A1c of 5.8 Percent in Children a Better Diagnostic Target to Diagnose Diabetes

Hemoglobin A1c has emerged as a recommended diagnostic tool for identifying diabetes and subjects at risk for the disease. This recommendation is based on data in adults showing the relationship between A1c with future development of diabetes and microvascular complications. However, studies in the pediatric population are lacking.

Researchers studied a multiethnic cohort of 1,156 obese children and adolescents without a diagnosis of diabetes (male, 40%/female, 60%). All subjects underwent an oral glucose tolerance test (OGTT) and A1c measurement. These tests were repeated after a follow-up time of 2 years in 218 subjects.

At baseline, subjects were stratfied according to A1c categories: 77% with normal glucose tolerance (A1c ,5.7%), 21% at risk for diabetes (A1c 5.7–6.4%), and 1% with diabetes (A1c .6.5%). In the at-risk-for-diabetes category, 47% were classfied with pre-diabetes or diabetes, and in the diabetes category, 62% were classified with Type 2 diabetes by the OGTT. The area under the curve receiver operating characteristic for A1c was 0.81 (95% CI 0.70-0.92).

The threshold for identifying Type 2 diabetes was 5.8%, with 78% specificity and 68% sensitivity. In the subgroup with repeated measures, a multivariate analysis showed that the strongest predictors of 2-h glucose at follow-up were baseline A1c and 2-h glucose, independently of age, ethnicity, sex, fasting glucose, and follow-up time.

In a large clinic based multiethnic cohort of obese children and adolescents, regardless of age and sex, an A1c of 6.5% had relatively low sensitivity and specificity for classifying Type 2 diabetes. There was poor agreement between A1c and OGTT criteria in classifying subjects with glucose values suggestive of Type 2 diabetes. The optimal threshold of A1c was 5.8% for identifying Type 2 diabetes, with a specificity of 87.64% and sensitivity of 67.7%, and 5.5% for identifying IGT. The diagnostic utility of A1c was examined according to ADA criteria with OGTT as the reference. Researchers observed that the use of an A1c of 6.5% would largely underestimate the prevalence of pre-diabetes and Type 2 diabetes. They said that these results suggest that, although A1c could be used as a clinical tool to identify Type 2 diabetes, along with fasting and 2-h glucose, the use of A1c by itself to pinpoint prediabetes and Type 2 diabetes is not recommended.

Researchers also said that their data are in agreement with those who reported using the National Health and Nutrition Examination Survey of 14,611 individuals aged <20 years, clearly showing that an A1c of 6.5% has a lower capacity to detect prediabetes and undiagnosed Type 2 diabetes than the OGTT. 

Studies in adults have clearly shown the utility of A1c in predicting Type 2 diabetes (12–14) and cardiovascular disease even in nondiabetic adults. Nevertheless, concerns in the use of A1c for diagnosing Type 2 diabetes have been recently raised in view of the poor relationship with fasting glucose, the overall lower diagnostic performance in some groups such as pregnant women and the elderly, and the risk of over diagnosing patients with anemia and those predisposed to rapid glycosylation. In addition, as previously stated, it should be noted that, despite the numerous advantages, the use of A1c as a diagnostic tool would largely affect national surveillance of prediabetes and Type 2 diabetes.

Different cutoff points have been reported when the ROC curve was used to identify the cutoff point for diagnosing Type 2 diabetes or prediabetes. A review on A1c as a screening tool for diabetes showed that three cutoff points (5.9, 6.1, and 6.3%) of A1c were advised as cutoff points for detecting diabetes in at least two different studies, and most studies identified a cutoff point of >6.1% as optimum for the detection of Type 2 diabetes. In addition, researchers concluded that at equivalent cutoff points, sensitivity was generally lower in detecting IGT for both A1c and fasting plasma glucose in both community- and hospital-based studies. Thus, the cutoff point identified in this study of 5.8% is somewhat lower than oftentimes reported, which might indicate that the population is of especially high risk. Although only a small percentage of subjects had a repeated A1c and OGTT after a follow-up of 2 years, we believe that the data are important, indicating that the best predictors of future diabetes or prediabetes are A1c and the 2-h glucose from the OGTT. Thus, both the cross-sectional and longitudinal data would argue in favor of the utility of performing both tests in obese youth for predicting future development of diabetes.

A few limitations are worth noting. There is no lean control group, a clinic based cohort was studied, and the follow-up group is small. Strengths include the large group of obese youngsters without known diabetes and the existence of data derived on the same day for both the OGTT and A1c. 

The American Diabetes Association suggested that an A1c of 6.5% underestimates the prevalence of prediabetes and diabetes in obese children and adolescents. Given the low sensitivity and specificity, the use of A1c by itself represents a poor diagnostic tool for prediabetes and Type 2 diabetes in obese children and adolescents.

Further investigation on the role of A1c in the diagnosis of prediabetes and diabetes in children and adolescents is needed. Prospective studies are especially important to examine the utility of A1c in pediatric populations in the prediction of diabetes-related comorbidities later in life.

Published online before print April 22, 2011, doi: 10.2337/dc10-1984 Diabetes Care April 22, 2011