All About Insulin
The following is excerpted from "Targeting Tight Control" by Robert S. Dinsmoor, published in JDRF's Countdown magazine, Spring 2004:
Insulin Analogs
In the last decade, one of the most important innovations in blood glucose control has been the advent of insulin analogs. Insulin analogs are versions of insulin that have been altered to achieve improved effect. Insulin lispro, the first insulin analog, introduced in August 1996 by Eli Lilly and Company under the brand name Humalog, is a rapid-acting analog that works much more quickly than regular insulin and lasts only about two hours, making it ideal for mealtime insulin injections. Whereas regular insulin is supposed to be taken 30 to 45 minutes before meals, Humalog is taken within 15 minutes of eating, which adds flexibility and convenience to meal planning. Furthermore, its rapid action more closely matches the body's natural rise in blood glucose after meals, so that it works when it is needed and disappears from the bloodstream by the time it isn't.
Studies show that blood glucose levels two hours after meals are significantly lower in people who use mealtime lispro compared with regular insulin. Another rapid-acting insulin analog called insulin aspart (manufactured by Novo-Nordisk as Novolog) was approved for marketing in the U.S. by the Food and Drug Administration (FDA) in June 2000.
In April 2000, the FDA granted marketing approval for insulin glargine (Lantus, manufactured by Aventis Pharmaceuticals). Once injected, insulin glargine forms a precipitate, which is absorbed very slowly and evenly into the bloodstream. Since its effects last nearly 24 hours with little variability and no peak action level, insulin glargine is an ideal "basal" or long-acting insulin. A number of studies have compared the use of insulin glargine with that of the most commonly used basal insulin, NPH. Results show that regimens using insulin glargine offer blood glucose control that is at least as good as—and sometimes better than—that seen with NPH insulin, and it produced fewer episodes of hypoglycemia and less weight gain.
"The other insulins we used to think of as basal insulins, NPH and ultralente, have large peaks in their action, and so it's no wonder our kids were having hypoglycemic seizures at night," says H. Peter Chase, M.D., professor of pediatrics and clinical director at the Barbara Davis Center for Childhood Diabetes in Denver and author of Understanding Diabetes, an educational book for families of children with type 1 diabetes. "Now, with Lantus, we have a true basal insulin. I think insulin analogs are just one of the ways we've been able to improve glycemic control without increasing the severe lows, as happened in the DCCT."
Insulin Pumps
Since first introduced in the late 1970s, insulin pumps have become smaller, "smarter," and easier to use. In addition, they allow users to fine-tune insulin output to come even closer to normoglycemia (normal, or nondiabetic, blood sugar level range).
The body's sensitivity to insulin is known to fluctuate throughout the day. For example, the action of certain hormones in the early morning makes the body less sensitive to insulin, so people with type 1 diabetes (juvenile diabetes) sometimes awaken with high blood sugars (the so-called "dawn phenomenon"). Pump users can now address this by programming a higher basal infusion rate in the early hours of the morning.
Doctors started using insulin lispro in insulin pumps, with good results, shortly after it became commercially available. As in injection therapy, lispro (as well as the more recently introduced Novolog) is ideal for the mealtime bolus. Furthermore, since lispro starts working so quickly and its effects last only a short while, blood glucose levels respond rapidly whenever the basal infusion rate is changed. Dr. Chase and colleagues at the Barbara Davis Center compared the use of insulin lispro with the use of regular insulin in insulin pumps in a study of young patients with type 1 diabetes. Their findings, reported in Diabetes, Obesity and Metabolism in 2000, showed that using insulin lispro in pumps significantly lowered HbA1c levels without increasing the number of hypoglycemic episodes.
Implantable pumps may be the next wave in insulin delivery systems. Experimental models have been studied extensively in research centers worldwide since the mid-1980s. These devices are surgically implanted in the abdomen and deliver insulin via the peritoneal cavity (the space within the abdomen, bounded by thin membranes, that contains the liver, stomach, and intestines), a mode of delivery that has been found to produce more reliable and reproducible levels of insulin in the blood than the route used by conventional insulin pumps. The most widely used implantable pump, manufactured by Medtronic MiniMed, is now commercially available in the European Union, although in the U.S. its use is restricted to investigational use only.
