Debate: Should the Artificial Pancreas Include Glucagon? (ADA 2020)

For the millions of people living with type 1 diabetes worldwide, the development of an effective system to automatically regulate blood sugar levels is of paramount significance. Artificial pancreas systems (APS) are being developed with the goals of automatically adjusting the delivery of insulin (and potentially, glucagon) based on glucose readings from a continuous glucose monitor (CGM), taking a lot of burden off patients, improving glycemic management, and enhancing safety.

What is the best way to approach the design of an artificial pancreas system? What are the pros and cons of including glucagon in the system alongside insulin?

Two experts debated this important issue at the American Diabetes Association (ADA) 80th Scientific Sessions last month.

Dr. Roman Hovorka, PhD, FMedSci from the University of Cambridge, argued against the inclusion of glucagon in the system, while Dr. Steven J. Russell, MD, PhD from the Massachusetts General Hospital, presented his case to support the use of a dual-hormone system. Both speakers disclosed several relationships with diabetes technology companies (including those working to develop APS).

Here is the summary of this interesting debate.

The Case for Single Hormone

Dr. Roman Hovorka highlighted some research outcomes of artificial pancreas systems that utilize insulin alone.  He presented data from several studies showing that these devices “improve time in target and time below target” as well as reduce A1c. However, the time in target range was only increased by ~11%, and the A1c improvements were modest, with the average A1c still above the ADA recommendations.

Dr. Hovorka explained that the vast majority of companies are currently moving forward with single-hormone systems. He also focused on a system developed by Cambridge that he’s very familiar with, showing data where ~95% time-in-range (TIR) was achieved. Notably, he remarked that a low-carb diet was also an important factor in this success case. Overall, however, only 7% of users were shown to achieve a time-in-range metric of >90%, although 28% achieved a TIR of >80%, 69% achieved a TRI >70%, and 86% achieved a TIR of >60%.

The presenter noted that one of the main issues currently hindering the efficacy of the APS is the delayed insulin absorption and action after subcutaneous insulin delivery. Adding glucagon into the system will not fix the issue, he noted, as “dual hormone delivery DOES NOT accelerate insulin absorption.”

While he acknowledged that glucagon could be useful in reducing low blood sugar risk in such systems, he also highlighted the complexity and high cost of such a system as barriers. In addition, he noted that the use of two separate cannulas could be burdensome, and for children, in particular. He also noted that the chronic delivery of glucagon subcutaneously requires more research to identify any risks.

In comparing the outcomes between single-hormone vs. dual-hormone systems, Dr. Hovorka noted that there was a slight increase in the TIR for the dual system (~78% vs. 71% in the longest studies), and the mean glucose (156 mg/dL vs. 140 mg/dL) was lower for those using the dual system. He also presented data to indicate that daytime hypoglycemia (in particular during exercise) could be reduced using a glucagon-insulin system, while a single insulin system was enough to eliminate hypoglycemia overnight. Furthermore, “comparative benefits of the single- and dual-hormone systems for improving HbA1c and preventing severe hypoglycemia remain unknown,” he underscored.

The Case for Dual Hormone

Dr. Steven Russell noted first that he believes “insulin-only hybrid artificial pancreas systems are the state-of-the-art in diabetes care” and that he is involved with projects that utilize both single- and dual-hormone approaches. Next, he went on to explain why he thinks a dual-hormone system would be more appropriate.

After pointing out that there are actually two hormones that are missing in type 1 diabetes – insulin AND glucagon, he suggested that in addition to further preventing hypoglycemia, a dual-hormone system can also help achieve lower average glucose and higher TIR than an insulin-only system. He presented several studies to support this point, including recent data from his project.

Importantly, Dr. Russell pointed out that by using micro-doses of glucagon to prevent or treat hypoglycemia could “oppose weight gain or encourage loss”. This is because using glucagon instead of carbohydrates to prevent or treat low blood glucose “promotes satiety and increases energy expenditure”.

While the speaker acknowledged the challenges associated with developing a dual-hormone system, he also noted that recent work has been bringing us closer to achieving this feat effectively. For instance, a number of stable glucagon formulations are now available (although not yet FDA approved for use in such a system). The safety studies that have been conducted have been reassuring.

Moreover, Dr. Russell addressed a common concern of glycogen store depletion, citing a 2015 study that indicated “no significant decrement in liver glycogen after repeated glucagon doses”. Importantly, he also presented some research showing that “users prefer the bi-hormonal system”, especially among those who aim for lower targets.

When addressing the potential increase in cost for a dual-hormone system, Dr. Russell had this to say:

“[The] significant increase in beneficial outcomes will justify the increase in cost… The difference in having no automation to single-hormone artificial pancreas is the same increment as you get going from a single-hormone artificial pancreas to dual-hormone… If one can justify adding automation, one could justify some additional expense to add the cost of the glucagon…”

Conclusions

Numerous artificial pancreas systems are currently being developed, with the vast majority opting for the insulin-only version. No doubt, the specific algorithms and insulin types used also play a paramount role in their efficacy and patient satisfaction. The use of glucagon remains a point of contention.

What are your thoughts on the subject?

Source: diabetesdaily.com

The Biggest News in Diabetes Technology, Drugs, and Nutrition: Highlights from ADA 2020

This content originally appeared on diaTribe. Republished with permission.

By Eliza Skoler, Jimmy McDermott, Matthew Garza, Divya Gopisetty, Frida Velcani, Emily Fitts, Karena Yan, Joseph Bell, and Rosalind Lucier

The diaTribe team attended the 2020 ADA 80th Scientific Sessions to share several of the greatest highlights from the virtual conference!

The American Diabetes Association (ADA) 80th Scientific Sessions was full of exciting news on advances and studies in diabetes technology, treatments, and nutrition. Click on the links below to learn more!

Diabetes Technology

Diabetes Drugs

Nutrition, Exercise, and Mindset

Access to Care and Policy

Diabetes Technology

The Next Generation of Automated Insulin Delivery Systems for People with Type 1 Diabetes – Updates from Four New Clinical Trials

The first day of ADA featured data on four clinical trials of the newest automated insulin delivery (AID) systems. In what was a packed (virtual) room, the session began with three highly anticipated presentations of studies on Medtronic’s MiniMed 780G Advanced Hybrid Closed Loop System (AHCL). Dr. Bruce Bode, presented the US adult pivotal trial. Here are the main results:

  • Big news – nearly 80% of participants achieved a time in range of more than 70% without an increase in hypoglycemia.
    • On average, AHCL therapy increased time in range to nearly 75% from a baseline of 68.8%.
    • Among adolescents, time in range increased to over 72% from a baseline of 62.4%.
  • AHCL therapy improved average A1C from 7.5% to 7.0%. This is what is sometimes called a “high quality A1C” in the field – hypoglycemia is low, and therefore not contributing to a “better” number.
  • How were these results achieved? Experts said that the lower algorithm target of 100 mg/dl (vs. 120 mg/dl) helped, along with an active insulin time (AIT) setting of 2-3 hours. If you use a pump, check what you have for this setting and talk to your healthcare professional about it to see if you can make changes (regardless of whether your pump can deliver insulin automatically).

Following Dr. Bode, International Diabetes Center’s Dr. Rich Bergenstal shared data from FLAIR, a trial comparing MiniMed 780G Advanced Hybrid Closed Loop (AHCL) with the 670G Hybrid Closed Loop (HCL) in adolescents and youth with type 1 diabetes (ages 14-29). This is the first ever head-to-head comparison of an AID system with a commercially available AID system. The study also had broad entry criteria: at start, 20% of participants were on multiple daily injections of insulin (MDI), 38% were not using CGM, and 25% had a baseline A1C above 8.5%.

  • Time in range over 24 hours increased from 57% at baseline to 63% with the 670G and to 67% with the 780G. Notably, 6% greater time in range totals nearly an hour and a half more time in range per day.
  • Compared to baseline, the number of participants achieving the international time in range consensus target of more than 70% was nearly two times higher with the 670G and almost three times higher with the 780G (22% and 32% of participants, respectively, compared to a baseline of 12%; see slide below).
  • This was the first time that a study measured participants meeting the combined metric of both time in range greater than 70% and time below 54 mg/dL less than 1% (see slide below). This is important since all therapy – and particulary automated insulin delivery – aims to decrease hyperglycemia and hypoglycemia.

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Image source: diaTribe

  • From a baseline average of 7.9%, those on the 670G achieved an average A1C of 7.6%, and those on the 780G had A1Cs that fell to 7.4% on average.
  • Both the 670G and 780G were considered safe when evaluating severe hypoglycemia or diabetic ketoacidosis (DKA).
  • Participants satisfaction favored the 780G over the 670G.

Today’s MiniMed 780G data finished with Dr. Martin de Bock’s study, which served as the clinical trial supporting 780G’s CE-Mark submission (and today’s announced approval in Europe). In a study of 59 people (ages 7-80 years, with an average age of 23) who had never used an insulin pump:

  • Average time in range increased to over 70% from 58% (a change of 12.5%) when using the 780G compared to a sensor augmented pump.
  • Overnight time in range increased to 75% from 59% when using the 780G compared to the sensor augmented pump.
  • The improvement in time in range was primarily driven by a 12.1% decrease in time in hyperglycemia (high blood sugar) with the 780G.

It was warming on Twitter to see Dr. de Bock with his three small children while also engaging in Q&A/Chat from their breakfast table. If you’re on social media, follow Dr. De Bock here.

The session concluded with Stanford’s Dr. Bruce Buckingham who presented data on Insulet’s Omnipod 5 Automated Glucose Control System, powered by Horizon. What fantastic data! The study assessed the safety and effectiveness of the fully on-body system over 14 days of use before starting the three-month pivotal study. Interestingly, this study was conducted during the winter holiday season when some of the lowest time in range is observed (typically a three percent drop); the system performed remarkably well in both children and adults, even during this challenging time period.

  • In adults, time in range increased to 73% on the hybrid closed loop system, up from 65.6% using standard therapy – this is the same as nearly two hours more time in range per day.
  • In youth, time in range increased to 70% on the hybrid closed loop system, up from 51% using standard therapy – what an increase, nearly five hours more per day.

These reductions in time in range were mostly driven by a decrease in hyperglycemia. Hypoglycemia was also very low to start. Dr. Buckingham eloquently emphasized, “… this is so important for families and people at night to go to sleep and not worry about hypoglycemia … for a number of kids, they got to go on their first sleepover during this study. It was really decreasing a lot of the burden and a lot of the thinking about diabetes.”

Tandem’s Control-IQ Real-World Data: Time in Range Increases 2.4 Hours Per Day

Tandem presented two posters featuring very positive real-world data from early Control-IQ users. Control-IQ was cleared in December 2019 and officially launched in January 2020.

The first poster, Control-IQ Technology in the Real World: The First 30 daysincluded at least 30 days of pre- and post-Control-IQ data from 1,659 participants. During the first 30-days of Control-IQ use:

  • Time in range increased by 2.4 hours a day (compared to pre-Control-IQ data) to 78%
  • The time in range improvement was driven by a 9.5% decrease in time spent above 180 mg/dl (that’s 2.3 hours less per day in hyperglycemia – wow!).
  • Average glucose levels fell from 161 mg/dL to 148 mg/dL.
  • Glucose management indicator (or GMI, an estimate of A1C) fell from 7.2% to 6.9%.
  • Users spent 96% of time in closed loop!
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The second poster, Glycemic Outcomes for People with Type 1 and Type 2 Diabetes Using Control-IQ Technology: Real-World Data from Early Adopters, looked at 2,896 participants with type 1 diabetes and 144 participants with type 2 diabetes, using at least 14 days of pre- and post-Control-IQ data.

  • Time in range was improved by 2.1 hours per day in the type 1 group to 77%
  • Time in range was improved by 1.4 hours per day in the type 2 group 79%
  • Both groups spent 96% of time in closed loop.

We learned so much at ADA about improving time in range, and we were moved by the power of automated insulin delivery in doing so, since it shows much greater time in range with what sounds like so less work for people and their healthcare teams.

To learn more about Control-IQ, check out the following articles:

A1C vs. Time in Range – Which Should be Used for Children with Diabetes?

A panel discussion of leading experts, moderated by JDRF CEO Dr. Aaron Kowalski, focused on the pros and cons of using A1C and time in range as primary metrics in diabetes care and management for children. As they debated the best marker of glucose management, they attempted to define the ultimate “goal” of diabetes care: is it preventing complications, spending less time in hyperglycemia and hypoglycemia, or improving mental and emotional wellbeing?

Dr. William Winter presented extensive evidence that A1C can predict a person’s risk of developing complications (kidney disease, heart disease, retinopathy, and neuropathy). While lower time in range has been associated with microvascular complications, experts agree that more studies are needed to determine its predictive accuracy for long-term outcomes. Dr. Thomas Danne presented results from the SWEET project that furthered the case for A1C as a measure of population outcomes: setting ambitious targets based on A1C could lead to significant improvements in outcomes for children with type 1 diabetes.

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Experts discussed cases in which A1C can be misleading and time in range may emerge as a more reliable measure of glucose control. Dr. Winter explained that population A1cs differ among racial and ethnic groups, leading to misdiagnosis (for example, African Americans have a higher A1c on average compared to white people). Very importantly, as diaTribe has reported on for many years in Beyond A1C research, A1C also does not demonstrate hypoglycemia, hyperglycemia, or glucose variability. According to Dr. Danne, healthcare professionals find CGM reports more helpful in identifying daily highs and lows and in adjusting therapy. This technology allows them to better work alongside families to set individual and measurable goals based on time in range – it is terrific to hear about this continued teamwork.

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SENCE

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Though Dr. Danne acknowledged the issue of access and affordability, he believes CGM use will continue to increase among children who are tech savvy. Dr. Daniel DeSalvo presented data from the SENCE and CITY to further support use of CGM among children with type 1 diabetes.

CITY

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Young children (two to seven years old) enrolled in the SENCE study saw their hypoglycemia (blood glucose under 70 mg/dL) and time spent over 300 mg/dL reduce by 40 minutes per day – that’s nearly five hours a week. Teens and young adults (ages 14 to 24) in the CITY study saw a 7% increase in time in range, which is almost two more hours per day spent in range – 100 minutes, to be exact!

The Use of CGM in Type 2 Diabetes — Is There Value?

Continuous glucose monitoring (CGM) has been a revolutionary tool; it gives people real-time updates on their blood glucose levels that can help to increase time in range (TIR). For most providers in diabetes, the value of CGM is now nearly universally supported (either “real-time” or “professional CGM”) even if all people with diabetes can’t get it. Reimbursement throughout much of the world has reinforced the value of CGM in type 1 diabetes almost everywhere, though the value of CGM for people with type 2 diabetes is still being explored.

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Dr. Philis-Tsimikas argued for CGM for type 2 diabetes given the technology’s ability to offer remote solutions for care management, provide direct feedback of behavior modification, and allow evidence-based changes to drug therapies. Dr. Philis-Tsimikas shared data from several CGM studies in people with type 2 diabetes on a variety of therapies (basal insulin alone, and oral and other medications), highlighting the improvement in clinical and behavioral outcomes. In what could be the most exciting set of results, people with type 2 diabetes who used real-time CGM (RT-CGM) intermittently for 12 weeks showed an average A1C reduction of 1 percentage point at the end of 12 weeks (compared to a 0.5 percentage point reduction in the blood glucose meter control group). During the 40-week follow up period, A1C was still significantly lower in the RT-CGM group.

Dr. Elbert Huang gave what we felt was a less persuasive view. He argued that in most cases, CGM use is not valuable for people with type 2 diabetes, on the basis of cost. Howerver this is based on outdated data – just yesterday at ADA, there was striking Late-Breaker data presented that showed very meaningful reductions in A1c by Dr. Eden Miller and Dr. Gene Wright (he’ll be speaking at the TCOYD/diaTribe Forum Monday night!) The study showed very meaningful A1C reductions in thousands of people with diabetes – starting A1C was 8.5%, which fell to 7.6% to 7.9% depending on the population. Dr. Huang presented two studies that showed that the cost ratio of CGM was different depending on the assumptions of costs related to the quality and quantity of lives impacted by type 2 diabetes. A QALY, by the way, is a “quality adjusted life year” that measures both quantity and quality (based on disease burden) of life years. We also strongly believe that many people become more engaged in their diabetes management due to a variety of factors that reduce stigma (no fingerstick tests required, etc.) and enable them to focus on how data and technology can work together to improve their results.

Dr. Huang suggests that less costly treatments (such as the use of ACE inhibitors to avoid high blood pressure or to prevent kidney disease) might be better areas of focus and certainly all experts would agree that focus here is important as well. He also mentioned potential negative psychological effects of constantly checking blood glucose readings using CGM and the fact that this technology may only work if it is shared with a person’s healthcare team – we agree integration with healthcare teams where available is a valuable point and also emphasize our learnings from ADA 2020 from many providers that emphasize, as Dr. Diana Isaacs did on Saturday, that CGM enables greater interest in diabetes management by people. While the technology is extremely important, Dr. Huang also expressed that it could be more valuable if the price of CGM declines or if it is shown to improve glucose management while also reducing the need for costly medicines, among other factors – these factors of cost are extremely important. CGM is going down in price on average and global pricing of $109/month is already available from FreeStyle Libre all over the world. While no one should have to pay $3/day on their own, we believe many more health systems are interested in investing more here due to the positive results they are seeing. We’ll be back with more data from the ADA 2020 Scientific Sessions on this and related fronts!

Parent Perspectives on DIY Closed-Loop

An observational study on Loop, a do-it-yourself (DIY) automated insulin delivery system (AID), used focus groups to gather the attitudes and experiences of parents and children using Loop. The study followed people using an AID system, continuous glucose monitor (CGM) readings, and a communications bridge device, called “RileyLink.”

Overall, parents felt that Loop had a positive impact on their family’s lives. They reported the following outcomes:

  • Improvements in emotional health as a result of a greater sense of security and normalcy, increased quality of life, and decreased parental stress.
  • Improvements in other areas of life, including management of children’s diabetes at school, quality of sleep, confidence in caregivers, and children’s ability to explore extracurriculars without supervision.

Dr. Anastasia Albanese-O’Neill presented survey results on what parents expect of school and diabetes camp staff to help their children manage their DIY closed-loop system. School nurses were also surveyed on their opinions regarding DIY. Here are some highlights:

  • 29% of parents expect that school staff will assist children with delivering a bolus.
  • Expectations of diabetes camp staff were lower than school staff – 23% of parents expect school staff to assist with carbohydrate counting and timing of bolus, while only 13% of parents expect diabetes camp staff to do those things.
  • Though 46% of school nurses had never heard of DIY before participating in the survey, 33% of them agreed that school staff should help students using DIY who cannot manage it independently.

This suggests a need for training on DIY and diabetes technology for school and camp staff.

Is Technology the Solution to Hypoglycemia? Dr. Bergenstal and Dr. Wilmot Debate

Dr. Richard Bergenstal from the International Diabetes Center (IDC) emphasized the advantages of using continuous glucose monitoring (CGM) for reducing episodes of hypoglycemia (low blood sugar) and other health complications in this debate with Dr. Wilmot. Both doctors are highly regarded, and we took this as a big opportunity to learn lots more rather than land only on one size, though it’s certainly hard to avoid saying yes to this question, from diaTribe’s perspective. Dr. Bergenstal eloquently explained that, on average, hypoglycemia is the biggest barrier to optimal blood glucose management, pointing to the fact that A1C levels increase when people fear going low (what he called the “ripple effect of hypoglycemia”). Luckily, with CGM reports, people can finally detect patterns in hypoglycemia and understand exactly how much time they are spending with blood glucose levels under 70 mg/dL in a day.

Evidence shows that closed-loop technology can reduce and even prevent hypoglycemia. In a study of 124 people with diabetes that Dr. Bergenstal shared, the use of automated-insulin delivery systems (AID) completely eliminated hypoglycemia. This was a historic win – previous studies (see slide below) using low glucose suspend systems (LGS) reduced hypoglycemia by 38%, while predictive low glucose suspend systems (PLGS) reduced hypoglycemia by 59%.

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Dr. Emma Wilmot argued that while these findings are exciting, technology is only part of the solution. Technology does reduce the risk of hypoglycemia, but is not available to all (particularly those from underserved populations) and is not suited to all. She said that unless CGM is also paired with structured education, it will not provide the significant and lasting improvements in hypoglycemia awareness that the diabetes community needs. We know, of course, how important education is – and diaTribe will be coming back to discuss this in an upcoming piece about a new article just published in Diabetes Care earlier this week (Diabetes Sisters’ CEO Anna Norton was a key author in the new consensus report)!

Early CGM use can help kids and predict T1D progression

The use of CGM across different populations – including people of various ages and different stages of type 1 diabetes – shows that CGM can accurately predict the progression of type 1 diabetes for people at risk. For those transitioning from “stage 2” to “stage 3”, continuous monitoring can also help prevent DKA, which many people with type 1 have at diagnosis. While there are no clinical guidelines at the moment for how to manage “stage 2” type 1 diabetes, the TESS study is currently evaluating the benefits of CGM use in this population. “Staging” of type 1 diabetes is fairly new and we will be thinking about this more as we consider how to further improve education about type 1 diabetes.

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Experts all agreed that earlier use of CGM could result in better diabetes management later on. Dr. Jan Fairchild studied the start and continued use of CGM in a pediatric population with early “stage 3” type 1 diabetes. Kids who started CGM at diagnosis had slightly higher CGM wear at 24 months, compared to kids who started within the first two years of diagnosis (78% vs. 66%, respectively), though this result was not significant. All children using CGM ultimately benefitted – they demonstrated a median A1C of 7.7% at 24 months, which was less than the clinic median A1C of 8.1%. Dr. Fairchild also mentioned the educational role that early CGM use could play, especially with a focus on time in range.

Diabetes Drugs

VERTIS-CV Trial of Steglatro and Heart and Kidney Health

Dr. Samuel Dagogo-Jack and Dr. Christopher Cannon presented highly anticipated results from the VERTIS-CV trial, which studied the effects of Merck/Pfizer’s SGLT-2 inhibitor Steglatro (ertugliflozin) on over 8,000 participants with type 2 diabetes and cardiovascular disease (CVD). The trial found that treatment with Steglatro reduced average A1C by 0.5 percentage points, lowered average weight by nearly five pounds, and reduced blood pressure compared to standard diabetes treatment. Steglatro also improved kidney function, as measured by eGFR, and reduced the number of study participants with heart failure.

The researchers agreed that the VERTIS-CV results confirm the current guidance on the use of SGLT-2 inhibitors to prevent and treat heart failure and diabetes-related kidney disease. As a reminder, the current ADA Standards of Care advise using SGLT-2 inhibitors in people with type 2 diabetes for reducing hyperglycemia (high blood sugar), improving blood pressure, and facilitating weight loss. SGLT-2 inhibitors have also been shown to improve heart and kidney health in people with and without diabetes.

Read more about the trial in our full article here.

New Data Shows Teplizumab Delays Diagnosis of Type 1 Diabetes

At last year’s ADA, we were very excited to report on trial results that showed teplizumab (pronounced Tep-pli-ZU-mab!) delayed type 1 diabetes diagnosis by two years, compared to placebo. The study enrolled 76 participants (55 children and 21 adults) who were the relatives of people with type 1 diabetes and did not have diabetes, and were at high risk for developing the condition (they had unstable blood glucose levels and at least two diabetes-related antibodies). On average, time to diagnosis of type 1 diabetes for the teplizumab group was four years, compared to two years with placebo. At the end of the trial, 53% of the teplizumab-treated group did not have type 1 diabetes, compared to 28% of the placebo group.

New follow up data, presented by Dr. Emily Sims (Indiana University), showed sustained reduction in the onset of type 1 diabetes. Previously, teplizumab had been proven to delay clinical onset by only two years in high-risk people; however, these new data support a delay of as much as three years, compared to placebo.

Furthermore, people who were treated with teplizumab showed a “striking reversal” in C-peptide decline (this is a common measure of type 1 diabetes) in the six months following treatment, after which C-peptide levels seemed to stabilize. These data suggest that the treatment helped stabilize beta cell function (the cells in the pancreas that make insulin) and that repeated teplizumab treatment at key time points may be able to further extend, delay, or even prevent diagnosis of type 1 diabetes. While not a cure, three years of living without daily diabetes management is certainly a meaningful outcome.

When will teplizumab become available? With an estimated six-month review time if Priority Review is granted, an FDA decision could be expected as soon as mid-2021.

SGLT-2 Inhibitors and GLP-1 Agonists to Prevent Heart Disease

Dr. Mikhail Kosiborod (University of Missouri-Kansas City) and Dr. Darren McGuire (University of Texas Southwestern Medical Center) debated the use of SGLT-2 inhibitors and GLP-1 agonists in primary prevention of heart disease (called cardiovascular disease, or CVD).

As background, primary prevention is using medication in people who do not have CVD in order to prevent CVD. This is different from secondary prevention in which a person who is diagnosed with CVD uses a medication to prevent progression of the disease.

Dr. Kosiborod started the session with a strong “yes” – SGLT-2 inhibitors and GLP-1 agonists should be used for primary prevention. However, primary prevention is difficult to prove: larger and longer trials are needed. Dr. Kosiborod believes that we do have enough evidence.

  • A meta-analysis of SGLT-2 inhibitor trials suggests that:
    • SGLT-2 therapy works to prevent heart failure regardless of whether a person has established CVD (based on hospitalizations for heart failure).
    • SGLT-2 therapy protects kidney health regardless of whether a person has established CVD.
  • The FDA has approved SGLT-2 inhibitor Farxiga for people with type 2 diabetes and established CVD, and those with risk factors for CVD. That is primary prevention!
  • REWIND showed that GLP-1 agonist Trulicity prevents major adverse cardiovascular events (MACE, which includes stroke, heart attack, and cardiovascular death) in people with and without established CVD.
  • The FDA agrees again here – Trulicity is approved for people with type 2 diabetes with CVD and those with risk factors for CVD.
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Next, Dr. Kosiborod looked at the population level. Worldwide, primary prevention with SGLT-2s and GLP-1s will significantly reduce cardiovascular events (compared to secondary prevention alone) because there are many people who are not diagnosed with CVD.

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Dr. Kosiborod believes this primary prevention is cost-effective and essential, given the high risk to the population. And many SGLT-2s and GLP-1s will become generic in the future.

Dr. McGuire argued that we are not ready for SGLT-2s and GLP-1s to be used in primary prevention. He pointed to a meta-analysis that showed no benefit of SGLT-2 inhibitors and GLP-1 agonists in atherosclerotic cardiovascular disease (ASCVD) outcomes compared to placebo in people without established ASCVD. In his analysis of REWIND, Dr. McGuire pointed to an absolute risk difference of 0.3% in people without established CVD taking Trulicity versus placebo (1.7 events for every 100 patient years, vs. 2.0 events for every 100 patient years). This would mean that you would need to treat 333 people without CVD to prevent one MACE – which would be $3.4 million in drug costs.

Both speakers agreed that SGLT-2 inhibitors have shown strong effects in primary prevention for heart failure and kidney outcomes. There was no significant debate on this point, as the data speak for themselves regarding the profound effect of SGLT-2 treatment in reducing these outcomes.

Weekly Basal Insulin – The Wave of the Future?

New types of insulin – once-weekly basal insulin injections – are being tested in clinical trials and may bring major developments to how people take insulin. In this session, Professor Philip Home, Dr. J. Hans DeVries, and Dr. Stefano Del Prato discussed the pros and cons and recent results from clinical trials of weekly basal insulin.

Prof. Home explained that weekly insulin could reduce hurdles in starting or maintaining insulin therapy for people with diabetes, especially those who are:

  • Afraid of injections
  • Hesitant to start insulin due to the change in lifestyle or impact on quality of life
  • Wary about handling devices
  • Already on a weekly injectable GLP-1 agonist

Weekly insulin could help people adhere to their prescribed therapy – but it will likely make dose titration and adjustments more challenging. One of the major challenges of weekly insulin is that people can’t modify insulin doses according to life disruptions (for example, sick days or increased physical activity).

Summary

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Dr. DeVries and Dr. Del Prato reviewed the various weekly insulins that companies are studying to evaluate their safety and how they affect diabetes outcomes in comparison to existing insulins. Dr. Del Prato highlighted results from a recent study that compared Novo Nordisk’s weekly insulin (icodec) to Glargine U100 (Lantus) in people with type 2 diabetes:

  • Both insulins showed a similar reduction in A1c.
  • Icodec showed improved glucose profiles for self-monitored blood glucose (SMBG).
  • Rates of hypoglycemia were low for both insulins.
  • Weight gain, which is common when starting insulin, was the same for both insulins.
  • Icodec did not show any new safety issues.

Research is still to come on weekly basal insulin, but it looks promising.

Farxiga for Diabetes Prevention? New Analysis of DAPA-HF Trial

Yale’s Dr. Silvio Inzucchi presented an analysis of the landmark DAPA-HF trial, suggesting that along with the heart health benefits of SGLT-2 inhibitor Farxiga, an additional benefit of preventing type 2 diabetes also exists.

As background, DAPA-HF examined the heart health effects of Farxiga (spelled Forxiga in Europe) in people with and without type 2 diabetes. The trial showed that:

  • Farxiga reduced heart-related death or worsening heart failure by 26% compared to placebo (a “nothing” pill).
  • The heart benefits were the same in people with diabetes and without diabetes.

Dr. Inzucchi’s new analysis showed that for participants who did not have type 2 diabetes at the start of the trial, treatment with Farxiga reduced the risk of developing type 2 diabetes by a whopping 32% compared to placebo. After 18 months, 4.9% of the Farxiga group had been diagnosed with diabetes compared to 7.1% of the placebo group. This is a big deal and anyone you know at high risk of type 2 diabetes should learn about these results and talk to their doctor or healthcare team.

We’re glad to see this important benefit – type 2 diabetes prevention – may be conveyed to people with heart failure who can now take Farxiga regardless of whether or not they have type 2 diabetes. As a reminder, Farxiga is the first SGLT-2 inhibitor drug to be approved for a non-diabetes specific population.

Metformin, GLP-1 agonists, and SGLT-2 inhibitors in Type 1 Diabetes

UCSD’s Dr. Jeremy Pettus moderated a session with three expert presenters from across the world: Dr. Irene Hramiak (Western University), Dr. Tina Vilsboll (Steno Diabetes Center Copenhagen), and Dr. Chantal Mathieu (University Hospital Gasthuisberg Leuven).

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Dr. Hramiak kicked things off discussing the current challenges and risks of insulin therapy, including hypoglycemia, weight gain, glucose variability, and diabetic ketoacidosis (DKA). According to data from the T1D Exchange, average A1C levels have not improved in the last decade, and adolescents continue to be a difficult group for glycemic management, despite increased use of pumps and continuous glucose monitors (CGM). How can adjunctive therapies (added to insulin) help?

The REMOVAL study looked at the effects of metformin in people with type 1 diabetes (40 years of age or older). Over three years, participants taking metformin saw the following benefits compared to those taking a placebo:

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  • A decrease in A1C of 0.13 percentage points
  • A reduction in insulin dose by 1.2 units
  • No change in the rate of minor or severe hypoglycemia
  • From a baseline body weight of 193 lbs (87.7 kg), a weight loss of 2.6 lbs (1.17 kg)
  • A reduction in LDL (“bad”) cholesterol by 0.13 mmol/L (5 mg/dL)

These data suggest that metformin did not have a clinically meaningful impact on glycemic management but may improve cardiovascular health in adults with type 1 diabetes. That’s disappointing, but something we’ve all wondered for years – now we know!

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Dr. Vilsboll continued the conversation by discussing GLP-1 agonists for type 1 diabetes. She reminded that adjunctive therapy has several important goals but does not replace insulin – which is the main treatment for people with type 1 diabetes.

Dr. Vilsboll provided an overview of the effect of GLP-1 drugs in the pancreas (on insulin-producing beta cells), liver, brain, kidneys, and other organs before sharing data from a trial on GLP-1agonists in type 1 diabetes.

The LIRA-1 Study evaluated 24 weeks of GLP-1 agonist use in people with type 1 diabetes and excess weight and found that GLP-1 treatment:

  • Did not have a statistically significant (meaningful) reduction in A1C compared to placebo.
  • Reduced body weight by 13.4 lbs (6.1 kg) compared to placebo (from a baseline of about 205 lbs, or 93 kg).
  • Increased gastrointestinal side effects (nausea, diarrhea).
  • Did not decrease the amount of bolus insulin required but reduced basal insulin by about five to six units per day.

The ADJUNCT trial was the longest such trial, involving 1,400 people with type 1 diabetes with an A1C between 7%-10%. In this trial, participants taking GLP-1 agonists experienced:

  • A clinically significant reduction in A1C of 0.54 percentage points compared to a baseline of 8.2% after 52 weeks.
  • A reduction in body weight that correlated with the dose of GLP-1 agonist: 10.8 lbs (4.9 kg) of weight loss with a 1.8 mg dose of GLP-1 agonist; 7.9 lbs (3.6 kg) with a 1.2 mg dose; and 4.9 lbs (2.2 kg) with a 0.6 mg dose.
  • An increased rate of symptomatic hypoglycemia, but no increase in severe hypoglycemia or DKA.
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In a more recent trial, MAG1C, researchers examined the use of GLP-1 agonist exenatide (Byetta) over 26 weeks in adults with type 1 diabetes. Researchers found that compared to placebo, the GLP-1 agonist did not decrease A1C but did decrease insulin dose and body weight. Researchers concluded that the GLP-1 agonist does not have a future as an add-on treatment to insulin in type 1 diabetes. We are not certain this is the correct answer, because it seems like TIR would’ve been useful to measure – but, there’s no fighting city hall.

The session concluded with Dr. Chantal Mathieu discussing the role of SLGT-2 inhibitors in people with type 1 diabetes. She pointed to three main trials: DEPICT with Farxiga, InTANDEM with Zynquista, and EASE with Jardiance.

Compared to placebo, participants taking Farxiga (either 5mg or 10mg dose) experienced:

  • Approximately a 0.45 percentage point drop in A1C by 24 weeks, and 0.2 to 0.3 percentage point decrease in A1C after 52 weeks.​
  • time in range increase of about 10% – a gain of almost two more hours of time in range per day

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  • A 10% decrease in both basal and bolus insulin.
  • A decrease in body weight of about 5.5 lbs (2.5 kg) with a 5mg dose, and about 7.7 lbs (3.5 kg) with a 10mg dose (from a baseline of 179 lbs, or 81 kg).
  • An increased risk of genital infection and urinary tract infections.
  • No increase in hypoglycemia.
  • An increased risk of DKA that rises with a larger dose.

The inTandem trial also showed a drop in A1C: after 24 weeks, participants taking Zynquista experienced a 0.5 percentage point drop in A1C compared to those taking placebo. Time in range also increased with Zynquista. There was a 77-minute increase in time in range with the 200 mg dose, and almost a three-hour increase for people taking the 400mg dose. The increased risks of DKA and genital infections were also observed in this trial.

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The EASE trial provided evidence that supported the effects of SGLT-2 inhibitors on the reduction of A1C – about 0.3-0.4 percentage points after 52 weeks. This study also used a much lower dose of 2.5 mg, which offered an intermediate effect – lowering A1C by about 0.2 percentage points and reducing body weight by 4 lbs (1.8 kg). Interestingly, there was no difference in DKA with the 2.5 mg dose compared to placebo.

Dr. Mathieu concluded by sharing her “bottom line” on the use of SGLT-2 inhibitors in type 1 diabetes and preventing DKA.

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To learn more about off-label drugs in type 1 diabetes, check out this article from Kerri Sparling.

What Therapies Are Best for People with Type 2 Diabetes at Risk of Heart Disease?

The world of diabetes is now focusing more than ever on preventing diabetes-related health complications. Not only is the treatment of diabetes about blood sugar (measured by A1C or time in range), but it is also about heart health, kidney health, and so much more. In 2019, data from large trials showed that GLP-1 agonists and SGLT-2 inhibitors have heart and kidney protection benefits.

As such, experts strongly emphasized using GLP-1 or SGLT-2 drugs for individuals at high-risk for heart attack, stroke, heart failure, or chronic kidney disease. They also named that GLP-1 and SGLT-2 therapies should become more accessible and affordable to people living with diabetes.

Studies have not yet evaluated the heart and kidney health benefits of metformin, compared to those of GLP-1s and SGLT-2s. However, trials have shown that metformin helps lower blood glucose and body weight, comes with a low risk of hypoglycemia, and is cost-effective.

If your healthcare professional has not brought up additional therapy options for you, we recommend you ask them to read this article and discuss your options.

A Debate on the Use of Sulfonylureas in Type 2 Diabetes

Sulfonylureas, or SUs (drugs like glimepiride, glipizide, gliclazide), are a commonly prescribed low-cost drug for people with type 2 diabetes across the world. At ADA 2020, experts Dr. Sophia Zoungas and Dr. Carol Wysham debated the role of SUs in the treatment of type 2 diabetes. While the two endocrinologists differed on how to interpret data from various studies, we came away from the debate with several important take-aways.

Benefits of SUs:

  • Like many other compounds available today, SUs can help lower A1C, especially at the beginning of use in diabetes management.
  • SUs are low-cost and can be an economical method of managing diabetes, at least in the short term.
  • The CAROLINA study demonstrated that sulfonylurea glimepiride is safe for the heart in people with type 2 diabetes.

Challenges of SUs:

  • The CAROLINA study showed that SUs lead to a greater risk of hypoglycemia than other type 2 diabetes medications (not including insulin).
  • All SUs are associated with weight gain, which itself is associated with cardiovascular disease for many people with diabetes.
  • Not all SUs are created equally – each SU might have different health risks, so more research needs to be done on this front.
  • Preventing long-term complications is possible with GLP-1 agonists and SGLT-2 inhibitors – SUs confers no cardioprotective advantages.
  • Without the cost advantage in the short-term, no one would use SUs.
  • Clinical trial investigators are sometimes discouraged from using SUs in major trials, as we understand it.

If you do use an SU, and have experienced hypoglycemia or weight gain, we encourage you to ask your healthcare professional if there is an alternative. To increase safety, we encourage you to check blood sugar as often as you can (or start using a continuous glucose monitoring device, if you can get access – see here if you are on Medicare) to minimize the risk of hypoglycemia.

The Debate on Metformin and Insulin Use During Pregnancy Continues

Traditionally, healthcare professionals have been advised to use insulin to treat pregnant women who have type 2 diabetes or gestational diabetes (GDM). Now, there is debate about whether metformin or other medications are equally effective alternatives to insulin.

Dr. Denice Feig presented data showing that in pregnant women with GDM, metformin use resulted in less maternal weight gain, less preeclampsia (pregnancy-related high blood pressure), lower birth weight, and less neonatal hypoglycemia (low blood sugar). Additionally, there is no evidence that metformin causes any abnormalities in babies, and the drug may reduce insulin resistance in the fetus. During the first trimester of pregnancy, metformin may be a reasonable alternative, if not a first-line treatment equivalent, to insulin. It is also cheaper, easier to use, and poses less of a risk for hypoglycemia (low blood sugar) than insulin.

While the data are promising, both Dr. Feig and Dr. Linda Barbour pointed out that long-term effects on the baby due to exposure to metformin during pregnancy may include a greater risk of being overweight, developing obesity, and having a higher BMI. Unfortunately, the data did not include pregnant women with type 2 diabetes; an ongoing study, MiTy, is currently studying these effects. Both Dr. Feig and Dr. Barbour emphasized that we need more data to decide the best treatment for pregnant women with diabetes – that may well be, and we also hope that better screening is in the works, so that those at risk of gestational diabetes can learn about it earlier and work with their healthcare teams to live with it successfully, which is eminently possible. Learn more about gestational diabetes in our recent article by Cheryl Alkon.

Nutrition, Exercise, and Mindset

New Physical Activity Recommendations for Adults and Children

Dr. Katrina Piercy and Dr. Ronald Sigal presented the 2018 Physical Activity Guidelines for Americans, with updates to the age-specific guidelines and evidence of even more health benefits. These are the recommendations for each age group:

  • Children ages 3-5 should be physically active throughout the day to support their growth, development, and motor skills. Though the US guidelines do not include a specific amount of time, Australia, the United Kingdom, and Canada recommend three hours per day.
  • Children ages 6-17 should do at least 60 minutes a day of moderate or vigorous physical activity.
  • Adults (under age 55) should do at least 150 minutes (2.5 hours) to 300 minutes (5 hours) each week of moderate-intensity activity, or 75 minutes (1 hour and 15 minutes) to 150 minutes (2.5 hours) each week of vigorous-intensity aerobic physical activity. Adults should also do muscle-strengthening activities at least twice a week. We were slightly surprised not to see adults urged to exercise every day like former head of CMS/FDA Dr. David Kessler does in his recent acclaimed book, Fast Carbs, Slow Carbs.
  • Older adults (above age 55) should do the recommended aerobic and muscle-strengthening activities for adults. They should also incorporate balance and functional training, such as standing on one foot or ballroom dancing.

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How do you determine the intensity of exercise? Dr. Piercy recommends the “talk test”: someone doing moderate-intensity aerobic activity can talk, but not sing, during the activity, while a person doing vigorous-intensity activity cannot say more than a few words without pausing for breath.

The speakers noted that while the most health benefits come with at least 150-300 minutes of moderate physical activity per week, any activity is beneficial: any time spent sitting that is swapped out for exercise (even light activity,) can lead to short-term and long-term health benefits. Read more about the guidelines here.

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Diabetes Self-Management Education and Support (DSMES) 2020 Consensus Report Recommendations

A group of educators made a strong case for the greater use of diabetes self-management education and support (DSMES). The benefits are many, including improvements in clinical, behavioral, and psychosocial outcomes, and greater diabetes knowledge and self-care behaviors. Dr. Margaret Powers stressed that compared to other treatments prescribed by healthcare professionals, DSMES and medical nutrition therapy produce few to no negative side effects for people with diabetes and are low cost.

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The experts discussed low DSMES participation rates across the nation and the factors that reduce referrals to diabetes education. Evidence shows that less than 5% of people newly diagnosed with diabetes who have Medicare insurance, and 6.8% of privately insured people with diabetes, have used DSMES services. The 2020 DSMES Consensus Report was created to address these concerns by outlining steps healthcare professionals can take to help people access DSMES services. The report recommends that healthcare professionals make referrals and encourage participation in DSMES at four critical times in someone’s diabetes journey: (1) diagnosis, (2) annually or when not meeting treatment targets, (3) when complicating factors develop, and (4) when transitions in life and care occur. It also suggests that awareness of, and access to, DSMES must be expanded (culturally and geographically), and financial support should be provided for use of DSMES services.

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Food as Medicine! Geisinger’s Fresh Food Farmacy

Michelle Passaretti (Geisinger Health System) presented data on the success of the Fresh Food Farmacy initiative. Fresh Food Farmacy was developed to meet the health needs of people with diabetes in Pennsylvania who do not have access to healthy foods (also known as being food insecure). diaTribe interviewed two leaders from Geisinger in 2018, Dr. Andrea Feinberg and Allison Hess; now, Fresh Food Farmacy has provided 482,219 total meals.

The data speaks to the power of food as medicine! The program participants had a:

  • 2 percentage point reduction in A1C from a baseline of 9%
  • 27% reduction in fasting glucose
  • 13% reduction in cholesterol (including a 9.9% reduction in “bad” LDL cholesterol)
  • 15% reduction in triglycerides

Fresh Food Farmacy also led to increased use of preventive care: flu shots increased by 23%, annual eye exams increased by 17%, and annual foot exams increased by 33%.

Compared to eligible individuals who did not participate, Fresh Food Farmacy participants saw:

  • 49% lower hospital admissions rates
  • 13% decrease in emergency department visits
  • 27% more primary care visits
  • 14% more endocrinologist visits

Participant surveys show significant improvements in quality of life, with 31% of people in the program rating their overall health as very good, compared to just 6% before participation. Additionally, 44% of Fresh Food Farmacy participants now rate their emotional and mental health as very good, compared to just 9% before the program. Passaretti emphasized that Fresh Food Farmacy is not a diet, but a lifestyle change, and that support for the individual’s entire household is necessary for success.

A Sneak Peek into the Film Blood Sugar Rising

Blood Sugar Rising is a film that powerfully articulates the need for a war on diabetes. During this panel moderated by our own Kelly Close, we heard from ADA CEO Tracey Brown, Rise and Root urban farmer Karen Washington, social media influencer and film star Nicole Egerer, film director David Alvarado, and incoming ADA Chief Scientific & Medical Officer Dr. Robert Gabbay.

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Many myths exist in diabetes. One is that if you get diabetes, it is your fault. Blood Sugar Rising dismantles some of these false narratives by showing the complexity of the disease and amplifying diverse voices of people in the diabetes community. Watch the film here if you are in the US and here if you are outside the US.

Tracey Brown ended with a powerful call to action: “What will we do when the burning bush stops burning? We need to move from words into action. We get one point for saying and nine points for doing. Each of us can use our voice, our monetary power, and our ears, and reach across the aisle to collaborate. This is what we need to do to bring diabetes down. We can make it happen, but only together. I’m full up of hope and courage that tomorrow is going to be better than today.”

Lifestyle Interventions for Type 2 Diabetes Remission

In a fascinating session on type 2 diabetes remission, several leaders in the field introduced data on how specific lifestyle interventions (diet and exercise) may help put type 2 diabetes into remission.

Alison Barnes presented data from the DiRECT trial, which focused on low-calorie diets (LCD). The trial compared an intervention group on an LCD (between 800-900 calories per day) to a control group receiving typical diabetes care. Remission was defined as achieving an A1C below 6.5% and stopping all diabetes medications. Results from the DiRECT trial were promising:

  • At one year: 4% remission in control group and 46% remission in the intervention group.
  • At two years: 3% remission in control group and 36% remission in the intervention group.
  • 64% of participants who lost more than 22 lbs (10 kg) were in remission at two years.
  • The intervention group dropped from 75% of participants on diabetes medications at baseline to 40% at two years (compared to 77% at baseline and up to 84% in the control group).
  • Average A1C decreased by 0.6 percentage points in the intervention group at 2 years.
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We thoroughly recommend Dr. Roy Taylor’s book Life Without Diabetes: The Definitive Guide to Understanding and Reversing Type 2 Diabetes – he provides a major connection to the DiRECT trial.

Next Dr. William Yancy spoke on low-carbohydrate diets (classified as less than 130 g carbs per day, with no overall calorie restrictions). In an analysis that compared the effects of nine different diets on glycemic outcomes in type 2 diabetes, the low-carb diet was ranked as the most effective dietary approach for lowering A1C.

Finally, Dr. Kristian Karstoft presented the U-TURN study on how exercise alone, or exercise and diet, may play a role in type 2 diabetes remission. U-TURN had two groups, one receiving standard care and one receiving intensive lifestyle intervention, which included diet and exercise components.

  • After 12 months, 37% of participants in the intervention group stopped using glucose-lowering medication and maintained glucose levels below the criteria for type 2 diabetes (effectively achieving remission).
  • Of the participants who achieved remission, the majority of them came from the group that consistently exercised the most.

The Need for a Personalized Approach to Obesity Treatment

Experts shared the latest data on different treatments for obesity. They focused on three approaches:

1. Lifestyle interventions:

  • The Look AHEAD trial tested whether reducing calories and exercising regularly would lead to diabetes remission. After one year, 11.5% of participants achieved diabetes remission with an average weight loss of 19 pounds (8.6 kilos). After four years, 7.3% of participants were able to maintain remission with an average weight loss of 10 pounds (4.5 kilograms).
  • The Diabetes Remission Clinical Trial (DiRECT) tested whether calorie restriction alone had an effect on diabetes remission. After one year, 46% of people in this study with type 2 diabetes achieved remission; after two years, 70% of the people who had achieved remission were able to maintain remission.

Participants in Look AHEAD had more advanced diabetes than in DiRECT, leading to the big difference in remission rates. The speakers emphasized that the longer someone has been diagnosed with diabetes, the harder it is to achieve diabetes remission.

2. Obesity medication:

  • Just 2% of people living with obesity are managing the disease with medication. However, many obesity medications can lead to weight loss, prevention of diabetes, and diabetes remission.
  • Combination therapy has shown success for managing obesity and type 2 diabetes. A study testing tirzepatide (a dual GLP-1 and GIP receptor agonist) in people with type 2 diabetes found a 1.7-2% decrease in A1C and an average weight loss of 12 pounds in just 12 weeks.

3. Bariatric surgery:

  • Experts agreed that bariatric surgery should be considered as a treatment option for people with a BMI greater than 35. Bariatric surgery can also lead to sustained weight loss and a decrease in diseases associated with obesity, including sleep apnea and heart disease.
  • It’s clear that obesity treatments must be determined at individual levels – we know that so much more is possible for people with diabetes to reach healthier weights and will be returning to this topic. In the meantime, if changing your weight is of interest, talk to your doctor about how to do this in the best way for you.

How Might Type 1 Diabetes Affect the Gut Microbiome? How Can We Use the Gut Microbiome to Treat Type 1 Diabetes?

Though the science is not yet conclusive, research continues on the relationship between the gut microbiome (made up of all the bacteria that live in the human digestive tract) and type 1 diabetes autoimmunity. Dr. Eric Triplett reviewed studies of the gut microbiome in babies with high genetic risk for type 1 diabetes. Three of the studies (DIPP, Babydiet, and DIABIMMUNE) showed an association between the species of bacteria living in the gut and the onset of type 1 diabetes. He then presented a study using data from the general population in Sweden (ABIS), which compared the gut microbiome of children with low, neutral, or high genetic risk for type 1 diabetes. The study found that high genetic risk for type 1 diabetes is associated with changes in the gut microbiome early in life.

Dr. Emma Hamilton-Williams shared unpublished research on the effect of high-fiber dietary supplements on gut microbiome composition and diabetes management in 18 adults with type 1 diabetes. Fibrous food breaks down into short-chain fatty acids (SCFAs) when digested. SCFAs are known to support gut health and regulate the immune system. The study found that the high-fiber supplements affected the species of bacteria living in the gut as well as their function (though these returned to baseline after the diet ended). Participants with better-managed diabetes at baseline had a stronger response to the dietary change – and experienced changes in their glycemic management: A1C levels decreased and less daily insulin was required. Further research on short-chain fatty acid supplements could shed lead on diabetes treatment and prevention.

Real World Stories: Supporting People at Different Stages of Diabetes

Dr. Neesha Ramchandani presented her work on young adults living with diabetes (ages 18 to 30). Through interviews, she found four main challenges: finding a balance between diabetes and life, feeling in control of diabetes, navigating the hidden burden of diabetes within their social circles, and wanting a better connection with their diabetes healthcare professional. One participant said, “Diabetes is like having a full-time job… you can’t 100% turn off. It always has to be a part of your thought process.” diaTribe has resources for teens here.

We then heard from Dr. Della Connor and Dr. Gary Rothenberg on the need to care for people who are living with diabetes post-kidney transplants and post-amputations. In all three talks, the experts emphasized the need to:

  • Build trust and comfort between people with diabetes and healthcare professionals.
  • Incorporate perspectives based on gender, race, and ethnicity into care.
  • Recognize the importance of a team approach, including care-partners.

Access to Care and Policy 

Soda Taxes: Are They Working?

Dr. Lisa Powell (University of Illinois at Chicago) presented compelling evidence in support of sugar-sweetened beverage (SSB) taxes and their ability to reduce soda consumption. Evidence suggests that taxes do reduce the consumption of sugary beverages – a 38 percent reduction in Philadelphia, PA and 21 percent reduction in Seattle, WA, for example – and incentivize soda companies to decrease the amount of sugar in their products, especially when the tax is dependent on the drink’s sugar content. Research also shows that while some consumers replace sodas and sugary drinks with other forms of sugar, such as candy or chocolate milk, the most common substitute is water.

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Dr. Martin White (University of Cambridge) and Dr. Rafael Meza (University of Michigan) presented promising data on how SSB taxes are working in the United Kingdom and Mexico, respectively. UK consumers overall have been switching to drinks with less sugar and most companies have been reducing levels of sugar in their products; however, taxes have not had a dramatic negative impact on the sugary beverages industry’s revenues overall. Similarly, Dr. Meza showed that Mexico’s overall sugar consumption has decreased since the implementation of the SSB tax, having the largest influence on people who drink lots of sugary drinks, and he noted that the current tax, which is about 10% of the beverage price, would have a significantly larger impact if doubled.

Dr. Powell pointed out that the most effective taxes require careful design. To significantly curb consumption of sodas, the SSB tax should be added into the shelf price, rather than applied at the register, and the tax ought to apply to a broad base of sugary-drinks (including sodas, juices, sports drinks, etc.) to avoid substitutions. Moreover, researchers must be mindful of cross-border shopping – this is when consumers purchase their beverages in places where the SSB tax doesn’t apply. This tax avoidance can heavily impact the effectiveness of the tax: for example, in Philadelphia, PA, consumers buying SSBs outside of Philly reduced the the impact of the tax from a 51% reduction in SSB sales to a 38% reduction.

Effects of Health Policy on Diabetes Care

Professor Rebecca Myerson (from the University of Wisconsin) shared key findings of a study on the impact of Medicaid expansion for people with diabetes:

  • Medicaid prescriptions for insulin increased by about 40%, even with rising insulin prices, meaning that more people with diabetes are receiving treatment.
  • Prescriptions for metformin also increased, suggesting that more people are getting treatment for early-stage diabetes.
  • About one-third of the other prescriptions are for newer medicines (such as SGLT-2 inhibitors and GLP-1 agonists) – promising trends for preventing diabetes complications and saving significant costs down the road.

Dr. Kasia Lipska from Yale School of Medicine discussed the importance of coverage for essential medicines and pre-existing conditions – two health policy issues that are front of mind for many Americans as the November election approaches. In addition to Medicaid expansion, the Affordable Care Act (ACA, or Obamacare) provided coverage for “Essential Health Benefits,” which includes prescription drugs, mental health services, emergency services and hospital care, preventive services and chronic disease management, and more. Dr. Lipska shared a study that found the ACA reduced the percent of income spent on family medical costs for people ages 18-64 with diabetes. This reduction was especially true for people whose family income was in the lowest bracket ($0-34,999 per year).

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Importantly, ACA also prohibited health insurance companies from denying people coverage or charging higher costs to people who have “pre-existing conditions,” including diabetes. Given the significant improvements in coverage and care, Dr. Lipska emphasized that getting rid of the pre-existing conditions provisions would be “a disaster for people with diabetes” – presumably diaTribe readers in the US would agree! Over half of those surveyed were in favor of expanding Medicaid programs in their state – this doesn’t surprise us, since there are so many states that do not have favorable diabetes care programs (for example, see our article on CGM coverage for people on Medicaid; although this was not part of the ACA, many cite it as helping improve care quickly for those that are able to access the benefit). She shared results of a Kaiser Family Foundation survey that emphasized the need for ACA provisions:

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Whole-Population Interventions Aim to Prevent Type 2 Diabetes

As type 2 diabetes rises in the United States (and around the world), organizations are working to prevent new cases and improve the health and wellness of entire communities. Simon Neuwahl (RTI International) showed models of the benefits of proposed changes, which includied soda taxes, worksite health promotion, and bike lanes. The models suggest that the introduction of these three societal reforms can reduce the rate of type 2 diabetes by 17% over the next ten years. In 2018, 1.4 million people were diagnosed with type 2 diabetes in the, US so a 17% decrease would prevent 2.4 million cases over ten years.

There is still a long way to go. The CDC is aiming for the rate of type 2 diabetes to drop by 21% by 2025. The efficacy of some reforms, like the soda tax, are well proven. But, experts like Professor Nicholas Wareham (University of Cambridge, England) believe that no single intervention can make a difference. Decreasing rates of type 2 diabetes will require societal and individual lifestyle reforms.

Thankfully, diverse groups recognize the need for holistic approaches to diabetes prevention. The CDC’s National Diabetes Prevention Program coordinates with both public and private organizations to connect people with diabetes or prediabetes to lifestyle change resources and programs. Neuwahl’s cost-effective model is adaptable to national, state, and local communities hoping to implement whole-population interventions. Together, his three proposed population-level reforms could directly improve the lives of 2.4 million people.

Source: diabetesdaily.com

Improving the Transition from Pediatric to Adult Care for Patients with Diabetes (ADA 2020)

At the American Diabetes Association (ADA) 80th scientific sessions, Dr. Robert Zimmerman MD, Vice-Chairman of Endocrinology and Director of Diabetes Center Cleveland Clinic, and his team discussed the importance of creating a smooth and seamless transition from pediatric to adult care.

This time of transition is considered a high-risk time for patients living with diabetes. Diabetes aside, these patients are dealing with other life stressors that often emerge at this point in their life. Coming off their parent’s health insurance, going off to college or out in the workforce, and having to pay their own bills can create a lot of stress. Because of this, patients often neglect their diabetes care. Having a transition plan in place from pediatric to adult care can help these patients feel empowered and equipped to handle their own diabetes care as they become young adults.

Key Takeaways

  • Each year, thousands of adolescents with both type 1 and type 2 transition to young adults and also from pediatric to adult care.
  • The developmental stage between ages 18-30 is defined as the period of emerging adulthood.
  • Due to life stressors, this is a period where many are distracted from their diabetes care.
  • During the first phase of transition, around age 18-24, many patients feel overwhelmed and have a tendency to reject parental control.
  • During the second phase of transition, at about age 25-30, the young adult tends to take on more responsibilities in life and usually starts to place more importance on diabetes management.
  • The period of emerging young adulthood is considered a high-risk time for patients with type 1 or type 2 diabetes.

Differences Between Pediatric and Adult Care

  • Pediatric Approach
    • Family-oriented
    • Holistic
    • Visits are with both child and parents
  • Adult Approach
    • The patient is autonomous in their care
    • Individualized counseling
    • The patient makes their own decisions regarding care

Major Risks During Transition

  • Suboptimal Glycemic Control
    • Only 32% of patients between 13-18 years old met ADA goals
    • 18% of children under 18 achieved the ADA recommendation for A1c
    • 56% of adults achieve an A1c of 7%
  • Neglect of Diabetes Care
    • Older teens and young adults tend to disengage from health care
    • Both short-term and long-term complications can occur as a result of neglecting care

Factors That Increase the Risk of Hypoglycemia and DKA

  • The loss of parental guidance
  • Less frequent doctor visits
  • Work/school stressors that take precedence over diabetes care
  • Consumption of alcohol
  • Change in physical activity
  • Different dietary patterns than once had under parental care
  • Lack of motivation to stay on top of health

Patients Face Many New Challenges During This Period

  • Psychosocial challenges include worrying about the future, lack of a plan or goal in place for managing their diabetes, feeling anxiety, or being overwhelmed with care, handling uncomfortable social situations regarding diabetes.
  • Psychological issues are prevalent during this time, although these can occur at any time while managing a chronic condition. Feelings of depression, anxiety, eating disorders and suicide are all concerns that need to be addressed during this time.
  • Pregnancy is another issue that arises during this period of emerging adulthood.
    • Contraception use is lower for adults with diabetes from the age of 20-44
    • 39% of adults with diabetes do not use contraception compared to 27% of adults who don’t have diabetes
    • An increasing number of women with pre-existing diabetes are becoming pregnant and having children
    • Only 1 in 4 women with diabetes age 16-20 were aware of the risks involved with getting pregnant with diabetes and the importance of optimizing glycemic control before and during pregnancy in order to maximize the odds of conceiving and delivering a healthy baby.
  • Other health risks that can happen at any age for people with diabetes seem to be most prevalent during these years: alcohol use, illegal drugs, smoking, driving and hypoglycemia.

Current ADA Recommendations for the Transition

  • Pediatric health care provider works with the patient and parent planning for transitioning starting up to 1 year prior
  • Preparation focusing on self-management for emerging teen
  • Preparation should include the differences between pediatric and adult care and should help guide the patient on major decisions such as health insurance, etc.
  • The provider should prepare and provide a list for the patient and new adult doctor summarizing the patient’s medications, assessment of skills, history, etc.
  • Healthcare providers need to recognize all the changes during this period can lead patients to neglect care.
  • The transferring provider should provide patients with specific referrals to adult physicians that would best fit the patient’s needs.
  • The transferring physician should empower patients and provide them with any educational materials and resources that can help them to stay on top of their diabetes care.
  • Care must be specific to the patient and strive to avoid both short term and long term complications.
  • The provider must evaluate and treat emerging teens with any disordered eating behaviors or affected disorders.
  • On-going appointments should take place every 3 months for patients on insulin and every 3-6 months for patients with type 2 who are not taking insulin.
  • Screening guidelines should be followed for both microvascular and macrovascular issues as well as the management of lipids and hypertension.
  • Birth control, drug use, driving, STDs, etc. should all be discussed with the teen and their parents by both the transitioning and adult physician.
  • Both providers should make sure the patient is getting primary and preventative health care and feels comfortable with the care and support they are receiving.

Transition Options Available at The Cleveland Clinic Foundation

  • Transition clinic: here, adolescents are taught how to manage their diabetes on their own. They are then introduced to the adult care endocrinologist who oversees the patient’s care after this first visit. The follow-up with the adult endocrinologist can happen on the transition floor or at Adult Endocrinology at the diabetes center.
  • Transition shared medical visit: In this instance, a shared medical appointment takes place instead of their traditional appointment and the goal is to make the transition as smooth as possible for the patient.
  • Adult endocrinology office visit: patient goes directly to the referred adult endocrinologist.

Cleveland came up with an Autonomy Checklist which helps patients to learn necessary information that they should have while transitioning to more autonomous care.

Group Visits

Cleveland Clinic put into place group visits that take place approximately every 3 months where they have an educational speaker, review A1cs, glucose readings and insulin adjustments to engage the adolescents as well as give individual exams.

Cleveland Clinic’s Transition Recommendations Moving Forward

  • Creating flexible appointments: nights, weekends and special availability while young adults are home from college are important. Virtual appointments and classes will likely be the main way of interacting for this group. Dr. Zimmerman stated that their office went from “1% virtual visits to 75% in approximately one week’s time”.
  • Building relationships: community support groups led by a provider, monthly events and taking advantage of organizations and apps like College Diabetes Network (CDN), where they can connect with others living with diabetes is useful.
  • Transition simulation nights where young adults going off to college can go through possible scenarios and problem-solve together as a group. Questions like “my insulin fell and cracked open, where can I get insulin in the middle of the night?” or “My blood sugar suddenly is dropping, but I am in the middle of taking an exam, what should I do?” would be addressed.

Conclusion

Young adults transitioning from pediatric to adult care are a high-risk group that needs a supportive and comprehensive system in place, where caretakers understand the unique complexities of this life stage. Creating a seamless and specific transition plan will help guide these patients to achieve optimal health during these years.

Source: diabetesdaily.com

A Letter to My 12 Year Old Self: Diabetes, 20 Years On

Dear Chrissy,

It’s June 20th, 2000, and right now you’re in the emergency department of the King’s Daughters Children’s Hospital in Norfolk, Virginia. You were supposed to be on a weeklong vacation with your siblings and parents, frolicking in the salty seawater and eating cotton candy on the boardwalk of Virginia Beach, but instead, on day three of the trip, you’ve been rushed via ambulance to the ER, feeling weak, nauseous, and on the brink of unconsciousness. You’re small. An active cheerleader in your middle school, you’ve lost over 30 lbs in a little under a month, which is striking on your lithe frame. Every nurse notices how underweight you are.

The glucometer at the Urgent Care your parents took you to this morning simply read, “HIGH”. When the nurse looks at your parents and says the words, “your daughter has diabetes”, it’s the first time you’ve ever seen dad cry. You’re completely terrified that the word “diabetes” has “die” as the first syllable. Are you going to die? Thankfully, no. Not today, and not within the next 20 years, either.

The next few years will be hard, actually, they all are. Sadly, even though diabetes is technically “manageable”, it never really gets any easier, but you’ll become tougher. You will try out four different insulin pumps before you find one, at the ripe old age of 30 (and spoiler alert, it’s tubeless). You’ll prick your tiny, fragile fingers literally thousands of times, but in 15 years (the time will fly by, I promise), you’ll use a seemingly magical machine that checks your blood sugar 288 times per day for you, without you having to do A THING, and it’ll transmit the numbers to your telephone (those things are cordless in the future, too). Eventually, but I’m getting ahead of myself now, those numbers will talk to your insulin pump for you, and make dosing decisions while you drive, or work, or makeout, or go running, or read a novel. Science is pretty neat.

Once you start the 7th grade, you won’t tell anyone about your new mystery disease. Honestly? You’re embarrassed. The only other people you’ve ever met with diabetes were your elderly next-door neighbor’s sister and Wilford Brimley, from TV. You make your mom pinky swear that she won’t tell your friends’ moms, and you promise yourself that you just won’t attend sleepovers until you go away for college. Please don’t do this to yourself. Spare yourself the heartache. Diabetes will give you physical battle scars and mental wounds, but it will also develop some of the most beautiful attributes people will love about you: your compassion for others, your enthusiasm to live in the moment, your fearlessness in the face of adversity, your humility, your grace.

You’ll be the only 13-year-old girl drinking Tab at your bestie’s summer birthday party. Don’t be embarrassed. Exotically-flavored seltzer waters will be all the rage in 20 years. You’re just ahead of your time.

You’ll grow up quickly. You were always conscientious, polite, and studious, but having diabetes will make you disciplined, strong-willed, and courageous–you won’t really have a choice in the matter. Diabetes will toughen you where you’re soft; diabetes will break you open.

You’ll become obsessed with counting carbs (trust me, this is good), and dosing correctly (also good), but will become preternaturally focused on food and nutrition. You will deny and deny and deny. You’ll eat an apple when everyone is enjoying an ice cream; you’ll swear that string cheese is more fun than cookies. This can sometimes be good in the name of a better hba1c, but please, let yourself be a child for a little while longer. You’ll cry, because having a chronic disease can be very lonely and sad sometimes, and it’s okay to be sad sometimes, too. Go to therapy. It’ll be worth it.

Your mom will make you go to diabetes camp. You will resist going at every turn. You will cry and scream, and when she drops you off at the loading dock of Camp Setebaid, you swear you’ll never talk to her again. But by night three, you will have forgotten all about the hardships of living amongst “nons”. You’ll meet some of your closest friends at diabetes camp, and they’ll last a lifetime. You’ll have camp crushes, and camp kisses, and still remember campfire songs until your mid-30s. You’ll go waltzing with bears, and do the polar bear swim, and learn how to build a campfire, and get lost in the woods under a velvety night sky, and will learn how to use a cleavus, and will eat two dozen chocolate chip cookies one night when you accidentally replace your dose of Lantus with Humalog (oops). You’ll pee your pants laughing, and cry every summer when camp ends. You’ll make many friends along the way–friends who get it, who get you, for the first time ever. You’ll lose some of them over the years, to diabetes, or depression, or both, and will weep at their funerals. Your best camp friend will be in your wedding party in 17 years.

You’ll become tough. You never asked for this life, but you sure have made a point of living it to the fullest. There will be many doctors who will try and tell you things you can’t or shouldn’t do: join the swim team, play competitive sports, travel abroad, go to college out of state, have children–and you’ll prove most of them wrong. You will learn to not take no for an answer. You’ll develop an iron will. You’ll become gritty as hell.

Diabetes will encourage your interests in health and well-being, and out of college you’ll be a social worker, eventually getting your master of public health (I don’t think this degree exists in 2000, but it’s coming down the pike). You’ll be a vegetarian. You’ll run marathons. You’ll climb something that’s called a 14er (I know you live in Pennsylvania, but someday, when you live in Colorado, this will be a very big deal). You’ll find your dream job of working in diabetes advocacy, that will take your passion and use it to help thousands of other people who struggle with the same issues you do. You’ll change lives for the better.

One day, you’ll meet a man at work, who’s sweet and kind and compassionate. One evening, still in the early days of dating, you’ll notice he bought three containers of glucose tabs and stored them in his pantry without telling you. “Just so you feel safe here,” he says. Three years later, you’ll marry him.

In 20 years, you won’t have everything all figured out, but you’ll know more about who you are, and who you want to be. And diabetes, in large part, has helped to craft that. I know you’re seeing dad cry right now, so why don’t you go give him a hug and let him know everything will be okay. Because, really, in time, it will be.

Love,

Christine

Source: diabetesdaily.com

Breaking Updates from TrialNet (ADA 2020)

TrialNet is a research effort that seeks to identify preventative and treatment strategies for type 1 diabetes. New data was just released at the American Diabetes Association (ADA) 80th Scientific Sessions. Here are the major highlights:

1. The optimal age for screening children at risk for type 1 diabetes

It is possible to screen at-risk individuals for the development of autoantibodies that are predictive of T1D development. This can reduce the likelihood of health complications due to a late diagnosis as well as allow patients to enroll in clinical trials aimed at preventing or delaying T1D onset. Researchers recently evaluated the sensitivity, specificity and predictive values based on the screening ages of children at risk for developing T1D. They concluded that it was best for two separate screenings to occur; one around the age of 2-3 years and another at around the age of 5-6 years. “Our data represent a starting point for these considerations that should be customized based on the population’s underlying disease characteristics and public health infrastructure,” they added.

2. Identifying those at risk

How do we identify those who are most at risk for developing T1D? Currently, beta cell function analysis, utilizing glucose tolerance tests and other, more invasive measures, are used. New research demonstrates that using a validated (in type 2 diabetes) mathematical tool may be able to help make this assessment for those at risk for type 1 diabetes from “fasting glucose and insulin measurements from a single time point.” This could afford a fast and relatively non-invasive way to predict risk in the future.

3. Antibody-positive individuals with very slow progression to type 1 diabetes

It is established that people can develop T1D at different rates, after the initial appearance of autoantibodies. New research aimed to characterize the features of “long-term non-progressors.” Interestingly, data revealed that those whose disease onset did not progress long after autoantibody detection, still had a decline in beta cell function, but nevertheless exhibited largely stable glucose profiles and c-peptide levels. Researchers speculate that glucose tolerance testing in those with autoantibodies may help identify those who are less likely to progress to T1D.

4. Pancreas volume and type 1 diabetes progression

New research demonstrates that not only is pancreas size at the onset of T1D and in those at risk smaller, pancreas size is also predictive of T1D risk. The study evaluated those with “stage 1” T1D (those who have two or more autoantibodies, but normal glucose tolerance) and found that their pancreas volume was significantly smaller than that of healthy controls (but significantly larger than those with “stage 3” T1D (showing autoimmunity and hyperglycemia, with symptoms). Although the sample size was relatively small, the data indicate that pancreas size (as measured by MRI) could be a predictive indicator of T1D development.

5. Oral insulin for those at risk of developing type 1 diabetes

Relatives of people with type 1 diabetes (T1D) who were identified as “high-risk” for also developing the condition participated in a prevention trial that used oral insulin (OI) in this population. While overall, the treatment did not appear to be effective in preventing T1D in initial analyses, a further analysis of patient subgroups revealed an interesting trend. Among those who were identified as being at the highest risk for developing T1D (high auto-antibody levels; hindered first-phase insulin response), data indicate that OI can “slow insulin decline”.

Read more about TrialNet and the work they’re doing here:

New Treatment Delays Type 1 Diabetes

Please share this article and stay tuned for more news from the ADA Scientific Sessions.

Source: diabetesdaily.com

Blood Sugar Trends Worsen for Youth, Yet Again (ADA 2020)

New research presented today at the American Diabetes Association (ADA) 80th Scientific Sessions revealed a continuing and troubling trend in glycemic management among children and young adults with type 1 and type 2 diabetes.

Faisal Malik MD, MSHS  of the University of Washington presented the new data from the SEARCH for diabetes in youth study effort, which involved five different research centers across the US and is funded by the Centers for Disease Control and Prevention (CDC) and the National Institute of Diabetes and Digestive and Kidney Disease (NIDDK).

Study Design

Researchers included over 6,000 young people with a diabetes diagnosis of at least one year in duration in the study. They evaluated and compared the trends in the overall HbA1c levels over time (years 2002-2019). They also evaluated these trends based on the study subjects’ duration of diabetes (1-4 years, 5-9 years, and 10+ years). The data were adjusted for location, age, sex, race/ethnicity, as well as for health insurance status.

Study Outcomes

The table below summarizes the findings of the changes in average A1c levels among youth in the US.

Malik et al. (Presented at ADA 2020)

The researchers concluded the following after completing their analysis:

“Despite increased availability of diabetes technology, newer therapies, and more aggressive glycemic targets over time, current youth and young adults with T1D in the U.S. have worse glycemic control than earlier cohorts. Similarly, participants with T2D diagnosed in childhood and diabetes duration of 10+ years exhibit the temporal trend of worse glycemic control in recent years.”

In particular, the worsening of glycemic management was especially prominent among those with type 1 diabetes of 5-9 years in duration and among those with type 2 diabetes of over 10 years in duration.

Additional key points include the following:

  • A large proportion of youth with diabetes are not meeting treatment targets. As per the ADA press release, “The estimated average A1C for the most recent cohort of youth and young adults with type 1 diabetes was 8.7%, while the most recent group with type 2 diabetes had an estimated average A1c of 8.5%.”
  • Those with type 1 diabetes in the following age ranges — 10-14, 15-19, and 20-24 years — continue to show a trend of worsening control as compared to the earlier matched cohort (2002-2007).
  • Those with type 2 diabetes who were 35 years and older also showed a worsening in glycemic management outcomes as compared to earlier.

Conclusions

Overall, this data reveals a troubling trend for many youth with diabetes in the US, as many are not meeting their targets and the higher A1c levels over time, despite advances in treatment in technology is troubling, to say the least.

Dr. Malik had this to say on the subject:

““These results suggest that not all youth and young adults with diabetes are directly benefiting from the increased availability of diabetes technology, newer therapies, and the use of more aggressive glycemic targets for youth with diabetes over time. Given the evidence highlighting the benefits of tight glycemic control, this study reinforces the need for interventions that combine the use of diabetes technology with effective behavioral and social approaches to improve A1C levels.”

Dr. Dana Dabelea, MD, PhD, from the University of Colorado, who chaired the symposium, added:

“Given the evidence of early complications despite current therapeutic approaches, continuing the long-term follow up of youth with diabetes is necessary to expand our understanding of its natural history, so the most appropriate approaches to primary, secondary, and tertiary prevention of diabetes and its complications can be developed and implemented.”

In summary, this data strongly indicates that better preventative, educational, and comprehensive treatment approaches and follow-up is critical to improving diabetes care for youth in the US.

Source: diabetesdaily.com

Experts Clash on Low-Carb Diets for Children (ADA 2020)

Experts came together virtually at the American Diabetes Association (ADA) 80th scientific sessions on Sunday afternoon to debate the potential pros and cons of utilizing low-carbohydrate diets among youth with type 1 diabetes. Dr. Belinda Lennerz, MD, PhD of the Boston Children’s Hospital discussed the pros of utilizing low-carb eating (defined, in this case, as <20-50g per day or <10% of the daily caloric intake) in this patient population, while Dr. Carmel Smart, Rd, PhD of the John Hunter Children’s Hospital argued about the potential cons. Each presenter made their case and were also allowed time to rebut. Here is the summary of the experts’ arguments.

Potential Pros of a Low-Carb Approach

Dr. Lennerz started by providing a historical overview of low-carb diets among patients with type 1 diabetes, noting that even after insulin became available, carb intake initially stayed low for patients. In fact, it was only once fat was implicated in the development of cardiovascular disease (CVD), that the recommendations to increase carbohydrate intake were made, to replace the calories lost by omitting fat. She also pointed out that currently there is no one-size-fits all recommendation for carbohydrate intake, and that guidelines state it should be individualized.

The presenter addressed the differences in carbohydrate intake levels in the “low-carb spectrum” and was also careful to quickly touch upon the important distinction of ketosis vs.  diabetic ketoacidosis (DKA). Ketones present at low levels due to eating low-carb are very different than the level of ketones seen in acidosis. Unfortunately, these terms that are often conflated, even by some clinicians, leading many to erroneously believe that low-carb diets are inherently unsafe for people with diabetes.

Dr. Lennerz went on to explain that many people with type 1 diabetes, including children, are successfully utilizing a low-carb dietary approach to better manage their diabetes.

Why might a low-carb diet appeal to someone with type 1 diabetes?” she asked, going on to talk about the issue of glycemic variability that many experience, noting that post-meal blood glucose levels are large component of overall glycemic control and variability. Furthermore, glycemic variability is an independent risk factor for heart disease. She presented a graph two patients with varying levels of glycemic management and noted that even the more tightly controlled patients still experienced frequent postprandial blood glucose excursions that were above their target level. More importantly, these blood glucose excursions, she argued, are largely caused by carbohydrate, due to a mismatch in insulin action and timing against carb digestion.

Moreover, she noted that today, children with type 1 diabetes have higher levels of overweight, obesity, and metabolic syndrome, potentially due to a higher carbohydrate diet and corresponding insulin use, or may be in part due to using too much insulin and consuming additional carbohydrates to treat low blood glucose levels.

Next, Dr. Lennerz outlined how low-carb eating could effect positive change for patients and contrasted the potential benefits again commonly-cited concerns of “inadequate carbohydrate intake”.  In short, low-carb eating could help patients minimize blood glucose excursions, which could offer numerous benefits, including:

  • Lower risk of hypoglycemia
  • Higher quality of life
  • Cognitive benefits
  • Better growth and development
  • Potential reduction in CVD risk (lower triglycerides, higher HDL cholesterol)

In contrast, she noted some common concerns, including:

  • Lower glycogen stores and potentially more hypoglycemia
  • Lower quality of life due to “restrictiveness”
  • Sufficient fuel (glucose) for the brain
  • Potential for nutritional deficiency (that could negatively affect growth and development)
  • Potential for increased cardiovascular disease risk (higher LDL cholesterol levels)

Importantly, Dr. Lennerz noted that the available scientific literature to “substantiate or refute these concerns” was scarce, essentially meaning that the commonly-discussed concerns are largely hypothetical.

Next, Dr. Lennerz dove into data from various research studies on low-carb diets in patients with diabetes, first noting positive benefits among patients with type 2 diabetes (improved A1c, insulin sensitivity, etc.), as well as highlighting several case studies that pointed to the safety of the approach in children, young adults, and adults with type 1 diabetes.

Notably, a study published in 2018 showed “unprecedented results” for adults and children in diabetes. These patients achieved clinically-normal A1c levels with little glycemic variability and a very low rate of diabetes-related hospitalizations. Contrasting the glycemic profiles of these patients with the average levels of glycemic management in the US provided a striking visual.

Dr. Lennerz also discussed the relevance of the patient lipid profile in CVD risk, stating that although some studies show elevations in LDL cholesterol levels on a low-carb diet, research shows that A1c and total daily insulin dose, among other factors, are much more important in qualifying CVD risk than LDL levels.

In summary, she stated,

“Generally, very low-carb diets are not recommended for type 1 diabetes in the guidelines because of potential hypothetical risks, though we don’t have any data to substantiate those risks. They are highly popular among patients, they are physiologically-plausible, and could be beneficial. Medical supervision is needed… to achieve nutritional sufficiency, appropriate insulin dosage adjustments, and ketone monitoring.”

Potential Cons of a Low-Carb approach

Dr. Smart began her presentation by stating that her goal was to bring awareness to families and clinicians about the “potential pitfalls” of low-carbohydrate diets and to “provide a voice” to those who follow a higher-carb eating plan but also achieve “optimal” results.

Is a low-carbohydrate eating pattern necessary to reach tightly-controlled glucose in children and what risks must be considered?” asked Dr. Smart. She went on to discuss that “not all carbohydrates are created equal”, underscoring the nutritional value of certain food with higher carb counts, in contrast to packaged and processed carbohydrates that are not generally recommended. The message that “you can eat anything you’d like and dose insulin for it” is an incorrect one, she stated, explaining that scientific evidence shows that different types of carbohydrates can have a different impact on glycemic profile.

She also noted that many children with whom she has worked are “fussy” eaters, underscoring the importance of offering a wide variety of options. Dr. Carmel went on to explain that advocating a “one size fits all” eating plan isn’t a good idea, because energy needs in children are based on growth and activity.

Similar to Dr. Lennerz, Dr. Carmel acknowledged that there is a lack of scientific data on low-carbohydrate eating in pediatric patients with type 1 diabetes. She went on to outline the following potential concerns about low-carb eating in children:

  • Higher fat intake
  • Too much focus on the specific amount of carb intake, instead of acknowledgement that “not all carbs are created equal”
  • Delayed blood glucose rise from fat and protein intake that impacts insulin requirements
  • Oversimplified messaging that may erroneously suggest that glycemic management on a low-carb diet requires little effort
  • Potential for negative effects on cognition
  • Potential for low adherence to a prescribed eating plan
  • Potential for poor growth and development
  • Inadequate nutrient intake
  • Risk of DKA (including euglycemic DKA)
  • Lack of “social normalcy”
  • Cost

Dr. Smart also pointed out that there have been some studies in adults with type 1 diabetes, where lowering the carbohydrate intake did not result in improved glycemia. However, the studies she cited involved a higher amount of carbohydrates, outside the established definition of “low-carb” in this discussion. She also went on to suggest the weight loss seen by some adults with type 1 diabetes on low carb diets may be a concern for growing children.

Dr. Smart went on to address several considerations on the only low-carb study in children (see above), warning that the most appropriate interpretations of the positive outcomes are limited due to potential selection and reporter bias. The presenter noted once more that there is a lack of evidence for or against the use of low-carb diets in youth and highlighted that many “national food agencies” recommend a “moderate carb” intake.

Finally, Dr. Smart presented her final argument, stating,

“There is an assumption that you cannot achieve target glycemia on a usual carb diet… In our clinic, over 83% of patients achieve target glycemia… It is indeed possible to match insulin, if given at the right time, and appropriately matched to the food profile to ensure that glycemic rises are not excessive.”

She went on to present some one-day blood glucose data from some of her patients, to demonstrate that insulin dosing could be optimized for higher-carbohydrate eating, and cited additional data on the A1c levels in her patients (6.4% +/- 0.9%), explaining that these patients eat plenty of carbohydrates (e.g., 170 g+ per day).

Dr. Smart explained that other behaviors, such as checking blood glucose levels frequently, and a deep understanding on how different foods impact blood glucose levels and the corresponding insulin dosing strategy, were much more important to achieving better glycemic control than the grams of carbohydrates consumed.

Rebuttals

The following notable quotes by each respective researcher in the rebuttal portion of the debate are presented below.

Dr. Lennerz:

“Healthy foods are important… I think nutritional sufficiency can be achieved with a very low-carb diet, and I think a hypocaloric status is often related maybe to a “fat fear”, where people are hesitant to eat adequate amounts of fat to compensate for the lost calories from carbohydrate…

I think we have to get away from the term “restriction” and see this rather as offering alternative food choices, and I think like any dietary approach in children, this has to be a family affair… If this is a choice a family is making, I do see a role for low-carb diets and very low-carb diets in a setting of a personal approach…

Given the complexity of diabetes care, I don’t think it’s easy to ask a family to also think of the glycemic index, protein, fat, fiber, and so forth, when they make their diabetes decisions… Some patients may choose to reduce carbohydrate intake instead of making these complex assessments.”

Dr. Smart:

“It is restricting the amount of carbohydrate, because these are commonly-eaten foods. Breads, cereals, pasta are commonly eaten foods across all cultures… You are asking families to restrict the foods that they eat.

It would be fair to say that families that are of high socioeconomic status have time and energy to do this…. If you then try to translate it across the board, other families then become guilty and think that they can’t do this.

It is extremely difficult to get energy intake [on ~30g/day carbohydrate intake] in active young people. I would be very interested to see some published dietary data on what these young people are eating, particularly as, fat and protein occur together in foods, so if you’re saying protein is satiating, you’d have to be eating very large amounts of fat… [Some] people eat… butter by itself… I don’t think most scientists and most clinicians would view that as healthy thing to do…”

transitioning to a low-carb diet

Photo by Brooke Lark (Unsplash)

Discussion

Should children with type 1 diabetes and their families consider a low-carb diet?

Currently, there is substantial scientific evidence on the health benefits of this approach for people with diabetes; in fact, numerous studies have shown significant benefits. However, more research is required to validate this in the pediatric population. Meanwhile, blood glucose management among children and adolescents is far from optimal, despite continuing treatment and technology advances. Concerns raised about low-carb eating in youth, while important, are largely hypothetical, further highlighting that more research is needed across the board on this topic.

Dr. Michael J Haller, MD, Professor and Chief of Pediatric Endocrinology at the University of Florida, who chaired the debate, concluded:

“Clearly not an issue where we’re going to come to an answer today. The research still needs to be done… Importantly, in personalized medicine, we are seeing that there are different ways to manage our patients. They can all achieve success. That’s important to understand.”

***

What are your thoughts on the subject?

Stay tuned for more from the ADA 80th scientific sessions!

Source: diabetesdaily.com

Updates on the Environmental Triggers of Type 1 Diabetes (ADA 2020)

The onset of type 1 diabetes (T1D) usually entails a genetic predisposition to developing the condition, as well as an “environmental trigger” (such as a viral infection, or another exposures). As we previously reported, a multi-center international research effort called TEDDY (The Environmental Determinants of Diabetes in the Young) has been investigating potential environmental triggers that may induce the onset of type 1 diabetes in children since 2004.

As described in the most recent press release:

“TEDDY is aiming to discover viruses and nutritional factors that interact with genes to “trigger” immune destruction of the beta cells, marked by the appearance of islet autoantibodies. The study enrolls infants identified as “at-risk” for developing T1D and follows them for 15 years to look for the appearance of various beta-cell autoantibodies and diabetes. TEDDY has also studied biomarkers that can predict faster or slower progression to diabetes after the autoimmune destruction has begun.”

Now, new data on environmental connections between type 1 diabetes as well as celiac disease were just presented today at the American Diabetes Association (ADA) 80th Scientific Sessions. Dr. Marian Rewers, MD, PhD from the Barbara Davis Center for Diabetes at the University of Colorado School of Medicine, along with other presenters, provided the new research updates.

Key Takeaways

Here are the major highlights:

  • It appears that beta cell destruction often begins very early in life; as early as in the first two years of life.
  • There may be two distinct subtypes of type 1 diabetes that are characterized by differences in their genetics, immune system, and various metabolomic markers.
  • The value of HbA1c as a predictive factor for developing type 1 diabetes may differ between youth and adults who develop the condition.
  • Presence of enterovirus B in stool samples is predictive of islet autoimmunity development in children.
  • The gut microbiome composition tends to be different in children who develop islet autoantibodies as compared to those who do not. The use of probiotics may help to mitigate this risk.
  • Use of antibiotics WAS NOT shown to be related to autoimmunity.
  • Vitamin D, vitamin C, and polyunsaturated fats may carry preventative benefits against autoimmunity, although this needs to be validated in further studies.

Another interesting update was concerning the environmental determinants of celiac disease. There is some overlap in the genetic factors that are associated with the development of type 1 diabetes and celiac disease. Interestingly, recent research has identified a link between the consumption of gluten early in childhood and an increased risk for developing celiac disease among those with a genetic predisposition.

Dr. Rewers had this to say in summary:

“While T1D and celiac disease share a lot of genetic characteristics, there are intriguing differences in the ways these diseases develop and progress,” added Dr. Rewers. “TEDDY is contributing exciting clues for design of future trials to prevent both T1D and celiac disease.”

Conclusions

The multidisciplinary international TEDDY research effort continues to uncover important pieces of the complex puzzle to explain exactly how and why certain individuals develop type 1 diabetes and other autoimmune conditions. Understanding the relationships between genetic predispositions to autoimmune disease and how they may be triggered is critical to the development of effective preventative strategies in the future.

Stay tuned for more research updates from ADA 2020!

Source: diabetesdaily.com

New Research: Hybrid Closed-Loop System Outcomes (ADA 2020)

Technology is truly changing the lives of many people with diabetes across the world. Advancements continue in many areas, including the development and testing of various automated insulin delivery systems.

The MiniMed 670G insulin pump system is the first of it’s kind in providing automatic insulin delivery adjustments based on continuous glucose monitoring (CGM) data. Now, two recent research studies, the results of which were just presented this weekend at the American Diabetes Association (ADA) 80th Scientific Sessions, are highlighting the positive outcomes of the system for young and adults patients.

Outcomes in Adult Patients

Dr. Stephanie Kim, MD, MPH, from the University of San Francisco, CA, presented the results of a single-center research study in adult patients with type 1 diabetes. The researchers enrolled 52 patients (47% female, average age 46 +/-12 years, average diabetes duration of 27 +/- 15 years) utilizing the Medtronic 670G system and started “Automode” delivery of insulin between 2017 and 2019, in an effort to evaluate the impact of automatic delivery on glycemic outcomes.

The study subjects were stratified into two groups, depending on baseline blood glucose levels (defined as A1c level of higher than 7.6% or lower than or equal to 7.5%). The A1c levels were evaluated at baseline (before starting Automode) and again approximately 17 months after starting Automode.

The data revelated that while the A1c level did not change significantly in patients in the lower A1c cohort, there was improvement in the group with baseline A1c>7.6%. These patients improved their A1c, on average, from 8.3% to 7.8% using this system.

Outcomes in Youth

Dr. Goran Petrovski, MD, PhD, of Sidra Medicine in Qatar, reported on the results of an observational study of children and young adults with type 1 diabetes who used multiple daily insulin injections (MDI) and switched to the MiniMed 670G hybrid closed-loop system. A total of 42 patients (ages 7-18, mean age 12 years) were enrolled in the study.

Excitingly, the study outcomes demonstrated considerable improvements to the average A1c levels (8.4% at baseline to 6.7% at 3-months follow-up, and 6.9% at 6-months follow-up) after initiating the hybrid closed-loop system therapy. Also, the time-in-range (defined in this study as blood glucose levels between 70-180 mg/dL) improved considerably with the use of this technology. Notably, no instances of diabetic ketoacidosis (DKA) or severe hypoglycemia were reported. The authors declared no conflict of interest and concluded that “children and adolescents with T1D can successfully initiate the HCL system, achieve and maintain better glycemic control than previous MDI regimen.”

Petrovski et. al. (Presented at ADA 2020)

Conclusions

Technology that can help people with diabetes better manage their blood glucose levels continues to improve. Notably, while the glycemic improvement in youth who transitioned from MDI to the automated system were considerable, the improvements were much more modest in the study on adults using this system who switched to Automode. Altogether, the data highlight the potential of technology to improve outcomes, while also revealing that technology use (at least as it stands today) is generally not enough on its own, to achieve optimal results. Patient education regarding diet, exercise, and the numerous intricacies of dosing insulin remain central to optimizing outcomes.

Source: diabetesdaily.com

New Therapy Shows Promise in Children with Newly-Onset Diabetes (ADA2020)

Research is ongoing around the world concerning the delay of progression and the prevention of type 1 diabetes. The etiology of the disease has been extensively characterized, but all the events and processes that drive and maintain autoimmune attack on the insulin-producing cells are still not fully understood.

One avenue of current investigation involves the clinical application of Tregulatory (Treg) cells. This population of immune cells have many functions, and importantly, serve to help the body recognize the self (“self-tolerance”) and to prevent aberrant attack on healthy tissues (autoimmune disease).

Dr. Piotr Trzonkowski, M.D., Ph.D from the Medical University of Gdansk in Poland has focused his career on investigating, developing, and applying cell-based therapeutic approaches. He presented his most recent work as part of the late-breaking poster session in the Diabetes Prevention category at the American Diabetes Association (ADA) 80th Scientific Sessions this weekend.

The research focuses on utilizing Treg cell therapy in combination with an antibody against a molecule called CD20. This molecule is expressed by immune cells populations (B cells) that are involved in mediating autoimmune disease (read more about anti-CD20 therapies here and about targeting B cells for type 1 diabetes therapy here).

Study Design

This phase II clinical trial utilized the combinational treatment (TrCD20) as part of a study that enrolled 36 children with a recent type 1 diabetes diagnosis. The participants were divided into three groups: control , Treg therapy alone, or the combinational therapy (TrCD20). All patients were followed for a period of two years, and various clinical parameters, such as blood glucose levels and beta cell function, were evaluated and compared between the groups.

Major Outcomes

The main finding in this study was that patients who received the combinational therapy fared better than the other groups with respect to multiple parameters, including fasting and stimulated c-peptide levels (c-peptide is a measurement of insulin production). Also, patients in both treatment groups exhibited lower HbA1c levels and lower fasting blood glucose levels throughout the study. The researchers noted that:

“TrCD20 group was in partial remission defined as insulin dose below 0.5 IU/kg up to +21 months. The longest insulin independent follow up lasted 18 months. The end of the remission in Tr group was noted at +18 month and in controls at +12 months. At the +24 months daily insulin requirement and HbA1c levels were significantly lower in TrCD20 as compared to control group.”

Conclusions

This phase II clinical trial demonstrated increased efficacy of combining cell-based therapy and antibody treatment to achieve longer beta-cell function in children with newly-diagnosed type 1 diabetes. Importantly, in addition to the potential glycemic management benefits, delaying the progression of type 1 diabetes at the early stages may also allow for the clinical application of several novel therapies aimed at halting disease progression.

For example, consider the following research that we have reported on over the last year:

Personalized Therapies for Type 1 Diabetes Take Center Stage 

TrialNet Updates: New Treatment Delays Type 1 Diabetes Onset 

“Inverse Vaccine” to Treat Type 1 Diabetes Passes Phase I Clinical Trial

We will continue to keep you posted of ongoing developments and promising new approaches. Please stay tuned for our ongoing coverage of the most recent research presented at the ADA Scientific Sessions.

Source: diabetesdaily.com

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