Gastrointestinal Issues and Cystic Fibrosis-Related Diabetes

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People with cystic fibrosis can experience complications in the pancreas, liver, and intestines that can lead to malnutrition, constipation, liver disease, CF-related diabetes, and other digestive issues -- including abdominal pain and poor appetite.

Pancreatic Insufficiency

The pancreas has tissue that makes digestive enzymes. The enzymes move from the tissue through a duct (tube), mixing with a bicarbonate-rich fluid that is produced in the duct. The enzymes and the fluid flow into the small intestine where the bicarbonate neutralizes stomach acid and the enzymes digest food. The fluid also hydrates the intestines. In most people with cystic fibrosis, this process is affected in the following ways:

  • Cystic fibrosis transmembrane conductance regulator (CFTR) proteins in the duct don't work properly, affecting the amount of fluid and bicarbonate that is produced. This lack of fluid causes the duct to become blocked. When this happens, the powerful enzymes that normally digest food back up into the pancreas and destroy the tissue.
  • When enzymes can't get into the small intestine, food is not broken down properly. For this reason, most people with CF cannot absorb the nutrients they need, and they can become malnourished. About 90 percent of people with CF have this problem, called “pancreatic insufficiency,” and need to take enzymes with every meal and snack to properly digest food.
  • About 10 percent of people with CF are “pancreatic sufficient,” which means they have enough CFTR protein function in the pancreatic duct that they do not need to take enzymes. However, they are still prone to blockages in the duct, which cause enzymes to back up and damage tissue, causing pancreatitis.
  • All people with CF have trouble making enough fluid and bicarbonate, which can lead to pain, cramping, gas, and constipation.

Research Underway

The Cystic Fibrosis Foundation has helped organize a group of gastrointestinal (GI) specialists to focus on the treatment and research of GI issues in CF. Called the Developing Innovative Gastroenterology Specialty Training program, or DIGEST, this group of GI doctors is developing best practices and gaining an improved understanding of abdominal symptoms to lead to better treatments.

Additionally, the CF Foundation is supporting clinical trials to test the effects of oral glutathione, an antioxidant that is important to the normal functioning of the intestine and lungs. Glutathione levels have been shown to be lower in people with CF. Oral glutathione may improve growth and decrease digestive inflammation in children with CF.

In this video, Meghana N. Sathe, M.D., associate professor of pediatrics and co-director of the pediatric CF center at the University of Texas Southwestern Medical Center/Children's Health, explains why people with CF can have problems with getting proper nutrition and experience gastrointestinal (GI) issues. She also discusses the GI Wellness study (now called the GALAXY study), which is being conducted by DIGEST doctors to gauge which GI symptoms affect people with CF the most, so that researchers can prioritize them for further study.

Current Treatments

To relieve the various symptoms associated with pancreatic insufficiency, people with CF can take various medications.

Cystic Fibrosis-Related Diabetes

In people with CF, continual scarring in the pancreas can lead to the development of cystic fibrosis-related diabetes (CFRD), a condition in which the pancreas doesn't produce sufficient insulin. More than 20 percent of people with CF have CFRD, which typically occurs in adulthood.

Research Underway

Researchers, funded by the CF Foundation, are examining the effect that the CFTR protein has on the development of CFRD to find ways to treat it. They are looking specifically at whether CFRD occurs because the CFTR protein is not present in islet cells -- cells in the pancreas that make hormones, such as insulin -- or in other cells in the pancreas. The Foundation also has funded research to understand the risk factors associated with developing CFRD, to improve treatment approaches, and to assess the impact of CFTR modulators on this condition.

Current Treatments

For more information, visit CFRD.

Cystic Fibrosis-Associated Liver Disease

People with CF also can experience problems in the liver because bile, a fluid that helps the body absorb fat, becomes abnormal and thick, blocking small bile ducts in the liver. The ducts become inflamed, which leads to scarring. Consequently, approximately 10 percent of people with CF develop a condition called CF-associated liver disease (CFLD).

In advanced CFLD, scarring (cirrhosis) can make it difficult for blood to flow through the liver and can cause blood to back up into the portal vein, the main vein going to the liver. This backup leads to increased venous blood pressure -- a condition called portal hypertension -- and can lead to complications such as fluid accumulation in the abdomen or bleeding from enlarged veins in the esophagus or stomach.

Developing Better Screening Methods

Because CFLD is difficult to identify in its early stages, doctors need better methods to diagnose it in time to minimize liver damage. In an innovative partnership with the National Institutes of Health (NIH), the Foundation is investigating the best methods of screening for the presence of liver disease. Researchers in the PUSH study are using ultrasound to see if they can identify biomarkers that would help them detect cirrhosis. If they are successful, scientists would be able to study how cirrhosis develops in people with CF and identify potential ways to treat it.

Current Treatments

People with CFLD do not have many treatment options, but a multidisciplinary approach that includes the CF care center team is recommended in clinical care guidelines. The team will determine the causes of specific liver abnormalities and treat them accordingly. This treatment can include nutritional therapy and a medication that thins the bile.

Colorectal Cancer

Colorectal cancer is a cancer that begins in the colon or rectum. Adults with CF have a 5-10 times greater risk of colorectal cancer than the general population and a 25-30 times greater risk after an organ transplant.

Although we do not know for certain why people with CF have a greater risk of developing colorectal cancer, it is thought to be associated with the CFTR gene mutation. In general, transplant recipients have an increased risk for all types of cancer because the medications they must take to prevent rejection weaken the immune system. 

Additional research is being conducted to understand the mechanism -- or the underlying process -- that causes this higher risk. In the interim, the Foundation convened a multidisciplinary team of experts to develop colorectal cancer screening recommendations

The Foundation also plans to conduct research to find ways to provide caregivers and people with CF more information to help inform their discussions about colorectal cancer screening.

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