A1c glucose test predicts the risk of CF-related diabetes, weight gain

Children with baseline A1c of 5.5%, higher have elevated risk for CFRD

Steve Bryson, PhD avatar

by Steve Bryson, PhD |

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A1c, a test that measures the average levels of sugar in the bloodstream, was able to predict the future risk of adult and pediatric cystic fibrosis-related diabetes (CFRD), a study shows.

Elevated CFRD risk was associated with an A1c value of 5.5% or above in children and 6% and above in adults. An inability to lose weight and body fat was also linked with higher A1c in adults.

Apart from predicting CFRD, the researchers suggested A1c could identify patients who needed more nutritional support. Their study, “A glycosylated hemoglobin A1c above 6% (42 mmol/mol) is associated with a high risk of developing Cystic Fibrosis-Related Diabetes and a lower probability of weight gain in both adults and children with Cystic Fibrosis,” was published in Diabetes & Metabolism.

The most frequent CF-related complication outside the lungs is CFRD, occurring in up to 18% of adolescents and 50% of adults. CFRD is associated with poorer outcomes, including accelerated lung function decline and/or weight loss.

The A1c test — also called the hemoglobin A1c, or HbA1c test — is a simple blood test that measures the average sugar levels in the bloodstream over the previous 2-3 months. A 6.5% or higher value is routinely used to diagnose type 2 diabetes in non-CF patient populations.

Studies that evaluated A1c as a screening tool for CFRD generated diagnostic thresholds between 5.5 to 6.1%, but the its ability to accurately detect or rule out CFRD varied widely.

Researchers in Canada explored whether A1c thresholds could be established to predict the risk of progression to CFRD in CF patients. They also wanted to find A1c thresholds associated with changes in weight and lung function.

Of the 289 eligible CF adults identified at the study’s start (baseline), 189 without diabetes were followed for a mean of 7.7 years, with regular assessments, including the oral glucose tolerance test (OGTT), to detect CFRD.

Among pediatric patients, 223 were eligible for baseline analysis at age 10, 124 of whom were included in a follow-up analysis at age 17. Assessments were completed for 93 patients at both ages 10 and 17.

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Consistent with previous reports, A1c’s diagnostic value was limited. Among adult patients, the ability of an optimal A1C threshold of 5.9% to correctly detect CFRD was 67% (sensitivity) and to rule it out was 71% (specificity). Similar results were obtained for threshold values generated based on the proportion of those who developed CFRD five and 10 years after baseline.

In 10-year-olds, an A1C of 5.7 % had an optimal sensitivity of 60% and a specificity of 46.8%. Based on the proportion of children who developed CFRD up to seven years later, an A1c of 5.7% showed similar optimal sensitivity and specificity values.

A higher risk of developing CFRD was found in patients with an A1c of 6% or more at baseline. After about 10 years, significantly more of those with an A1c above this level developed CFRD than below 5.5% (50% vs. 15%).

Children with a baseline A1c of 5.5% or higher were at an elevated risk of developing CFRD. By the age of 17, half of children with a baseline A1c value of 6% or more developed CFRD, whereas less than 20% of those under 5.5% developed it by 17.

“We highlight the important differences in potential thresholds between adults [6%] and children/adolescents [5.5%] in the same study,” the researchers wrote, suggesting there are differences in disease-related processes between the age groups.

An A1c below 6% was significantly associated with an increase in BMI, whereas adults with a value of 6% or higher failed to put on weight or BMI over follow-up.

“An A1c threshold of 6% as a threshold above which adults stop gaining weight in CF may illustrate a threshold at which a relative insulin deficiency may lead to a shift from anabolic to catabolic metabolism,” the researchers wrote. Catabolic metabolism is the process of breaking down molecules for energy, while anabolic metabolism uses energy to build new molecules.

Lastly, A1c was not related to the rate of lung function decline.

“Future prospective studies should examine whether a threshold of 5.5% or 6% is optimal for screening in children,” the researchers said. “Use of A1c as a first-line screening test could simplify screening and identify patients that might require more nutritional support.”