Research is the bread on which we make our diabetes sandwich.
It made sense in my head, but now that I read it, it sounds ridiculous.
Anyway, research is very, very important stuff. It helps us separate fact from fiction. It reveals new and better ways to do things. And it leads to the development of leading-edge products. Without quality research, all we have are sandwich innards with nothing to hold it together.
OK, no more food metaphors, I promise.
The American Diabetes Association’s 2023 Scientific Sessions, held in San Diego in mid-June, featured some of the brightest minds in the diabetes field sharing their latest findings.
Terri Ryan and I were there representing Integrated Diabetes Services and covering as much as possible.
Here are some of the highlights:
Exercise Research
Workout Timing
Comparisons were made between pre-meal (or fasting) and post-meal exercise. In one study, resistance exercise performed first thing in the morning produced an average glucose rise of 20 mg/dl, versus a 16 mg/dl average drop when the same workout was performed in the afternoon. Fasting exercise offers the advantage of increasing glycogen storage in muscles and producing less of a glucose drop compared to exercise performed later in the day. But it does tend to increase appetite and lead to higher calorie intake at breakfast. Post-meal exercise contributes to better post-meal glucose control (less “spiking”), but also leads to a higher body temperature and heart rate during exercise (which can hinder performance) and may contribute to stomach upset. When it comes to weight loss, most studies have shown little difference between fasting and post-meal exercise.
Combo Workouts
For those who like to perform both strength (resistance) and cardio (aerobic) exercise in the same session, the order of the workouts can make a difference. Because strength exercise tends to produce glucose-raising counterregulatory hormones, performing strength exercise before the cardio portion of the workout can help reduce the risk of hypoglycemia
Exercise Intensity
For those who take insulin, extra carbohydrates or mealtime insulin reductions are often used to prevent hypoglycemia during cardiovascular exercise. However, the intensity of the workout dictates the amount of carbohydrate or insulin reduction needed. It appears that the needs increase steadily up to about 70-75% of VO2 max (a “moderately challenging” pace), then drop off quickly. At exercise intensities of 80% VO2 max (very challenging) or higher, the body produces enough counterregulatory hormones that much less carbohydrate and/or insulin dose reduction is needed to maintain a stable glucose level.
Foot Ulcer Risk
Diabetic foot disease is caused by a combination of neuropathy and poor blood flow, compounded by repeated pressure. Physical inactivity has been named a major risk factor for the development of foot ulcers, primarily because physical activity is important for maintaining sufficient circulation in the lower extremities. But how much physical activity is required? Researchers found that too much variability in physical activity often precedes ulceration – going for extended periods of time with little activity, and then being overly active – similar to a “weekend warrior” approach. What’s recommended is a moderate amount of physical activity on a daily basis. The type of activity was found to be far less important than the regularity/frequency.
Daily Step Counts
To illustrate the short-term impact of physical activity on insulin sensitivity, researchers at York University studied the relationship between daily step counts and time in-range in people with type-1 diabetes. They found that average time in-range was 2% higher and time above-range was 2% lower on days when participants accumulated at least 7,000 steps. Similar studies in Japan showed a strong positive correlation between daily step counts and time in-range, and a negative correlation between sedentary behavior and average glucose and time in-range.
Risk Factors for Delayed-Onset Hypoglycemia
Many people see their glucose drop several hours after exercise, and perhaps overnight. A group of exercise specialists from North America and the United Kingdom studied the effects of exercise timing and length on nighttime hypoglycemia. They found a “dose-dependent” effect: longer workouts have a greater tendency to produce delayed-onset hypos… particularly workouts lasting longer than 90 minutes. They also found that exercise performed in the evening was significantly more like to produce nighttime hypoglycemia than workouts performed earlier in the day.
What’s New With Glucagon
Ready-to-use, Stable long-term
The old red- & orange-box glucagon kits were apparently more of a problem than most people realized. Besides being very difficult to use in an emergency, the mixture would start losing potency as soon as 24 hours after it was reconstituted. Compare that to the new-generation kits (G-Voke Hypo Pen from Xeris, Baqsimi nasal spray from Lilly, and Zegalogue from Zealand) which are equally effective as traditional glucagon, ready-to-administer, and have a shelf life of up to 2+ years. Both G-Voke and Baqsimi contain glucagon that is identical to human glucagon. Zegalogue is an “analog” – it has a different chemical structure than humal glucagon, but has similar effects in the body. However, the nausea rate with Zegalogue is considerably higher than the other two, with 57% of recipients experiencing GI upset in clinical trials.
Glucagon in a pump?
The long-term stability of liquid (aqueous) glucagon has opened the door for companies such as Beta Bionics to move ahead with development of a dual-hormone insulin pump. By administering glucagon when glucose is falling, the system’s algorithm can be more aggressive while effectively minimizing the incidence of hypoglycemia. No “basal” glucagon is administered, only small boluses based on a person’s weight. In early trials, the degree of glucose variability with the dual-hormone system was extremely low. Approximately 70% of glucose readings were held within a range of 130 to 150 mg/dl. On the downside, the dual-hormone system requires two tubes and two infusion sets to connect the pump to the body.
Glucagon before exercise
Studies on the use of small doses of glucagon for preventing hypoglycemia during exercise produced positive results. Compared to decreasing basal insulin at the time of exercise (which failed to prevent hypoglycemia), taking 10-20% of the glucagon dose required to treat severe hypoglycemia 5-10 minutes before exercise did help prevent hypoglycemia in the majority of subjects.
Pregnancy Updates
Nutrition Recommendations
A group of experts debated the pros/cons of following a low-carb diet during pregnancy. Given the importance of keeping post-meal glucose levels below 140 mg/dl, it seems reasonable to give this approach consideration. However, too little carb can be harmful. “Starvation” ketones can develop when not enough carb is consumed, and ketones have been shown to negatively impact a baby’s cognitive development. So, what about “reduced” carbs? Research has shown that a diet with 40% of calories coming from carbs produced no difference in a baby’s birth weight than a diet with 60% of calories from carbs. Low glycemic-index diets, by contrast, have been found to produce lower insulin requirements, maternal weight and birthweight than low carb diets. In fact, it was proposed that the traditional guidelines recommending at least 175g carbohydrate per day during pregnancy be updated to 220g in order to promote support maternal brain function and fetal brain development.
AID System Usage
In recent years, more pregnant women have made use of automated insulin delivery (AID) systems despite the lack of official FDA approval of their use during pregnancy. Data presented at the conference showed that women achieve pregnancy targets (63-140 mg/dl) 70% of the time on AID systems, versus 55% of the time on conventional pump/CGM equipment. Overnight, the control is even better – 85% of time in-range with AID systems. Of course, some AID systems have limitations that may make it challenging to stay within such a tight glucose range.
Experts recommended several strategies for achieving the best possible outcomes:
- Use the lowest allowable targets (100 mg/dl during 1st trimester, 90 mg/dl during 2nd & 3rd)
- Raise targets during labor and delivery
- Manually correct hyperglycemia between meals
- Limit use of “fake carb” entries for correcting highs to once every two hours
- Check glucose on a fingerstick meter before treating lows and use less carb than usual for treatment
- Split boluses when consuming high-fat meals
- Use longer pre-bolus times as the pregnancy proceeds
- Consider use of open loop at night if a persistent glucose rise or drop occurs
- Avoid prolonged suspensions of basal delivery (>90 minutes)
The Power of Time-In-Range
Dr. Viral Shah and his colleagues at the Barbara Davis Center in Colorado studied CGM (continuous glucose monitor) data in adults with type-1 diabetes to see if time-in-range (percent of the day with glucose between 70 and 180 mg/dl) can predict the risk of long-term complications. For decades, hemoglobin A1c has been the only metric associated with long-term health problems in people with diabetes. The problem with A1c is that it is a surrogate measure of one’s overall glucose average and fails to reflect the quality of one’s diabetes management (highs and lows can still produce a decent overall average). CGM, by contrast, generates averages over an extended period of time (similar to A1c) but also reveals the degree of hyperglycemia and hypoglycemia that contributes to that average.
The DCCT study back In the 1990s proved that tight glucose control (as measured by A1c) reduces the risk of long-term complications such as retinopathy, nephropathy and neuropathy. But what if a CGM metric, such as time-in-range, could do the same thing? Guess what. It does.
Over seven years, study participants who developed retinopathy spent an average of 52% of time within the range of 70-180, whereas those who avoided retinopathy spent 62% of time in-range. A detailed analysis of the data showed that every 5% increase in time-in-range correlated with a 16% decrease in retinopathy risk. And when a tighter range (70-140) was used, the risk goes down 26% for every 5% increase in time-in-range.
Sleep and Glucose Management
Presenters emphasized the interaction between sleep quality and glycemic control in people with type-1 diabetes. In one study, sleep restriction (reducing sleep from 8 hours/night to 4 hours) reduced insulin sensitivity by 14%. Overall sleep duration of >6 hours was associated with a significantly lower A1c than those who sleep 6 hours or less. Irregular sleep schedules (varying time going to sleep by more than 60 minutes) was associated with an A1c increase of 0.5%, while consistent sleep patterns were associated with less hyperglycemia overall.
Update on Once-Weekly Insulin
Both Lilly and Novo Nordisk have been working to bring a once-weekly ultra-long-acting basal insulin to market. Intended primarily for people with type-2 diabetes, both Novo’s icodec and Lilly’s efsutira could potentially be used by those with type-1 as well. Both require a large “loading” dose to get started, followed by dosage adjustments based on fasting glucose readings. For those already taking mealtime insulin, icodec was found to reduce mealtime insulin requirements. Use of weekly basal insulin has been shown to improve time-in-range and reduce the incidence of both hypoglycemia and hyperglycemia. Both icodec and efsutira are in phase 3 trials and may be available within the next year.
New Product News
Senseonics (a division of Ascensia) presented studies on its Eversense E3 12-month implanted glucose sensor.
A feasibility study showed that the sensor produced good accuracy in 97% of subjects over a full year, with accuracy similar to the current 180-day sensor. Minor skin irritation was the primary adverse event.
There is a new entrant in the adhesives marketplace.
SkinGrip has launched a full line of adhesive patches to help secure all brands of CGM sensors (Dexcom, Libre, Medtronic) as well as OmniPod patch pumps. Flexible cotton/spandex patches are pre-cut and hold up well in water. They come in a variety of stylish colors. Visit theskingrip.com for more information.
Do you or someone you love sleep through CGM alerts?
SugarPixel is the first dedicated “alarm clock” that displays glucose levels/trends and emits powerful audio and vibratory alerts. Syncs with Dexcom G6 or G7.
A new, convenient option is available for those who want to screen loved ones for autoantibodies that may lead to type-1 diabetes. Enable Biosciences has developed a mail-in sample collection kit that requires just a simple fingerstick. Insurance billing is provided, where applicable. For more information or to request a kit, visit type1testing.enablebiosciences.com
Those who remember the infamous “Glucowatch” know that non-invasive glucose monitoring has its challenges. Hagar, an Israeli company, thinks it may have overcome those challenges. Using radio waves, its GWave device measures glucose in venous blood without having to prick or pierce the skin. Because it does not measure interstitial fluid, there is not the “lag time” associated with current CGM systems. As a result, the accuracy in clinical trials was found to be similar to that of fingerstick glucose meters (MARD 6.7%). Large-scale studies are underway. If all goes well, GWave could be available as early as 2025.
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