Cystic Fibrosis Related Diabetes

Cystic fibrosis-related diabetes (CFRD) is a type of diabetes that affects individuals who have Cystic Fibrosis. CFRD is an entity unto itself, having several aspects that make it different from other forms of diabetes.

Cystic Fibrosis (CF) is one of the most common genetic defects among the Caucasian population, and it is a devastating, systemic disease. When CF was first being diagnosed, children with this disorder rarely lived to reach their teens]; now the average life expectancy  of an individual with CF is around 36 years. Still horrifically short, but better. The fact that people with CF are living longer means they acquire other disorders, including a type of diabetes. It has been shown that with increasing age in the CF population there is increasing incidence of diabetes mellitus.  Roughly 20% of adolescents with CF have diabetes and about 50% of adults with CF have CFRD (1).

CFRD is not as straight-forward to diagnose as type 1 and type 2 diabetes, so it’s important for laboratory professionals to be aware of this disease. People with CF who have diabetes may not always have hyperglycemia. Also hemoglobin A1c (Hgb A1c) values, which is a test recommended by the ADA for diagnosing diabetes, may not be elevated in these patients. The oral glucose tolerance test (OGTT) is recommended for diagnosis of CFRD, and yet even these results may be equivocal in CFRD patients (2). Nonetheless, the ADA/CFF guidelines suggest that all CF patients over 10 years of age should be screened yearly for CFRD using the OGTT. In addition, at least one study in the literature has found that when performing an OGTT on CFRD patients, a glucose level at the 1 hr time point correlates best with the patient’s lung function (3). Thus, if your lab performs OGTT on individuals with suspected CFRD, the physician requesting the test may want the glucose value on a one hour time point as well as the standard 2 hour OGTT.

Individuals with CF who get CFRD tend to have weight loss, protein catabolism, worsened lung function and significantly increased mortality compared to CF individuals without diabetes. The increased mortality is directly related to decreased pulmonary function, rather than to the atherosclerotic vascular disease seen in other types of diabetes. Insulin therapy is the recommended therapy for CFRD.

-Patti Jones

References:

  1. Moran A, Brunzell C, Cohen RC, Katz M, Marshall BC, Onady G, Robinson KA, Sabadosa KA, Stecenko A, Slovis B. Clinical care guidelines for cystic fibrosis-related diabetes.  Diabetes care 33(12):2697-2708. 2010.
  2. Rana M, Munns CF, Selvadurai H, Donaghue KC, Craig ME. Cystic fibrosis-related diabetes in children – gaps in the evidence? Nature Reviews: Endocrinology, 6:371-378. July 2010.
  3. Brodsky J, Dougherty S, Makani R, Rubenstein RC, Kelly A. Elevation of 1-hour plasma glucose during oral glucose tolerance testing is associated with worse pulmonary function in cystic fibrosis. Diabetes Care, 34:292-205. 2011.

Estimated Glomerular Filtration Rate (eGFR)

A colleague, upon checking her lab test results after an annual physical, was horrified to discover a flagged eGFR result of 57 ml/min/1.73 m2; even more so after her research indicated this result could mean she had stage 3 chronic kidney disease. She immediately called her primary care physician, who informed her that since her creatinine value hadn’t changed in more than 25 years (it had been 0.9 at 29 years of age and again at 59 years of age), he ignored the eGFR as useless. So what’s the purpose of an eGFR? If physicians are ignoring it, is it necessary and important to report it with every creatinine value?

Chronic kidney disease is an increasingly huge problem facing the American population. According to the the National Kidney Foundation (NKF) Kidney Disease Outcome Quality Initiative (KDOQI) Guidelines more than 4% of the American population suffers from stage 3 chronic kidney disease, with another 3% in stage 2 and 3% in stage 1. It’s well known that renal function decreases with age, and recent estimates suggest that roughly half the US population is over the age of 50. Although creatinine is the most commonly used marker of renal function, it is a remarkably insensitive marker of renal function loss, and new markers are just being discovered and validated. Glomerular Filtration Rate (GFR) is considered the best estimate of kidney function; however it’s not simple to measure.   eGFR is an estimated GFR, calculated from the creatinine the age, gender and race of the patient. It is a way of assisting in the early diagnosis of kidney disease. To help make this diagnosis, urine albumin is an important test to use along with eGFR. In addition, both should be abnormal for >3 months in order to make the diagnosis. Early diagnosis can help prevent progression to renal failure.

The equations for calculating eGFR have evolved and improved, from the early 6-parameter formula which came out of the Modification of Diet in Renal Disease (MDRD) study, to the most recent 4-parameter CKD-EPI formula. For adults, the CKD-EPI formula is increasingly being considered the most useful of these formulas. Formulas are also available for children, and online calculators are easy to find.

Patti Jones