The astonishing power of insulin to restore health and well- being to rapidly deteriorating newly diagnosed Type 1 diabetic patients is as remarkable now as it was in 1922. After Banting gave insulin to Elizabeth Hughes in that year, she wrote to her mother that “it is simply too wonderful for words this stuff.” Insulin to this day always has this effect; the challenge now is to optimise control in order to maintain health throughout life.
Insulin is also needed to enhance well-being and control in many Type 2 diabetic patients when the natural progression of their disease has lead to loss of optimal control. The potential to reduce the development of long-term diabetic complications as demonstrated by the UKPDS (see page 42) has led to a recent explosion in conversions from tablets to insulin. The difficult decisions which surround the need for insulin in this situation, together with benefits, uses and misuses of insulin have been described in the previous chapter.
The use of insulin must be tailored to meet individual requirements. The aim is to achieve the best possible control in the circumstances, avoiding at all costs the disabling hypoglycaemia which can occur if control is excessively tight. In some elderly patients and those who lack motivation, it is therefore wise to aim only at alleviating symptoms and not to attempt very strict control.
Types of insulin
Soluble insulins
These were first introduced in 1922. They have a rapid onset of action (within 15-30 minutes)and a relatively short overall duration of action of six to eight hours. They play an important part in both daily maintenance of diabetic patients by subcutaneous injection, and also in managing emergencies, when they can be given intravenously or intramuscularly. Other insulin preparations are not suitable for intravenous or intramuscular use.
New recombinant insulin analogues
These have a very rapid onset and very short action, and have been developed by altering the structure and thus the property of the insulin. The preparations available in the United Kingdom at present are Insulin Lispro (Humalog) and Insulin Aspart (Novo Rapid). They have some advantages because they may be given immediately before meals (or even immediately after meals if necessar y). By virtue of their ver y short action, there is less hypoglycaemia before the next meal, and when they are used before the main evening meal nocturnal hypoglycaemia is effectively reduced.
There is a risk of postprandial hypoglycaemia if they are used before a meal with a ver y high fat content because of the delayed gastric emptying. Duration of action is short and does not normally exceed three hours, and their use is therefore inappropriate if the gap between meals exceeds about four hours. Preprandial blood glucose levels are slightly higher than with conventional soluble insulins.
They are also ideal for use in continuous subcutaneous insulin infusion pumps (CSII).
Protamine insulins
These are medium duration insulins introduced in Denmark during the 1930s. Isophane insulin is the most frequently used insulin in this group.
Insulin zinc suspensions
These were first introduced during the 1950s; there are several preparations with widely ranging durations of action. There are limited indications for using insulins with a very long duration of action (ultratard).
Insulin glargine
This is a new prolonged action, soluble insulin analogue (clear solution) forming a microprecipitate after subcutaneous injection. Its onset of action is after about 90 minutes, it has a prolonged plateau rather than a peak, and lasts 24 hours or more. Thus it mimics more closely the basal insulin secretion of healthy people. When taken at bedtime it reduces the incidence of nocturnal hypoglycaemia, and also reduces the prebreakfast hyperglycaemia. It does not appear to reduce symptomatic or severe hypoglycaemia during the day, and there is no significant beneficial effect on overall diabetic control. More extensive clinical experience in using this insulin is still needed.
Insulin mixtures
Some preparations of insulin are presented as proprietar y mixtures in either vials or pen cartridges, eliminating the need for patients to mix insulins in the syringe. The most popular mixture contains 30% soluble insulin and 70% isophane, whereas the whole range also includes ratios 10%/90%, 20%/80%, 40%/60%, and 50%/50%. These insulin mixtures represent a considerable advantage for many patients, especially those who find it difficult to mix insulins in the syringe or those whose visual acuity is impaired. Details of the types of insulin available in the United Kingdom are shown in the box.
Selection of insulin
The choice of insulin preparation is based on the duration of action. Although insulins can be broadly classified as having ver y short, short, medium or long duration of action, their effect varies considerably from one patient to another and can be discovered in the individual patient only by trial and error. There are several preparations of medium acting insulins, but those most often used are either one of the isophane preparations or less frequently Human Monotard zinc insulin preparation (see box on page 19).
Insulin mixtures
These are all mixtures of a short acting soluble insulin (or ver y short acting insulin analogue) with a medium acting isophane insulin (or insulin analogue). The number after the insulin name indicates the percentage of the short acting insulin, for example, “30” or “M3” indicates 30% soluble insulin mixed with 70% isophane insulin.
- Human Mixtard 10 (pen only)
- Human Mixtard 20 (pen only)
- Humulin M2 (pen only)
- Human Mixtard 30
- Pork Mixtard 30
- Humulin M3
- Pork 30/70 Mix
- Human Mixtard 40 (pen only)
- Human Mixtard 50
- Humulin M5
- Insuman Comb 50
- Insuman Comb 15
- Insuman Comb 25
Insulin analogue mixtures
- Humalog Mix 25 (pen only)
- Humalog Mix 50 (pen only)
- NovoMix 30 (pen only)
Insulins are available in vials for use with syringe and needle; in cartridges for use in insulin pens; or in preloaded pens. The insulins listed above are available in one or more of these preparations.
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