American Diabetes Association Conference Highlights: Technological Breakthroughs

Bioprinting the pancreas and bioengineering cell therapies show promise

With Amy Hess Fischl, MS, Margaret Pellizzari, MBA, MS, Jennifer Salyor PhD, Persis V. Commissariat, PhD, Anna Floreen Sabino, MSW, Dana C. Crawford, PhD, Naveed Sattar, MD, PhD, Audrey Parent, PhD, Maika Sanders, MD, and Francesca Spagnoli, MD, PhD

By studying embryonic mouse pancreatic development, which is similar in humans, bioprinting may one day become an option in pancreatic transplantation.

Mealtime insulin bolus injections get creative

The mini-symposium, “Creative Mealtime Boluses for Pumps and Multiple Daily Injections,” explored data-backed ideas on the best methods for insulin bolus injections after meals and the type of patient-clinician conversations that are taking place regarding these injections.

Amy Hess Fischl, MS, RDN, LDN, BC-ADM, CDE, Department of Pediatric and Adult Endocrinology, University of Chicago, discussed some of the history of carb counting, which started in the 1920’s, followed by today’s insulin to carb ratio (ICR) estimations. Meals vary individually on protein, fat, and carb content each of which affect glucose absorption. Effects of fiber, caffeine and sugar alcohols need also be taken into consideration.

The degree of accuracy in ICR estimates, Hess Fischl points out, depends on numeracy and literacy of the patient, their motivation to determine the correct insulin dosing, and the value they see in determining it.

Basically, there is no straight forward algorithm for prandial insulin use. She stated, “It is important as clinicians that we are confirming how patients are actually counting. Are they measuring and weighing to identify whether they are truly estimating appropriately or are they using the ‘wag’ method- which is very common.”

This can lead to creative conversations between patients and clinicians about how they determine ICR and the level of accuracy which they are comfortable with.

While there may be no strict algorithms, Margaret Pellizzari, MBA, MS, RN, CDCES, CDCT, FADCES, Diabetes Program Manager, Pediatric Endocrinology, Northwell Health (Lake Success, NY) gave some fast and reliable options for determining prandial insulin bolusing. She described three types of boluses to help keep glucose levels within target ranges:

  • Normal bolus: delivers insulin all at once and can be used for most meals
  • Extended or square bolus: delivers insulin over a designated period of time and can be used for extended meals (i.e. buffets, holidays eating)
  • Combination or dual wave bolus: delivers a portion of the insulin as a normal bolus and the remainder as an extend bolus, suitable for high fat or high fat/high carb meals

Both Pellizzari and Hess Fischl emphasized the importance of being mindful of the macronutrient content of meals, snacking, and timing the intake of carbs, fats, and proteins relative to insulin injections.

“Adulting” with Type 1 Diabetes Online

The session “Improving Type 1 Diabetes Management in Young Adults—Time to (Re)Strategize?” took an in-depth look at how to support young Type I diabetes (T1D) patients as they transition from being a pediatric patient to a young adult (YA) that is going to college or entering the job market. The three presentations were linked by their connection to the College Diabetes Network, which helps YAs and parents move forward and tips for endocrine specialists as they support their transitioning T1D patients.

Jennifer Saylor Ph.D., associate professor in the Department of Behavioral Health and Nutrition, School of Nursing, University of Delaware, discussed ways to help parents let their T1D YA move towards independence by taking over the day-to-day management of their disorder.

Dr. Saylor stated that parents are typically worried about relinquishing managerial control and being left out of “the process”.

With the US Federal policy that restricts the release of medical information once the child reaches 18, many parents feel left out of the information loop and let down when physicians fail to realize how dependent many T1D YAs continue to be despite being “of age”.

Dr. Saylor encouraged clinicians to address parental concerns and to help them navigate a new role in the management of their child’s T1D while the YA develops their own independent coping strategies for disorder.

Persis V. Commissariat PhD of the Joslin Diabetes Center, Harvard Medical School said, “Young adulthood was the most challenging period when it came to T1D care. The added pressure to be successful in all areas of life interferes with diabetes self-care which can make a young adult feel worse, physically and emotionally.”

When dealing with a YA, either transitioning out a pediatric endocrine practice or entering an adult one, Dr. Commissariat offered several points for clinicians:

  • Validate difficulties the YA patient is feeling, as their diabetes makes all the new events in their life even more challenging
  • Eliminate failure and inspire hope by acknowledging that some approaches don’t always work, but with time and action things will get easier
  • Talk up the benefits of a full-team approach (nutritionists, exercise trainers, etc) and encourage them to seek out and ask for support from team members, friends, and peers
  • Try a little “hand holding” by checking in with the YA patient more frequently during the transition to college or their first job
  • Encourage them to be open about their disorder with peers, professors, and employers to build these individuals into a new support system appropriate to their new position in life

Anna Floreen Sabino, MSW, CDES, is the program director for the College Diabetes Network (CDN). CDN is a resource for YAs with T1D providing opportunities to connect with other T1D students on campus, offering peer-leadership programs, and both printed and online educational materials.

CDN is present on over 160 college campuses with more than 3500 student members. They host an annual young adult survey which helps the network adapt and identify developing trends among YAs with T1D. Some of the initial impressions from the most recent 2020 survey were presented by Drs. Saylor and Commissariat.

Capturing and using electronic registry health record data

The “Biobanks and Electronic Health Records in Diabetes Care and Research” session provided evidence on the value and importance of electronically available data registries during this age of precision medicine.

Previously, large epidemiological data sets were acquired using cross-sectional cohort data collected over long periods of time. Dana C. Crawford, Ph.D., associate professor at the School of Medicine at Case Western Reserve University, explained that while valuable, these studies suffered from two problems:

  • Data tended to lack ethnic, gender, and age diversity.
  • Depth of data only came over extensive periods of time.

Today, access to electronic health records and biobanks can provide richly in-depth data on an ethnic, age, and gender diverse population sample almost immediately.

One problem that must be overcome, in countries like the United States, is the standardization of data input. For example, weight can be put in as kilograms (kg) or pounds (lbs), and these errors can be difficult to find, especially in large data sets.

Using weight and BMI as an example, Dr. Crawford presented on a novel method, the Adjacency-Based Longitudinal Outlier Extrapolation (ALOE) approach, which allows for:

  • Identifying transcription
  • Transposition
  • Non-standardized data points
  • Creating an unbiased estimation for missing ones

Naveed Sattar MD, PhD from the University of Glasgow. continued the conversation by presenting on recent findings about Type 2 Diabetes and the risk of cardiovascular disease using large national population health record data bases from Scotland, Sweden, and the UK.

One finding in particular, using the large UK Biobank registry, found that individuals in the pre-diabetic A1c range were typically older, had higher BMIs, higher blood pressure, and tended to smoke.

It was these factors that put them at higher risk for cardiovascular disease and not their pre-diabetic status, as was previously speculated based on small sample studies. In regards to national data registries, Dr. Sattar said,“The real value now of large national registries and biobanks is actually deciding what the important questions are, using these registries in a really efficient and profitable manner.”

Bioengineers are hiding B-cells, mimicking interstitial flow, and recapitulating organ niches

The session, “Bioengineered Cell Therapy for Diabetes”, presented data from three projects each tackling a common problem in islet cell transplantation. Audrey Parent PhD, assistant professor at the UCSF Diabetes Center, stated the overarching goal:

“Islet transplantation has been a game changer for patients with Type I Diabetes. It is a very efficient treatment. The main challenge is that there are not enough islets to transplant everyone who would benefit from them. In order to solve the supply problem, we need alternative sources for islet cells.”

Dr. Parent and her lab are working on developing immune-cloaked beta cells for allogeneic islet transplantation. Using induced pluripotent human stem cells, they have been able to create beta-cells lacking all Human-Leukocyte Antigen (HLA) class II markers and most HLA class I markers.

The investigators chose to retain HLA-A2 in their cell line, which is a marker expressed by nearly 50% of Caucasians, which allows the cells to be identified as similar within that population. Blocking nearly all HLA markers did not alter stem cell differentiation into beta-cells. In their mouse transplant studies, the immune-cloaked beta cells survived longer than the wild-type, suggesting engineered beta cells can be hidden from the immune system.

Organs are made up diverse tissues which in turn are comprised of heterogeneous cell populations. The next presentation expanded the idea of transplanting cells by researching options for transplantable pancreatic tissues.

Maika Sanders, M.D. Director of Pediatric Diabetes Research Center, UCSD, gave an update on “organs on a chip” or microchip technology. This technology is designed to re-create conditions between the heterogeneous cell population that make up pancreatic tissue. In this case, beta cells, vascular endothelial cells, as well as the pancreatic alpha and delta cells.

Under the right conditions, these cells self-aggregate into an islet spheroid in which nutrient rich media flows. The flow allows control over the microenvironment and simulates the interstitial movement of molecules between cells within the spheroid. Using this technology, the survival, function, and interactions of the heterogeneous cells can be studied in detail providing information on tissue development.

Bioprinting the pancreas

The final presentation pulled our view even further out, looking at the embryonic development of different tissues that make up the pancreatic organ. Francesca Spagnoli, MD, PhD, a group leader at the Centre for Stem Cells & Regenerative Medicine at King's College, London, presented data on bioprinting different engineered pancreatic tissues that make up the pancreas.

Bioprinting, incorporates cells into a 3D biomaterial based on the understanding of extracellular matrix composition, cell positioning, cellular interactions, and environmental cues. Time must also be taken into account.

The pancreas, as an organ, has multiple niches with distinct functions that change during embryonic development into adulthood. By studying embryonic mouse pancreatic development, which is similar in humans, bioprinting may one day become an option in pancreatic transplantation.

Drs. Bjugstad, Crawford, Parent, Pelizzari, Sabino, Sanders, Saylor, and Spagnoli report no conflicts with regard to discussing these studies. Hess Fischl reports financial interests with Abbott and Xens Pharmaceuticals. Dr. Philips reports financial interests associated with AbbVie Inc. Diasome Pharmaceuticals, Eli Lilly, GlaxoSmithKline, Novartis Pharmaceuticals, Novo Nordisk, Pfizer, and Sanofi-Aventis. Dr. Sattar discloses relationships with Amgen, AstraZeneca, Boehringer Ingelhein International, Eli Lilly, Novo Nordisk, Pfizer and Sanofi.

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