A Deep dive into the 2021 ADA Scientific Sessions Report

June 2021 marked the 81st Annual Scientific Session of the American Diabetes Association.

Many on the Integrated Diabetes Services clinical team feel that “Scientific Sessions” is code for “Lots of research presented in a way that very few people can understand, and even fewer can apply.” 

To help more people benefit from the findings, here is our interpretation of many of the conference’s key presentations.

Sarah Picklo Halabu’s Reports
IDS Director of Nutrition Education

Session: Dietary Strategies to preserve Beta Cell Function

For those in the early stages of T1D (or in the “honeymoon” phase), is there a dietary approach that can be used to keep beta cells functioning as long as possible?  Most research involves non-human (mouse) studies, so the applicability is somewhat questionable.  In one study, 24-hour fasting and intermittent fasting were found to be beneficial to beta-cell function by reducing insulin resistance, weight, and intracellular stress.

Session:  Obesity Discoveries, Directions and New Developments

For those in the early stages of T1D (or in the “honeymoon” phase), is there a dietary approach that can be used to keep beta cells functioning as long as possible?  Most research involves non-human (mouse) studies, so the applicability is somewhat questionable.  In one study, 24-hour fasting and intermittent fasting were found to be beneficial to beta-cell function by reducing insulin resistance, weight, and intracellular stress.

The focus of this session was diabetes prevention.  The most effective weight reduction strategies continue to be:

• Adjustment to medications
• Dietary changes
• Exercise
• Cognitive-behavioral therapy
• Group education (Surprisingly, virtual programs during covid demonstrated more weight loss and A1c reduction than traditional in-person programs)
• Weight loss surgery (gastric bypass is more effective than sleeve procedures for weight loss and reduction of insulin resistance)

It should be noted that severe caloric restriction increases plasma ghrelin (hunger hormones) in obese and overweight individuals, and may work against weight loss, weight maintenance, and body fat composition improvements.

Session:  Insulin Delivery Systems

Not surprisingly, hybrid closed loop systems improve glucose time in range and A1c, reduce severe hypoglycemia and user burden, and cause few negative outcomes.

Tandem addressed racial disparities in glucose results among those their Control IQ hybrid closed loop system.  During the first 21 days of use, Black/African American users saw the greatest improvement in glucose control while Asian Americans achieved the best average glucose and time-in-range.

Rice University presented some interesting data on the best ways to estimate insulin-to-carb (IC) ratios.  Traditionally, a “500 rule” (500 divided by total daily insulin) has been used to come up with an initial IC ratio.  Researchers analyzed data from Tidepool data sets for more than 100 kids and adults using pumps and CGMs, and came up with the following formulas for estimating the IC ratios (divide by total daily insulin, in units):

The presenters noted that these are just general estimates; true IC ratios can be affected by protein and fat intake, physical activity, and variations in insulin sensitivity.

Dana Roseman’s Reports
IDS Director of Technology and Applied Research

Session: Diabetes Mental Health

It is well-established that there is a strong link between depression both type-1 and type-2 diabetes.  Those diagnosed with depression are at an increased risk of diabetes complications and poor glucose control.  However, with depression treatment, outcomes appear to be greatly improved.  Although it is not certain why people with diabetes are at an increased risk for depression, it is interesting to note that people with undiagnosed diabetes do not exhibit a greater incidence of depression.

A strong link has been established between mental disorders treated with antipsychotic medications and the development of cardiovascular disease.  Triglycerides, in particular, may be affected adversely by the use of antipsychotic medications.

There is an estimated 50% increase in non-diabetes-related eating disorders since the start of the COVID pandemic.  Recent research shows that 31% of people with type-1 diabetes omit insulin at some point in order to lose weight.  Being diagnosed with type-1 diabetes increases the risk of developing an eating disorder by 20%, and dropout from eating disorder treatment is greater for those with type-1.  This is particularly troubling, as 34% of type-1s diagnosed with an eating disorder were found to die prematurely.

Session:  Diabetes and Metabolism through the Lifespan

Time restricted Feeding (for example, not eating before or after 6pm) has been found to be a better approach for resetting the metabolism, improving insulin sensitivity and achieving weight loss than calorie restriction – particularly for males.

The benefits of plant-based and ketogenic diets were discussed extensively.  Research has shown that both increase longevity.  However, plant-based diets are more beneficial for heart health and cancer prevention, while ketogenic diets are more beneficial for brain health.

Session: Treatments and Prevention of Hypoglycemia

Fear of hypoglycemia continues to be a barrier to management.  So here’s some good news.

Glucagon microdosing was found to be an effective way to prevent or treat mild hypoglycemia – especially during sports and with an upset stomach (gastritis).  Doses are age-based:

under 2yrs:  2units (20 mcg)

2-15 years based on age:  1u (10 mcg) per year (7 years = 7 u/70 mcg)

>15 yrs:  15u (150 mcg)

Compared to hybrid closed loop adjustments for preventing hypoglycemia (i.e. automated reductions to basal insulin), microdosing glucagon was found to be superior.  It was also found to be equivalent to glucose tablets for treating lows, with less post-treatment hyperglycemia.

The new nasal and autoinjector glucagon options from Lilly (Baqsimi) and Xeris (GVoke) were found to be superior to traditional glucagon in terms of users’ ability to actually USE them.  Big surprise!  Also, glucagon as second hormone in pump therapy was found to be better for preventing lows than simply stopping basal insulin delivery, due to the prolonged action of rapid-acting insulin.

Alica Down’s Reports
IDS Director of Patient Care and Education

Session:  Intersection of Diabetes, Heart & Kidney Health

There has been an uptick in cardiovascular complications in young people with diabetes.

Atherosclerotic cardiac disease is most common.  SGLT2 inhibitors (meds that increase urinary glucose output) appear to increase the energy performance of heart muscle and produce other effects that reduce cardiac events.  These meds also reduce fluid volume and blood pressure, resulting in reduced rates of hospitalization for heart failure.  GLP1 receptor agonists are also associated with improved kidney function and reduce rates of heart failure and stroke.  This is secondary to reduced markers for inflammation and coagulation.  Comparative studies using older-generation diabetes medications (sulfonylureas) showed no heart or kidney benefits.

Overall, for those with existing kidney disease, beneficial therapeutics include:

• Reduced protein diet
• Weight loss (especially bariatric surgery)
• Use of blood pressure medications (ace inhibitors and angiotensin-renin blockers)
• Use of SGLT2 inhibitors (particularly dapagliflozin and sotagaflozin)
• Use of GLP1 receptor agonists

Session: Beta Cell Replacement Innovations

The JDRF beta cell consortium is working to bring together all the necessary elements for building a portable, scalable automated cell growth program.  This includes:

• Locating beta cell sources (from human stem cells or pigs)
• Refining implantation methods (research focuses on delivering adequate oxygen and nutrients to cells implanted either below the skin or in the abdominal cavity.  Options include oxygen injection,  electrochemical creation of oxygen, scaffolding, bio-engineered perfusion, or enhancing local blood flow)
• Protecting the cells (encapsulation or use of algenate)
• Editing genes (to reduce autoimmune targeting or increase cell resistance to immune attack)
• Modulating the immune system (use of rabdomycin in a gel to physically block immune attack)

Digital psycho-social impact in treatment

A pretty useless talk on using apps to track eating and behaviors. (big news is that they are not particularly good at it unless the user wears two tracking methods: like an apple watch and earbud, or earbud and google glass! )

One interesting app used aggregated data including additional apps, GPS location and proximity to other app users, to correlate glycemic outcomes with locations, peoples, or activities. The app can then remind the user, in real-time, that their BG tends to run higher when they are at work, or hanging out with Jessica etc. This was interesting but the AI is not scalable at this time.

Their goals were also to identify behavioral phenotypes to allow for more proactive notifications, but as we know people’s management behaviors are not so easily stratified.

Session: Management of atypical diabetes

Exocrine pancreatic insufficiency (EPI, insufficient production of digestive enzymes) is present in 25-30% of people with type-1 and type-2 diabetes.   It often develops prior to diabetes (usually prior to age 40).  Symptoms include fatigue, weight loss, swelling, bleeding disorders, excess gas, and nervous system disorders.  A stool (feces) test can determine if EPI is present. Enzyme supplementation can significantly reduce blood sugar/medication needs

Cystic Fibrosis (CF)-induced diabetes often appears as occasional severe high glucose levels after meals with normal glucose in-between.  Best treated with low basal insulin doses and aggressive rapid-acting insulin at meals. Enzyme supplementation can significantly reduce blood sugar/insulin needs

Post-transplant diabetes is caused by the steroid and anti-rejection medications required on an ongoing basis.  Diabetes develops in 10-40% of transplant recipients within one year.  Rates are highest for heart and lung transplants, followed by kidney and liver. Treatment ranges from simple oral medication to full intensive insulin therapy.  Studies have shown significant reduction of and delay in onset of diabetes when basal insulin is initiated immediately following transplant – particularly when steroids and cyclosporin are in use (the insulin dose can be tapered as steroids are reduced). Use of an insulin pump to deliver the insulin was found to be superior to taking long-acting insulin by injection.

Session:  Treatment of PCOS in Diabetes

50% of women with PCOS (polycystic ovary syndrome) are normal weight; heredity is a stronger risk factor than obesity.  Women with PCOS are 7x more likely to develop type-2 diabetes, but many of the genes associated with type-2 are NOT found is most women with PCOS, so there must be a physiologic cause rather than simply a genetic predisposition.

Women with PCOS over-produce testosterone and androgen hormones, so tailored genetic medications may lead to effective treatment.

Surprisingly, exercise in women with PCOS shows very little impact on insulin sensitivity (exercise is VERY effective for improving insulin sensitivity in people with type-2 diabetes).

But exercise does provide other benefits:  it helps to reduce testosterone levels (which improves self-image), reduce depression, and improve menstrual regularity and aerobic capacity.

Using GLP-1 medications in women with PCOS and diabetes showed more benefits than DPP4 medications.  DPP4s help increase weight loss and normalize menses but do not impact androgen profiles or fertility rates.  GLP1s have been shown to normalize menses, help with weight loss,  improve fertility over metformin alone, and reduce free testosterone levels.

Jenny Smith’s Reports
IDS Director of Lifestyle and Nutrition

Session:  Advances in diabetes and pregnancy

Canadian researchers shared some key results from their research on women with gestational diabetes.  The use of a real-time (live data) continuous glucose monitor during pregnancy definitely improves outcomes (frequent fingersticks were deemed insufficient to capture both hypoglycemia and post-meal hyper glycemia).  CGM use produced 50% less macrosomia and less infant hypoglycemia at birth. For the mom, A1c and time-in-range improved significantly.

UK researchers took a close look at the dietary patterns of mothers with diabetes during pregnancy.  Mothers of larger babies tended to consume more unhealthy (processed, high-glycemic-index) carbs than mothers of normal-weight babies.  Investigators theorized that the elevated post-meal blood sugars caused by these types of foods was responsible, reinforcing the importance of proper meal planning during pregnancy.

Something the pump companies won’t be happy about:  The CONCEPT study showed that pump users actually had 5% less time in range and worse pregnancy outcomes than women taking multiple daily injections.  Our thinking is it isn’t the device, it’s the lack of guidance and self-management training provided to far too many pump users.

And what about that magical reappearance of insulin production that occurs during pregnancy in some women with type-1 diabetes?   Most women were found to have no detectable c-peptide (a surrogate measure of insulin production by the pancreas) at all times of pregnancy.  For women with a detectable c-peptide through the pregnancy, the level was found to be highest at 24 weeks.  Women in this group were typically diagnosed as young adults and had type-1 diabetes for only a few years.  Then there were women with NO detectable c-peptide for the first 24 weeks of pregnancy, but developed some c-peptide by 34 weeks.  90% Of the babies born to these women were large, and 42% experienced neonatal hypoglycemia, leading to the conclusion the c-peptide was the result of fetal hyperinsulininism (the baby, and not the mom, was producing excess insulin).

Not surprisingly, use of hybrid closed loop systems during pregnancy produced positive results.  Tandem’s Control-IQ system stayed in closed-loop mode 97% of the time, increased time in the recommended 63-140 mg/dl range by 18%, and led to significant improvements in the critical post-meal period.  Speaking of which, researchers at Harvard University concluded that A1c alone is a poor predictor of birth weight.  Glucose variability, especially during the 1st and 2nd trimesters, plays a significant role in large-for-gestational-age development.

Session:  Timing Is Everything—The Role of Your Circadian Clock

Scientists at the Hebrew University of Jerusalem explained that circadian rhythm is largely controlled by light.  The circadian clock is “reset” by the increased presence of light in the morning, as sensed by the retina.  Metabolism is closely linked to the circadian clock.  Obesity, in particular, is often related to disruptions in circadian rhythm.

Sleep deprivation has been linked to technology use, consumption of highly processed food and caffeine later in the day, as well as alternating shift work, late food intake and inappropriately timed medication use. The effects of poor sleep quality/quantity include insulin resistance.  With intermittent fasting gaining popularity, it is important to know that late eating disrupts the sleep cycle.  Analysis of CGM comparing “unrestricted” food intake to 3 meals a day without anything after 6pm showed that later dinner prevents glucose from returning to baseline for overnight and thus decreases overall sleep quality.  Glucose levels overnight drive several endocrine hormone responses and can influence glucose and hunger levels in the daytime as well.

It appears that the circadian clock’s start and end times are altered by the content of meals.  High-fat diets lead to delay circadian rhythm turn-on.  Researchers conducted tests with small/med/large meals at various times of the day.  People who consumed a large breakfast lost more weight than those who had a large dinner.  Late eaters tended to be overweight/obese, have high insulin resistance, and elevated triglycerides.  In fact, eating meals just 3 hours later in the day translated into 3kg less weight loss than someone eating earlier.  Other noteworthy effects of meal sizes & timing:

• People with type-2 show lower glucose levels for lunch and dinner and overnight with a larger breakfast compared with the large dinner meal group.
• Breakfast is needed to “prime” (energize) beta cells – priming is done better for the full day if the early AM is a relatively large meal, as this pushes beta cells to produce more insulin from the start of the day
• Those who skipped breakfast had higher glucose rises (peaks) after lunch and dinner compared to those who ate breakfast.
• In terms of meal frequency, those who had three meals per day spent more time in a normal glucose range than those who had six meals.  Also, three meals daily produced more weight loss than six meals, even when the calorie content was equal.

Session: Is There an Ideal Time to Exercise?

There was considerable conversation about whether exercising at the same time of day helps to keep exercise consistent.  Morning is often considered the ideal time of day to achieve higher levels of exercise performance and consistency.  Morning exercise means fewer events and scheduling conflicts, protected time for exercise, simplified planning (especially for those who take mealtime insulin), and less coping/problem solving required.  One study showed that elevated levels of cortisol in the morning produce better exercise performance.

The Look AHEAD study compared people who exercised at different times of a day.  It showed that people who varied their exercise times engaged in the most overall moderate/vigorous physical activity (the morning exercise group was 2nd most active).  Men who exercised in the morning were found to have the best overall fitness level.

On the contrary, post-bariatric surgery patients accumulated the most overall physical activity when exercising at a consistent time of day, specifically the morning.  This benefit persisted for a full year of follow-up:  exercise was more frequent and of longer duration when performed at a consistent time of day… and morning exercisers fared better than those who exercised later in the day (afternoon exercisers had the worst consistency).  A Women’s Health study looked at the association between daily step counts and the timing of physical activity.  It found that participants with fewer step counts in the morning had a 26% greater risk of obesity compared to those who had most of their step counts by noon.

Session:  Insulin as a Driver of Cancer

Diabetes is associated with an increased risk of many forms of cancer, including pancreatic, uterine, kidney, breast, and endometrial.  Insulin is a signal for cells to store fuel and grow.  More insulin (as occurs in people who are insulin resistant or taking more than they need) can contribute to tumor growth.  In breast cancer studies, black women were twice as likely to be insulin resistant than white women, and were also twice as likely to have poor outcomes with their breast cancer treatment.

Can diet influence cancer outcomes?  Apparently, yes.  Women with type-2 diabetes and endometrial cancer were found to have decreased levels of circulating insulin and decrease tumor growth when following a ketogenic diet.  Colorectal cancer can be affected directly by diet since food comes in direct contact with gastrointestinal cells.  A study of adolescents found that consumption of simple sugars (particularly sugar-sweetened beverages) correlated directly with colorectal tumor growth.

Gary Scheiner’s Reports
IDS Owner, Clinical Director

Session:  Medtronic’s Extended-Wear Infusion Set

Medtronic is developing an infusion device that will hopefully give us much more than the 2-3 days we currently get.  The new/improved design includes a medication on the canula that helps to reduce local inflammation at the insertion site.  The first large-scale study on the set included 259 people using the MiniMed 670G, with a goal of achieving seven days of quality infusion set life.  Here are some of the key results:

• The seven-day survival rate was 75%.  25% of the time, users had to change the set before seven days due to site problems or uncontrolled glucose levels.
• Of more than 3,000 extended-wear infusion sets used in the trial, there were only eight cases of hyperglycemia directly related to a product flaw.
• Average time-in-range was 74% when using the Extended-Wear Infusion Set.
• Users reported greater convenience of use, ease of insertion, and comfort of wear with the new set.

Medtronic’s Extended-Wear Infusion Set has been submitted to the FDA and is awaiting approval.

Session:  Real world data on the MiniMed 770G

Medtronic launched the MiniMed 770G hybrid closed loop system last November.  770G is similar to the 670G, but it uses Bluetooth to share and view data, and has an updated algorithm that generates fewer alarms/alerts.

Here’s data from over 11,000 users over the age of two:

• Average time-in-range (70-180 mg/dl) was 71% (better at night than during the day)
• 56% of users achieved at least 70% Time in Range.
• Average glucose was 156 mg/dl
• Users spent 1.8% of time below 70 mg/dl, and 0.4% of time below 54 mg/dL.  This corresponds to approximately 27 minutes per day and 6 minutes per day, respectively.

Session:  Inhaled insulin shows positive results

In a phase 2 clinical trial, the ultra-rapid acting inhaled insulin Afrezza was tested in 30 children with type 1 diabetes.  The goal of the trial was to observe the action profile and safety of the insulin.  The study showed that most of the insulin reached the bloodstream around 10 to 15 minutes after inhalation and dissipated after about two hours.  The peak action (blood glucose-lowering effect) took place 30 to 60 minutes after inhalation – similar to the action profile seen in adults.

No severe hypoglycemia occurred and the only side effect observed was a cough in the early stages of inhalation.  The researchers concluded that Afrezza was safe in this group and that a phase 3 clinical trial could be started.

In another study, of adults with type 2 diabetes who have erratic glucose levels, the use of Afrezza was shown to greatly improve Time in Range during the day from 39% to 62%.  Time below-target increased from 0.8% to 2.3%

Omnipod 5 Study Report

Three pivotal studies showed that Omnipod 5, Insulet’s new hybrid closed loop system that is awaiting FDA approval, is safe and effective for people of all ages with type-1 diabetes.  OmniPod5 utilizes the OmniPod patch pump, Dexcom G6 sensor, and a control algorithm app that resides on an Android phone.

The following results were obtained from three months of use:

• Young children (ages 2-6) saw time-in-range increase from 57% to 68%, A1c decrease from 7.4% to 6.9%, and time below 70 mg/dl decrease from 2.2% to 1.9%.  No severe hypoglycemia or DKA was reported.  Overnight time-in-range (midnight to 6am) increased significantly, from 58% to 81%, and parents/caregivers reported significant improvements in their sleep quality.
• School-age children  (ages 6-14) saw time-in-range increase from 52% to 68%, A1c decrease from 7.7% to 7.0%, and time below 70 mg/dl increase slightly from 1.4% to 1.5%.
• Adolescents and adults (age 14-70) saw time-in-range increase from 65% to 74%, A1c decrease from 7.2% to 6.8%, and time below 70 mg/dl decrease from 2.0% to 1.1%.

Following the initial three-month trials, 92% of adults and adolescents, and 99% of children, chose to continue using Omnipod 5 for an additional one-year trial.

Session:  Control-IQ in older adults

Hybrid closed loop systems are all the rage among the young and middle-aged.  But what about older adults?  Dr. Elena Toschi presented an analysis of real-world data from older adults (average age 70) who started using Tandem’s Control-IQ automated insulin delivery system. Researchers compared CGM data from prior to starting Control-IQ with data from three months after starting Control IQ.  Apparently, older folks take pretty well to the system.  Time-in-range (70-180 mg/dl) increased from 64% to 87%, and time in a hypoglycemic range (below 70 mg/dl) fell from 2.8% to 1.9%.