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Insulin Analog

A man-made substance resembling insulin in which the molecular structure has been altered for a more desirable effect.

Insulin is a hormone, or chemical messenger that is released into the bloodstream to be transported throughout the body. Most hormones, including insulin, are proteins, which means that they are made up of molecules called amino acids. About 20 common varieties of amino acids exist, and the sequence in which they are bound together to form a protein molecule determines both the structure and function of the protein. The human insulin molecule consists of two chains of amino acids, called the A chain and the B chain, which are made up of 21 specific amino acid molecules and 30 specific amino acid molecules, respectively.

In insulin analogs, however, different amino acids are added or substituted at certain positions along the A and B chains. These changes, while altering insulin action times, do not hinder the molecules’ ability to control blood glucose levels in the body. (In this way, insulin analogs may be compared to beef and pork insulin, which differ from human insulin by three amino acids and one amino acid, respectively. These animal insulins were widely used before the advent of the recombinant DNA technology that is now used to manufacture human insulin and insulin analogs.)

One rapid-acting insulin analog is insulin lispro, which is marketed by Eli Lilly and Company as Humalog and became commercially available in 1996. The structure of the insulin lispro molecule is identical to that of human insulin except that the amino acids at two positions on the B chain, B28 and B29, are reversed. This causes the molecules of insulin to disassociate from one another more rapidly after injection, leading to much faster absorption into the bloodstream. As a result, insulin lispro starts acting much more quickly than Regular insulin — within 15 minutes, compared to Regular’s 30–60 minutes — and lasts for a shorter amount of time — three to four hours, compared to Regular’s six to 10 hours. Because of its fast action, insulin lispro should be taken within 15 minutes of eating, while Regular should be taken 30–45 minutes before meals to allow for its slower action. Ideally, insulin taken to “cover” a meal should be reaching peak effectiveness as blood glucose level is peaking. For most people, insulin lispro’s faster action time makes it more convenient than Regular, and studies have shown that blood glucose levels two hours after meals are significantly lower in people who use mealtime insulin lispro as compared with Regular insulin.

Another rapid-acting insulin analog called insulin aspart (marketed by Novo Nordisk as NovoLog) was approved for marketing by the US Food and Drug Administration (FDA) in 2000. In insulin aspart, the amino acid aspartic acid replaces the amino acid proline at position B28. A study published in the journal Diabetes Care in 2003 found no difference between insulin aspart and insulin lispro in terms of action time and effectiveness.

A third rapid-acting insulin analog called insulin glulisine (marketed by Sanofi-Aventis as Apidra) was approved by the FDA in 2004 and became available to consumers in 2006.

In addition to being used for mealtime injections, rapid-acting insulin analogs are also used in insulin pumps. Indeed, the majority of pump users now use either lispro or aspart (rather than Regular). Not only do these analogs work well for mealtime boluses, but they also adjust blood glucose levels rapidly when basal infusion rates are changed. However, any interruption in insulin delivery (because of pump malfunction, for example) can rapidly lead to high blood glucose since the rapid-acting insulin analogs are quickly cleared from the bloodstream.

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