Screening for Cystic Fibrosis-Related Diabetes: Matching Pathophysiology and Addressing Current Challenges

Sensitivity and specificity of cystic fibrosis-related diabetes screening methods: which test should be the reference method?

“…However, many CF clinical teams have criticized this standard screening method for several reasons: it is perceived as invasive and inconvenient, which translates into a low adherence rate (between 25% and 50% of patients actually take the test annually) [1,3] and thresholds used to diagnose CFRD are those used in patients with type 2 diabetes validated based on the risk of retinopathy, which could be different than the ones capturing the increased risk of accelerated CF clinical decline. Indeed, rather than fasting and 2-h glucose values, a high 1-h OGTT value is more strongly associated with early clinical deterioration [4]. Moreover, simple alternative methods validated for type 2 diabetes (e.g.…”

“…Moreover, simple alternative methods validated for type 2 diabetes (e.g. fasting blood glucose or HbA 1c ) have a low sensitivity in CF and, thus, cannot be used [3,4].…”

“…CGM is more and more accessible, painless, does not require fasting and allows a detailed glucose profile in real life conditions, which cannot be observed during the OGTT and might, thus, be used as a screening test in populations at high risk for diabetes [4]. However, unlike the well-accepted criteria to evaluate glucose control in patients with established diabetes, there is no consensus on diagnosis criteria for diabetes using CGM [2].…”

Cystic Fibrosis-Related Diabetes Screening in Adults: A Gap Analysis and Evaluation of Accuracy of Glycated Hemoglobin Levels

“…Cystic fibrosis-related diabetes (CFRD) is the most common extrapulmonary comorbidity of CF and is estimated to affect approximately one-quarter of all individuals with CF in North America; its prevalence increases with age (4,5). CFRD has pathophysiologic features of both type 1 and type 2 diabetes mellitus, with insulin deficiency and resistance (6). CFRD is more common in individuals with severe cystic fibrosis transmembrane conductance regulator mutations and is associated with a higher degree of exocrine pancreatic dysfunction (2,7).…”

“…The main argument against the use of A1C levels in screening for CFRD is the potential lack of correlation between A1C levels and OGTT results (14). This argument has been debated and is based on the premise that A1C levels can be falsely low in people with CF due to a reduction in red blood cell life span resulting from inflammation, hypoxia and splenic sequestration in individuals with portal hypertension (6,14). The 2010 American Diabetes Association guidelines (11) state that A1C levels should not be used for CFRD screening, a recommendation based on results from 6 studies in 477 patients, in which a subset of individuals had OGTT diagnoses of CFRD even though their A1C levels were "normal" (9,(12)(13)(14)(15)(16).…”