Hormone Infusion Improves Pancreatic Insulin Production in Cystic Fibrosis Patients with or at Risk
Medication therapy based on the hormone glucagon-like peptide-1(GLP-1) may help regulate natural insulin production in cystic fibrosis, potentially offering a better way to prevent and ultimately manage diabetes than daily insulin injections
PHILADELPHIA— Cystic fibrosis is well-known for attacking the lungs through thick blockages of mucus, but those with the condition often also develop diabetes because of the way cystic fibrosis can affect the pancreas. Since diabetes has been linked to worse lung function, this creates a vicious cycle, with diabetes acting as a multiplier on the patient’s already damaged lungs. However, new research shows that infusing a hormone called glucagon-like peptide-1 (GLP-1) into patients with cystic fibrosis who have diabetes or are at risk for it can improve function of impaired islet cells in the pancreas, which help keep blood sugar in check. This research was published in Diabetes. “This finding supports the likelihood that GLP-1 agonist medications could have therapeutic benefit in the treatment and possible prevention of cystic fibrosis-related diabetes,” said the study’s co-senior author, Michael Rickels, MD, the Willard and Rhoda Ware Professor in Diabetes and Metabolic Diseases in the Perelman School of Medicine at the University of Pennsylvania. “Better treatment of cystic fibrosis-related diabetes is critical for preserving pulmonary function, and we are now testing longer-term effects of a GLP-1 agonist on metabolism in a separate clinical trial.” Almost nine out of 10 people with cystic fibrosis also experience pancreatic insufficiency, a condition in which the pancreas is unable to produce enough of the enzymes needed for proper digestion. An estimated one in five people with cystic fibrosis currently have diabetes. A significant complicating factor is that these patients often don’t respond to insulin injections in the same way as people who have diabetes but not cystic fibrosis. GLP-1 is an intriguing target because it is a hormone involved in digestion. In the pancreas, it helps control insulin production, contributing to the body’s natural blood sugar balance. As such, this hormone is heavily tied to the functioning of pancreatic islet cells. Searching for a more effective treatment for cystic fibrosis patients who are pancreatic-insufficient, Rickels and co-senior author Andrea Kelly, MD, a professor of Pediatrics at the Children’s Hospital of Philadelphia (CHOP), tested two different types of hormone infusions. These hormones are known to improve the function of islet cells in the pancreas. While the study’s subjects received 90-minute continuous infusions of one hormone or the other, the thought is that medications called agonists that are longer-acting versions of these hormones in the body could be quickly injected just once a week, a contrast to daily multiple insulin injections. The study was conducted among 36 patients. They received either the GLP-1 hormone or an infusion of the glucose-dependent insulinotropic polypeptide (GIP) hormone. Then, they also each received a placebo infusion on another occasion to serve as a comparison to the hormone infusion. Natural insulin production in patients who received the GLP-1 hormone rose significantly compared to when they received placebo infusion. Equally important, the researchers saw no change in the body’s insulin production among those who were infused with GIP. This likely means that loss of function tied to the hormone GIP is more complex than what was discovered about GLP-1. “Identifying the mechanisms underlying diabetes in cystic fibrosis offers the possibility of developing interventions to prevent or delay diabetes development and ease the treatment burden for people with established cystic fibrosis-related diabetes,” Kelly said. “This work may also provide additional insight into islet function that may be relevant for other forms of diabetes.” Rickels and Kelly are conducting a new clinical trial of a currently available GLP-1 agonist as a proof-of-concept of the therapeutic value for this patient population to see whether weekly administrations of the agonist for six weeks has the same effect as the continuous infusions the team already studied. If the weekly agonist doses prove effective, it could be an alternative to daily insulin injections, which can be inconvenient and inconsistent. “Our hope is to delay or significantly reduce the need for complex insulin management through preserving islet function and insulin secretion in individuals with cystic fibrosis, potentially via a once-weekly GLP-1 agonist injection therapy,” Rickels said. This study was supported by the National Institutes of Health (R01 DK97830, K23 DK107937, UL1 TR001878, P30 DK19525, T32 DK007314), and the Cystic Fibrosis Foundation (RICKEL19A0-I).
Penn Medicine is one of the world’s leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation’s first medical school) and the University of Pennsylvania Health System, which together form a $9.9 billion enterprise. The Perelman School of Medicine has been ranked among the top medical schools in the United States for more than 20 years, according to U.S. News & World Report's survey of research-oriented medical schools. The School is consistently among the nation's top recipients of funding from the National Institutes of Health, with $546 million awarded in the 2021 fiscal year. The University of Pennsylvania Health System’s patient care facilities include: the Hospital of the University of Pennsylvania and Penn Presbyterian Medical Center—which are recognized as one of the nation’s top “Honor Roll” hospitals by U.S. News & World Report—Chester County Hospital; Lancaster General Health; Penn Medicine Princeton Health; and Pennsylvania Hospital, the nation’s first hospital, founded in 1751. Additional facilities and enterprises include Good Shepherd Penn Partners, Penn Medicine at Home, Lancaster Behavioral Health Hospital, and Princeton House Behavioral Health, among others. Penn Medicine is powered by a talented and dedicated workforce of more than 47,000 people. The organization also has alliances with top community health systems across both Southeastern Pennsylvania and Southern New Jersey, creating more options for patients no matter where they live. Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2021, Penn Medicine provided more than $619 million to benefit our community.