- In this prospective study, 77 patients with cystic fibrosis, with or without cystic fibrosis–related diabetes (CFRD), had repeated measures of HbA1c and had continuous glucose monitor (CGM) data collected at two or three time points over three months
- CGM-derived measures of hyperglycemia and glycemic variability were significantly correlated with important CF outcomes, including body mass index and pulmonary function
- Mean HbA1c was strongly correlated with average glucose on CGM (r2, 0.71; P<0.001), and this relationship was similar to correlations previously seen in patients with type 1 or type 2 diabetes
- Certain CGM measurements were better able than HbA1c to distinguish between patients with and without CFRD
- These findings lay the groundwork for the use of CGM as a tool for diagnosis of CFRD and support the need for additional studies validating CGM as a screening tool for predicting CF-specific outcomes
Cystic fibrosis–related diabetes (CFRD) is the most common non-pulmonary complication of CF, and its onset is typically insidious. An annual two-hour oral glucose tolerance test (OGTT) is recommended for CF patients over the age of 10 years, as results have been correlated with important pulmonary and nutritional outcomes. Unsurprisingly, though, compliance with this burdensome test is low.
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Continuous glucose monitoring (CGM) has been validated in patients with CF and has been shown to detect early glycemic variability otherwise missed on OGTT.
Melissa S. Putman, MD, a dual-trained adult and pediatric endocrinologist in the Diabetes Clinical Research Center at Massachusetts General Hospital, and colleagues recently conducted a prospective observational study of the broader clinical utility of CGM in CF. The findings they report in The Journal of Clinical Endocrinology & Metabolism suggest CGM is worth investigating as a diagnostic and screening tool for CFRD.
The 77 participants in the study were 18 to 70 years old and had an established diagnosis of CF. At the baseline visit, those without preexisting CFRD underwent an OGTT and those with preexisting CFRD had hemoglobin A1c measured. The participants were re-evaluated three months later.
At each study visit, participants had a CGM device placed and wore it for 14 days. Those who had a CF exacerbation or required supraphysiologic systemic corticosteroids had an additional visit one month after the exacerbation, followed by a final study visit three months later. That subgroup, therefore, had up to three 14-day CGM sensor periods included.
Of the 77 study participants:
- 25 had preexisting CFRD at baseline
- 6 were diagnosed with CFRD after the baseline OGTT
- 22 had abnormal glucose tolerance on the baseline OGTT
- 24 had normal glucose tolerance on the baseline OGTT
CGM and Clinical Outcomes
CGM measures of hyperglycemia and glycemic variability were significantly correlated with important CF-specific outcomes, including forced expiratory volume in one second and body mass index.
These correlations were stronger than those of HbA1c, suggesting CGM results are clinically meaningful and perhaps more relevant than HbA1c for the care of CF patients.
Average Glucose and HbA1c
Mean HbA1c was strongly correlated with average glucose on CGM (r2, 0.71; P<0.001), and this relationship was similar to correlations previously seen in patients with type 1 or type 2 diabetes.
However, HbA1c doesn't capture the glycemic variability that can occur in mild CFRD. It therefore may not perform as well as CGM as a screening test for CFRD or in identifying the clinical effects of dysglycemia.
CGM and Dysglycemia
The researchers investigated whether CGM can distinguish different categories of dysglycemia in CF:
- Participants with CFRD had significantly higher average glucose levels, longer time in hyperglycemic ranges, and greater glycemic variability than participants with normal or abnormal glucose tolerance
- However, CGM measures were not significantly different between those with normal or abnormal glucose tolerance
Thus, CGM may not be the best approach for distinguishing milder degrees of glucose intolerance in patients with CF.
CGM Cutoff Values
The team also calculated cutoff values for key CGM measurements. Several were better able than HbA1c to distinguish between patients with and without CFRD:
- % time >140 mg/dL (cutoff of 17.5%)—AUC, 0.94; sensitivity; 87%; specificity, 95%
- % time >180 mg/dL (cutoff of 3.4%)—AUC, 0.94; sensitivity, 90%; specificity, 93%
Laying the Foundation
The cutoff values identified in this study may aid in the work of developing CGM criteria for the diagnosis of CFRD. Ultimately, long-term prospective studies may also show that CFRD is a useful screening tool for predicting CF-specific outcomes.
CGM would have notable benefits for CFRD screening, as sensors can be placed easily at a clinic visit. In addition, CGM comprehensively assesses glycemia occurring in a patient's typical environment, allowing for the identification of patterns to guide management, including insulin therapy if needed.
Learn more about the Diabetes Clinical Research Center
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