Abnormal Blood Sugar Levels in CF Tied to Higher Risk of Exacerbations

Patients more likely to have sudden worsening of lung symptoms

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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People with cystic fibrosis (CF) who have abnormal glucose tolerance — higher-than-normal blood sugar levels after eating — are more likely to experience clinical exacerbations of worsening lung function, according to a new study.

This was found to be true even for patients who don’t meet the criteria for a diagnosis of cystic fibrosis-related diabetes (CFRD) — a common complication for people with CF.

Researchers found that determining abnormal blood sugar levels in CF patients through broader testing may help identify those at risk for exacerbations.

“Our study demonstrated that [such testing] … may predict increased incidence of [pulmonary exacerbations] in patients with CF,” the team wrote.

The study, “The utility of glucose area under the curve from the oral glucose tolerance test as a screening tool for cystic fibrosis-related diabetes,” was published in the journal Pediatric Pulmonology.

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Testing for blood sugar levels in CF

Because CF-related diabetes, or CFRD, is common among people with the genetic disease, it is routinely tested for in patients. A standard assessment for CFRD is the oral glucose tolerance test, or OGTT.

A typical OGTT begins with a blood sample being taken from an individual who has not had anything to eat or drink for at least eight hours. The patient then consumes a sugary drink, and additional blood samples are taken over the next two hours. If blood sugar levels increase beyond a certain cutoff (usually 200 mg/dL after two hours), CFRD is diagnosed.

“However, some cystic fibrosis (CF) patients demonstrate abnormal glucose profiles not reaching levels required for CFRD diagnosis and are, therefore, left untreated,” the researchers wrote.

Instead of using a single cutoff at just one point in time, here researchers evaluated the utility of a statistical measure called “area under the curve of glucose” or G-AUC. This measure is calculated from data at all time points assessed in the OGTT, so it “mathematically represents a more continuous indicator of glucose metabolism during the OGTT,” the researchers wrote.

The analysis included data from OGTTs performed in 81 people with CF, with a mean of three tests per patient. Among the patients, the mean age was 19.7 years, and 44% were female.

Based on the standard cutoffs, at the most recent OGTT, 16% of patients had CFRD and 54% showed no abnormalities in glucose metabolism. The remaining patients were classified as impaired glucose tolerance (IGT) and/or had values in the indeterminate range (INDET) — basically meaning they showed increases in blood sugar levels, but not at 200 mg/dl or higher at two hours of OGTT as in the CFRD group.

“Data from the current study suggests that glucose AUC may be more sensitive to glycemic abnormalities than standard OGTT alone,” the scientists wrote.

Statistical analyses showed that a G-AUC cutoff of 295 mg hours/dL or higher could correctly identify 95% of people with abnormalities in glucose metabolism, and 93% of those with normal results.

Further analyses showed that patients with a G-AUC value at or above this cutoff were significantly more likely to experience pulmonary exacerbations — sudden worsening of lung symptoms, often related to an infection — over two years of follow-up.

In fact, the 295 mg hours/dL cutoff correctly identified 69% of patients who experienced an exacerbation and 63% of those who did not.

Notably, not all of the patients with G-AUC values above this cutoff met the CFRD definition, and G-AUC remained significantly predictive of exacerbation risk even after accounting for other clinical variables, including standard measures of lung function.

“Patients who do not fulfill the criteria for CFRD may have abnormal glucose metabolism identifiable by abnormally high G-AUC values, which may be associated with more” pulmonary exacerbations, the researchers concluded.

The team said that further study is warranted to assess whether insulin treatments may help reduce exacerbations for people who show blood sugar abnormalities.

“The potential advantage of insulin therapy based on G-AUC and the subsequent reduction in [pulmonary exacerbations] merits a prospective randomized clinical trial,” they wrote.


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