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Reducing Lows: Riffing with Professor Simon Heller on TIR and More

By Frida Velcani and Emily Fitts

Professor Simon Heller is known globally for his renowned research on hypoglycemia; hear his opinion on using Time in Range in diabetes management

“To reduce lows, I explain to people with diabetes that they should spend at most an hour below range and avoid spending more than 15 minutes a day below 54 mg/dL. These are things people can grasp quite quickly,” said Simon Heller, a Professor of Clinical Diabetes at the University of Sheffield in the United Kingdom. The reasons why Time in Range (TIR) should be part of every diabetes management toolbox are clear. Whether it's reducing time in hypoglycemia (also called time below range, or TBR, with glucose less than 70 mg/dL) or one’s risk of developing long-term complications (by reducing time above range, or TAR, with glucose above 180 mg/dL), spending more hours each day in-range can bring tremendous health benefits. Professor Heller is a Director of Research and Development and an honorary consultant physician at the Sheffield Teaching Hospitals Foundation Trust in Sheffield, England. He is widely known for his research on understanding the causes of hypoglycemia (low blood glucose) and developing technological and therapeutic interventions to improve diabetes self-management. We spoke with Professor Heller recently to hear his perspectives on TIR.

Professor Heller just presented at the European Association for the Study of Diabetes’ (EASD) virtual 2020 conference that we reported on last month, discussing two fascinating initiatives that have potential to meaningfully improve how we define and manage hypoglycemia. The International Hypoglycemia Study Group (IHSG) and Hypo-RESOLVE are raising awareness about “level 2 hypoglycemia” (defined as blood glucose levels less than 54 mg/dl). At level 2 hypoglycemia, people with diabetes are at increased risk of severe symptoms including hypoglycemia unawareness, impaired brain function, and an irregular heartbeat. We admire Professor Heller’s work and leadership that is prompting organizations like JDRF, ISPAD, and EMA to collaborate and incorporate this classification of severe hypoglycemia into clinical trials. As we understand it, the FDA does not at this time recognize level 2 hypoglycemia – we are hopeful that ongoing work with JDRF and other advocacy organizations, including diaTribe, will lead to global harmonization of this standard.

The Takeaway: We learned a great deal from this interview, especially from Professor Heller’s focus on continuous glucose monitor (CGM) metrics. Professor Heller’s perspectives also taught us more about hypoglycemia and how people can avoid it. Monitoring TIR (and being able to examine GMI in as little as 14 days, as an informal “predictor” of A1C) helps people in more direct ways than going out to get an A1C lab test every three months and then not being able to understand the overall results until they see their healthcare professional again.

Read on to learn why Professor Heller prefers using TIR over A1C during the COVID-19 pandemic to help contextualize and assess diabetes management.

Emily: How do you use TIR in diabetes management, and how does it relate to hypoglycemia?

Professor Heller: Since the COVID-19 outbreak, my clinic has shifted to using video and phone visits. When it’s not considered safe to go to the hospital to get an A1C test, continuous glucose monitoring has helped keep my patients and me on the same page. It’s allowed us to discuss their TIR and other CGM metrics. I have had people email me just to say that they appreciated our discussion and to update me on their TIR. As healthcare professionals, we should remember that the person with diabetes is the expert. When looking at glucose highs or lows on the CGM reports, it’s important to ask them, “Why do you think this might be happening?”

A1C is not as meaningful of a concept as TIR for people with diabetes – people generally find A1C more challenging to compare to their average glucose levels. To reduce lows, I explain to people that they should spend at most an hour below range (less than 4% of their glucose values below 70 mg/dL) and avoid spending more than 15 minutes a day below 54 mg/dL (less than 1% of glucose values). These are things people can grasp quite quickly. If people with hypoglycemia unawareness can start to avoid these frequent lows, they should be able to identify warning signs of hypoglycemia again within three or four weeks.

Frida: We know that TIR is not yet considered a primary metric of diabetes care in most clinical practice guidelines. What is the most recent evidence to support the widespread use of TIR? 

Professor Heller: An interesting poster based on the DEVOTE clinical trial was presented at the American Diabetes Association’s 2020 conference. The trial data included 5,774 people with type 2 diabetes who had at least six self-monitored blood glucose (SMBG) measurements that were used to calculate a “derived TIR.” The analysis found that every 10% increase in TIR was associated with a 6% relative risk reduction for MACE – MACE is defined as non-fatal heart attack, non-fatal stroke, and cardiovascular death. This data lends itself to the possibility that we can use TIR to predict diabetes complications, possibly even more so than A1C. (You can read more about these results here.)

The Hypo-RESOLVE project, which I am currently a part of, is consolidating glucose data from multiple CGM trials to gather insights on the link between TIR and the risk of hypoglycemia. We are interested in understanding whether spending time below 70 mg/dl or 54 mg/dl could predict a severe hypoglycemic episode later on (also known as “hypoglycemia begets hypoglycemia”). We are also actively exploring patient-reported outcomes (such as quality of life), health economics, and other measures related to hypoglycemia in brand new clinical trials.  

Emily: Thank you for all this work! What do you think are the biggest obstacles to adopting TIR that people with diabetes and healthcare professionals face?

Professor Heller: TIR on its own is not helpful unless you tie it with education. People need to be equipped to interpret the information they are seeing on their CGM, as highlighted by Dr. Emma Wilmot in a presentation she gave with Dr. Rich Bergenstal at the American Diabetes Association’s 2020 conference.

I think specialists have to be persuaded to use TIR first; then the broader population of healthcare professionals will follow. Many specialists don’t interpret Ambulatory Glucose Profile (AGP) reports on a regular basis and as a result, don’t have a good understanding of the tool yet. However, once they get a feel for it, they’ll see that it’s not incredibly complicated because the same things will come up over and over again. For example, they’ll notice that glucose values progressively go up when people don’t match their boluses with their food or when they’re not covering their snacks in the evening. I believe conversations between healthcare professionals and people with diabetes about these patterns will help them recognize the value of TIR.

Frida: We so appreciate all your valuable research and additional work on hypoglycemia, Professor Heller, and your work supporting people and healthcare professionals on Time in Range.  

Looking Forward: As more people turn to CGM to manage their diabetes, we would like to see participants in clinical trials also wearing these devices. Incorporating CGM into clinical trials can provide us with immediate feedback on how diabetes therapies impact hypoglycemia and hyperglycemia, weight, cardiovascular disease (CVD), and chronic kidney disease (CKD) outcomes. If a person with type 2 diabetes has heart disease, kidney disease, or heart failure (or is at high risk of heart disease) it’s recommended that they discuss SGLT-2 inhibitor or GLP-1 agonist medications with their healthcare professional. More information from clinical trials about these therapies would be helpful for developing personalized treatment plans.

This article is part of a series on Time in Range. 
The diaTribe Foundation, in concert with the Time in Range Coalition, is committed to helping people with diabetes and their caregivers understand TIR to maximize patients' health. Learn more about the Time in Range Coalition here

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