Should Time in Range Replace Hemoglobin A1C?
Nov 23, 2020, 13:00 PM
By Diana Isaacs, PharmD, BCPS, BCACP, BC-ADM, CDCES, FADCES
The hemoglobin A1C has long been considered the gold standard to measure glycemic management in people with diabetes. Higher A1C’s are associated with microvascular and macrovascular complications of diabetes. However, there are some important limitations to A1C. It’s based off of an average and gives no information about glycemic variability. Imagine if you put one foot in ice cold water and one foot in boiling hot water. You could say that your feet are room temperature. Obviously neither foot feels good! This is similar to glucose levels. A person could spend a ton of time in hypoglycemia and hyperglycemia, and achieve an A1C in target range. Likely, the person would not feel well and not be achieving good clinical outcomes.
There are some important limitations to A1C. It’s based off of an average and gives no information about glycemic variability.
Now we have an amazing new metric called time in range (TIR), which represents the percentage of time spent between 70-180mg/dL. The goal for most people with type 1 and type 2 diabetes is to spend at least 70% of TIR. For older adults or those at high risk of hypoglycemia, 50% TIR is acceptable. Studies have demonstrated that 50% TIR correlates well with approximately an 8% A1C while 70% TIR correlates well with a 7% A1C. However, until recently, we didn’t have much information linking TIR to long-term clinical outcomes like cardiovascular mortality.
The INDices of Continuous Glucose Monitoring and Adverse Outcomes of Diabetes (INDIGO) study was designed to assess the effects of TIR on microvascular and macrovascular events and mortality in people with type 2 diabetes. The mean age of participants was 61.7 years at baseline. They all wore professional CGM for 3 days during their hospital stay to establish TIR. During a median follow-up of 6.9 years, 838 deaths were identified and 287 were due to cardiovascular disease. Lower TIR was associated with an increased risk of all-cause and CVD mortality. Adjusting for age and sex, relative to the highest TIR group (>85%), those with 71%-85% TIR had a 43% higher risk of CVD-related death, those with 51%-70% TIR had a 66% higher risk, and those in the lowest ≤50% TIR group had more than twice the risk (HR=2.15). Each 10% reduction in TIR was associated with 5% higher CVD mortality.
This study does have some important limitations: TIR was based on a period of wear of just 3 days during a hospitalization where they were fed the same diet and the CGM accuracy at the time of the study wasn’t as strong as it is today. While more studies are certainly needed, this provides some exciting evidence for the link between TIR and mortality. As CGM use increases, will TIR ultimately overtake A1C as the preferred metric? You can assess it much more frequently. It is not affected by blood transfusions and other conditions that affect red blood cells. And most importantly, it can provide a direct assessment of glycemic variability.
What do you think? You can learn more about TIR and access free resources to share with your clients at DiabetesEducator.org/GlucoseMonitoring. ADCES members can also access a free 14.5 hour CE-accredited CGM Certificate Program that includes a curated group of peer-reviewed publications, product-specific videos and downloadable guides and patient tools to have at your fingertips.
- Battelino T, Danne T, Bergenstal RM et al. Clinical Targets for Continuous Glucose Monitoring Data Interpretation: Recommendations From the International Consensus on Time in Range. Diabetes Care. 2019 Aug;42(8):1593-1603. doi: 10.2337/dci19-0028
- Lu J, Wang C, Shen Y et al. Time in Range in Relation to All-Cause and Cardiovascular Mortality in Patients With Type 2 Diabetes: A Prospective Cohort Study. Diabetes Care. 2020 Oct 23:dc201862. doi: 10.2337/dc20-1862.
About the Author
Diana Isaacs, PharmD, BCPS, BCACP, BC-ADM, CDCES, FADCES is a certified diabetes care and education specialist, and holds board certifications in pharmacotherapy, ambulatory care and advanced diabetes management. She is the continuous glucose monitoring (CGM) program coordinator and endocrinology clinical pharmacy specialist at the Cleveland Clinic Diabetes Center. Her role includes clinical practice, teaching and research. Isaacs also provides medication management and runs a robust CGM shared medical appointment program.
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