SAN DIEGO (FRONTLINE MEDICAL NEWS)Long-term cystic fibrosis survivors are prone to a singular form of diabetes, according to Katie Larson Ode, MD.

Medical advances have dramatically boosted life expectancy for people with cystic fibrosis, allowing some to survive into middle age. “As more of our patients live longer, [cystic fibrosis–related diabetes (CFRD)] will become a much more common problem for endocrinologists, educators, nurses, and nutritionists to address,” said Dr. Ode, a pediatrician at the University of Iowa in Iowa City. “Proper management of cystic fibrosis-related diabetes is lifesaving for our CF patients.”

An estimated 30,000 people in the United States have cystic fibrosis; half of them are over 18 years old, according to the Cystic Fibrosis Foundation.

“CF is caused by a defect in an important chloride channel that regulates the salt and water content of secretions,” said Antoinette Moran, MD, professor and division chief of pediatric endocrinology and diabetes at the University of Minnesota, Minneapolis, while speaking at the annual meeting of the American Association of Diabetes Educators. “This affects many organs, but death is generally due to chronic obstructive lung disease.”

In the 1950s, few children with CF lived past elementary school age. Now, researchers estimate that the median life span for babies born and diagnosed in 2010 could reach more than 50 years ( Ann Intern Med. 2014 Aug 19;161[4]:233-41 ), according to the Cystic Fibrosis Foundation.

But as they age, CF patients’ risk for CFRD also increases.

A 2009 study led by Dr. Moran ( Diabetes Care 2009 Sep;32[9]: 1626-31 ) tracked 872 CF patients from three periods in the 1990s and 2000s and found CFRD in 2% of children, 19% of adolescents, and 40%-50% of adults. “For a typical CF patient, the chances of developing CFRD by age 40 are roughly 80%,” said Andrew Norris, MD, PhD, of the departments of pediatrics and biochemistry at the University of Iowa.

CF patients who inherit a mild form of the disease often have less risk of CFRD. The condition is “primarily due to insulin insufficiency, caused by fibrotic destruction of islets and perhaps an intrinsic defect in beta-cell function related to the primary CF chloride–channel defect,” Dr. Moran said. “Up to 80% of CF patients with severe mutations will eventually develop diabetes.”

CF patients aren’t limited to one form of diabetes. “Occasionally a patient may be unlucky enough to have more than one type,” Dr. Moran said, since the diseases have separate pathophysiologies. While rare, type 1 appears to be more common than type 2, which is often linked to obesity; CF patients struggle to put on weight. “It would be highly unusual for a CF patient to develop type 2 diabetes,” Dr. Norris said.

The specialists said patients with CFRD are unique among diabetics for several reasons:

• Microvascular complications are rare. “After many years of diabetes, CFRD patients are at risk for microvascular complications, but they tend to be less common and less severe than in other forms of diabetes, likely because CF patients still make some of their own insulin,” Dr. Moran said.

• Macrovascular complications are not seen. “This is important because recommendations given to people with other forms of the diabetes to reduce risk of macrovascular complications – weight loss, low-fat diet, low-salt diet, etc.– do no apply in CF and can actually be harmful,” Dr. Moran said.

• Insulin is especially crucial. “Maintaining weight and lean body mass is critical for survival in CF, so the chief clinical concern with CFRD is nutrition and the potential impact of insulin insufficiency on mortality,” Dr. Moran said. “Insulin replacement is the only approved therapy for CFRD. Treatment is very similar to that of type 1 diabetic patients in a honeymoon state. Very early on, patients may receive a single dose of basal insulin only or of premeal rapid-acting insulin only. Eventually most CF patients require basal-bolus insulin therapy.”

Doses tend to be lower than in other diabetics, she said, “except for when CF patients are acutely ill. During acute illness, CF patients become insulin resistant and require high insulin doses.”

Still, “once I start insulin, my goal is to deliver as large a dose as the patient can safely tolerate, to maximize anabolic impact,” she said.

The physicians offered these tips about tracking and treating CF patients:

• Screen CF patients via oral glucose tolerance testing on an annual basis, starting no later than age 10. Don’t trust hemoglobin A1c levels or fasting glucose levels, Dr. Norris said, because they are not sensitive enough. In fact, Dr. Moran said, “HbA1c is spuriously low in CF. “Even mild diabetes can be immediately detrimental to a CF patient’s lung health and mortality risk,” Dr. Norris said. “If you wait until the onset of classic diabetes symptoms or until the fasting glucose or hemoglobin A1c is elevated, you will have done a great disservice to the CF patient, as preventable potentially life-threatening lung damage may have already occurred.”

• Check into your center’s testing protocol. “Unfortunately, current screening rates are markedly insufficient at many centers,” Dr. Norris said. “I encourage endocrine teams to reach out to their affiliated CF treatment center to discuss and help implement screening.”

What’s next? The University of Iowa’s Dr. Larson said he is hopeful about advances in medical care. “Currently, patients must follow an extremely complex regimen of airway clearance, inhaled antibiotics, and oral medications, typically with recurrent hospitalization with increasing age and eventual death from lung disease or lung transplant,” she said. “However, in the past few years, we have had a dramatic change for a percentage of our patients with the development of small molecules that can actually fix the chloride-channel defect itself.”

The treatment seems to arrest and even improve lung disease in eligible patients, she said. “So the future seems very bright for CF.”

The Cystic Fibrosis Foundation has developed a 3-year Envision program to train adult and pediatric endocrinologists in the care of CFRD and endocrine issues.

Dr. Moran had no relevant disclosures. Dr. Norris has consulted for Vertex Pharmaceuticals, which makes cystic fibrosis therapeutics, in the past year. Dr. Larson Ode reports that her research is funded by the National Institutes of Health and the Cystic Fibrosis Foundation.