We systematically evaluated a variety of nonfasting screening tests used in the clinical setting for identifying dysglycemia in a population of overweight and obese adolescents and found reasonable test performance for the 1-h GCT and the random glucose. In contrast, test performance for HbA1c, fructosamine, and urinalysis was poor. Our findings have direct relevance for future recommendations for screening and diagnosis of dysglycemia among overweight and obese children and adolescents.
The poor test performance of HbA1c
is notable given recent changes in diagnostic guidelines for prediabetes and diabetes (11
), which advocate the use of HbA1c
for identifying children and adults with diabetes (HbA1c
≥6.5%) and prediabetes (HbA1c
5.7–6.4%). We found that HbA1c
had less than acceptable test performance for children with dysglycemia. Although the majority of patients in our study had prediabetes, two of three children with diabetes would have been missed using the ADA recommendation of 6.5%, with HbA1c
levels of 5.1 and 5.2%.
Our findings are consistent with recent studies of HbA1c
test performance in children. Using a nationally representative sample from National Health and Nutrition Examination Survey (NHANES) 1999–2006 (24
), we found that an HbA1c
threshold of 6.0% had low sensitivity for identifying overweight or obese children with prediabetes; sensitivity was 1.1% for identifying children with IFG (based on an FPG ≥100 mg/dL) and 0% for identifying children with IGT (based on a 2-h postload glucose ≥140 mg/dL), despite having high specificity for both outcomes (99%). In addition, the AUC for HbA1c
was relatively low at 0.61 for predicting IFG and 0.53 for predicting IGT. Another study of a large cohort of obese children has also reported lower sensitivity for HbA1c
). In contrast, adult studies have shown higher sensitivities for dysglycemia in the range of (20–25%) and higher levels of discrimination (26
To our knowledge, the HbA1c guidelines have yet to be reviewed or endorsed by pediatric organizations such as the American Academy of Pediatrics. If the guidelines were to be endorsed by these organizations, this would most likely result in increased uptake of the test by providers, which could potentially lead to a significant proportion of missed cases of prediabetes and diabetes in the pediatric population.
Either the nonfasting 1-h GCT or the random glucose represent promising screening tests for use in the pediatric primary care setting, as these are tests that clinicians can easily order the same day of the visit. This would exclude a substantial proportion of children who would have to return for testing, and subsequently, only the subset of children with glucose levels surpassing specified thresholds of either nonfasting test would then have to undergo more formal testing with an FPG or a 2-h OGTT to confirm the diagnosis. Possible test thresholds to consider for the pediatric population for the 1-h GCT include cutoffs of 110 or 120 mg/dL, which would result in sensitivities of 63 and 44% and false-positive rates of 37 and 19%, respectively. Comparable thresholds using random glucose levels could include cutoffs of 100 or 110 mg/dL, which would result in sensitivities of 55 and 30% and false-positive rates of 33 and 12%, respectively.
Studies in adults have also found random glucose and 1-h GCT to be promising tests to use for screening for prediabetes and diabetes in adults. The Screening for Impaired Glucose Tolerance Study evaluated test performance of random glucose and 1-h GCT and found that both tests showed reasonable discrimination for identifying dysglycemia, with estimates of AUC of 0.72 for random PG and 0.82 for 1-h GCT, although their definition of dysglycemia was slightly different (IGT, IFG ≥110 mg/dL, or diabetes) (21
). Similarly, studies in pregnant women to screen for gestational diabetes mellitus have reported reasonable test performance, hence, the use of this test as an initial screen to determine which women need full 3-h OGTT tests to look for gestational diabetes mellitus (28
We found a very low sensitivity of urine dipstick for detecting dysglycemia, despite the fact that it was measured 1 h after ingestion of 50 g glucola. Sensitivity was even lower than for adult studies, which have reported sensitivities ranging from 18 to 64% (29
). Because the renal glucose threshold is ~180 mg/dL, the sensitivity of this test for detecting diabetes would be expected to be better for diabetes than for prediabetes. However, in our study urine dipstick detected only two cases of prediabetes and failed to identify any of the three individuals with diabetes. Urinalysis is reportedly still being used for diabetes screening in the pediatric primary care setting (9
); therefore, providers should perhaps be dissuaded from using this test in clinical practice.
We found no differences in test performance based on postprandial time or time of day, which contrasts with studies in adults that have reported improvements in test performance for random blood glucose with a longer postprandial period (>2 h) prior to the test (21
). We also assessed test performance for predicting IFG and IGT as separate outcomes. Regardless of the outcome measure, test performance remained poor for HbA1c
and fructosamine. However, when using IGT, we found significant improvements in test performance for the 1-h GCT. Both IGT and IFG predict risk for developing diabetes, but because of convenience previous screening recommendations have prioritized the use of FPG. Studies have shown that a stimulated glucose is a better predictor than FPG of progression from IGT to diabetes (30
). Furthermore, FPG will often miss cases of IGT and diabetes (31
), further lending support for the use of random glucose or the 1-h GCT test in clinical practice.
Strengths of our study include the systematic evaluation of the performance of nonfasting tests in a pediatric population, the use of a gold standard 2-h OGTT for classifying children with dysglycemia, a reasonable study sample size, and the substantial proportion of minority children who were included in the study. We also acknowledge limitations of our study. According to the ADA, two positive tests are required to make a diagnosis of prediabetes or diabetes (20
), and studies have reported a lack of reproducibility of the diagnosis of prediabetes using the 2-h OGTT in children (15
). Therefore, children in our cohort with 2-h postload glucose levels >200 mg/dL may not have been classified as having diabetes if a second test had been performed, which could result in improvements in test performance. Although it would have been ideal to perform two 2-h OGTTs, we elected to perform one given the additional burden on participants. Furthermore, clinical research studies of adults, including the Diabetes Prevention Project (33
), or the Screening for Impaired Glucose Tolerance Study (27
), have classified participants’ glucose status using just one test.
With the new guidelines, HbA1c
would now be considered the gold standard for diabetes, but studies have demonstrated significant differences in diabetes and prediabetes prevalence depending on the definition of diabetes used (FPG vs. 2-h postload glucose vs. HbA1c
). Although it may be logical to use a chronic measure of hyperglycemia such as HbA1c
rather than an acute measure such as glucose, longitudinal studies in children are needed to understand which tests are most predictive of later development of diabetes. We elected to compare the nonfasting tests against the definitions of diabetes that have been historically used in the pediatric literature for purposes of comparability with other pediatric studies.
Our population was a convenience sample of overweight and obese children from southeast Michigan rather than a systematic sample from a well-defined target population. Although we had adequate representation of black and white children, there were no Hispanic children in the sample. Furthermore, given the sample size, we did not have the power to assess test performance according to each Tanner stage. Therefore, generalizations must be made accordingly. We had to power our study to the outcome of dysglycemia given the low prevalence of childhood diabetes. However, we note that this is reflective of the epidemiology of type 2 diabetes in the U.S., which still has a very low prevalence in the adolescent population (0.02%), particularly compared with adults (23
). The ADA screening guidelines were established in 2000 (3
) based on reports of dramatic increases in type 2 diabetes among adolescents, but subsequent population-based epidemiologic studies have not revealed a large burden of childhood type 2 diabetes. Identification of children with prediabetes, which has a much higher burden in the pediatric population, could be considered a useful by-product of diabetes screening, which would provide the opportunity for directing targeted interventions at children at highest risk for developing diabetes.
Because of the high burden of childhood obesity, the CDC estimates that approximately 2.5 million children in the U.S. potentially qualify for diabetes screening based on the ADA screening guidelines (35
), highlighting the need for effective and practical strategies for screening. Random glucose and particularly 1-h GCT, given its possible greater predictive capacity for incident diabetes (36
), represent promising screening tests for use in the pediatric primary care setting. Future studies are needed to assess the feasibility, acceptability, and cost-effectiveness of these alternative screening strategies compared with current recommendations and to assess the impact of systematic prediabetes and diabetes screening on pediatric health outcomes.