HbA1c Predicts Diabetes Risk in Children and Adolescents

Liam Davenport

January 04, 2017

The risk for type 2 diabetes can be predicted and presence of prediabetes can be identified using the HbA1c test with the same accuracy as that for other, less convenient tests, confirm US researchers.

Examining data from a long-term study in an American Indian population, the team found that there was no significant difference between HbA1c, fasting plasma glucose (FPG), and 2-hour postload plasma glucose (2hPG) concentration tests in identifying children who later developed diabetes.

The research was published in the January issue of Diabetes Care.

Coauthor Madhumita Sinha, MD, from the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, in Phoenix, Arizona, said that the benefit of the HbA1c test is its convenience.

She told Medscape Medical News that, when assessing an overweight or obese child aged 10 years, "most pediatricians would…do a fasting blood sugar." However, she noted that "in my opinion, no kid is fasting at 8 o'clock in the morning."

Crucially, Dr Sinha believes that, despite the study being conducted in a population known to have a higher risk of developing diabetes, the results are generalizable to other groups.

She said that, alongside having followed the population for over 40 years, the "advantage" that the researchers had was being able to conduct all the tests in the same laboratory.

"This is a unique data set," Dr Sinha noted, "and since all the lab tests were done at our own facilities in Phoenix, it's very standardized."

The American Diabetes Association (ADA) recommends that asymptomatic children and adolescents be screened for type 2 diabetes if they are aged ≥ 10 years, have a body mass index ≥ 85th percentile for age and sex, and have at least two additional risk factors.

The risk factors include type 2 diabetes in a first- or second-degree relative, minority race or ethnicity, and maternal history of diabetes or gestational diabetes.

While measuring HbA1c in children is convenient, as it does not require fasting, and a single test can diagnose and monitor glycemic control, there have been few studies examining the association between HbA1c in childhood and the risk of developing diabetes.

Therefore, the researchers measured HbA1c, FPG, and 2hPG concentrations in a longitudinal study of residents in an American Indian community followed from 1965 to 2007.

The current analysis included 2095 children without diabetes aged 10 to 19 years at enrollment, who were monitored to age 39 years, and 2005 adults aged 20 to 39 years, who were monitored to age 59 years.

Of the children and adolescents, 18.8% were overweight and 53.1% were obese, while the equivalent rates in adults were 19.1% and 73.8%, respectively.

The prevalence of prediabetes as assessed by HbA1c ≥ 5.7% was 3.0% in the children and adolescents and 8.4% in the adults, while that assessed by FPG ≥ 100 mg/dL was 9.2% in children and adolescents and 21.1% in adults. Impaired glucose intolerance, as determined by 2hPG ≥ 140 mg/dl, was 8.1% in children and adolescents and 17.3% in adults.

The median time to diabetes diagnosis or the last examination before the onset of diabetes was 5.2 years in the children and adolescents and 4.6 years in the adults. Incidence patterns of diabetes were similar in children and adults, although rates were higher in adults.

The researchers found that male children and adolescents in the highest HbA1c category (5.7% to 6.4%) at baseline had a fourfold higher incidence of diabetes during follow-up vs those in the lowest HbA1c category (≤ 5.3%). Female children and adolescents in the highest HbA1c category had a sevenfold increased incidence of diabetes over those in the lowest category.

In boys, girls, and men, the areas under the receiver operating characteristic curve (AUC) for HbA1c were not significantly different from that for FPG or 2hPG. In women, HbA1c had a lower AUC than 2hPG, at 0.63 vs 0.70 (P = .0012).

"The lack of a significant difference in AUC between HbA1c and the glucose measures suggests that all three tests have the potential to offer the same level of sensitivity and specificity, depending on the threshold chosen," the authors write.

However, the reason for the "poorer performance of HbA1c in adult women is uncertain," according to the authors. They point out that iron deficiency has been shown to be common in women and linked to higher HbA1c. However, the theory could not be explored due to the lack of iron examinations in the current study.

Among children and adolescents who met the ADA recommended screening criteria for diabetes, the estimated 10-year cumulative incidence of diabetes in those with HbA1c ≥ 5.7% was 78% vs 23% in those with an HbA1c < 5.7%, giving a positive predictive value (PPV) of 78% and a negative predictive value (NPV) of 77%.

For FPG ≥ 100 mg/dL, the PPV was 36% and the NPV was 78%, while the PPV and NPV for 2hPG ≥ 140 mg/dL was 52% and 80%, respectively.

The researchers conclude that HbA1c "can be used to assess risk for diabetes in children or to identify children with prediabetes with the same confidence as FPG or 2hPG."

Dr Sinha added that the next step for the team is to look at the relationship between baseline HbA1c levels and the development of diabetes complications.

This research was supported by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases. The authors reported no relevant financial relationships.

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Diabetes Care. 2017;40:16-21. Article

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