Injecting Insulin

The discovery of insulin in the early 1920s was undoubtedly one of the most important breakthroughs in medicine of this age. In 1922 Leonard Thompson, a young boy of fourteen, weighing just over four and a half stone, was the first to receive an injection of insulin. Hailed as a miracle cure at the time, it has since prevented the deaths of hundreds of thousands of people, myself and three family members included.

---

Commercial Production of Insulin

There are a number of different types of insulin available from a number of manufacturers. You need to know which insulin(s) you are using, plus how and when they act.

Source

Early insulin preparations were crude extractions from the pancreases of pigs or cows. These  preparations were purified, but they still contained a number of additional substances such as  proinsulin, insulin derivatives and other active peptides found in the pancreas. Improved purification  methods have reduced the content of these. Animal insulins are still available in the UK from CP Pharmaceuticals Ltd.

The insulin that humans produce differs very slightly in structure from that of pigs(porcine) and  cows (bovine). Porcine insulin differs by one amino acid molecule and can be modified to human insulin by enzyme treatment. Such ‘human’ insulin is called semisynthetic human insulin or enzymatically modified porcine insulin.

Human insulin produced by ‘recombinant DNA technology’ is referred to as biosynthetic human insulin. DNA, encoding the human insulin molecule, is inserted into bacteria or yeast and the insulin is ‘manufactured’ on a large scale.

The source of the insulin may be indicated on the label by a two- or three-letter code:

Different Types of Insulin

The new fast acting insulin analogues are derived from modifications of the natural human insulin molecule. A single change in molecular structure encourages the insulin to exist as a monomer, so that it is absorbed much more rapidly. Its biological function, in terms of lowering blood glucose, is unaltered by the subtle change in molecular structure.

Ultra-fast insulins (also called ultra-rapid or ultra-rapid-acting insulins) are a newer type of mealtime (bolus) insulin designed to act more quickly than traditional rapid-acting insulins. They’re and are designed to more closely mimic the natural insulin response of a person without diabetes and are better suited to control blood glucose spikes that occur after eating.

IMPORTANT NOTE: Ultra-fast insulins are not yet available in New Zealand, and need to be sourced from overseas.

Intermediate and long acting insulins are specially formulated to modify the duration of action. The insulin is complexed with zinc and/or protamine and is only released slowly from these complexes after it has been injected.

The new long acting insulin analogues are also derived from modifications of the natural insulin molecule.

GLARGINE (Lantus) The structure of insulin glargine differs from that of native human insulin by 3 amino acids. It has a glycine in place of an asparagine at position A21 and 2 arginines added to the carboxyl terminal of the B chain at positions 831 and B32.25,27 These amino acid substitutions shift the isoelectric point of the molecule closer to neutral (from pH 5.4 to 7.0), making the molecule more soluble within the acidic environment of the vial hut insoluble at the neutral pH of the injection site. Ultimately, the formation of microprecipitates at the injection site slows absorption of insulin glargine into the circulation. The addition of small amounts of zinc (30 pg/mL) to the commercial insulin glargine formulation furhter stabilizes the molecule and helps delay absorption time. Furthermore, the substitution of glycine for asparagine at position A21 alters the association properties of this insulin, making its hexamer structure more stable. Because of these changes, absorption of insulin glargine is delayed, prolonging the duration of effect and providing a fairly constant basal insulin supply.

Insulins are broadly categorised by their action profiles*:

* The times given are approximate guidelines only. Action profiles are affected by the insulin type, injection area, size of the dose, ambient temperature and exercise of muscle close to the injection site.

More information on insulins available in NZ Diabetes New Zealand have introduced a useful guide to what’s available here in New Zealand: >> click here.

 

Using Insulin Effectively

If it were just a case of ‘Jab-and-Go’ then I would not be writing these pages. Unfortunately, insulin therapy is far from the ideal solution. It may keep us alive, but it is often inconvenient, and frequently yields inconsistent or unpredictable results. However, it is the only option for many of us right now, so we must learn how to make the most of it.

Injection sites

Insulin is injected into the fat layer just beneath the skin. If injected into a muscle (‘intramuscular) or a vein (intravenous) then the insulin is absorbed into the bloodstream too quickly and can cause sudden or severe hypoglycaemia.

The use of insulin pumps is considered on a separate page]

Suitable injection sites include the following:

It is important that the same area is not repeatedly used again and again – this can cause hypertrophy (sometimes called lipohypertrophy, but this is not the same as lipoatrophy (see below)). Hypertrophy refers to the accumulation of fat deposits in the area, leading to ‘lumpy’ skin. Often the area becomes numb and injections seem less painful – you may feel reluctant to change injection site. Insulin injected into such areas, however, is poorly or erratically absorbed and this often leads to fluctuating blood glucose levels.

A local immune reaction at the injection site can cause lipoatrophy (sometimes referred to as lipodystrophy). In contrast to hypertrophy, fatty tissue under the skin is diminished and dents appear at the injection site. This was more common with the early porcine and bovine insulin preparations.

Absorption of insulin

There is considerable day-to-day variation in the rate of absorption of insulin from any given site; this seems to be most apparent with intermediate or long acting insulins. Anything that affects local blood flow to the injection site will affect the insulin absorption.

In addition, you should also remember that for most insulins, the insulin molecules need to dissociate from their clusters before they will be absorbed, so anything that affects this dissociation rate will also affect the rate of absorption. It is hoped that absorption of the new fast acting insulin analogues will prove to be less erratic because this variable has effectively been removed.

The following are just a few factors which are known to influence the absorption of insulin:

With care, you can use your knowledge to your advantage. Firstly though, you must adopt some sort of routine, a baseline from which to work. Stick to particular injection sites at particular times of the day. Then, suppose your blood glucose is slightly high; you may choose to inject into your abdomen, rather than your usual arm. As with all deviations from routine, it is advisable that you monitor the effects closely with blood glucose testing.

Injection devices

There are a number of different tools available to help with injecting insulin. These include pens, jet injectors and pressure injectors.

There are now a wide variety of pen needles available. Which particular one is most suitable to you will depend on your skin thickness and your body fat/muscle ratio. It is always best to check with your Diabetes Team to ensure that you are using the most appropriate needle length.

Insulin delivery devices available in NZ Diabetes New Zealand have introduced a useful guide to what’s available here in New Zealand: >> click here.

Insulin requirement

The total daily amount of insulin required by an individual depends on a number of factors:

Usually about half of the daily requirement is needed as ‘background’ insulin. This is the insulin which is required just to keep the body ticking over. The other half is needed specifically to cope with food intake.

If you have Type 2 diabetes, then the amount of insulin you need will additionally depend on how much insulin (if any) you are producing and your level of insulin resistance.

If you have just been diagnosed with Type 1 diabetes, then your insulin requirements may remain low, or decrease during the initial ‘honeymoon period‘. This is until the last few remaining beta cells have been destroyed by the autoimmune process.

In some people, insulin requirements have also been noted to change with the seasons and with the phase of the menstrual cycle.

In rare cases, some patients develop high levels of antibodies to injected insulin –  these people have trouble maintaining near normal blood glucose levels, in spite of ever increasing large doses of insulin. Bovine insulin is most ‘antigenic’, porcine less so. With the advent of ‘human’ insulin it was hoped that antibody production against injected insulin would be negligible; sadly this has not been the case. Perhaps it is not surprising, at least in patients with Type 1 diabetes, given the autoimmune mechanisms which lie at the root of the disease process.

---

Page updated: Apr 2025

---