Structure of Insulin
Peptide hormone composed of 2 amino acid chains (A and B) connected by disulfide bonds
Reflects endogenous insulin secretion
C peptide
Synthesis pathway of insulin
Preproinsulin –> proinsulin, proinsulin is then cleaved into insulin
Insulin binds to insulin receptor also known as
Tyrosine kinase receptor
Metabolism of insulin
When insulin is injected exogenously, the degradation profile is altered. The kidneys degrade (~60%), the liver (~30- 40%) (Reverse of endogenous)
In renal impairment, insulin administration
There is a decline in exogenous insulin requirments & increased risk of hypogylcemia
The biological action of insulin depends on
On he absorption from SC depot
Therapeutic Indications of Insulin
1) All patients with Type 1 DM
2) Type 2 DM uncontrolled on oral agents
3) Pregnancy
4) Acute illness, surgery, infections
5) Diabetic emergencies
Gold standard administration of insulin for T1DM
Pumps, continous basal infusion + user-command bolus
Inhaled form of insulin
Afrezza
Rapid acting insulin
Lispro, aspart, glulisine
Short acting insulin
Regular (soluble), Humulin R
Intermediate acting insulin
NPH (Neutral protamine hagedorn)
Long acting insulin
Glargine, detemir
Ultra-long acting insulin
Degludec
Rapid acting insulin, ONSET PEAK DURATION
ONSET 10-15 min
PEAK 1hr
DURATION 3-4hr
Short acting insulin, ONSET PEAK DURATION
ONSET 30-60min
PEAK 2-3hr
DURATION 6-8hr
Composition of NPH
Insulin complexed with protamine and zinc
Mechanism of NPH
Protamine delays absorption
Appearance of NPH
Cloudy suspension (must be mixed)
Disadvantages of NPH
Pronounced peak & Risk of nocturnal hypoglycemia
NPH, ONSET PEAK DURTION
Onset: 2-4 hrs
Peak: 4-10 hrs
Duration: 12-18 hrs
Use of NPH
Usually given twice daily (BD) for basal coverage.
Glargine mechanism & duration
Precipitates at neutral body pH forming crystals that slowly release the insulin
~24 hrs