His modest but technologically advanced study centered on only 18 vials of prescription insulin. But what researcher Alan Carter, adjunct University of Missouri-Kansas City School of Pharmacy faculty member, discovered about them has sent the giant diabetes industry reeling and raised concern among patients and their advocates.
Carter examined insulin bought at multiple pharmacies, supplied by different wholesalers, in Kansas and Missouri. The concentration, or number of insulin units in the liquid solution, was labeled as 100 units per milliliter. But they averaged less than half of what they were labeled—and none met the 95-unit minimum standard. His discoveries were published Dec. 21 in the Journal of Diabetes Science and Technology.
“Our findings are quite alarming and need to be further explored,” said Carter, who also is a UMKC School of Pharmacy alumnus. “My hope is that a larger, fully comprehensive study will be conducted sampling both the U.S. and European supply chains to examine any impact the supply chain may have on insulin.
“This will take unprecedented cooperation between disparate groups not accustomed to working together—not to mention it won’t be cheap,” he added.
Carter performed the research while working as a contract researcher at MRIGlobal, a not-for-profit contract research firm next door to UMKC’s Volker Campus. Even though the study was small, it has raised concern among diabetes experts, patient advocacy groups and insulin makers — including the American Diabetes Association. Carter’s findings also have been reported by the Associated Press and published in dozens of news sources including the Washington Post.
Insulin is a natural hormone secreted by the pancreas. Many people with diabetes are prescribed insulin because their bodies don’t produce insulin (type 1 diabetes) or don’t use insulin properly (type 2 diabetes). About 6 million Americans inject synthetic insulin each day. The study raised alarm, for starters, because without enough insulin, diabetics can eventually suffer from a multitude of serious complications: blindness, limb amputations and life-threatening damage to the kidneys and heart.
The U.S. Food and Drug Administration requires that insulin batches are tested before leaving the factory. The insulin must be kept cool as it is shipped to a warehouse and then to pharmacies. The FDA conducts spot checks during the process.
Carter wonders whether his results might help explain why insulin users sometimes find a dose doesn’t work as well as normal. Doctors usually attribute that to patient error: not injecting enough insulin before a meal, not following dietary guidelines or skipping exercise.
Carter isn’t faulting the two manufacturers of insulin, Eli Lilly and Novo Nordisk, and shared the study with them before it was published. Instead, Carter thinks the insulin might have gotten too cool or too warm somewhere between the factory and the pharmacy, causing some of the molecules to break apart.
Or, it’s possible that the insulin molecules “stick together” so tightly during shipping and storage that when a dose is given, some clumps don’t come apart. When injected, the doses would be diluted and agitated enough in the bloodstream to break the clumps up quickly and work as expected.
“A rough analogy: think of mixing flour and water,” Carter said. “If stirred vigorously, the clumps will break up. If not stirred well, the clumps remain.”
In response to the study, endocrinologists and experts have cautioned patients not to change their insulin routine.
“We strongly urge patients to talk with their doctors and pharmacists about any concerns they have with their insulin or diabetes treatment plan,” wrote William T. Cefalu, chief scientific, medical and mission officer for the American Diabetes Association, in a blog post.