanism of action of regular human insulin (short acting insulin)?
A
- similar to endogenous human insulin
- self aggregate in subQ tissue so delayed onset
- need to inject 20-30 mins prior to meals
- higher hypoglycemia risk than rapid acting insulin
- the only insulin group that is given as IV in emergency at hospitals
- clear appearance
12
Q
What is the mechanism of action of NPH?
A
- combination of recombinant human insulin with protamine
- crystals precipitate so NPH insulin released slower causing longer duration of action compared to regular insulin
- only insulin with cloudy appearance
- high hypoglycemia risk because of inter patient variability of NPH action and long peak effect so patient needs to eat a meal at peak time
- typically twice a day dosing
- can be mixed with rapid and short acting insulin into single injection
13
Q
What is the mechanism of action of long acting insulin?
A
- act for 18-24 hours so just once a day dosing, takes care of basal insulin needs
- glargine formulated at pH 4 so at pH 7.4 it forms aggregates that slowly release insulin over time
- detemir has C14 fatty acid chain which increases self association into hexamers and di- hexamers. detemir also binds to albumin so this additionally prolongs detemir action
- both have clear appearances
- have lower intra-subject variation and reduced hypoglycemic risk compared to NPH
14
Q
Which insulins can be mixed?
A
can mix :
- NPH + regular insulin
- NPH + rapid acting insulin
- degludec (ultra long acting insulin) + rapid acting insulin
cannot mix :
- glargine and other insulins bcs of incompatible pH
- detemir and other insulins
- glulisine (short acting) can ONLY be mixed with NPH
15
Q
What factors influence insulin pK?
A
- injection site : abdomen has faster absorption that arms/butt/thigh
- injection depth : delivery to muscle instead of SubQ (the norm) causes greater absorption due to greater vascularisation of muscle layer and this can cause conflict in onset, peak time etc
- larger volumes delay absorption
- exercise and massage of injection site and heat all increase rate of insulin absorption
16
Q
How can steroids affect glucose levels?
A
- can exacerbate hyperglycemia in patients with known diabetes
- also cause DM in patients without hyperglycemia prior to glucocorticoid therapy
- so DM patients undergoing steroid therapy should have their glucose levels monitored closely and insulin levels may need to be increased
17
Q
What are the risk factors for hypoglycemia?
A
- advanced age
- renal impairment bcs kidney impt for clearing insulin
- intensive insulin regimen
- poor oral intake or prolonged fasting
18
Q
What are the symptoms of hypoglycemia?
A
- dizziness
- tremor
- shaky hands
- feeling hungry
- weakness and confusion
- sweating
- manage by drinking fruit juice/ glucagon administration or glucose tablet intake
