When Does Insulin Start Working? Many Factors Affect Absorption

A major challenge in diabetes therapy is to match the insulin with food and exercise. Changes in the amount of time that it takes for insulin to be absorbed into the bloodstream can be a critical factor in obtaining diabetes control. Both the amount of insulin and its timing are critical, and both of these can be influenced by a wide range of variables. Here is a list of factors which every person taking insulin should be aware of.

Type of Insulin

The type of insulin is the most obvious change that influences insulin absorption. Regular insulin is absorbed faster than NPH or Lente insulin, which are absorbed faster than Ultralente insulin.

Mixing insulin can sometimes change their absorption kinetics. Regular and NPH insulin can be mixed in virtually any proportion with little or no effect on their action. The insulin of the Lente series, Lente and Ultralente insulin, are very high in zinc and can slow the absorption of regular insulin by about fifteen minutes.

Species of Insulin

The species of insulin can also be important. For many patients human insulin works faster than pork or beef insulin and may not last as long. For Regular insulin, this is often an advantage, as we want this insulin to work fast. But for NPH insulin, it may mean that the insulin will not last through the night, especially if you are taking only a single shot of insulin each morning.

Site of Injection

The site of injection can be critical. It can take up to 50% longer for insulin to be absorbed from the leg than from the abdomen (or stomach area). Not only does the time for absorption of insulin vary with the site, but so does the total amount absorbed. Regular insulin peaks in the bloodstream about 90-120 minutes after it is injected into the thigh. Because of the subcutaneous enzymes, only about 60-65% of the insulin is absorbed. After injection into the arm, it peaks in about 75 minutes whereas an injection into the abdomen takes only 60 minutes. Because the insulin is absorbed faster from the abdomen, less is destroyed by the subcutaneous enzymes. Thus, regular insulin injected into the abdomen may be up to 25% more powerful than the same amount of insulin injected into a thigh.

Health care workers have always told patients to rotate their injection sites. This minimizes some of the traumatic and biochemical effects of insulin in the local areas. Recently, most diabetes health professionals have modified this policy to suggest that patients should rotate their injections to the same type of site at the same time each day.

For example, you may choose to give your morning injection in the abdomen and the evening injection in the thigh, but if you do, you should give your shot every morning into the abdomen and every evening into either the left or right thigh. Because of the significant area and the rapidity of insulin absorption from the abdomen, some patients choose to give all of their injections in this site. This is particularly popular among patients performing intensive insulin therapy (three or more injections per day or an insulin pump). Patients who use exclusively their abdomens are generally careful to rotate among the many possible sites in this region.

Four External Factors Influencing Insulin Absorption

I. Temperature

The temperature of the injection site can strongly influence the rate of absorption: the warmer the area the faster the absorption; the colder, the slower. For example, regular insulin injected into a thigh peaks in the bloodstream at 90 minutes. If the leg is immersed in cold water, this time increases to 120 minutes, but when immersed in warm water, it falls to less than 40 minutes. The amount of insulin absorbed can also vary substantially. A warm thigh may absorb almost twice as much insulin as a cold thigh.

The practical implications of this are obvious. Taking your insulin injection and then taking a hot shower, sauna or going into a hot tub will increase the rate of absorption of insulin and may lead to an insulin reaction. Alternatively, going out into the cold with only thin slacks or hosiery can lead to the absorption of less insulin and serious high blood sugars. For most patients, the best advice is to avoid extremes of temperature at injection sites. Occasionally (and only after a thorough discussion with a physician), patients may use a hot shower to speed and increase the power of insulin.

II. Exercise

A similar effect is seen with exercise, although the full effect of exercise is much more complex than just its effect on insulin absorption. Exercising a region will lead to a dramatic increase in the rate of absorption of insulin and the amount absorbed, similar to that seen when warming the region. Although the clinical implications are complex, as a simple rule, peop-le with diabetes should generally avoid injecting into an area that will be heavily exercised in the next 4 hours and should check their blood glucose before exercise. If their blood glucose is less than 150 mg/dl, they should eat some simple carbohydrate, such as glucose tablets, before exercising (the amount will vary with the type and duration of the exercise and the initial blood glucose). If it is above 300 mg/dl they should probably postpone the exercise.

III. Technique

Injection technique can make a major difference in the rate and amount of insulin absorbed. As seen in Figure 2, we normally inject insulin into the subcutaneous fat. Under varying conditions, however, insulin might be injected into the subdermal space (between the skin and the subcutaneous fat), the epimuscular space (between the subcutaneous fat and the muscle), or intramuscularly (into the muscle). Absorption of insulin from each of these sites is different and all are faster than absorption from the subcutaneous tissue.

a) Injection of insulin into the sub-dermal space is an unusual event. It can occur if you insert the needle at too great an angle or use a very short needle. Insulin absorption from this area is not very well studied, but it seems to be very fast. It is difficult to reproducibly inject into this space, and few try.

b) Injection into the epimuscular space can occur with some degree of regularity, and some Dutch physicians train their patients to inject into this area. To do so requires considerable skill and an area with only a small amount of subcutaneous tissue (a thin area). Insulin absorption from this area seems to be very fast, both because the insulin spreads out as a thin layer between the muscle and the subcutaneous fat and because there is a very high blood supply to this area.

c) Intramuscular injections have been of some concern, particularly in Europe. Some areas, such as the outside of the thigh, may have very little subcutaneous tissue. When you inject into one of these areas without pinching up the skin, you may go through the subcutaneous tissue and directly into the muscle. This creates two problems: injection of insulin into the muscle often hurts, and insulin is very rapidly and completely absorbed from the muscle. Insulin injected into a muscle may peak in the bloodstream in as little as 15 minutes. This is much faster than the 90 minutes normally required for injection into a thigh, and up to twice the amount of insulin may be absorbed. Some health professionals have suggested shorter needles to overcome this, but to be truly certain that you would avoid intramuscular injection, the needles would have to be only 1/8 of an inch long and then there would be problems of leaking insulin out of the injection site and subdermal injections. A far better approach is to make sure that you pinch up the skin and therefore thicken the subcutaneous tissue before injecting.

IV. Injection Devices

The type of device may alter insulin absorption. Although most people with diabetes use syringes to deliver insulin, there are the alternatives such as jet injectors, insulin pens and insulin pumps. In addition, there are some experimental techniques such as the use of “sprinkler” needles. Insulin injected by syringes or pens is deposited as a single large drop (Figure 3). Since this minimizes the area for absorption of insulin, movement of insulin to the blood is slow. In contrast, the insulin delivered from a jet injector disperses upon hitting the skin and forms multiple small droplets. Since the surface area of these multiple droplets is much larger, insulin is absorbed about 15 minutes earlier after jet injection than after a syringe or pen. One type of experimental needle delivers insulin through minute holes in the wall. Insulin is also absorbed faster from this “sprinkler” needle.

These various factors can work for or against you in your quest for better blood glucose control. Understanding the components described above will help you avoid some of the major problems that cause low and high blood sugar and may allow you and your doctor to work out the best possible diabetes regimen for you.

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