06:52am Sunday 05 April 2020

Researching a difficult disease before it becomes common


Some of the most critical medical research is done when the subject is important but access to information is scarce.

That’s the problem UC Davis Health endocrinologists are navigating with cystic fibrosis and diabetes. For them the question is, how do you discover, and battle, the causes of diabetes in cystic fibrosis patients — science that could lead to breakthroughs on a number of fronts — when clinical trials are difficult to assemble and the incidence of that form of diabetes has just begun to grow?

The ongoing work of the UC Davis Health Division of Endocrinology, Diabetes and Metabolism and Adult Cystic Fibrosis Clinic is led by John Yoon, an accomplished diabetes researcher. He is working toward understanding cystic fibrosis-related diabetes (CFRD) with research that also has potential to help battle all forms of diabetes.

“We’re trying to understand what is happening at the molecular level,” Yoon said. “there are still fundamental questions about how diabetes develops in cystic fibrosis that remain unanswered. Our hope is that learning more about CFRD will also be applicable to other forms of diabetes as well.”

Part of the difficulty is the lethal nature of cystic fibrosis. The average lifespan for a CF patient born after 2013 is 44 years, but that is a relatively recent, and positive, development. Life expectancy for those born in earlier is much shorter. Besides the tragedy of lost lives, the shorter lifespans make it difficult to study CFRD, which is more often seen in CF patients who do live longer.

“CF patients face a 40 to 50 percent chance of developing CFRD as they age,” Yoon said, “but the incidence of CFRD now is still relatively small.”

Longer lifespans increases the chances of CFRD

CFRD is uncommon below age 10, rises to about 20 percent by age 20, and to 30 percent for CF patients while in their 20s. The likelihood continues to increase dramatically as CF patients age — to 30-40 percent of CF patients in their 30s, and 40-50 percent of CF patients in their 40s.

“Most CF patients who are alive — about 75 percent — are younger than 30 years old,” Yoon said. “Many of them have a likelihood of developing CFRD if they survive into adulthood.”

Yoon and his team are trying to head off that growing wave of CFRD cases coming soon.

“It’s hard to do research and trials because of the small number of patients,” he said, “so we have to organize multi-center trials, which takes much more care.”

Yoon and his team are also addressing the questions about CFRD using cell cultures and animal models, and they draw from science across UC Davis and academic medicine worldwide to aid their own groundbreaking work.

A unique molecular path to diabetes

The prevalent thinking has been that CF kills off pancreatic cells that produce digestive enzymes and causes scarring, which in turn damages neighboring insulin-producing pancreatic cells known as beta cells. Some have suggested that the lack of a functional cystic fibrosis gene may directly affect insulin secretion from beta cells — an idea possibly supported by the observation that drugs that improve the function of a defective cystic fibrosis gene also help with insulin secretion. Yoon believes a complex interplay of metabolic disturbances in CF contributes to CFRD and that understanding the early events in CFRD development is key.

“We can alter the cystic fibrosis gene in cells to try to mimic what happens in patients’ cells who develop CFRD,” he said. “We also have an animal model of cystic fibrosis that we study to understand what is going on in tissues that affect glucose metabolism.”

In addition, his team studies the treatment patterns of patients diagnosed with CFRD in recent years in an attempt to find areas of improvement.

Linking endocrinology with a clinic dedicated to CF patients

Treating patients is more than theoretical for Yoon and his team. He sees diabetes patients at UC Davis Medical Center as well as at the UC Davis Adult Cystic Fibrosis Clinic. The clinic has assembled a multi-disciplinary team that includes pulmonologists, consulting specialist physicians, nurses, nutritionists, social workers, respiratory therapists and clinical pharmacists. Patients there have access to the newest technologies such as insulin pumps or continuous glucose monitors.

“CF patients have difficult and frightening lives,” Yoon said. “We can help them live well into adulthood, but we also want to help them live more comfortable and happier lives. We’re working to advance clinical care, and the research we’re doing has potential to help CF patients and to impact other forms of diabetes.”




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