Use both HbA1c, CGM metrics for optimal diabetes management
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Key takeaways:
- Studies have found discordance between HbA1c and glucose management indicator.
- HbA1c remains the standard for diagnosing diabetes.
- Providers should use CGM metrics and HbA1c for diabetes management.
Providers should use both HbA1c values and continuous glucose monitoring data to manage diabetes and prevent complications, though HbA1c should remain the standard for diagnosing diabetes, according to two speakers.
Several factors may lead to HbA1c discordance for people with diabetes, and two measurements that include glucose management indicator (GMI) and HbA1c can help prevent diabetes-related complications, according to Irl B. Hirsch, MD, professor of medicine at University of Washington School of Medicine in Seattle, who spoke during a parallel session at the International Conference on Advanced Technologies & Treatments for Diabetes.
Speaking in the same session, Elizabeth Selvin, PhD, MPH, professor at the Johns Hopkins Bloomberg School of Public Health, said HbA1c should remain the gold standard for diagnosing people with diabetes, and discordance can also occur with CGM metrics. Both speakers concluded there is a role for both CGM metrics and HbA1c to be used in diabetes care moving forward.
“Embracing CGM mean glucose, time in range and the many other CGM metrics, while retaining laboratory HbA1c testing, can optimize glucose control and prevent complications in patients with diabetes,” Selvin said during the presentation.
Factors linked to HbA1c discordance
There are several etiologies that can cause HbA1c discordance from blood glucose, including hematologic conditions, conditions such as chronic kidney disease or chronic liver disease, medication effects, physiological reasons such as first and third trimester of pregnancy or age, and assay interference, Hirsch said.
However, Hirsch added that HbA1c discordance goes beyond physiology and other conditions. A study published in 2008 found that red blood cell survival may affect HbA1c, with shorter red blood cell age possibly causing a lower HbA1c value and longer red blood cell age potentially leading to a higher HbA1c value.
Discordance between GMI and HbA1c also exists and may be due to the accumulation of advanced glycation end products. A study published in Diabetes Care in 2022 uses the metric called glycation ratio, which is GMI divided by HbA1c. Adults with a glycation ratio of less than 0.9 were defined as having a fast-glycator phenotype. In the study, adults who were fast glycators had a higher HbA1c than slow glycators (8.6% vs. 7.5%; P < .001), and the fast-glycator group had increased risks for several diabetes-related complications.
“The question is, is HbA1c discordance related to both the red blood cell life span differences and to the rates of protein glycation, the latter which may be related to the risk of microvascular complications, or are these high glycators only people with longer red cell life spans,” Hirsch said during the presentation.
A high discordance between GMI and HbA1c could lead to improper diabetes management, according to Hirsch. Hemoglobin glycation index is a value calculated by subtracting the difference between GMI and HbA1c. In the ACCORD analysis published in Diabetes Care in 2015, adults with a high hemoglobin glycation index had a higher risk for hypoglycemia than those with low or medium values, and adults with a high hemoglobin glycation index receiving intensive therapy had higher total mortality.
Because both GMI and HbA1c are required to calculate glycation ratio or hemoglobin glycation index, providers should assess both measures, Hirsch said.
“Using glycation ratio or hemoglobin glycation index, and using both GMI from CGM and HbA1c, may be a more important method of predicting diabetes complications than using either of these numbers alone,” Hirsch said.
HbA1c remains gold standard for diagnosis
Even as CGM continues to evolve, HbA1c remains the standard for diagnosing diabetes, Selvin said. She said some of the advantages of HbA1c are that it is less variable than a glucose reading, serves as a better index of glycemic exposure, is strictly standardized, remains unaffected by acute factors and is robustly associated with long-term macrovascular and microvascular complications.
Two limitations of HbA1c are assay interference and that some conditions, such as altered red cell turnover, can impact measurements. However, Selvin said, fasting glucose has several limitations, including diurnal variation, laboratory calibration, high variability between individuals, and it captures only a single moment in time. Selvin said these limitations are why providers should measure both HbA1c and fasting glucose to confirm a diabetes diagnosis.
“Unless there’s a clear diagnosis, such as a hyperglycemic crisis or overt hyperglycemia, diagnosis requires two abnormal test results,” Selvin said. “The reason we recommend confirming any elevated test result is to reduce the possibility of a false-positive diagnosis.”
Selvin said GMI provides an advantage by taking CGM mean glucose and converting it into an estimated HbA1c value that is familiar for providers and patients. However, she said, many studies have found a 0.5 percentage point or greater discordance between GMI and HbA1c. Additionally, in a study published in Diabetes Care in 2024, CGM sensors from two different manufacturers worn at the same time were placed on 176 adults with type 2 diabetes. The GMI readings between the sensors differed by 0.5 percentage points or more for 26% of participants. Conversely, Selvin said, other studies have found no discordance between two different HbA1c assays.
Several factors could lead to HbA1c and GMI discordance, according to Selvin. Those factors include CGM or HbA1c measurement errors, duration of CGM wear, timing of HbA1c measurements and imperfections in the GMI equation. Selvin added that HbA1c and CGM glucose are different entities and said she would not expect them to perfectly align.
“Instead of relying on GMI as a surrogate for HbA1c, we need to educate people and emphasize the use of CGM mean glucose alongside laboratory HbA1c testing,” Selvin said.
Selvin added that CGM metrics should not be used for diagnosis, due to a lack of evidence on associations with hard endpoints, no calibration across different types of devices, a lack of sufficient accuracy and because it is unclear which CGM metric should be used. Selvin added that the a single CGM device is six to 10 times more expensive than an HbA1c measurement.
References:
Cohen RM, et al. Blood. 2008;doi:10.1182/blood-2008-04-154112.
Hempe JM, et al. Diabetes Care. 2015;doi:10.2337/dc14-1844.
Maran A, et al. Diabetes Care. 2022;doi:10.2337/dc22-0980.
Selvin E. Diabetes Care. 2024;doi:10.2337/dci23-0086.
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Hirsch I, et al. Parallel session 02: CGM diabetes quality measures. Presented at: International Conference on Advanced Technologies & Treatments for Diabetes; March 6-9, 2024; Florence, Italy (hybrid meeting).
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