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Study Sheds Light On Cystic Fibrosis-related Diabetes

Date:
July 7, 2006
Source:
University of Florida
Summary:
A University of Florida study in animals suggests diabetes in cystic fibrosis patients is not caused by the destruction of insulin-producing cells in the pancreas -- as is often the case in patients with the traditional form of type 1 diabetes -- but by differences in how these cells function.

A growing number of cystic fibrosis patients are battling a second, often deadly complication: a unique form of diabetes that shares characteristics of the type 1 and type 2 versions that strike many Americans.

Many of these patients are teens who take enzymes to help digest their food and undergo daily physical therapy to loosen the thick, sticky mucus that clogs their lungs. But despite treatments that are helping thousands to live decades longer than ever before, when diabetes strikes, their life expectancy plummets — on average by two years for men and an astounding 16 for women.

Now a University of Florida study in animals suggests diabetes in cystic fibrosis patients is not caused by the destruction of insulin-producing cells in the pancreas — as is often the case in patients with the traditional form of type 1 diabetes — but by differences in how these cells function. The findings were published this month in the American Diabetes Association’s journal Diabetes.

Cystic fibrosis patients with diabetes produce some insulin on their own, but they require daily injections to boost their levels when eating so they can properly use sugar and other food nutrients for energy. At times they also become very resistant to the insulin they do make, similar to people with type 2 diabetes.

“For the longest time, the development of diabetes in cystic fibrosis has been thought to be chronic destruction of pancreas, so eventually you get loss of the insulin-producing beta cells,” said Dr. Michael Stalvey, an assistant professor of pediatrics at UF. “Our study provides some early evidence to suggest there is an inherent difference in beta cell function.”

Cystic fibrosis patients suffer recurrent episodes of infection and inflammation that slowly destroy the lungs. The pancreas is also affected, interfering with proper digestion. The disease stems from a faulty gene that blocks the normal passage of salt and water through the body’s cells. It is this gene deficiency that is proposed to cause insulin-producing cells to malfunction, Stalvey said.

About 30,000 Americans have cystic fibrosis, making it the nation’s most common lethal hereditary disorder. On average, they will not live past 35, though some are living through their 40s and even into their 60s. As each year passes, the likelihood they will develop diabetes increases. As many as 16 percent of all patients with cystic fibrosis also have diabetes, a number that is expected to rise as overall life expectancy for cystic fibrosis patients increases. Half will show signs of diabetes by age 30 and will suffer a rapid decline in overall health and lung function, muscle mass and body mass index.

“It’s becoming more and more frequent because of the increasing age of patients,” Stalvey said. “That’s part of the reason why new recommendations call for screening patients 14 years and older yearly with an oral glucose tolerance test. Each year we know their likelihood of developing diabetes gets higher and higher.

“These young people, teenagers or young adults in their early 20s, have been fighting all their lives to stay healthy and keep their nutrition up,” he added. “Now they’ve just been given something that potentially will overwhelm them. It’s a huge thing for them, given the consequences that diabetes means to their underlying condition.”

In the UF study, researchers developed the first animal model for the study of cystic fibrosis-related diabetes. They used mice that scientists from the University of North Carolina engineered to be missing the gene that makes the protein responsible for transporting salt and water across the cell membrane. People with cystic fibrosis have a mutated form of this protein.

UF scientists administered a low dose of a chemotherapy drug that weakened insulin-producing cells but did not destroy them. They then tested the animals’ ability to regulate their blood sugar while fasting and after receiving glucose, simulating the rise in blood sugar that occurs after eating food.

Animals with the protein deficiency were more sensitive to the effects of the chemotherapy drug and had more difficulty regulating blood sugar levels, both while fasting and after receiving glucose. Mice that were still able to produce the crucial protein that prevents cystic fibrosis were able to maintain normal blood sugar levels, even after the drug had damaged some of their insulin-producing cells.

“This goes beyond improving our understanding of patients with cystic fibrosis-related diabetes; it also will help us improve our understanding of other forms of diabetes and help us work on strategies for a future cure,” Stalvey said.

Stalvey’s collaborators included Dr. Desmond Schatz, Dr. Terence Flotte and Mark Atkinson. The study was supported in part by the Lawson Wilkins Pediatric Endocrinology Society, the Cystic Fibrosis Foundation and the National Institutes of Health.

“Twenty-five percent of adolescents and 40 percent of adults with cystic fibrosis have diabetes, and diabetes is associated with poorer survival in this population,” said Dr. Antoinette Moran, division head of pediatric endocrinology and director of the Pediatric Diabetes Program at the University of Minnesota Medical School. “The cause of cystic fibrosis-related diabetes is not completely understood, but it is clearly different from other forms of diabetes. The study by Stalvey and colleagues is important because it is the first to show that there are intrinsic abnormalities in the insulin-producing cells of the pancreas related to the genetic defect that causes cystic fibrosis.”


Story Source:

The above story is based on materials provided by University of Florida. Note: Materials may be edited for content and length.


Cite This Page:

University of Florida. "Study Sheds Light On Cystic Fibrosis-related Diabetes." ScienceDaily. ScienceDaily, 7 July 2006. <www.sciencedaily.com/releases/2006/07/060707093341.htm>.
University of Florida. (2006, July 7). Study Sheds Light On Cystic Fibrosis-related Diabetes. ScienceDaily. Retrieved October 20, 2014 from www.sciencedaily.com/releases/2006/07/060707093341.htm
University of Florida. "Study Sheds Light On Cystic Fibrosis-related Diabetes." ScienceDaily. www.sciencedaily.com/releases/2006/07/060707093341.htm (accessed October 20, 2014).

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