NPH Insulin: Mixing Is Critical for Best Results

With commentary by study author Geremia Brunetto Bolli, MD, professor of endocrinology, Perugia University School of Medicine, Perugia, Italy

Patients on insulin known as NPH (Humulin N, Novolin N) are often reminded that they need to re-suspend it before use by shaking it or rolling it in the palm of their hand.

NPH insulinHowever, doctors know that patients often hurry and don't take the time to mix up this kind of insulin before using it. Now, a new study suggests how crucial that step is. Italian researchers compared the effects of mixing or not mixing NPH insulin on the insulin concentrations in the blood.

"It is well known that NPH insulin needs resuspension prior to its use," says Geremia Brunetto Bolli, MD, professor of endocrinology at the Perugia University School of Medicine in Perugia, Italy, who led the study. "However, the different glucose lowering effect of re-suspended versus non-resuspended NPH was not known," he says.

In his study, he found that non resuspended NPH insulin ''may result in an approximately twofold difference" in the effect on insulin levels in the blood. His study was published online Sept. 10 in Diabetes Care. So it is important that NPH is properly resuspended prior to its use, says Dr. Bolli.

Other insulins that don't require mixing have often replaced NPH. Ideally "people with type 1 diabetes should not use NPH," he says, but be switched to newer types. "However, NPH is still used a lot in type 2 diabetes, either as NPH or mixed with rapid insulin," he says. Two common reasons people are still using NPH: “Limited health insurance coverage, or lack of insurance,” says EndocrineWeb Advisory Board Member Amy Hess Fischl, MS, RD, LDN, BC-ADM, CDE, an advanced practice dietitian at the University of Chicago Kovler Diabetes Center.  She adds that pre-mixed insulin is still quite popular in the type 2 population because it is a fixed 2 injections per day versus multiple daily injections that could be 4 or more injections per day.

NPH is an intermediate-acting insulin, usually reaching the bloodstream 2 to 4 hours after injection, the American Diabetes Association (ADA) says, peaking 4 to 12 hour later. It is effective for about 12 to 18 hours, the ADA says. "If the patient is obliged to use NPH for some reason, they should strive to spend two minutes of their time prior to each injection to resuspend NPH," says Dr. Bolli. He reports receiving honoraria from sanofi-aventis and Eli Lilly & Co for consulting and scientific advising.

Dr. Bolli evaluated 11 people with type 1 diabetes. He looked at the effects of mixing the insulin as instructed or not. When the insulin was not mixed, insulin blood levels were either reduced or increased.  The duration of the effect also varied greatly, depending on whether or not it was mixed properly. For instance, when it was mixed property, the insulin action lasted for nearly 12 hours, but when it wasn't, it could last as briefly as about 9 hours.

The study findings make good sense, according to Spyros Mezitis, MD, an endocrinologist at Lenox Hill Hospital, New York, who says that this is not new information. "We already knew if you don't resuspend it [NPH] right, you aren't going to get as good a result," he says. But the new study adds some scientific support and hard numbers to what is common knowledge about the need to mix up the insulin before injecting.

NPH insulin use is probably more common overseas, he says, but is still in use in the U.S. "If you don't turn it upside down, the insulin doesn't disperse equally," Dr. Mezitis says. And it doesn't work as well. "The blood sugar is not going to be controlled as well."

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