As the number of young persons developing type 2 increases, so has the awareness of clinicians on the importance of identifying children at risk to help prevent the deleterious effects of diabetes once established. Studies in adults with type 2 diabetes have identified specific risk factors for disease development, and a great deal of focus has been on identifying prediabetes in an attempt to improve prevention.
For both children and adults, obesity remains one of the key risk factors for developing type 2 diabetes. Children who are overweight or obese, therefore, are seen as potentially at risk of developing diabetes.
To date, little data are available on how to assess children at risk of developing type 2 diabetes. Assessment, therefore, has relied on data derived from adult studies and extrapolated to children. As such, the evidence base on which assessing risk of diabetes in children is limited at best and should be looked at with some caution.
This was an underlying message in a talk presented at the 2017 American Academy of Pediatrics (AAP) National Conference by Philip Zeitler, MD, PhD, professor of Pediatrics and Clinical Science and section head, Endocrinology, University of Colorado School of Medicine Anschutz Medical Campus, Aurora, Colorado, titled “Not yet diabetes: Assessing and managing children at risk.”1 In his presentation, Zeitler emphasized that although type 2 diabetes is on the rise in adolescents, it is still rare and not the main complication that clinicians should be focusing on when they see a child who is obese.
“Glucose is not the most common problem in obese kids; in fact, it is pretty darn rare,” Zeitler said, emphasizing that other disorders associated with obesity such as elevated triglycerides, fatty liver, and high blood pressure are much more common. “People should be thinking about these other more common conditions and not get too lost looking for prediabetes,” he said.
In his talk, Zeitler spoke about ways to assess and manage prediabetes in children while underscoring this main message that diabetes is not the most important potential disease risk for obese children and of the need to address obesity in all children regardless of their potential diabetes risk. To help clinicians get a better footing as to the real problem of prediabetes in children, he opened his talk by defining what prediabetes is and the limits of its utility in children.
Prediabetes is a concept, not a thing
Zeitler began with a brief overview of the pathophysiology of prediabetes, citing a number of studies in children that looked at impairments in glucose homeostasis in overweight children.
Overall, he underscored the difficulty of establishing prediabetes in children based on measures such as fasting plasma glucose (FPG) and the oral glucose tolerance test (OGTT) to assess risk factors predictive of impaired fasting glucose (IFG) or impaired glucose tolerance (IGT)—the intermediate phase between normal glucose tolerance and type 2 diabetes identified as prediabetes in adults. For example, some data suggest that impairments in insulin resistance and declining β-cell function may indicate children at heightened risk of developing type 2 diabetes, but these data are based on glucose testing measured against the specific cutoff threshold of less than 140 mg/dL established as defining prediabetes in adults.
This cutoff point, he cautioned, is defined in adults only and does not necessarily translate to children.
Compounding the difficulty of identifying prediabetes is the evolving criteria for diabetes itself. Zeitler reminded the audience that diabetes is defined by an increased risk for microvascular complications. Initially, he said, diabetes was based on a correlation of fasting glucose with increased incidence of retinopathy. In 1979, this correlation was based on a random or OGTT of greater than 200 mg/dL or FPG test of greater than 140 mg/dL, and in 1997 this changed to a FPG of greater than 126 mg/dL and the same OGTT. In 2009, the hemoglobin A1c test became standardized with a cutoff point of greater than 6.5 indicative of diabetes.
“Prediabetes is even more squishy than diabetes,” said Zeitler. “Diabetes is based on future cardiovascular risk, but prediabetes is based on the future risk of diabetes.”
Emphasizing that all the measures currently used to define diabetes are based solely on data derived from studies on adults, Zeitler underscored the need to recognize that prediabetes risk may not be the same for children. “The future risk of diabetes is not the same if you use the same criteria in children,” he said, highlighting as well that a “high-normal” glucose and A1c may be normal in puberty.
For example, he said that although the data suggest that adults with an A1c between 5.7% and 6.5% have increased risk for development of future diabetes, he highlighted data showing that an A1c of less than 6% in children actually indicates a nearly 0% chance of progressing to diabetes in a reasonable amount of time.
This is important because many children with elevated A1c or glucose levels are likely to spontaneously regress without any intervention because of changes in insulin resistance in puberty. (This is described more fully in the section “Management of prediabetes" below.)
All said, Zeitler questioned whether prediabetes is a useful concept when applied to children because of the high regression rate in children without any intervention. More useful, he suggested and emphasized, is recognition of the other more common metabolic complications associated with obesity in children, including high blood pressure, elevated triglycerides, and fatty liver.
1. Zeitler P. Not yet diabetes: Assessing and managing children at risk (F4019). Presented at: American Academy of Pediatrics National Conference and Exhibition; September 19, 2017; Chicago, IL.