Diabetes in cystic fibrosis: breaking out of the vicious circle?

Cystic fibrosis is often associated with pancreatic insufficiency and diabetes. Can GLP-1 agonists help improve treatment in this particular patient population?

Cystic fibrosis is known for attacking the lungs through thick deposits of mucus. Since cystic fibrosis also attacks the pancreas, those affected often develop diabetes. Because diabetes is in turn associated with poorer lung function, a vicious circle is created in which diabetes puts even more strain on a patient’s already damaged lungs. However, new research shows that infusion of the hormone glucagon-like peptide-1 (GLP-1) in patients with cystic fibrosis who have or are at risk of diabetes may improve the functioning of the impaired islet cells in the pancreas. This research paper was published in the journal Diabetes released.

“This finding supports the likelihood that GLP-1 agonists may have therapeutic utility in the treatment and possible prevention of cystic fibrosis-related diabetes,” says Michael Rickels, study co-author and professor of diabetes and metabolic diseases at the Perelman School of Medicine from the University of Pennsylvania. “Better management of cystic fibrosis-related diabetes is critical to maintaining lung function, and we are now testing the longer-term metabolic effects of a GLP-1 agonist in a separate clinical study.”

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GLP-1 or GIP: Which hormone performs better?

Almost nine out of ten people with cystic fibrosis also have pancreatic insufficiency. It is estimated that one in five people with cystic fibrosis currently has diabetes. To make matters worse, these patients often do not respond to insulin injections in the same way as people who have diabetes but do not have cystic fibrosis.

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In search of a more effective treatment for cystic fibrosis patients whose pancreas is not working properly, Rickels and co-author Andrea Kelly, professor of pediatrics at Children’s Hospital of Philadelphia (CHOP), tested two different types of hormone infusions: 36 patients received either that Hormone GLP-1 or glucose-dependent insulinotropic polypeptide (GIP) as an infusion. Both hormones are known to improve the function of the islet cells in the pancreas. The patients then received a placebo infusion on another occasion, which served as a comparison to the hormone infusion.

The natural insulin production of the patients increased significantly when GLP-1 was administered compared to the placebo infusion. Furthermore, the researchers found no change in the body’s insulin production in those who received a GIP infusion. This likely means that the loss of function associated with the hormone GIP is more complex than what has been discovered with GLP-1.

“Identifying the mechanisms underlying diabetes in cystic fibrosis offers the opportunity to design interventions to prevent or delay the development of diabetes and reduce the burden of treatment for people with existing cystic fibrosis-related diabetes,” said Kelly. “This work could also provide additional insights into islet cell function that may be relevant to other forms of diabetes.”

GLP once a week instead of daily insulin

Rickels and Kelly are currently conducting a new clinical trial with a GLP-1 agonist to demonstrate therapeutic value in this patient population. They also want to determine whether weekly administrations of the agonist for six weeks have the same effect as the continuous infusions that the team has already studied. If proven effective, weekly doses could provide an alternative to daily insulin injections, which can be uncomfortable and inconsistent.

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“Our hope is to delay or significantly reduce the need for complex insulin regimens by preserving islet cell function and insulin secretion in people with cystic fibrosis, potentially through once-weekly GLP-1 agonist injection therapy,” said Rickels .

This article is based on a press release the University of Pennsylvania. We have the original publication for you here and linked in the text.

Image source: Austin Neill, unsplash.



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