The different types of insulin for type 1 diabetes


Type 1 diabetes involves a deficiency of insulin production due to an autoimmune destruction of the insulin-producing cells of the pancreas, in other words the beta cells of the islets of Langerhans.

As a result, these cells can't produce insulin in adequate amounts to maintain normal glucose homeostasis. This leads to hyperglycaemia (excess of glucose in the bloodstream) and weight loss, accompanied by ketoacidosis (acid build-up), during which the body breaks down fat into fatty acids and ketones.

Type 1 diabetes usually begins in the teenage years, but may have an earlier or later onset, with the hallmark being the presence of diabetic ketoacidosis either at presentation or in the absence of insulin therapy.

Type 1 diabetics require insulin therapy to maintain normal glucose and lipid metabolism. This is non-negotiable, and there are really no other alternatives in the management of this condition, which can be life-threatening.

a. Human insulin vs. insulin analogues

Insulin was previously harvested from animal pancreas, but this form of insulin included impurities, which lead to allergies in some people. Current insulin preparations are manufactured using recombinant DNA technology and can be broadly classified into two categories:

  • Human insulin, which is identical to human insulin in structure.
  • Human insulin analogues, in which one or two amino acids of human insulin are changed or substituted.

Contrary to what one would expect, human insulin (Actrapid, Humulin N, Insuman, Humulin 30/70, Actraphane and Insuman 30/70) given subcutaneously (beneath the skin) doesn't act optimally. This is due to delayed or variable absorption, which leads to day-to-day variations in glucose.

This led to the development of the human insulin analogues, which have a more consistent absorption and distribution profile. Examples are Apidra, Humalog, Novorapid, Lantus, Levemir, Novomix 30 and Humalog Mix 25.

b. Duration of action

The next factor in classifying insulin is the duration of action:

Rapid-acting insulins are the insulin analogues such as Apidra, Humalog and Novorapid that have an onset of action of approximately 15 minutes. They peak at approximately 30 to 90 minutes and have a duration of action of 3 to 5 hours. The rapid-acting insulins are used 5 to 10 minutes prior to or at mealtimes and typically cover the post-meal blood-glucose surges, provided that the dose is correct.

The regular short-acting insulins are human insulins that can be used as before-mealtime insulin instead of the above-mentioned rapid-acting insulin. Regular insulin has an onset of action of approximately 30 to 60 minutes, a peak at between 1 and 2 hours, and a duration of action of more or less 3 to 5 hours.

Examples of regular insulins are Insuman, Actrapid and Humulin R. The regular insulin is typically taken 30 minutes prior to a meal.

Both regular and rapid-acting insulins are used in sliding-scale regimens (when the dose of insulin is adjusted in accordance with the results of blood-glucose levels), as well as intravenous infusions for emergencies.

The intermediate-acting insulins (Humulin N , Protophane ) are regular insulins that, when attached to zinc or NPH (Neutral Protamine Hagedorn), have an altered onset, peak and duration.

These insulins are usually taken every 12 hours, always beneath the skin. They have an onset of action of approximately 3 hours, they peak at more or less 8 hours, and they have a duration of action of about 20 hours. Note that these are approximate numbers that may vary.

The long-acting insulin analogues are Lantus and Levemir. Lantus, which has a duration of action of 24 hours without a peak level, is taken once daily. Levemir has a more contentious duration of action that is dose-dependent. This form of insulin is taken once or twice a day, depending on the degree of control that is needed.

Then there are the fixed-dose combinations of rapid or short-acting insulin and intermediate-acting insulin in fixed-dose combinations of 25%:75%, 30%:75% or 50%:50%. The first number of the ratio applies to the percentage of rapid- or short-acting insulin in the mixture.

Examples are:

Novomix 30:
- 30% insulin aspartate, 70% protaminated insulin aspartate
- taken 5 to 10 minutes before a meal

Humalog mix 25:
- 25% insulin lispro, 75% protaminated insulin lispro
- taken 5 to 10 minutes before a meal

Humalog mix 50:
- 50% insulin lispro, 50% protaminated insulin lispro
- taken 5 to 10 minutes before a meal

Actraphane/ humulin30/70:
- 30% short-acting insulin, 70% intermediate-acting insulin
- taken 20 to 30 minutes before a meal

Reviewed by Dr Suresh Rajpaul (MbChB, FCPsa)
May 2009

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