INSULIN

Thomas Higgins, M.D.

Effective use of insulin requires an understanding of insulin action. There are five main issues which are important in that they can affect the degree of glucose control:

• insulin preparation
• size of the injection
• injection technique
• site of injection
• subcutaneous blood flow

Insulin preparation: The time of onset, peak activity, and duration of action of subcutaneous insulin preparations can only be approximated. The usually quoted data are based upon the administration of small amounts of insulin to a small number of nondiabetic volunteers. Furthermore, the degree of absorption of any dose, both between individuals and in the same individual, can vary from day to day by as much as 25 to 50 percent, leading to unexplained fluctuations in glucose control. This effect is greatest with longer-acting insulin and least with rapid-acting insulin. Thus, a dose of NPH or Lente insulin given before the evening meal may be sufficient to last through the night in one individual but may dissipate in another, resulting in fasting hyperglycemia. Regular or clear insulin was the fastest acting insulin until 1996 when Lispro (Humalog) was introduced. Regular insulin conglomerates together and needs to break apart after injection before it is active. Lispro does not form these aggregates and is active at the time of injection. A second rapid acting insulin similar to Humalog (Aspart) is nearing FDA approval.

Most longer acting insulins are cloudy because they represent insulin suspensions and contain retarding agents such as protamine which is used in NPH & zinc which is used in Lente. These retarding agents delay the insulin action. Newer long acting insulins are being released for use in the United States which do not depend on a retarding agent & remain in solution. The advantage of these newer long acting insulins are both an absence of the need to roll the insulin bottle prior to use & a smoother action. The first product to have been approved will is Glargine. Glargine has an onset of action of 1 to 3 hours followed by a flat level of action with a fall off in action at around 24 hours.

Inhaled insulin is now in clinical trials and may make premeal insulin more acceptable to more people.

Size of subcutaneous depot: The variability in absorption is increased and net absorption is decreased with increasing size (number of units) injected. This can become a limiting factor in patients who are insulin resistant and require large doses given several times per day. Conversely, one of the reasons why insulin pumps are so successful is that only regular (or Lispro) insulin is used and the size of each injection is very small.

Injection technique: Both the angle of needle entry and the depth of penetration affect the rate of insulin absorption. Very shallow insertion can cause a painful injection into the skin which is not well absorbed. In comparison, a perpendicular injection in a lean area may result in a injection into muscle with more rapid absorption.

The recommended technique is to use an area of the body in which about one inch of fat which can be pinched between two fingers. The syringe, with a 0.5 inch microfine (27G) needle, is inserted perpendicular to the pinched skin up to the hilt of the needle and the insulin is then injected. It is no longer recommended to pull back on the syringe before injection or to remove the needle if blood is obtained.

The common practice of cleaning the skin with an alcohol swab before injection may not be necessary. As an example, a study found that there was no difference when the usual injection technique was compared with injections through clothing. The only problem with the latter was a occasional blood stain on the clothing.

Site of injection: In the past patients were taught to rotate insulin injection sites because the insulin preparations contained impurities which caused local reactions in the skin. With the new insulin preparations, purity of the preparations is no longer a concern and rotation of injection sites is now a common cause of day-to-day variability in glucose control. Insulin is absorbed fastest from the abdominal wall, slowest from the leg and buttock, and at an intermediate rate from the arm; at any of these sites, insulin absorption varies inversely with subcutaneous fat thickness. These differences can be useful clinically. Premeal regular insulin should be rapidly absorbed, and injection into the abdominal wall may therefore be preferable. On the other hand, slower absorption from the leg or buttock may be desirable with the pre-evening meal dose of intermediate-acting insulin to ensure a duration of action that lasts through the night.

Alterations in subcutaneous blood flow : The degree of insulin absorption is also determined by the rate of subcutaneous blood flow. Thus, insulin absorption is reduced by smoking and enhanced by any modality which increases skin temperature, including exercise, saunas or hot baths, and local massage. These effects are more marked with regular insulin than with longer acting insulins.

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