Should time in range replace HbA1c as the primary metric in pediatric diabetes care?
Use of HbA1c to assess glycemic status is limited by numerous factors. HbA1c lacks the ability to detect the degree and frequency of inter- and intraday acute glycemic excursions, that is, hyperglycemia and hypoglycemia. The accuracy of results can be corrupted by certain medical conditions, such as anemia, iron deficiency and hemoglobinopathies. Additionally, HbA1c does not provide an accurate measure of average glucose due to a wide range of mean glucose concentrations for a given level; for example, 128 mg/dL to 190 mg/dL for 7% HbA1c (Beck RW, et al. Diabetes Care. 2017;doi:10.2337/dc17-0636).
Continuous glucose monitoring technologies address these limitations with their ability to directly observe glycemic excursions and daily profiles as they occur. This allows users to take remedial action in response to problematic glycemia and informs both users and their clinicians on the need for therapy adjustments and lifestyle modifications. An international consensus panel recently published evidence-based findings recommending use of percentage of time in range and time below range as a composite measure of glycemic control, supported by other metrics reported in the ambulatory glucose profile (Battelino T, et al. Diabetes Care. 2019; doi:10.2337/dci19-0028). These recommendations were immediately endorsed by leading professional organizations, including the American Diabetes Association, the American Association of Clinical Endocrinology, the Association of Diabetes Care & Education Specialists, the European Association for the Study of Diabetes, the Foundation of European Nurses in Diabetes, the International Society for Pediatric and Adolescent Diabetes, JDRF and the Pediatric Endocrine Society.
Whereas HbA1c testing remains the gold standard for assessing the long-term risk for diabetes complications, retrospective analysis of percentage of time in range or percentage of time below range, in conjunction with other CGM metrics, facilitates more informed clinical decision-making. As adoption of CGM continues to grow, health care providers must embrace this technology and utilize these metrics in clinical practice to improve glycemic control and clinical outcomes.
David G. Marrero, PhD, is director of the University of Arizona Center for Border Health Disparities at the University of Arizona Health Science, professor of public health in the division of endocrinology at the University of Arizona College of Medicine, and a former president of Health Care and Education at the American Diabetes Association.
When looking at HbA1c vs. time in range, it is important to first define a metric of interest. To choose the proper metric, we need to know what our goals or targets are in treating type 1 diabetes.
The best current marker for risk for complications is HbA1c. It predicts diabetes in adults, and it diagnoses diabetes in children and adults. Although not an earlier marker of diabetes, HbA1c is an easily accessible marker that you can perform on a single blood draw at any time of day or night. HbA1c predicts risk for diabetes complications, and we know therapeutically that if we reduce HbA1c, it is going to reduce risks for microvascular and neuropathic complications. A 30-year overview of the Diabetes Control and Complications Trial (DCCT) and Epidemiology of Diabetes Interventions and Complications (EDIC) studies clearly shows a legacy effect of lowering HbA1c early is associated with a reduction in cardiovascular events and microvascular complications in the long term.
HbA1c has its limitations. It reflects 2 to 3 months of glycemia, with the last month influencing 40% to 50% of the overall HbA1c concentration. So, it is biased. It provides no assessment of hypoglycemia or glycemic variability. It is a number. HbA1c does not instruct clinicians or patients about how improved glycemic control can be achieved. A desirable HbA1c does not equate to zero risk for complications. Various analytic or medical conditions can produce biased HbA1c results; clinicians must be aware of this.
Despite limitations, there is good evidence that HbA1c is a master biomarker of diabetes. Analytically, the assays are robust and are more reproducible than fasting plasma glucose or an oral glucose tolerance test, although not as sensitive. But I should say that this is really an apples and oranges comparison. It could very well be that time in range or other parameters do predict complications with equal power as HbA1c. That said, the challenges to CGM are cost, patient acceptability and insurance hurdles. HbA1c, for better or for worse, is accessible to all.
William Winter, MD, is a professor of pathology and pediatrics at the University of Florida.