By Neil Osterweil
Reviewed By Charlotte Grayson
In 1922, Canadian researchers Frederick Banting and Herbert Best discovered that the "pancreatic extract" they had identified and isolated appeared to reverse the symptoms of diabetes in dogs. Their work would transform for the better the lives of millions of people with diabetes.
Commercial production of the extract, known as insulin, began the same year. But the early insulins for human use were fairly crude preparations, full of impurities that spurred the patient's immune system to mount an attack against the life-saving substance.
Today's insulins, however, are highly refined, highly purified products that come in a variety of forms, each tailored to meet a specific need of people with diabetes. In this article, we take a peek at emerging forms of insulin that hold the promise of eliminating the need for injections, look at insulin delivery devices, and review currently available insulins and how they are used.
What Insulin Does and Where it Comes From
Insulin is a hormone that signals the body that it has been fed. It helps cells to take in and use carbohydrates, and in the liver converts blood sugar (glucose) into a special form for storage (glycogen). Insulin also slows the breakdown of fats and the release of fatty acids from fat tissues.
Insulin is normally produced and secreted by the beta-islet cells of the pancreas. But in type 1 diabetes, the immune system attacks and destroys the cells as if they were foreign invaders, robbing the body of its ability to regulate glucose. As a result, people with type 1 diabetes must take daily injections of insulin.
Most insulin in use today is human insulin pumped out in large batches by genetically modified bacteria. Although animal-source insulins (from pigs and cows) have been in use for decades and are chemically and genetically nearly identical to human insulin, diabetes experts say the human-derived product is less likely to provoke an adverse reaction from the immune system. Still, there are some patients, particularly older people who have been using animal source insulins for decades, who maintain that they get better blood sugar control from animal insulins, and they have pleaded with the companies that make animal insulin, Eli Lilly and Novo Nordisk, to keep animal-source insulins available.
All currently available forms of insulin must be injected. Insulin cannot be taken orally, because stomach acids break it down before it has a chance to work. But that may soon change.
According to the American Diabetes Association, there are several products in clinical trials or in development that may eventually eliminate the need for insulin injections. These include inhaled (aerosolized) insulin, oral sprays, insulin skin patches, and insulin pills that are specially designed to release insulin in the liver.
In addition, several companies are working on devices that will take the sting out of blood glucose testing, using various non-invasive techniques for reading blood sugar accurately, without the need for fingersticks or test strips. One is currently available -- the Glucowatch -- although the device is currently not intended to replace blood sugar checks with fingerstick monitors.
As of this writing, there are no inhaled or oral insulins on the market, but at least two of the inhaled forms are in late-stage clinical trials. In addition, two insulin pills have begun early human testing, and there is one insulin skin patch currently under investigation.
Although today's insulin needles are very thin and cause only minimal discomfort for most people, there are many people with diabetes -- particularly those who are newly diagnosed -- who may be squeamish about the need for multiple daily self-injections. Luckily, there are several different alternative delivery systems, which, while they still require penetration of the skin, may provide a kinder, gentler choice for insulin delivery.
Insulin pumps are beeper-sized devices that deliver insulin through a small catheter (tube) inserted into the body. They deliver a continuous background dose of insulin and extra doses, at the touch of a button, prior to mealtimes.
Insulin infusers use a needle or catheter (thin tube) inserted into the skin to create a temporary portal through which insulin can be injected. They can be left in place for two to three days, unless infection develops.
Jet injectors shoot a tiny stream of insulin under pressure into the skin, a little like the needleless injection devices used in large-scale vaccination programs. They can sometimes bruise the skin if not used properly, and it may take time for the user who switches from needles to jet injections to adjust to the differences.
Insulin pens are small, portable devices that contain a needle and an insulin cartridge containing a measured dose of insulin. Because they can easily fit in a pocket or briefcase, they're particularly convenient for people who travel or who can't find a private place to use a syringe.
Some insulin pens deliver smaller insulin doses, which can be especially helpful for managing diabetes in young children, who generally require only fractions of adult doses of insulin. One company even has a product that combines a blood glucose meter with an insulin pen for added convenience.
Injection aids help guide the needle into the skin or conceal it from view, which can be helpful in public situations.
Insulins are classified into five basic categories based on their speed of action, when they peak (when they have the strongest effect on lowering sugars), and duration in the body. (Please note: If you have been told by your doctor that you need to inject insulin, check with him or her for specific instructions about what to use, how much, and when.)
Rapid-acting insulins get to work fast and leave the body almost as quickly. The pattern most closely mimics the body's natural patterns of insulin secretion. Rapid-acting insulins help to prevent post-meal spikes in blood sugar levels.
- Insulin lispro (Humalog) starts working within five to 15 minutes of injection, and does most of its blood-sugar lowering action within 30 to 90 minutes. It finishes working by five hours.
- Insulin aspart (Novolog) starts working in 10 to 20 minutes, lowers blood sugar most from one to three hours after injection, and is gone from the body by five hours.
Short-acting insulin is given up to 30 minutes before a snack or meal.
- Regular insulin goes to work in about 30 minutes, has its peak action between two and four hours, and finishes working by about four to eight hours.
Intermediate-acting insulin can be taken in the morning or at bedtime to provide a more steady "background" level of insulin.
- NPH insulin (N) and Lente insulin (L) both start working within two to six hours, are most active at lowering blood sugar from six to 12 hours after injection, and are cleared from the body in 16-24 hours.
Long-acting insulin, like intermediate-acting insulin, is used to provide a steady dose throughout the day, and may be helpful at keeping blood sugar levels within a target range if a meal or snack is skipped.
- Ultralente is a long-acting insulin that starts working in six to 14 hours, is most active between 10 to16 hours after injection, and is cleared from the body in 24-28 hours.
Very long-acting insulin is the new kid on the diabetes therapy block. It is taken at bedtime, starts working in one hour, and provides even lowering of blood sugar for 24 hours, without a peak effect, and then it is cleared from the body.
- Insulin glargine (Lantus) is the only long-acting insulin available as of this writing.
The FDA cautions that Lantus should not be mixed together in a syringe with any other form of insulin before use.
Dosage and administration of insulin vary according to patient size, age, site of injection, physical activity levels, and lifestyle. Some people with type 1 diabetes may inject a mixture of short- and intermediate-acting insulins twice daily: one dose before breakfast and the second before the evening meal.
Intensive therapy regimens, which are recommended by researchers as the most effective means for preventing or moderating the complications of chronic diabetes, usually entail frequent blood-glucose monitoring with insulin injections tailored to match the test readings. People who are on intensive therapy regimens may inject themselves four or more times a day to keep their blood sugar levels within as tight a range as possible.
Many patients use premixed insulin preparations, although some people prefer to mix their own. Older patients who may not require tight glucose control and very young patients who may have some remaining insulin production may be able to limit injections to once a day.
Originally published March 17, 2003.
Medically updated June 18, 2004.
SOURCES: National Institute for Diabetes & Digestive & Kidney Diseases. National Diabetes Education Program. American Diabetes Association. University of Toronto.
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