Testing glycated hemoglobin (HbA1c) appears to predict children’s diabetes risk as well as fasting plasma glucose and 2-hour postload plasma glucose, according to a study on more than 2000 American Indian children.
Testing glycated hemoglobin (HbA1c) appears to predict children’s diabetes risk as well as fasting plasma glucose and 2-hour postload plasma glucose, according to a study on more than 2000 American Indian children.1
Researchers studied children without diabetes aged between 10 and 19 years and monitored them through age 39 years. Using a fasting plasma glucose of equal to or greater than 126 mg/dL, a 2-hour postload plasma glucose of 200 mg/dL, and an HbA1c of 6.5% or more to define incident diabetes, they found the sensitivity and specificity for identifying diabetes risk in children and adolescents were similar among the tests.1
Girls were 7 times and boys 4 times as likely to get incident diabetes during the follow-up if they had an HbA1c of 5.7% or higher. The 10-year cumulative incidence of diabetes in those with an HbA1c of 5.7% or higher was 78% compared with 23% among children whose HbA1c was lower than 5.7%.1 That’s quite remarkable, according to Hebatullah M. Ismail, MBBCh, MSc, PhD, clinical director of diabetes, Children’s Hospital of Pittsburgh of UPMC, Pennsylvania.
“This study is of particular relevance to pediatricians, as it highlights the increasing rate of type 2 diabetes development in high-risk populations/ethnicities, which in this case is the American Indian overweight/obese population with a family history of diabetes,” Ismail says. “HbA1c measurement is particularly convenient in children given it is a single sample that does not require fasting.”
The study helps to fill an important gap in knowledge in that it looks longitudinally at trying to predict which children are going to develop type 2 diabetes, according to David W. Cooke, MD, associate professor of pediatrics and interim director of pediatric endocrinology at Johns Hopkins University School of Medicine, Baltimore, Maryland.
“We’ve extrapolated from the adult literature with all these other measures of glucose control, whether it be fasting blood sugar or the 2-hour plasma glucose or the glycated hemoglobin (HbA1c),” Cooke says. “I don’t know that this study is a definitive one that gives us the absolute answer, but it’s the first one that says yes, there are markers of glucose control that identify an increased risk of diabetes in adults, which seem to correlate fairly similarly in children. The A1C that’s higher than normal but not diagnostic of diabetes in a child does put that child at a high risk of having a diabetes diagnosis in . . . the next 5 to 10 years.”
For pediatricians at the front lines, it’s important to understand that the prevalence of type 2 diabetes in children, teenagers, and young adults has increased in the last 15 years, according to Eric I. Felner, MD, MSCR, professor, Division of Endocrinology and Diabetes, Department of Pediatrics, at Emory University School of Medicine, Atlanta, Georgia.
The American Diabetes Association reported in its Diabetes Forecast magazine data that suggest type 2 diabetes in 10- to 19-year-olds increased 21% between 2001 and 2009-an increase driven by Hispanic and non-Hispanic white children and not Native Americans, Asian/Pacific Islanders, or African Americans.2 Also, there has been a rising prevalence of childhood obesity among American Indian children during the last 4 decades, according to a recent study.3
“In addition, these children, teenagers, and young adults are at increased risk for fatty liver disease and cardiovascular disease,” Felner says. “The use of the HbA1c test in children at risk for diabetes appears to be an acceptable marker (as good as fasting and 2-hour post-glucola blood glucose levels) in determining which children, adolescents, and young adults are at risk to develop diabetes in the future.”
Physicians’ interpretation of the significantly high incidence rate of diabetes observed in children with HbA1c of 5.7% or higher enrolled in the study should be taken with caution, according to Mauri Carakushansky, MD, division chief of endocrinology, Department of Pediatrics, at Nemours Children’s Hospital, Orlando, Florida.
“It should be noted that all subjects evaluated in the study were of American Indian origin, and young American Indians are known for having disproportionately high rates of diabetes and obesity,” Carakushansky says.
American Diabetes Association statistics that show 7.6% of non-Hispanic whites compared with 15.9% of American Indians/Alaskan natives are diagnosed with diabetes.4
“Therefore, additional studies are needed to determine more precisely the incidence rate of diabetes in children of different ethnicities presenting with an abnormal HbA1c,” Carakushansky says.
Cooke says he agrees that generalizing the findings to other populations isn’t a given, but he notes that, in general, studies of American Indians have translated into the general population.
Another potential limitation is the study’s size. Even though the study was done on thousands of children, the numbers that went on to diabetes were small, according to Cooke.
“The number of actual children that had that higher risk A1C result that then went on to diabetes really only amounted to 2 boys and 16 girls [and only 62 children had that elevated A1C],” Cooke says.
Metabolic syndrome also is a growing health concern in the United States and around the world, according to Carakushansky.
“With the global epidemic of childhood obesity, there is growing concern that the metabolic complications associated with obesity, such as insulin resistance/type 2 diabetes and hyperlipidemia, are on the rise in the pediatric population,” Carakushansky says. “People with metabolic syndrome can have diabetes, and vice versa. Both are risk factors for cardiovascular disease and both are closely associated with obesity.”
The most common medical comorbidities associated with obesity include metabolic risk factors for type 2 diabetes-high blood pressure, high cholesterol, impaired glucose tolerance; and metabolic syndrome-according to a review published in 2014.5
Metabolic syndrome, or insulin-resistance syndrome, is closely tied to prediabetes and type 2 diabetes development, according to Ismail. The body’s attempt to compensate for increased insulin demands and decreased insulin sensitivity, secondary to weight gain and physical inactivity, often is a losing battle. The beta cells cannot keep up with increased insulin demands, which increases risks for progression to prediabetes and diabetes, she says.
“Losing weight and exercising can reverse insulin resistance and help prevent or delay development of obesity-related type 2 diabetes in children and adolescents at risk for diabetes. Therefore, it is crucial that pediatricians emphasize the importance of and counsel patients on maintaining a healthy weight and exercising daily,” Ismail says.
Cooke says a takeaway from this study is that the same aspects about metabolic syndrome in adults pertain to children.
“The fact that adults with metabolic syndrome have an increased risk of diabetes is also true in kids. This isn’t earth-shaking news. We’ve known that kids with metabolic syndrome are at risk for type 2 diabetes, so this just reinforces that this similarity also pertains to the general magnitude risk of dysglycemia,” Cooke says.
The study, according to Cooke, should reassure primary care providers that risk identification with A1C seems to be as useful as gold-standard tests and is a lot easier to do.
“The accuracy-the positive predictive value and negative predictive value of the area under the curve-seems to be better with the A1C than with the actual glucose measures,” Cooke says. “The caveat there is that very small numbers of children were diagnosed, so I’m not sure that I would say with any degree of confidence that A1C is better as a predictor than those other tests, but it appears to be as good, at least in terms of how accurate it is.”
Pediatricians and others are still left with the uncertainty of how treatment might differ for a child identified as having prediabetes. Would it be different than how pediatricians would treat an overweight child?
“You’re still going to suggest that they lose weight and increase their activity level, but I don’t think we have enough data to say that you should start metformin on these individuals. So, I don’t know . . . if it changes recommendations on what you do with [patients with prediabetes],” Cooke says. “I think you can be honest with individuals that their risk of going on to develop diabetes is higher if they have A1C in that higher category than if their A1C is in a lower category. I haven’t seen any data to indicate that that information and knowledge alters the success of that individual losing weight and increasing [his/her] activity level.”
Lifestyle changes are considered the mainstay of prediabetes and metabolic syndrome management, Carakushansky says.
“The overweight or obese child with mild HbA1c elevation (between 5.7% and 5.9%) requires counseling on healthy diet and exercise along with additional labs (such as fasting glucose, insulin, and C-peptide) to determine if there is a state of insulin resistance. [Higher] HbA1c levels [at or greater than] 6.0% would require a more immediate referral to a pediatric endocrinologist,” Carakushansky says.
Pediatricians should reserve HbA1c screening for type 2 diabetes or prediabetes in asymptomatic children aged 10 years or older with a body mass index equal to or greater than the 85th percentile and have at least 2 additional type 2 diabetes risk factors. Those risk factors include type 2 diabetes in a first- or second-degree relative, being an at-risk minority race or ethnicity, having signs of insulin resistance, or maternal gestational diabetes, Carakushansky says.
One important note, according to Ismail: HbA1c is not reliable in patients with anemia or hemoglobinopathies, and in certain ethnic groups such as African, Mediterranean, and Southeast Asian populations.6
Drs Ismail, Cooke, Feiner, and Carakushansky have nothing to disclose in regard to affiliations with or financial interests in any organizations that may have an interest in any part of this article.
1. Vijayakumar P, Nelson RG, Hanson RL, Knowler WC, Sinha M. HbA1c and the prediction of type 2 diabetes in children and adults. Diabetes Care. 2017;40(1):16-21.
2. Gebel E. More kids than ever have type 2 diabetes. Diabetes Forecast. Available at: http://www.diabetesforecast.org/2012/nov/more-kids-than-ever-have-type-2-diabetes.html. Published November 2012.
3. Vijayakumar P, Wheelock KM, Kobes S, et al. Secular changes in physical growth and obesity among southwestern American Indian children over four decades. Pediatr Obes. December 6, 2016. Epub ahead of print.
4. American Diabetes Association. Statistics about diabetes. Overall numbers, diabetes and prediabetes. Available at: http://www.diabetes.org/diabetes-basics/statistics/. Last edited December 12, 2016. Accessed January 30, 2017.
5. Pulgaron ER, Delamater AM. Obesity and type 2 diabetes in children: epidemiology and treatment. Curr Diab Rep. 2014;14(8):508.
6. National Institute of Diabetes and Digestive and Kidney Diseases. For people of African, Mediterranean, or Southeast Asian heritage: important information about diabetes blood tests. Available at: https://www.niddk.nih.gov/health-information/health-topics/diagnostic-tests/people-african-mediterranean-southeast-asian-heritage-important-information-diabetes-blood-tests/Pages/index.aspx. Published October 2011. Accessed January 30, 2017.
Ms Hilton is a medical writer who has covered health and medicine for 25 years. She resides in Boca Raton, Florida. She has nothing to disclose in regard to affiliations with or financial interests in any organizations that may have an interest in any part of this article.