It's enough to drive one crazy sometimes! Despite having just tested the blood sugar, weighed out the meal, taken all things into account, measured out the insulin dose exactly, the blood sugar still doesn't reach the desired level. Why is this so? One reason could lie with the insulin itself, or even the way it is injected. Those who know why insulin sometimes acts differently can be more prepared, and can even use it to their own advantage.

How does insulin work? This is a question that children and adolescents frequently ask their parents. And no wonder. Insulin is, namely, the crucial factor in their therapy. It must imitate the insulin secretion from the pancreas as accurately as possible—something that the modern insulins are able to do pretty well.

The differences in the various insulins lie in their profiles, i.e., how fast they take effect, when they reach maximum effect, and for how long they take effect. These differences in profiles are specified by the manufacturer. However, as each type of insulin is developed under strict standardized conditions, this information should only be taken by the user as a general guideline. The actual effect of each type of insulin can be influenced by many factors. This is what makes it often so difficult to calculate the correct dose.

Big differences despite identical dose
If one uses a modern insulin pen correctly, it is very likely to administer the exact amount of insulin. This same dose, injected by the same person and in the same place, however, can work very differently if injected at a different time of day—by up to a factor of 25%! The effect can even vary by a factor of 50% if the same dose is injected by another person.

These differences are hard to explain, leaving many quite frustrated when, under seemingly identical conditions (same dose, same time, same circumstances), the insulin effect on the blood sugar varies quite considerably from one day to the next. What other factors are involved? Those who know this can be better prepared for such fluctuations, and can even use them to advantage.

Method of injection
How the insulin is transported into the body has a profound effect on how it works. Today, people inject insulin with an insulin pen, a one-way syringe, or a pump catheter, into the fatty tissue that lies directly under the skin. All these methods are relatively painless and enable accurate dosage. Insulin can also be injected intravenously, making its onset of action extremely rapid and, like the other methods, extremely accurate. (This method, however, being mainly only used in clinical situations is of little relevance for the everyday user.)

Theoretically, one can also inject insulin straight into the muscle (intramuscular), which hastens the onset of action even more. However, this method is more painful than the conventional ‘subcutaneous’ way.

People have also been known to inject insulin straight through their clothing. This doesn’t allow for such a good ‘pinch’ and, therefore, the muscle can easily be accidentally reached. This makes for an unexpectedly rapid onset of action, raising the risk of hypoglycaemia.

Choosing the best injection site
Choosing the best injection site is also of major importance. Administed into the abdominal area, insulin works very quickly. This is why the abdomen is a very good place for mealtime insulin. For the basal insulin, in which a longer duration of effect is desired, it is preferable to inject the insulin into the leg.

Watch the temperature
The surrounding temperature also has an influence on how quickly the insulin reaches the bloodstream (absorption). If the temperature rises from, say, 20° C to 35° C, the rate of absorption of normal insulin into the cells is increased by a factor of 50 to 60 percent, i.e., at a faster rate than it is needed. A hot bath, or even a sauna at a temperature of around 80° C, for example, can raise the rate of absorption by up to 110 percent! Even when the temperature fluctuation is not that extreme, it still influences the rate of insulin absorption to quite an extent.

In other words, if insulin is injected just before a hot bath, for example, there is a substantial risk of hypoglycaemia. Similarly, if the injection site is massaged, the same effect can take place. A massage increases the blood circulation in the subcutaneous fatty tissue, causing the insulin to be carried into the bloodstream at a faster rate.

Colder temperatures, on the other hand, decrease the speed at which insulin is absorbed into the bloodstream. Many parents have been known to report that their child’s blood sugar levels are higher when on holiday in the snow, and this despite the increased physical exertion.

Insulin dose
Insulin dose also has an influence on its action. When the dose is increased, it takes longer for it to set in, allowing for higher blood sugar levels in the meantime. Smaller doses are absorbed into the blood much faster, speeding up the onset of action.

Insulin requirement varies
Some external factors, such as increased physical exertion or infections, alter the body’s insulin requirement. As these tend to be more obvious, they can explain swings in blood sugar more clearly—unlike the other factors already mentioned.

Hormonal swings
Individual hormonal swings also influence the action of insulin—one more reason to regularly monitor blood sugar and to keep retrospective records.
In children, growth hormones play a major role in that they tend to increase insulin requirement. At the onset of puberty, when sexual hormones are being released, adolescents require more insulin. In addition, the insulin action in this period is more difficult to predict, due to the spasmodic nature of hormone production.

Many females with type 1 diabetes notice that their blood sugar levels rise just before menstruation. A Hungarian study found that the female participants required around 3 IU of insulin more before menstruation vs. during menstruation. The reason for this lies in the fact that, before menstruation, more oestrogen and progesterone are released. These hormones tend to increase insulin resistance.

Summary
Although manufacturers specify the effect of each individual insulin, this should be taken as a guideline by the user, as many factors influence in the way each insulin takes effect. Take, for instance, the injection site: It is preferable to inject mealtime insulin into the abdomen rather than the leg.

Warmer conditions increase the circulation of the skin, enabling the insulin to be more rapidly absorbed into the bloodstream, speeding up its onset of action. Cold has the opposite effect. Depth of penetration, physical activity, thickness of the subcutaneous fatty layer, and insulin dosage also affect the action of insulin, along with infections and weight gain.

Hormonal changes, such as growth and sexual hormone production in children and adolescents, alter insulin requirement. Women and girls should especially observe the discrepancies in insulin requirement before and during their period.

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Dr. med. Thorben Kracht
Centre for Pediatric Diabetology and Endocrinology
Hanover
e-mail: kracht(at)hka(dot)de