NPH insulin, protamine and intermediate action
NPH (neutral protamine Hagedorn) insulin, also called isophane, is insulin combined with protamine, a protein additive that slows absorption, giving an intermediate, medium-length action.
Remember
NPH insulin is intermediate-acting because protamine slows its absorption, so it starts working after about 1 to 2 hours, is strongest at about 4 to 8 hours and lasts about 12 to 18 hours.
NPH insulin is insulin that has been combined with protamine, a protein additive, so that solid insulin particles form in the vial. After injection into the subcutaneous tissue (the layer of fat under the skin), the insulin is released from these particles gradually. That slow release delays the onset (the time before it starts to work) and makes the effect last longer than that of a rapid-acting analogue (a laboratory-modified insulin that starts working within minutes).
The standard figures for an intermediate-acting insulin such as NPH are an onset of 1 to 2 hours, a peak (the time of strongest glucose-lowering effect) at 4 to 8 hours, and a duration (how long it keeps working) of 12 to 18 hours. Adding 4 to 8 hours to the injection time gives the peak, so a morning dose at 07:00 peaks between 11:00 and 15:00. These timings are approximate, because absorption varies with the injection site, technique and the person: other references quote wider ranges, with a peak of about 3 to 12 hours and a duration of about 11 to 24 hours.
This medium-length action suits basal insulin (the background cover that works between meals and overnight), and NPH is often given twice daily. The peak is when the glucose-lowering effect is strongest, so hypoglycaemia (abnormally low blood glucose) becomes more likely then if meals are delayed or small.
A rough ladder of durations helps to place it: rapid-acting insulin lasts about 3 to 5 hours, short-acting (soluble) insulin 6 to 8, intermediate-acting 12 to 18, and long-acting about 24 or more. On that ladder, NPH is the intermediate-acting insulin, between short-acting soluble insulin and the long-acting analogues.
Key facts
- Stands for
- Neutral protamine Hagedorn; the insulin is also called isophane insulin.
- Why it is slow
- Protamine, a protein added to the insulin, slows its absorption from the injection site.
- Onset
- About 1 to 2 hours after an injection under the skin.
- Peak
- About 4 to 8 hours after the dose, so a 07:00 injection peaks around 11:00 to 15:00.
- Duration
- Around 12 to 18 hours.
- Use
- Basal cover, often given twice daily.
- Example UK brands
- Humulin I and Insulatard.
Exam traps
- Amino acid changes are how rapid-acting analogues (laboratory-modified insulins) are made, because they speed absorption, whereas NPH insulin gets its delay from protamine in the vial and not from any change to the amino acids.
- The time an effect first appears is often confused with the time of greatest effect: NPH starts to work about 1 to 2 hours after injection, but it peaks at about 4 to 8 hours after the dose.
- A steady, peakless profile lasting about a day belongs to a long-acting insulin such as glargine (a long-acting analogue), not to NPH, which lasts about 12 to 18 hours and has a recognisable peak.
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