Why A1c Alone Is Not Sufficient to Guide Glucose Goals
Since the advent of continuous glucose monitoring, people with type 1 diabetes have been asking a fundamental question, “What should my blood sugar goals be?” It’s a seemingly simple question with a lot of nuances and, somewhat surprisingly, not a clear answer. We seem to agree as diabetes providers that keeping your overall average glucose, i.e., A1c, less than 7% is a place to start. From there, we conclude that an average glucose around 150 mg/dL sounds reasonable. But are all A1cs of a certain value created equal when it comes to long-term complications? Does it matter how you get to that average glucose and what time you spend in different glycemic ranges? These are the questions we are now struggling with, and this leads us to the debate of time in range (TIR) versus time in tight range (TITR).
How Time in Range Was Created
While the discussion around TIR has been going on for over a decade, the term really became a household phrase in the diabetes community in 2019. That year, the Advanced Technologies & Treatments for Diabetes (ATTD) Congress published revised guidelines on CGM glycemic targets, as agreed upon by a global panel of technology experts. The panel defined TIR as time in glucose range between 70–180 mg/dL. This range was established considering 1) the lower threshold of 70 mg/dL, below which counterregulatory hormones are secreted; 2) the upper threshold of 180 mg/dL, above which postprandial glucose should not peak; and 3) what could realistically be achieved as a goal for individuals with diabetes, considering the most current technology available at the time.
The next task was defining targets for each glucose range, with recommendations landing on a goal for most people as TIR greater than 70% and time below range less than 4%. These targets were selected since it was felt at the time that these goals could be reasonably achieved with hybrid closed-loop (HCL) systems. HCL systems (such as Tandem Control-IQ, Omnipod 5, and MiniMed 780G) have enabled tighter glycemic control and reduced the risk of hypoglycemia. These recommendations were further strengthened by data on associations between TIR and progression of diabetes complications.
The Relationship between Time in Range and A1c
However, before TIR could be fully accepted, a relationship between TIR and A1c needed to be established. Researchers analyzed data from randomized trials and demonstrated that a TIR of 70% corresponded with an A1c ∼7% and that every 10% increase in TIR corresponded to a 0.6% decrease in A1c. Thus, a relationship was established and TIR became the new standard.
With Advanced Diabetes Tech, Do We Need Advanced Diabetes Goals?
Technology has boomed since the ATTD guidelines were passed, with the rapid development of more CGM and HCL systems that offer improvements in essentially all areas of HCL therapy. It is against that backdrop that we ask ourselves, “Can we do better than a goal of 70–180 mg/dL? Is it time to tighten things up?”
A group of researchers studied time in tight range (TITR) (70–140 mg/dL) and its relationship with TIR, with the aim of exploring TITR targets as a novel goal in T1D management. They conducted a retrospective analysis using real-world data in Medtronic MiniMed 780G HCL system users.
The investigators demonstrated that the use of this particular HCL system resulted in an increase in TITR of around 12% (about 2.5 hours per day). Interestingly, the increase in TIR was roughly the same, and the percent time in the 140 to 180 mg/dL range was maintained post-HCL. In other words, when glucose improved, it was generally because of an increase in time between 70 and 140 mg/dL and not due to an increase in the time spent in the 140- to 180-mg/dL range. The authors go on to correlate findings between TITR and A1c. The result was that aiming for TITR of ∼45% would align with a predicted A1c of <7%. Is 45% the new 70%? This has not been determined.
Limitations with the Current Time in Tight Range Studies
So we can establish what a TITR goal might be, but would recommending that people strive for this goal be beneficial? The current study cannot answer this question, as it was not a trial in which people were instructed to aim for this goal. It is our concern that should that goal be implemented, the result would be an increase in hypoglycemia, an increase in correction boluses, “fake carb” entry, and generally more aggressive insulin dosing.
There is a common type of T1D patient who strives for perfect glycemic control and, as a result, is constantly hypoglycemic. These are some of the most challenging people to treat, and they often concern providers the most. We need to be careful not to heighten fears of hyperglycemia by redefining what hyperglycemia is for our patients. Changing guidelines from staying between 70 and 180 mg/dL to staying between 70 and 140 mg/dL without documented data on the benefits would represent a major shift in our current management and messaging.
In Summary
There is certainly good news in that technological advancements are now offering the possibility of achieving glucose levels close to euglycemia (a normal level of sugar in the blood). However, doing so introduces a new dimension of anxiety related to the constant vigilance required to maintain tight glycemic control with all the associated emotional and psychological issues. Balancing the pursuit of tight glycemic control with quality of life is a crucial aspect of individualizing glycemic goals. To incorporate the findings of this study into new glycemic goals, it is essential to replicate the data using multiple HCL systems across diverse age groups, particularly those with a higher risk of hypoglycemia. To bring about a shift in clinical care using these new metrics, it is imperative to establish their correlation to clinical outcomes and long-term complications. Therefore, prospective studies detailing how aiming for TITR impacts time spent within specific CGM glycemic ranges, diabetes complications, and other outcomes are required.
The final question we are left with is this: “Is TITR an interesting new metric, or is it the new standard?” For us, it is too early to make TITR a new recommendation for the masses. It may come with time, but not yet.
Additional Resources:
A Dose of Dr. E: Why the A1c Sucks (And Why Time in Range Is More Important)
OK;;;Dr. Koch, in Bryn Mawr, PA