Recombinant Insulin

Therapeutic insulin is a recombinant form of endogenous insulin, with changes made to increase solubility and influence speed of dissociation. Insulin is used in the treatment for type I and II diabetes.

 

 

Mechanism

Insulin's biological activity is described in detail here.

A unit of insulin will lower blood glucose by 1-2 mmol.

 

 

Preparations

 

  • rapid-acting
  • short-acting
  • intermediate-acting
  • long-acting
  • inhaled

Rapid-acting (Humalog lispro, NovoRapid aspart)

Formulated as monomers; their quick action means they can be injected just at meals or post-meals. Better control and coodination with intake reduces risk of hypoglycemia.

  • onset: 10-15 min
  • peak action: 30-90 min
  • duration of 3-5 hours

 

Short-acting (regular insulin: Humulin R, Novolin GE Toronto)

present as hexamers; dissolution into dimers and then monomers results in 3 absorption rates.

These are rarely used due to their longer onset, compared to rapid-acting.

It must be injected 30-45 min before a meal.

  • onset: 30-60 minutes
  • peak action: 2-4 hours
  • duration: 6-8 hours

Intermediate-acting (Humulin N, Novolin NPH)

Neutral protamine Hagendorn: Protease degradation of protamine responsible for long effects.

Important to replace basal insulin levels. There is a pronounced peak potentially causing hyopglycemia, reducing meal timing flexibility. It can be useful in covering lunch if people are not injecting in the afternoon.

  • onset: 1-4 hours
  • peak action: 4-10 hours
  • duration: 12-18 hours

The suspension must be mixed thoroughly to avoid variable absorption.

Long-acting (glargine/Lantus, determir/levenir)

Crystalin insulin that slowly dissolves. Similar to NPH but associated with less nocturnal hypoglycemia. It is more costly.

  • onset:2-4 hours
  • no real peak
  • duration of 24-28 hours

Inhaled Insulin

  • kinetics and dynamics similar to rapid-and short-acting insulin
  • onset after 3o minutes
  • peak effects at 2-2.5 hours
  • duration of 6-8 hours

 

Insulin requirements vary with age

 

 

Dosing Schedules

  • Type I Diabetes
  • Type II Diabetes
  • Dose Corrections

Type I Diabetes

An intensive approach is preferred in T1DM.

Type II Diabetes

Once maximal control is derived from lifestyle and oral hypoglycemics, insulin should be considered in T2DM.

 

To begin, choose 0.5-1 unit/kg for the day. Split this into 40-50% basal insulin and 50-60% bolus.

Basal - NPH BID; optimize bedtime dose first. Bolus - divided breakfast, lunch, and supper.

 

A bedtime NPH dose, starting at 10 units and titrating upwards by 1-2 units (NEJM, 1992).

Dose Corrections

Sliding scale is not recommended alone, as it is a reactive, not corrective.

A correction factor is better, whereby units are added to ac doses ON TOP of a basal rate.

 

100 rule

100/ total daily insulin = amount 1 unit will decrease BG (in mmol/L)

 

 

Adverse Drug Reactions

 

Excess insulin can cause severe hypoglycemia or insulin shock.

Inhaled insulin may cause pulmonary fibrosis, hypotension, or allergic reaction

 

Early Morning Hyperglycemia

Early morning hyperglycemia can be due to two differing mechanisms.

The Symogi effect...

The dawn phenomenon...

 

Long-acting insulins are not yet used in pregnancy, as we don't know what they do.