The Next Frontier in Diabetes

As I discussed in my previous article “Raising the Bar on Outcomes,” the discussions around Time in Tight Range (TITR) are picking up steam. This was another hot topic at?the Advanced Technologies and Treatments for Diabetes (ATTD) congress this year. In a discussion hosted by diaTribe and moderated by Professor Tadej Battelino during the conference, the panel raised some really important insights to consider as we introduce this new metric to people with type 1 diabetes (PWT1D). ?

First a refresher on TITR. This new metric tightens the Time in Range metric many are familiar with by lowering the upper threshold of the range from 180 mg/dL (10 mmol/L) down to 140 mg/dL (7.8 mmol/L). This new range would help reduce time spent with higher glucose levels and bring individuals closer to a blood sugar level akin to someone not living with diabetes, clinically referred to as euglycemia.

Hyperglycemia often gets overshadowed by discussions around fear of lows, but the health consequences of highs — both short- and long-term — are well-documented and can be devastating. In addition to the acute complications, such as diabetic ketoacidosis (DKA), high glucose levels can lead to chronic complications like eye disease, kidney disease and nerve disease, and in children, it can even lead to impaired brain function and brain damage.1-5 It’s heartening to see the heightened focus on hyperglycemia given all we know about its adverse effects on health and well-being.

I think an important part of the discussion around goals and targets is how they came to be in the first place as it provides context that explains why we’re now exploring a tightening of this range.

The Advent of CGM

There’s no doubt that the introduction of continuous glucose monitoring was a significant development for people living with diabetes. It allows real-time monitoring of glucose levels vs. HbA1c, which is an average derived from a 3-month historical view. Data is currency in the world of diabetes as it informs real-time therapy — imperative with at least 42 factors impacting how blood sugars respond on any given day. CGM allowed the introduction of Time in Range, which measures the percentage of time an individual spends with glucose in the range of 70-180 mg/dL. The international consensus that’s now reflected in treatment guidelines is that a person living with type 1 diabetes should aim to spend more than 70 percent of their time in this range.6

But how did we land at 180 mg/dL as the upper threshold when we know that individuals without diabetes spend most of their time with blood sugars in the range of 70-140 mg/dL?

According to Robert Vigersky, MD, Medtronic Diabetes’ Chief Medical Officer, the upper threshold was set to 180 mg/dL because it is the highest glucose should be 1-2 hours after a meal. When it exceeds 180 mg/dL, glucose is not reabsorbed as it passes through the kidney and spills into the urine. Before glucose monitoring by a blood glucose meter or CGM, people with diabetes monitored their glucose levels, testing for urine glucose several times a day. This “urine test” method was burdensome and was neither a timely nor precise reflection of what was actually going on in the body. With the introduction of CGM and the ability to measure glucose in real time, this method became outdated.

Technology has made considerable advancements since then, making it easier for individuals to achieve better outcomes using automated insulin delivery systems. Today, many experts are evaluating whether the Time in Range standards developed in 2019, which were based on what was achievable at that time, can or should be improved on.

Outcomes at the Expense of Quality of Life?

Diabetes management is a lifelong journey that is relentless and exhausting. At Medtronic Diabetes, we strive to develop new therapies to try to put diabetes management in the background as much as possible. We don’t want glycemic outcomes to come at the expense of quality of life, but we also don’t want quality of life to come at the expense of outcomes. PWT1D shouldn’t have to make that tradeoff.

Blood sugar swings are unpleasant - like being on a rollercoaster day in and day out - but there’s also a discomfort that comes from other burdens like complications or even from your own technology. So, the question is, does maintaining tighter glucose management with technology lead to increased burden?

Our data shows quite the opposite. In fact, 94% of MiniMed? 780G system users say it’s improved their quality of life (QoL) with 88% saying they’re experiencing better sleep and 93% saying they’re satisfied with the impact the system is having on their mealtimes – which we know is one of the most challenging aspects of diabetes.*,§,7

But how did we get to these QoL improvements? It’s because the technology itself has become less burdensome. The unnecessary or unactionable alarms and alerts are reduced, the time people spend letting the system do the work has increased (e.g., fewer closed loop exits), and the frequent blood glucose tests nearly eliminated. In a recent analysis, MiniMed? 780G system users saw a significant reduction in device use burdens compared to their previous technology.8 This same analysis also showed that, impressively, the diabetes management burden – a recently developed metric that assesses five key elements of diabetes burden* - was significantly reduced for MiniMed? 780G system users.8 Ultimately, people who use diabetes tech want their devices to be as seamlessly integrated, intuitive, and as low-touch as consumer tech and we know we’re getting closer to creating a parallel experience.

Still, though, high satisfaction and ease of use with AID systems is only worth applauding if diabetes management and outcomes are at the forefront of what the technology delivers. Across our real-world data from around the world, the use of our AID system delivers an average Time in Range of 80% when recommended optimal settings are used.9,10 Our latest data presented at ATTD this week shows that the system is helping users achieve a greater than 50% Time in Tight Range (57% when recommended optimal settings are used!). ?11 TITR can serve as a supplementary metric for those desiring tighter management — a great next step in their diabetes care that gets them closer to euglycemia.

Short of a cure for diabetes, our aspiration is to help PWT1D achieve the glucose levels of those who don’t have diabetes. It is hard to argue that maximizing the amount of time people spend in this optimal glucose range isn’t a positive given it’s associated with decreased risk of retinopathy, nephropathy, neuropathy, and cardiovascular disease.12-23 But, these positives shouldn’t come at the expense of increased burden or at the risk of increased hypoglycemia. Thankfully, PWT1D don’t have to make that trade-off. These conversations should be introduced with empathy and understanding that diabetes is hard, and PWT1D need to feel ready to take this next step in their diabetes care. It’s up to all of us to make this as easy as possible for them and we’re certainly committed to doing just that.

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*The diabetes management burden assesses five key elements of diabetes burden: time of burden, mean sensor glucose, standard deviation in sensor glucose, time above range >180 mg/dL (TAR), time below range (TBR). The goal is for the burden to eventually be as close to that of a healthy individual.

?Due to inherent real-world study limitations, caution is advised when attempting to extrapolate these results to new patients. There could be significant difference

§Refers to SmartGuard? feature. Individual results may vary

Sources:

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2.?Semenkovich K, Berlin KS, Ankney RL, Klages KL, Keenan ME, Rybak TM, Banks GG, Alemzadeh R, Eddington A. Predictors of diabetic ketoacidosis hospitalizations and hemoglobin A1c among youth with Type 1 diabetes. Health Psychol. 2019 Jul;38(7):577-585.

3.?Foland-Ross LC, Tong G, Mauras N, Cato A, Aye T, Tansey M, White NH, Weinzimer SA, Englert K, Shen H, Mazaika PK, Reiss AL; Diabetes Research in Children Network (DirecNet). Brain Function Differences in Children With Type 1 Diabetes: A Functional MRI Study of Working Memory. Diabetes. 2020 Aug;69(8):1770-1778.

4. ?uput Omladi? J, Slana Ozimi? A, Vovk A, ?uput D, Repov? G, Dovc K, Bratina N, Avbelj Stefanija M, Battelino T. Acute Hyperglycemia and Spatial Working Memory in Adolescents With Type 1 Diabetes. Diabetes Care. 2020 Aug;43(8):1941-1944.

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7.?Medtronic data on file: MiniMed?780G users survey conducted in April – May 2021 in UK, Sweden, Italy, Netherlands and Belgium. N 789

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