The switch to AID can improve HbA1C and TIR
The growing body of research on automated insulin delivery (AID) highlights the benefits of this technology for people with type 1 diabetes, said Professor Pratik Choudary of the University of Leicester, U.K., who discussed the results of the ADAPT study on the second day of the ATTD 2022 conference in Barcelona, Spain.
ADAPT examined the use of Medtronic’s MiniMed 780G AID system in people with type 1 diabetes and compared it to people using a continuous glucose monitor (CGM) and multiple daily injections of insulin therapy (MDI).
The results were monumental, Choudary said, pointing out that among the study participants on AID, the average A1C decreased by 1.8 percentage points and average Time in Range (TIR) increased by over 8.2 hours a day (34.2 percentage points).
ADAPT Trial Results
Decrease in A1C from start of trial (percentage points)
Increase in TIR from start of trial (percentage points)
Participants on AID
Participants on CGM+MDI (control group)
Editor’s note: Because the MiniMed 780G was not approved for use, the study used the MiniMed 670G pump with the MiniMed 780G algorithm. For simplicity, we refer to it here as the MiniMed 780G System.
The overwhelming fear of long-term complications is dwindling and is being replaced by freedom that I’ve never experienced before.Choudary shared a quote from Alesha Walpole, 26, a participant of the ADAPT study who said that with AID, “The overwhelming fear of long-term complications is dwindling and is being replaced by freedom that I’ve never experienced before.”
Professor Tomasz Klupa, head of the Center for Advanced Technologies in Diabetes Department and Chair of Metabolic Diseases Jagiellonian University Medical College, Kraków, Poland, also presented the results of a similar study in which the AID was evaluated in people with type 1 diabetes who previously used a blood glucose meter (BGM) and MDI insulin therapy over three months.
Results showed that around 75% of participants on AID achieved an A1C of less than 7% and a TIR target of at least 70%. Additionally:
Change in TIR from start of trial (percentage points)
Change in TBR from start of trial (percentage points)
Participants on AID
Increased by 15.7
Decreased by 6.6
Participants on BGM+MDI (control group)
Decreased by 1.3
Increased by 0.6
Participants in both studies also reported improved quality of life. ADAPT study participants reported decreased fear of hypoglycemia and an increase in treatment satisfaction. In Klupa’s study, participants reported improved wellness, freedom in their diets, and improved working productivity.
Dr. Robert Vigersky, Medtronic’s chief medical officer, said, “The results of the ADAPT trial and the outcomes of clinical trials in adults and children demonstrate that patients on MDI with high A1C can substantially benefit from initiation of the MiniMed 780G system. This may democratize the use of hybrid closed-loop systems by causing a paradigm shift in who is regarded as a candidate for automated insulin delivery systems.”
Artificial intelligence in diabetes
Devices like continuous glucose monitors (CGM) and health trackers, such as Fitbits and Apple Watches, are becoming more prevalent, giving people greater access to their own health data – from glucose levels to heart rate to step counts. When collected across populations, this leads to an immense amount of data that experts sometimes refer to as “big data.”
At the ATTD 2022 conference, we heard from a few experts who have been working on how researchers and healthcare providers can use this big data to improve diabetes management.
What is the role of artificial intelligence in diabetes care?
Artificial intelligence is a rapidly developing field and encompasses the use of computers to process large amounts of data and detect patterns. To understand how this works, think about how your healthcare professional can look at the wealth of information included in your ambulatory glucose profile (AGP) report created from your CGM data and then use it to inform decisions about your treatment.
If a computer analyzes the data and treatment decisions for 100,000 people, it might be able to detect trends for how particular glucose patterns lead to certain, specific treatment interventions that may not be as obvious when looking only at individual data. And this can be scaled ever larger and more precise the more data that is used.
Dr. Mark Clements, pediatric endocrinologist at Kansas City Children’s Mercy and chief medical officer at Glooko, has created a model called the “Diabetes Data Dock” that compiles data from people’s electronic medical records, wearable fitness trackers, apps, and surveys. Computers algorithms can then be used to process this information and detect patterns that offer predictive insights.
“I predict in the future, we [healthcare professionals] will be like the weatherman, forecasting outcomes,” Clements said.
Challenges and Applications of Artificial Intelligence
Today, many people’s CGM data is not used to its full potential, and sometimes it is not even used at all. As Dr. Moshe Phillip, director of the Institute for Endocrinology and Diabetes at the Schneider Children’s Medical Center of Israel, pointed out that one survey showed that, “Only 60% of people who use CGM actually looked at the data and made an analysis based on the data.”
He acknowledged that although we now have access to a huge amount of data, the question still remains, “What do we do with it?”
His team has developed a platform that uses artificial intelligence to create a clinical decision support system (CDSS) called the DreaMed Advisor Pro. This system’s algorithm is able to provide insulin dosing recommendations that are very similar to the recommendations made by expert physicians, said Phillip.
In the six month Advice4U clinical trial published in Nature, participating youth with type 1 diabetes received insulin dosing advice from either an expert physician or from the DreaMed Advisor Pro CDSS, referred to as “endo.digital” in the study. The researchers found that there was no difference in Time in Range (TIR) or percentage of readings in hypoglycemia (glucose levels below 54 mg/dl) between the physician and CDSS groups.
The goal is to eventually provide CDSS data to primary care physicians so that they have an additional resource to use, Phillip said, “It’s like knocking on the door of a colleague and asking, ‘What would you do in this situation?’”
The CDSS has the potential to improve clinical outcomes, access to care, and use of healthcare resources. Phillip said he anticipates greater integration of digital diabetes care in the future, allowing more frequent interaction between people with diabetes and their healthcare team instead of relying solely on short appointments a few times per year.
Hybrid Closed Loop is Effective for Children and Older Adults
Researchers previously connected glucose sensor data from CGM devices to insulin dosing algorithms, and insulin pumps, creating a “hybrid” closed loop by which a person’s glucose sensor and pump could talk to one another, but which still required users to manually administer mealtime boluses.
While there has been much research in support of hybrid closed loop algorithms for adults, there has been scant evidence for its use in children and older adults. At the ATTD 2022 conference, researchers presented new data in support of hybrid closed loops (HCL) for children.
Unique challenges facing children
Dr. Julia Ware, from the University of Cambridge in the United Kingdom, discussed some barriers to the management of diabetes in children, including unpredictable eating patterns, high susceptibility to hypoglycemia, and high variability in insulin requirements.
Ware also noted that children are “often hypo unaware and struggle to communicate hypoglycemia symptoms.” Because children have a higher insulin sensitivity while having a lower total daily dose, the margin of error for insulin dosing is very small.
Parents will often describe diabetes as totally taking over their life. Parents don’t sleep worrying about hypoglycemia and leaving their child alone.Parents of children with diabetes also experience increased burden of care and poor sleep, Ware said. “Parents will often describe diabetes as totally taking over their life. Parents don’t sleep worrying about hypoglycemia and leaving their child alone.”
Dr. Julia Lawton of the University of Edinburgh in Scotland added that “some parents described having given up their jobs or moving to part time employment,” which adds to financial stress. She said that we are struggling to address these physical and psychological problems in young children and their families.
Benefit of hybrid closed loops
Hybrid closed loops use CGM data to adjust the basal insulin rate on insulin pumps. This helps alleviate the high variability of insulin requirements that children often face. The CamAPS FX system, or Cambridge Artificial Pancreas System, uses an algorithm developed at Cambridge. This algorithm is important since it coordinates how much insulin to deliver based on CGM data.
A qualitative study found that HCL use results in higher Time in Range (TIR) and fewer highs and lows. “Parents praised the CamAPS FX system for providing a level of input that went beyond their own human capabilities,” Lawton said. By automatically correcting insulin dosage, “parents noted that it had taken away a lot of the work required from diabetes management,” she added. Parents could now focus just on what their child was eating for bolus dosing.
“Alongside clinical benefits and reduced workloads, parents noted a wide range of quality of life benefits,” such as sleeping better or experiencing less worry and anxiety about their child, Lawton said. Parents commonly talked about “getting part of their lives back and being able to resume normal activities, sometimes for the first time in years, whether this be something simple like sitting downstairs reading a book uninterrupted or going out for a meal as a couple.”
Additionally, the children experienced improved mood, concentration, and sleep. As diabetes management moved into the background, the children felt more normal and their siblings also benefited.
Drawbacks of hybrid closed loop
Lawton noted that some criticisms and concerns have been raised about hybrid closed loops, especially among parents who thought the algorithm was too slow to respond. “Parents who were micromanagers before hybrid close loops found it difficult to step back and hand over control to the system,” she said.
This anxiety often led parents to step in and correct insulin dosing as soon as they felt glucose levels went too high or too low rather than allowing the system to operate without interference, Lawton said. Others found carrying a smart phone was too difficult for young children and yet others experienced suboptimal performance due their devices going out of range. Perhaps in the future, she said, smaller smart devices, such as a smart watch, will be used.
Research on hybrid closed loops
Clinical trials on hybrid closed loop therapy have also shown the benefits of early adoption for children with type 1 diabetes. Dr. David Maahs, a pediatric endocrinologist at the Stanford School of Medicine, reviewed the results of the 4T study.
The 4T study, or the Teamwork, Targets, Technology and Tight Control (4T) Study, investigated whether the health benefits of earlier use of diabetes technology in children outweighed the required learning curve. The study provided 135 children, who were newly diagnosed with type 1 diabetes, a CGM (Dexcom G6) soon after their diagnosis.
The 4T study found that early CGM initiation is well received by patients and families and led to lower average A1C, which suggests that earlier CGM access might have had a positive impact for the newly diagnosed children. Those who opted in for remote monitoring had a lower average A1C, suggesting that by providing the healthcare team with access to their remote data, it allowed them to receive more frequent dosing recommendations from their healthcare provider resulting in better outcomes.
These findings provide strong support for greater HCL use among children. Not only does HCL decrease physical and emotional burden of care, it leads to significant improvements in TIR.
Can the Omnipod 5 AID work for people with type 2 diabetes?
Automated insulin delivery (AID) has been shown to improve diabetes management for people with type 1 diabetes, but there is little data on whether or not these algorithms could also be used by people with type 2 diabetes.
However, for the first time, data from Insulet’s Omnipod 5 AID eight week feasibility study, which was presented as a poster at ATTD 2022, showed that the system improved A1C and Time in Range (TIR) for people with type 2 diabetes. The study included 24 people with type 2 diabetes – half were on multiple daily injections (MDI) of insulin and half were using basal insulin only.
The group on MDI at the start of the trial dropped their A1C by an average of 1.3 percentage points and improved their TIR by 3.4 hours per day. The group on basal insulin at the start of the trial dropped their A1C by an average of 1.4 percentage points and improved their TIR by 5.9 hours per day.
A1C at start of trial
A1C at 8 weeks
TIR at start of trial
TIR at 8 weeks
Group that was on MDI at start
Group that was on basal only at start
In addition, both groups saw Time Above Range (TAR) reduced and spent little to no Time Below Range (TBR).
This study helps show that the current AID algorithms may be able to benefit people with type 2 diabetes on insulin.
Diabeloop’s AID algorithm shows impressive real-world data
Diabeloop’s automated insulin delivery (AID) algorithm, called DBLG-1, was released in Europe in 2019 for people with type 1 diabetes. Though it is not yet approved for use in the US, recent real-world data from Germany was released at the ATTD 2022 conference showing improvements in Time in Range (TIR)
Diabeloop currently has over 7,000 users in Europe on its DBLG-1 algorithm, which works with the Dexcom G6 continuous glucose monitor (CGM) and Roche’s Accu-Chek Insight or ViCentra’s Kaleido insulin pumps.
In a subset of the real-world data that included 974 people, TIR improved from 54.6% to 73% (an average increase of around 18.4 percentage points or 4.4 hours per day). In addition, Time below 70 mg/dL was only around 0.9% for this group and time below 54 mg/dL was around 0.1%.
In the entire data set which included 1,917 users:
- 60% of users had a TIR greater than 70%
- 98% of users had a Time Below Range (TBR) of less than 5%
- 48% of users had a glucose management indicator (GMI) less than 7%
- 47% of users achieved all three of these goals
To learn more about Diabeloop, read our article, “Diabeloop’s AID System Improves Time in Range and Quality of Life.”
Diabetes technology: One size fits nobody
Continuous glucose monitoring (CGM) has undeniable benefits, but its learning curve can be overwhelming for people with diabetes.
In addition to learning how to use all of the features of diabetes technology, people with diabetes must also learn how to respond to the wealth of data and information.
The burden of trying to chase straight glycemic control can be overwhelming.“We know that the mental burden of these devices and therapies are underappreciated,” said Katharine Barnard Kelly, PhD in Health Psychology from the University of Southampton. “The burden of trying to chase straight glycemic control can be overwhelming.”
According to Kelly, CGM has incredible benefits, including improvements in A1C, but this device also comes with several burdens. Ultimately, wearing a CGM can sometimes feel like a double-edged sword. It’s a balancing act that involves:
- Improved awarenessof impact on food and behaviors, but this can cause anxiety that what you’re doing is not working.
- Alarmsthat prompt people to respond to highs and lows, but these alarms can feel intrusive.
- Allows collaborative management(such as with friends, family, and other caregivers), but sharing your CGM data with others can be quite personal and make someone feel judged.
- Data frequencyallows people with diabetes to stay informed throughout the day, but too much data can create pressure to tailor your whole life around diabetes. “It’s impossible to know when it’s enough and when it’s too much. There are no rules about how often you must pay attention to your data,” Kelly said.
- Ability to see the directionof your glucose levels and respond accordingly, but this creates a need to understand what the up and down arrows mean and worry about how to respond.
Kelly provided tips for overcoming the hassle that comes with wearing a CGM:
- Wear your CGM as much as possible.
- Share your data in a way that works for you.
- Make alerts and alarms your friend, not your foe.
- Review your results regularly.
- Know your personal glucose targets.
- Have a solid plan for prevention or responding to hypoglycemia.
- Explore the big, bad world of food.
- Use the trend arrows to help you understand what is really going on.
- Time in Range – try to aim for above 70%.
- When diabetes is driving you crazy, remind yourself what you want your CGM to help you with.
These challenges are not unique to CGMs. Difficulties with other diabetes devices and technology can lead people to quit using hybrid closed loop systems and pumps, according to Dr. William Polonsky, president and co-founder of the Behavioral Diabetes Institute in San Diego, California.
For example, 20% of people who used an insulin pump quit due to issues with wearability, problems with it working properly, and finding the pump too complicated. Another study found that 34% of people who quit their Dexcom Seven Plus, an older generation CGM system, said that the numbers couldn’t be trusted, and 26% reported that there were too many false alarms.
People with diabetes who quit using their technology do so largely due to two reasons, according to Polonsky.
- People felt the benefits of the technology were not sufficient. In other words, they were often disappointed in their results.
- People experienced several hassles with the technology. For example, people found the devices unreliable, experienced disconnection and skin irritation issues, and didn’t like the number of alarms.
We know the major reason people are more likely to use diabetes CGM or any diabetes technology is because they trust the deviceConfidence in a device is especially important. “We know the major reason people are more likely to use diabetes CGM or any diabetes technology is because they trust the device,” Polonsky said.
He provided a few recommendations for device manufacturers, people with diabetes, and healthcare providers to address some of these issues.
- Improvement in technology – continue making strides in device innovation.
- Set reasonable expectations based on one’s lifestyle.
- Provide comprehensive training when a person with diabetes first starts on a new device.
- Engage with and develop online support networks (like videos or social media accounts) that can provide answers to any problems that may come up.
Healthcare providers and people with diabetes both have a role to play in making sure that device users feel confident in using their technology. Dr. Ananta Addala, pediatric endocrinologist at Stanford University, discussed DiabetesWise as a way to make this happen.
DiabetesWise is a resource to help people with diabetes find the technology that will work best for their preferences and lifestyle. They also have a resource for healthcare providers that can help providers recommend devices that work best for the people with diabetes in their care.
According to Addala, DiabetesWise is about increasing awareness of the options available to people with diabetes so that they can find the best device to fit into their lives.
With increased knowledge and skills comes greater confidence that people are getting the tech that they want so that everyone gets the care they would like“With increased knowledge and skills comes greater confidence that people are getting the tech that they want so that everyone gets the care they would like,” she said.
When trying out a new device, remember that it will work differently for each person so it’s important to get something that is tailored to your lifestyle and preferences.
Bringing Time in Range to those with type 2 diabetes
Time in Range (TIR) continued to be top of mind at the 2022 ATTD conference, with experts discussing the potential use of CGM for people with type 2 diabetes.
People with type 2 diabetes are much less likely to be on a CGM, however, and a panel of experts suggested that an increased understanding of TIR and better communication between healthcare providers and people with type 2 about the metric could be useful in making treatment decisions and providing support.
In June 2021, landmark results from the MOBILE clinical study demonstrated how using CGM could significantly improve TIR and lower A1C in people with type 2 diabetes on basal insulin. However, according to Dr. Steve Edelman, professor of medicine in the Division of Endocrinology, Diabetes & Metabolism at the University of California, San Diego, there was large variability within the group using CGM, leaving questions about why people with type 2 diabetes responded to CGMs inconsistently.
Edelman and Dr. William Polonsky, president and founder of the Behavioral Diabetes Institute in San Diego, California, described how communication and language around CGM data can help people achieve their glucose management goals.
“A 70% [TIR] target means that nobody needs to be perfect, and nobody can be perfect,” said Polonsky, “We can stop talking about the ‘grade’ of A1C that can make people feel like a failure.”
Both experts agreed that as many as a quarter of A1C measurements taken in the doctor’s office can be misleading. Edelman also highlighted the need for more education about TIR and CGM to increase use among people with type 2.
“The most underused motivational tool in diabetes care is the way we talk about numbers with our patients,” he said. “Patients with type 2 diabetes need to understand the importance of trend arrows and alerts. Some may not want to wake up at night, disturb their partner, and choose not to set alerts for highs, but this can defeat the purpose of the CGM.”
The use of a CGM can also help people with type 2 feel more motivated, Edelman said, explaining that with a CGM, people can see their real-time glucose levels and their TIR, which, as he put it, “can help people see tangible evidence that their treatment is working.”
As research on CGMs has continued to support the positive impact they have on diabetes management, CGM data has gone from a tool for analysis to one for adjustment and taking action.
Dr. Rich Bergenstal, executive director of the International Diabetes Center Minneapolis, Minnesota, describes this as a “paradigm shift” in the use of CGM and management of type 2 diabetes.
“In primary care, doctors have looked at the glucose profile, but it hasn’t helped them change their therapy or guided them,” Bergenstal said. Similar to Edelman, Bergenstal suggested a simplified model, based on TIR and Time Below Range, to determine treatment adjustments for people with type 2 diabetes on insulin. This could help make the information from CGM more actionable for primary care providers and people with type 2 diabetes.
Panel experts agreed that CGM can become a valuable tool for people with type 2 diabetes going forward.
CGM should and will be the standard of care for people with type 2 diabetes at all stages of their natural history, from prediabetes to multiple daily injections“CGM should and will be the standard of care for people with type 2 diabetes at all stages of their natural history, from prediabetes to multiple daily injections,” Edelman said. “CGM can help us to guide and support our type 2 diabetes patients efficiently and effectively, make realistic goals for TIR, and promote collaborative discussion to enhance our patient’s engagement in their own care.”
The awareness and use of Time in Range – Opportunities for improvement
https://www.dagensdiabetes.se/83a32f3c-1dfd-4c9b-a92f-e487e36cc946" alt="/var/folders/5x/c87f6bf924d2b459ssbwrv1h0000gn/T/com.microsoft.Word/WebArchiveCopyPasteTempFiles/Screen%20Shot%202022-04-30%20at%204_12_11%20PM-min(1).jpg" />At ATTD 2022, Julia Kenney, advocacy program manager at The diaTribe Foundation, presented two posters on the awareness and use of Time in Range (TIR). Despite the many studies highlighting the benefits of TIR, there are gaps in our understanding of the levels of awareness and use of TIR among people with diabetes.
To better understand these two meaningful pieces of data, diaTribe and dQ&A conducted a survey of 958 adults with diabetes and 44 caregivers of children and/or adults with diabetes using the dQ&A U.S. Patient Panel (dQ&A is a market research company focused on people with diabetes).
Awareness of TIR
Overall, people with type 1 diabetes were the most aware of TIR (67%) while those with type 2 diabetes on no medications (22%) or on basal insulin only (31%) were the least aware of this metric.
Awareness of TIR was also associated with a person’s use of a continuous glucose monitor (CGM). While 57% of CGM users were aware of TIR and knew a lot about it, only 2 percent had never heard of it. In contrast, almost half of CGM non-users had ever heard of TIR.
However, across the board, more than three in four CGM non-users felt TIR could be “somewhat helpful” or “extremely helpful” with their diabetes-related treatment decisions.
The data highlighted a significant lack of TIR awareness among people with type 2 diabetes and CGM non-users. It suggests that there may be opportunities to increase awareness through improving access to CGM and through the education of healthcare providers on strategies for leveraging CGM to monitor glucose levels.
Click to view the poster on the awareness of TIR.
Use of TIR
Overall, people with type 1 diabetes were the most likely to be using TIR (58%), while those with type 2 diabetes on no medications (12%) or on basal insulin only (18%) were the least likely to use TIR in goal setting and diabetes management.
People with type 1were the most likely to identify improving TIR as one of their top three diabetes health goals (47%) while those with type 2 diabetes on no medications (4%) or on an SGLT-2 or GLP-1 (12%) were the least likely.
Additionally, 30% of people with type 1 diabetes identified TIR as the most important diabetes metric compared to 8% of people with type 2. The most important diabetes metric for both groups was A1C: 40% of people with type 1 diabetes and 70% of people with type 2 diabetes chose this metric.
The data highlights that people with type 2 diabetes and CGM non-users were less likely to use TIR or identify it as an important diabetes metric. It also shows that people with type 1 are prioritizing TIR as an important personal goal in their diabetes management. In order to increase the use of TIR, it’s important to continue increasing access to CGMs.
It’s important to increase the awareness and adoption of Time in Range because people with diabetes and their health care providers should have the information and data they need to make informed health decisions“It’s important to increase the awareness and adoption of Time in Range because people with diabetes and their health care providers should have the information and data they need to make informed health decisions,” Kenney said.
Click to view the poster on the use of TIR.
Progress Made Towards the Global Adoption of Time in Range
In April 2022, 32 of the world’s premier diabetes experts gathered in Barcelona, along with representatives from industry, advocacy, and regulatory bodies, to discuss the use of continuous glucose monitors in clinical trials. The lively discussion is expected to have a great impact on propelling the use of Time in Range globally.
Read the full coverage here.
Updates on Automated Insulin Delivery
Automated insulin delivery systems are becoming more advanced and over time have become more widely adopted within the diabetes community. At ATTD 2022, experts presented updates on this emerging technology including results on the iLet Bionic Pancreas and MiniMed 780G.
Read the full coverage here.
WhatsApp and Professional CGM Used to Treat Diabetes in India
India is a developing country where diabetes is highly prevalent. Leading endocrinologists shared how they utilize the messaging service WhatsApp and Professional CGMs to overcome barriers.
Read the full coverage here.
The future of once-weekly insulins
Since the discovery of insulin over 100 years ago, significant advancements have made the drug safer and more effective for people with diabetes. Despite this long history, experts continue to strive towards biologically engineered insulin that more closely mimics the action of insulin from the pancreas of someone without diabetes. Experts at the ATTD conference in Barcelona, Spain discussed two once-weekly basal insulins currently being investigated in clinical trials.
Experts drew attention to the two ultra-long acting insulins that are furthest along in the approval process: basal insulin Fc (BIF) and Icodec. Each of these drugs requires only a single injection per week, which could potentially reduce the stress from frequent insulin injections and improve the likelihood that people are able to consistently follow their insulin regimen.
Dr. Juan Pablo Frías, medical director and principal investigator at Velocity Clinical Research in Los Angeles, California, explained that to develop the ultra-long acting property of BIF, researchers used the same method that was used in developing the long-lasting effects of once-weekly GLP-1 drugs. Frías discussed the latest phase 2 clinical trials for BIF, which are investigating the drug in people with type 2 diabetes.
The evolution of basal insulins has led to [insulins] with longer and flatter time-action profiles and less frequent dosing, which is a greater convenience for patients“The evolution of basal insulins has led to [insulins] with longer and flatter time-action profiles and less frequent dosing, which is a greater convenience for patients,” said Frías.
In one study, the effects of BIF were compared to treatment with degludec, a once-daily basal insulin. Over the course of the 32-week trial, participants significantly improved their A1C with both treatments, and BIF was deemed “non-inferior,” meaning that it was as effective as the currently available basal insulin in lowering A1C. Additionally, participants using BIF had lower rates of hypoglycemia and less variability in their glucose levels, as measured by a continuous glucose monitor (CGM). Frías announced that BIF is now being investigated in a larger phase 3 clinical study, including people with type 1 and type 2 diabetes, lasting 78 weeks in total.
Farther along in the research process, Icodec is another once-weekly basal insulin currently being investigated in six different phase 3 trials across the globe. On April 28, 2022, Novo Nordisk released results from one of these trials, comparing icodec with once-daily insulin degludec. The trial, which included 526 people with type 2 diabetes, found that people using the once-weekly icodec achieved a greater reduction in A1C compared to those using degludec (0.93% vs. 0.71% decrease, respectively). There was no significant difference in the estimated rates of hypoglycemia.
Dr. Andrej Janez, professor of internal medicine and head of the department of endocrinology at University Medical Center Ljubljana, Slovenia, also reported the results from several phase 2 trials for icodec, including 600 people with type 2 diabetes across all studies. According to Janez, participants who were given icodec required significantly lower insulin doses compared to those on the once-daily insulin glargine. There were also no significant differences in body weight changes or rates of hypoglycemia between the two groups.
“After 100 years of insulin, these molecules still have a bright future, and [once-weekly basal insulin] is the way towards it,” said Janez.
New Drug Tirzepatide Shows Extraordinary Results For Obesity and Type 2 Diabetes
Clinical trial results published by Lilly show that Tirzepatide could potentially be one of the most effective drugs ever developed for weight loss. Experts discuss these results and more at the ATTD 2022 conference in Barcelona, Spain.
Read the full coverage here.
Screening and Prevention of Type 1 Diabetes
Throughout the 2022 ATTD conference in Barcelona, Spain, experts from around the globe discussed the latest advancements in technology and therapy that can benefit people with type 1 diabetes. In the final session, experts gathered to discuss new models for public health screening for type 1 diabetes and ways to potentially curb the continued increase in the number of people living with type 1 diabetes.
Dr. Thomas Danne, director of the Department of General Pediatrics Endocrinology/Diabetology & Clinical Research at the “Auf der Bult” Hospital for Children and Adolescents, Hannover Medical School in Germany, described population screening for type 1 diabetes as a “paradigm change” in addressing the rise in the prevalence of type 1 diabetes.
Public health screenings for type 1 diabetes seek to identify whether a person has formed a specific set of “autoantibodies,” which, over time, can trigger the autoimmune response that destroys pancreatic beta cells that make insulin, leading to type 1 diabetes. Those who have two or more of these autoantibodies are at an increased risk for being diagnosed with type 1 diabetes.
Public health screening for autoantibodies can drastically reduce the rate of diabetic ketoacidosis (DKA), which is often how people are initially diagnosed with diabetes.
According to Dr. Moshe Phillip, director of the Institute of Endocrinology and Diabetes at the National Center for Juvenile Diabetes at Schneider Children's in Israel, between 30% and 40% of people diagnosed with type 1 diabetes were diagnosed due to an episode of DKA. This condition can be life-threatening, so population-screening methods that can minimize episodes of DKA can potentially save lives.
According to Phillip, of those who are positively screened for more than two autoantibodies, 70% develop type 1 diabetes within 10 years, increasing to 84% within 15 years. He described this period as a multi-year “window” to possibly delay or prevent clinical type 1 diabetes.
Along with limiting DKA, Danne explained that advantages to population screening include reducing psychological distress around diagnosis, lowering the risk for hospitalization, and controlling the transition to insulin therapy.
Danne and Phillip each described recent efforts to screen for type 1 diabetes at the population level. The Global Platform for the Prevention of Autoimmune Diabetes(GPPAD) is an effort that seeks to identify infants with an elevated genetic risk for type 1. GPPAD has several participating sites across Europe, with the hopes of screening newborns within the first seven days of life for risk, as well as additional preventative treatment from ages 4 to 7 months for those at higher risk.
Phillip discussed the Antibody Detection Israel Research (ADIR) project, a national screening program in Israel that plans to screen 50,000 children to identify those at risk for developing type 1 diabetes. The process includes two screenings, the first at 9 to 18 months, and the second at either age 2-3 or 4-5. Researchers are still assessing which of these is the most optimal age window for screening. Children with more than two antibodies will follow up with additional interventions.
“We think this is a model for a national screening program, promising screening technology, and could change the paradigm of type 1 diabetes prevention,” Phillip said.
Antibody screenings for type 1 diabetes use only four microliters of blood, approximately the amount obtained from a fingerstick, making the test itself relatively easy. However, problems still remain in identifying who should be screened and how to intervene once screened. According to Phillip, approximately 90% of people diagnosed with type 1 diabetes have no family history of the disease.
Currently, there is no approved medication to delay or prevent the onset of type 1 diabetes, however, there are several being studied for possible approval in the future. The farthest along is teplizumab, which Danne described as a potential “gamechanger,” has shown encouraging clinical trial results. Within a study of those who screened positively for autoantibodies, teplizumab delayed the onset of type 1 diabetes by almost three years (32.5 months).
Teplizumab may have benefits for several years even after a small amount of treatment, said Dr. Jay Skyler, professor of Medicine, Pediatrics, & Psychology in the Division of Endocrinology Diabetes & Metabolism at the Miller School of Medicine in Miami, Florida. He explained that more than five years after just a 14 day treatment with teplizumab, 18% of teplizumab-treated patients still did not have clinical diabetes, compared to only 6% in the placebo group.
Experts on the panel agreed that there are significant benefits to public health preventative screening for type 1 diabetes, especially during childhood for those who have a higher genetic risk.
What We Wish You Knew and Why: Open-Source DIY AID, Access, and Stigma
At the ATTD 2022 conference, diabetes advocates delivered presentations on open-source AID, access to insulin and diabetes supplies, and diabetes stigma in the #dedocº Symposium.
Read the full coverage here.
Comprehensive Approaches to Addressing Hypoglycemia
At ATTD 2022, several researchers presented on projects aimed at understanding and addressing the impact of hypoglycemia. While diabetes technology is helpful and effective, it can only go so far. Read about other approaches in minimizing the harm that hypoglycemia can cause.
Read the full coverage here.
Exercise and diabetes: Early results from the T1-DEXI trial
Everyone can benefit from exercise, and for those living with type 1 diabetes, exercise and physical activity can improve insulin sensitivity, reduce the chances of developing diabetes-related complications, and improve quality of life.
However, exercising with type 1 can sometimes be a challenge due to its varying effects on glucose levels. Until now, we didn’t know exactly how or why different types of exercise habits affected glucose levels during and after activity differently.
The T1-DEXI trial set out with a goal to understand the impact of exercise on glucose levels. It is the first large-scale study to collect data from real-world exercise activities while tracking a range of factors including insulin and glucose data, physical activity, stress levels, as well as the timing and composition of meals. The data was collected using a Dexcom G6, a chest strap heart monitor, a Verily Study Watch, and the T1-DEXI smart phone app.
On the second day of the ATTD 2022 conference, Dr. Michael Riddell, of the Muscle Health Research Centre at York University in Toronto, Canada, presented exciting preliminary data on T1-DEXI. The study included almost 500 adult participants with type 1 diabetes who were using either a closed loop insulin pump, multiple daily injections of insulin (MDI), or an insulin pump. At the start of the trial, each participant was randomized to perform aerobic, high intensity interval training (HIIT), or resistance exercise using structured, thirty minute videos over the course of four weeks. The participants also logged their meals and unstructured exercise activities.
Overall, 15,000 individual exercise sessions were recorded over the course of the study. Though, unsurprisingly, the results clearly showed that aerobic exercise led to the greatest drop in glucose (around 20 mg/dL) compared to HIIT (15 mg/dL) or resistance training (9 mg/dL), ultimately there was a lot of variation from individual to individual.
What T1-DEXI showed however, is that there are “a number of variables that can predict the variability in the [glucose] response to exercise, and some of these are quite novel,” said Riddell. “For example baseline heart rate is a great predictor of change in glucose. Surprisingly to me, the lower the baseline heart rate, the greater the change in glucose during exercise.”
Other factors that had a significant effect include the exercise type, rate of change in glucose before exercise, insulin on board, the time of day, sex, glucose level and A1C at the start of exercise, and Time in Range and Time Below Range (from the last 24 hours).
Additionally, “On those days where people were doing structured forms of exercise, their Time in Range was better compared to all other days,” Riddell said. “And the change in Time in Range is quite clinically relevant, with almost a 10% improvement in Time in Range.”
More results from the T1-DEXI study will be shared at the American Diabetes Association’s 2022 Scientific Sessions this coming June in New Orleans. In addition the T1-DEXIP study, which aims to evaluate the effects of exercise on glucose levels in children is still recruiting. Learn more here.
Considering mental health and treatment satisfaction in type 1 diabetes
Glucose management has long been thought of as the most important indicator of quality of life for people with type 1 diabetes. However, a look at the growing body of research around patient-reported outcomes (PROs) in clinical diabetes care suggests that other factors might be more meaningful.
A PRO, as summed up by Harsimran Singh, health psychologist and leader of the behavioral research team at Tandem, is “a direct report from the patient, either a phone call, survey, or conversation, that asks the patient questions about how they feel and what they like.” Singh and other experts on the third day of the 2022 ATTD conference in Barcelona, Spain, discussed the importance of PROs and the urgent need to include them in future care and clinical trials .
Diabetes distress can be a common result of feeling burned out from the physical and emotional demands of diabetes management.
“About 40% of people with type 1 diabetes live with distress,” said Dr. Mike Davies, senior director, clinical sciences at Lexicon Pharmaceuticals. “And once it happens, it tends to persist,” resulting in stress, anxiety, depression, eating disorders, and many other negative mental health consequences.
Davies highlighted results from two studies (inTandem 1 and inTandem 2) of sotagliflozin, a SGLT-2 inhibitor with the brand name Zynquista. These studies, which included only people with type 1 diabetes, found that the drug significantly improved treatment satisfaction and reduced overall feelings of diabetes distress. These results were due to many different factors including weight change, perceived safety of the drug, and risk for hypoglycemia. It should be noted however, that the use of this medication did increase the risk of diabetic ketoacidosis (DKA).
When selecting the most appropriate treatment for people with type 1 diabetes, clinicians should consider how treatment affects the whole person, looking beyond A1C alone“When selecting the most appropriate treatment for people with type 1 diabetes, clinicians should consider how treatment affects the whole person, looking beyond A1C alone,” said Davies. This extends beyond medications, including diabetes technologies such as continuous glucose monitors (CGM) and insulin pumps.
To illustrate the importance of looking beyond glucose management in measuring the effectiveness of treatment, Singh referenced early efforts at creating an insulin pump and glucose sensor in the 1960s. The proposed device was impractical, extremely heavy and had to be worn as a backpack. As a result, it was never manufactured nor used by people with diabetes.
Singh, from her experience at Tandem, shared findings from a survey about what factors people with diabetes prioritize when considering an automated insulin delivery (AID) system. Respondents reported that they preferred a system that they trusted and controlled, had good features, and that had the largest impact on ease of management. The priority of glucose management is notably excluded from this list, which, according to Singh and other experts in the session, could also be a byproduct of satisfaction with their devices, improving a user’s engagement in their care.
Because diabetes distress may be experienced by people with diabetes of all ages, the panelists emphasized that PRO measures should be considered at all points throughout life, which could be supported by clinical trials for devices and medications.
“The psychological burdens [of type 1 diabetes] can start in childhood and persist throughout life,” said Dr. Jigar Rajpura, a health economist at Novo Nordisk. “When children reach adolescence, they may go through an identity crisis of coming to terms with their diabetes diagnosis. Eating disorders and depression are unfortunately common.”
Dr. Sanjoy Dutta, chief scientific officer at JDRF said: “The disease burden changes throughout the journey with type 1 diabetes, depending on the individual.”
The panelists said that there is a need for more research studies that have PROs as a main outcome to see how changes in glucose affect PROs in the trials.
Sleep in children with diabetes
On average, children and teens with type 1 diabetes get about 26 less minutes of sleep each night and experience more sleep disturbances compared to those without type 1 diabetes. Less sleep and poor sleep quality are likely to result in a higher A1C, decreased insulin sensitivity, and other self-management challenges.
In addition to the effects that poor sleep can have on the body, it can also affect a person’s behavior which can lead to poorer food choices, less exercise, and less blood glucose monitoring, said Professor Sarah Jaser, a pediatric psychologist at Vanderbilt University in Tennessee, who presented sleep study results at ATTD 2022 in Barcelona, Spain. Poor sleep, she said, can also affect one’s mental awareness and reduce blood flow to the brain.
Jaser described the factors that prevent children from getting quality sleep, including:
- School start times (which are often very early in the morning)
- Screen time and social media
- Shifts in circadian rhythms
- Increased extracurricular and academic demands
The balancing act of using diabetes technology is well documented, with devices having incredible benefits but also several burdens. Along those lines, the use of diabetes technology can have both positive and negative effects on the quality of sleep in children with type 1 diabetes.
One study found that hybrid closed-loop insulin systems improved sleep quality but woke children up in the middle of the night with alarms (leading to less time asleep).
“Emerging technologies may have potential to reduce diabetes-related sleep disturbances,” said Jaser, “but we need realistic expectations of the benefits.”
In order to ensure that children and caregivers get enough sleep, Jaser emphasized the importance of identifying barriers and contributors to sleep in children and teens. She proposed a sleep intervention program that aims to analyze these factors and determine if a sleep-promoting intervention could help.
Though the study did not find any change in a child’s sleep duration or quality, it did find that parents in the study reported better sleep quality over three months compared to those who did not complete the sleep program.
The study also points to the need to continue understanding the barriers to quality sleep and how they vary by person. Especially since many challenges that prevent children with diabetes from getting quality sleep are similar to the general population (needing to get up early for work or school, using a screen before bed, and evening plans).
Children, parents and caregivers, and healthcare providers should work together to fully understand what factors affect sleep quality and how they can be addressed
Read more about the link between sleep and diabetes:
- Sleep: The Most Forgotten Blood Sugar Strategy
- The Most Destructive Diabetes Landmine: Lack of Sleep?
Women’s Health & Diabetes Technology – The Latest
At ATTD 2022, researchers discussed the latest research on pregnancy, menstrual cycles, and overall health outcomes in women with diabetes. Diabetes technology can be a valuable tool to improve women’s health and empower people with real-time health data.
Read the full coverage here.
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