Researchers: Insulin Dose has Been Miscalculated for Decades

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Key points:

  • New research suggests that a large portion of a diabetic's insulin dose is unlikely to work as expected.
  • Assumptions about how insulin assembles with a specific distribution of molecular clusters has been incorrect for decades.
  • The new research can provide a much more accurate dosage for the 45 million children and adults who receive daily insulin injections.

A new study suggests a large portion of a diabetic's insulin dose is unlikely to work as expected. For decades, it was assumed that insulin assembles with a particular distribution of molecular clusters of either one, two, or six molecules. In fact, pharmaceuticals have been designed based upon this assumption.

Now, for the first time, researchers at the University of Copenhagen have shown that this critical belief is wrong.

"It is now apparent to us that we’ve gotten things wrong by 200 percent,” said Nikos Hatzakis, professor in the department of chemistry and the study’s lead author. “There are only half as many single molecules in insulin compared to what we thought. Conversely, there are far more six-molecule clusters than we assumed. Ultimately, if this is basic research insights apply in human body, it means that when we believe to be administering a certain dose, it may only be half the dose with the rapid-acting effect in the body that we had expected.”

The research team began by directly observing the process in which each insulin molecule joins forces with other molecules to assemble into clusters. This allowed them to see how fast each cluster forms while examining about 50,000 clusters. Knowing the exact distribution of different clusters in a given amount of insulin is fundamental when developing medications that need to have either short- or long-acting effects in the body. The difference between rapid and slow-acting insulin preparation is dependent upon how quickly the molecules assemble in clusters and how they disassemble.

Additionally, the study findings, published in Communications Biology, reveal that cluster formation is a much more complex process than once presumed. The clusters can both grow and shrink at far more different intervals than previously supposed.

The study results could expand the ways in which insulin preparations are designed, possibly reducing fluctuations in patients’ blood sugar—which has always been a challenge, even with the (once thought to be) correct medication.

 

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