A Quick Review of ADA 2022

This year’s annual Scientific Sessions of the American Diabetes Association were held in fun & festive (aka hot & humid) New Orleans.

By Gary Scheiner MS, CDCES

The good news is that the meeting was extremely engaging and filled with cutting-edge research news.  The bad news is that it was so engaging that I didn’t have a moment to enjoy all the “fun & festive” stuff that New Orleans is famous for.  

Meeting attendance was down compared to prior in-person conferences (thank you, COVID), so I had an opportunity to spend quality one-on-one time with many of the people who are directly involved with the latest research and product developments.  Since our practice focuses on caring for patients using intensive insulin therapy, I gravitated towards the symposia and exhibits that are more pertinent to insulin users.

Here’s a synopsis of what I discovered:

DIABETES TECHNOLOGY UPDATES

Tandem is planning to submit their long-awaited “T:Sport” pump to the FDA later this year.  Although it will launch under a different name, T:Sport will definitely appeal to active people.  It is a small patch-style pump that adheres directly to the skin.  But unlike OmniPod, T:Sport is not disposable.  It will have a separate 90-degree soft-canula infusion set connected to the pump by a few inches of tubing… so the pump can be used again and again.  It will hold up to 200 units of insulin and include just one button for administering manual boluses.  All the other programming will be administered through a smartphone app.  And the Control IQ automated-insulin-delivery algorithm will be built right in.

BTW, Tandem says the patch for upgrading their current t:slim pump to work with Dexcom G7 will be ready to launch shortly after G7 receives FDA approval.  It will involve a simple software update on the pump itself, so no hardware changes will be needed.

On the infusion set front, Capillary Biomedical showed off prototypes of their new extended-wear infusion set, the Steadi-Set.  Their innovative design features a very flexible canula reinforced by a thin steel coil that is wound inside the canula.  You can bend it and twist it all you like – it won’t kink or pinch.  It also has a three-side opening along the 13mm angled canula so that obstacles at the tip won’t prevent the insulin from continuing to flow.  Cap Bio also designed their tubing so as to prevent loss of the preservative that is so essential to keeping the insulin working properly.  Studies conducted in California this past year showed excellent results:  7+ days of trouble-free wear, and accelerated insulin action the longer the set is worn.  I had a chance to wear one myself (without insulin):  The inserter was extremely easy to use, the insertion was painless, the adhesive held the set on securely for a full seven days, and I experienced no site irritation or inflammation.  For more details, go to Capillary Biomedical.

Medtronic also shared the results of studies on their new extended wear infusion set.  Based on the current Mio Advance, Medtronic’s engineers made no changes to the set itself.  Instead, they focused on the insulin that makes its way into the body.  Their theory is that impurities, particulates and broken pieces of insulin, called “fibrils” (caused by agitating the insulin in the pump) is the source of many of the problems seen at infusion sites.  They designed a filter to keep impurities from entering the tubing, and similar to Capillary Bio, redesigned the tubing to make sure the preservative stays intact.  Combined with stronger adhesive to minimize vertical movement of the canula below the skin, the new 7-day extended wear set not only lasted a full seven days for the vast majority of users, it also produced a 2.8% improvement in time-in-range compared to their traditional three-day sets.  Users reported less site discomfort, fewer accidental site pull-outs, and far fewer unexplained high glucose levels.

Beta Bionics announced the results of its pivotal trial on the iLet insulin-only (no glucagon) Bionic Pancreas.  The system was built with simplicity and the everyday user in mind.  The credit card-sized pump houses the automated insulin delivery algorithm, and requires only the user’s weight to begin self-adjustment of insulin delivery.  That’s right – only weight.  No basal settings, carb ratios or correction factors.  Carb counting is also not necessary – the user only has to specify if their meal is of the usual size, less or more.  The study included a diverse population of children and adults from a wide range of socio-economic backgrounds.  After three months of use, overall time-in-range improved by 11%, and A1c came down an average of .5%.  Even those who were using a hybrid closed loop system previously saw an improvement in A1c by an average of 0.3%.  Time spent with glucose below 54mg/d (3mmol/l) was a mere 0.33%.  Beta Bionics is also working on a dual-hormone (insulin and glucagon) system, but hopes to launch their insulin-only version sometime next year.

Abbott was proud to show off its new Libre 3 Continuous Glucose Monitoring System, right on the heels of FDA approval.  The new sensor/transmitter combo, about the size of a penny and weight of a Cheerio, automatically sends readings to the user’s smarphone every minute (no scanning required).  Each sensor can be used for up to 14 days, and produced excellent accuracy in pivotal studies (MARD near 8%).  The Libre 3 app sports customizable high/low alerts and generates a variety of on-screen graphs and statistics.

Speaking of Abbott, plans are underway to incorporate continuous ketone monitoring into its CGM system.  The glucose-ketone sensor will be similar in size to the Libre 3.  Ketone monitoring is important for everyone with diabetes during an illness, as it can help guide proper medical care in order to avoid ketoacidosis.  It is also useful to insulin pump users as a way to determine whether elevated glucose levels are due to under-bolusing or a more serious problem with the insulin or insulin delivery.  Abbott plans to conduct pivotal trials on their continuous ketone monitor in 2023.

Ascensia, which recently acquired the Eversense CGM from Senseonics, presented data on its recently-approved 6-month implanted sensor, the Eversense E3.  In addition to doubling the sensor life, E3 requires fewer calibrations than the previous Evensense system (one per day after day 21, compared to two per day) and better overall accuracy (MARD 8.5% compared to 9.1%).

NEW DIABETES THERAPIES

The hottest news item at ADA 2022 had to do with the weight loss potential of tirzepatide (brand name Mounjaro), Eli Lilly’s novel dual-action GIP/GLP-1 receptor agonist.  

Mounjaro is a once-weekly injectible medication that has multiple benefits for people with diabetes.  In addition to offering the usual benefits of a GLP-receptor agonist (slower gastric emptying, appetite suppression, blocked glucagon release, enhanced insulin secretion by the pancreas), the GIP content leads to improved insulin sensitivity.  So besides improving glucose control, Mounjaro produces some astounding weight loss.  In just over one year, obese trial participants achieved an average of 16% to 22% weight loss, depending on the dose that was given.  Putting it in practical terms, a person weighing 250 pounds could expect to lose about 50 pounds.  Mild-to-moderate gastrointestinal side-effects were common.  Mounjaro is currently approved for treatment of type-2 diabetes in adults.  Lilly is awaiting FDA approval for use of Mounjaro in the treatment of obesity.

Recent research has revealed the benefit of the SGLT2 inhibitor class of glucose-lowering agents in reducing the onset and progression of kidney complications in people with and without diabetes.  Clinical trials and observational studies, mostly involving type 2 diabetes patients, have shown that use of an SGLT2 inhibitor can slow the decline in glomerular filtration rate (GFR), reduce the onset of microalbuminuria and slow or reverse the progression of proteinuria.  However, SGLT2 inhibitors can be costly and have certain side effects.  Now, a new blood test called KidnyIntel, can be run to determine a person’s risk for progressive kidney better than traditional tests such as GFR and albumin-to-creatinine ratio. To learn more, visit kidneyintelx.com.

RESEARCH & CLINICAL SYMPOSIA

A four-part symposium on pregnancy and diabetes shed light on several key areas.  Fasting glucose levels are naturally 2-3 mg/dl lower during pregnancy in non-diabetic women, so it is reasonable to set lower acceptable premeal targets during pregnancy in women with T1D.  However, post-meal glucose tends to rise 14 mg/dl at mid-pregnancy, owing to the challenges caused by insulin resistance during this phase.  Likewise, appropriate post-meal targets should be met by women with T1D.

We often observe that women with T1D require less insulin in the early stages of pregnancy, and this appears to be related to an increase in 1st-phase insulin secretion by the beta cells of the pancreas.  In fact, beta cell mass has been shown to be 1.4X pre-pregnancy levels in women with T1D at mid-pregnancy.  Researchers theorize that this is related to increased blood flow to the pancreas and production of hormones called lactogens.  This results in progressive insulin production through pregnancy, as measured by C-peptide levels (near-zero pre-pregnancy, 42% at 8 weeks gestation, 97% at 33 weeks).  There is also evidence that T1 women with some residual beta cell function at the onset of pregnancy see the most significant increase in beta cell proliferation and insulin production during pregnancy.  Unfortunately, things return to pre-pregnancy levels soon after delivery.  Future research will look at the changes that take place during pregnancy in hopes of replicating it in both men and women in a non-pregnant state.

In a separate symposium focusing on exercise during pregnancy, researchers reported that moms who performed cardio exercise regularly during pregnancy had babies with a healthier birth weight and increased aerobic capacity.  The babies also had better blood lipids and motor skills, and a lower BMI for up to five years.  Not to be outdone, women who performed resistance (strength) exercise during pregnancy had babies with even better birthweight, lower BMI, and superior motor skills.

Another team of researchers examined the impact of exercise on glucose levels in women vs men.  They reported that women rely more heavily on fat for fuel, resulting in a lesser decline in glucose levels than men when performing similar types of exercise.  Women also deplete their glycogen stores (concentrated sugar stored in muscle) more slowly than men, so the risk of delayed-onset hypoglycemia after intense exercise is slightly less.  Menstrual cycles were also found to impact glucose responses during exercise.  More dietary carbohydrate was needed to prevent hypoglycemia during the luteal phase than during the follicular phase, due to a shift towards greater fat metabolism as a fuel source.  High glucose was found to be more common after exercise during the follicular phase.  For menopausal women, resistance training was found to be extremely important for maintaining healthy bone density, muscle strength and insulin sensitivity.  Resistance training may include weight lifting, calisthenics, use of resistance bands, as well as water-based exercise.

A great deal of attention was paid to the “time in range” as a metric for evaluating glucose control (compared to A1c).  Some even proposed looking beyond time in-range, specifically at time in severe high and low glucose ranges (with the lows weighted more heavily than the highs) for determining true safety and health risks.  One group dug deeply into the data and found that post-meal glucose levels have a significant impact on time in-range, particularly when time in-range improves (similar to the relationship that exists between post-meal glucose and A1c).

Here’s the breakdown:

The bottom line: If you want to improve your time in-range, you’d better pay attention to your after-meal glucose levels and minimize the “spikes”!