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IOWA Magazine | 03-04-2021

Iowa Research Injects Hope for People with Diabetes

More than one in 10 Americans have diabetes, a chronic condition in which the body cannot effectively process blood sugar, and diagnoses are increasing around the world. Why? University of Iowa researchers are working to find answers—and improve the lives of those with the demanding disease.
Liv Schaller PHOTO COURTESY THE SCHALLER FAMILY Liv Schaller

If Liv Schaller could live one day without diabetes, the 13-year-old wouldn't run out and order a cheeseburger with fries at the nearest fast-food restaurant. Nor would she scarf down a pint of ice cream.

Nope. Instead of indulging in forbidden high-carb foods, she would simply enjoy a day without worry. A day without checking her blood sugar. A day without counting carbs. A day without carefully planning her food intake and injecting insulin before each meal.

At age 6, Liv was diagnosed with Type 1 diabetes, in which the immune system attacks the insulin-producing cells in the pancreas. Without insulin, the body is unable to take up glucose and use it for energy, leading to excessive breakdown of fat and muscle and a dangerous condition called ketoacidosis. Ever since her diagnosis in 2013, Liv has traveled from her home in Carthage, Illinois, to Iowa City every three months to receive care at University of Iowa Stead Family Children's Hospital. She totes insulin, needles, and a glucometer everywhere she goes. As a person with Type 1 diabetes, she requires frequent injections of insulin to stay alive.

The cumbersome routine of checking her blood sugar, counting carbohydrates, and measuring insulin is the easy part, Liv says. In fact, advances in technology now allow her to wear an insulin pump and a continuous glucose monitor, small devices that make it even easier to follow her blood sugar levels and administer insulin. But they don't take away the stress of having the disease, one she will have for the rest of her life.

"I would just love to not have to think about it all the time" -LIV SCHALLER

"I think people would be surprised to learn about the mental strain of having diabetes. It's not just physical," says Liv, an eighth grader who likes science and math, hanging out with friends, and making earrings. "I would just love to not have to think about it all the time."

SEARCHING FOR ANSWERS

Doctors and scientists at the University of Iowa are working to bring this peace of mind to Liv and improve the lives of the estimated 463 million people worldwide with Type 1 and Type 2 diabetes. The imperative is clear: sustained high blood sugar can lead to serious health issues such as heart and kidney disease, blindness, nerve damage, limb amputation, and even death.

At the university's internationally respected Fraternal Order of Eagles Diabetes Research Center, more than 90 investigators seek answers on what causes the disease and potential new treatments. A $25 million gift commitment from the Fraternal Order of Eagles in 2008 provided the catalyst needed to coordinate existing diabetes-related research on the UI Health Care campus, recruit top researchers, and boost innovative new studies into the disease and its complications.

The university established the Fraternal Order of Eagles Diabetes Research Center with dedicated office and lab space in the Pappajohn Biomedical Discovery Building, a campus facility where interdisciplinary teams work on pressing health issues. They conduct research in a variety of disciplines, including internal medicine, ophthalmology, physical therapy and rehabilitation science, health and human physiology, neuroscience, chemistry, biomedical engineering, economics, biology, psychological and brain sciences, and computer science.

"We have assembled at Iowa one of the deepest and strongest benches in the world in the area of diabetes research," says E. Dale Abel, director of the center. "The work we are doing really runs the gamut—and we're busy."

THE STRUGGLE TO ADJUST

In 2004, Daniel Ivory was putting in long hours at a post office job to support his family of five while also investing time and money to open a drive-thru coffee shop in Clinton, Iowa. Shortly thereafter, he found out his pregnant wife had a life-threatening blood clot. A diagnosis of Type 2 diabetes seemed to pile on.

Lydia and Daniel Ivory PHOTO: JUSTIN TORNER Lydia and Daniel Ivory

It was a stressful time in Ivory's life. Although he immediately began a regimen of insulin and oral medications, he didn't take care of himself. It was a challenge every day not to reach for the salty and crunchy snack foods he craved—and he often wasn't successful. Making matters worse, a bridge adjacent to the coffee shop closed, cutting off customers, and he ultimately had to close the business. When he later took a factory job, he found it wasn't convenient to periodically step away and check his blood sugar. So he didn't.

"I was basically living on sugar and caffeine. I remember not wanting to think about my health because there was so much other stuff going on." —DANIEL IVORY

"For years, I was basically living on sugar and caffeine. I remember not wanting to think about my health because there was so much other stuff going on, and I didn't actually want to make the life adjustments I needed to make," says Ivory, who had no family history of diabetes. "Not only was my blood sugar out of control, I was keeping everything to myself. I think the stress exacerbated the diabetes."

Ivory's wife survived, and the couple now has six children and three grandchildren. He is enrolled in an online baccalaureate program in business administration. While he still wrestles with food cravings, Ivory has learned to identify his triggers for unhealthy eating. As a result, his A1c—a blood test that measures average blood sugar over the previous three months—has gone from 11.5 to 7.4, just above the desired goal of 7.0.

"The low-carb diet has been a huge adjustment. I love to cook. I love every kind of food out there. Diabetics have to be so intentional about what they're eating, and that's challenging because all the foods that are bad for them are easy, quick, and everywhere," he says. "It's taken me a really long time to get my head wrapped around this disease. I've learned that being angry and depressed is not productive. Taking control is much more empowering. It's not easy, but I am learning how to do it."

Ivory credits two developments for helping him manage the disease: advances in technology and a new family diagnosis.

"You can put it aside when it happens to you, but not when it happens to one of your children," says Ivory, noting that his 11-year-old daughter, Lydia, was diagnosed with Type 1 diabetes in 2020. "That made diabetes more real for me. When it happens to somebody you love, someone you're responsible for, that's a completely different realm."

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Clinton, Iowa native Daniel Ivory and his daughter Lydia formed a strong bond after both being diagnosed with diabetes and receiving care at UI Hospitals & Clinics.

WHAT IS DIABETES?

Diabetes is a chronic disease in which the body is unable to effectively process blood sugar. Insulin is a hormone secreted by the pancreas that removes sugar from the blood and stores it in muscle, fat, and liver cells. In Type 1, there is an insulin deficiency due to autoimmune destruction of insulin-producing cells in the pancreas; in Type 2, the more common form of the disease, there is insulin resistance in combination with progressive failure of insulin-producing cells to compensate.

Both types appear to be linked to genetics, and lifestyle and environmental factors may also play a role in both. Some women develop diabetes during pregnancy, which puts them at increased risk for developing Type 2 diabetes postpartum. People with Type 1 diabetes must inject insulin to live. Type 2 often can be controlled with diet and exercise, and sometimes may be treated with medications or insulin injections.

Inadequately treated diabetes can lead to major health complications, such as heart and kidney failure, stroke, limb amputation, blindness, chronic pain, and death.


Support advancements in research and diabetes care through the Diabetes Center Research and Development Fund.

Ivory and his daughter both receive care at University of Iowa Hospitals & Clinics, and both wear continuous glucose monitors, unobtrusive devices that share blood sugar data via Bluetooth every five minutes—some 288 readings per day. "This device has been a game changer," he says. "All I've got to do is tap the screen of my phone and I know exactly what my blood sugar is—and whether it's going up or down. There's also an alarm if my blood sugar gets too high or too low. The advances that have been made since I was diagnosed are just tremendous. Those absolutely have to continue."

INSIDE THE RESEARCH CENTER

As leader of the Fraternal Order of Eagles Diabetes Research Center, Abel works to usher in advances that could benefit diabetes patients like Ivory. Internationally recognized for probing the link between diabetes and heart disease, Abel studied medicine at the University of the West Indies in Jamaica, traveled to Oxford University as a Rhodes Scholar, and conducted research at Harvard University and the University of Utah. Iowa intrigued him.

"When I visited Iowa City, I saw that there was already a basic core of researchers on campus that could form the nidus of something bigger, and the environment was incredibly collegial," he says. "Not only did people seem to be very generous, they had a strong desire to rally around a compelling vision. That motivated me to take the leap."

Since Abel took the reins in 2013, the center has recruited 27 investigators to Iowa and supported 29 research proposals from faculty across campus through a pilot grant program. Studies in the center are wide-ranging. Examples include investigating how altered metabolism in muscle, liver, and fat cells contributes to obesity and diabetes; deciphering mechanisms for appetite regulation; exploring why insulin-producing beta cells fail; developing better testing to identify Type 1 diabetes risk; identifying new biomarkers for gestational diabetes; and understanding how mitochondrial dysfunction can lead to diabetic complications such as heart failure or nerve damage. The center also has become a major hub for training the next generation of diabetes researchers from around the world.

"We have already received new funding in excess of the gift that started the center," Abel says. "So not only is the return on investment high, but I think we are likely to make discoveries that will significantly advance our understanding of both the pathogenesis of diabetes and its complications, and that will lead to new therapies."

Investigators already are making exciting discoveries. In 2020 alone, a study in Abel's lab suggested that the high-fat, low-carb ketogenic diet mitigates heart failure, a leading cause of death in people with Type 2 diabetes, while a team working with Abel and UI geneticist Val Sheffield discovered that exposure to electromagnetic fields may be a safe and noninvasive way to manage blood sugar. In neuroscience and pharmacology, Matthew Potthoff and his team learned that a liver hormone promotes weight loss by signaling to the brain to reduce sugar intake, and they are using that knowledge to develop new treatments for obesity and obesity-related diseases like Type 2 diabetes.

Many new studies have similar potential, whether by examining environmental factors that contribute to diabetes risk, or finding out how diabetes alters muscle gene expression and leads to muscle atrophy, or learning more about how activating an integrated stress response in brown fat cells can increase metabolism.

Andrew Norris (00R), a pediatric endocrinologist at UI Stead Family Children's Hospital, studies Type 2, gestational, and cystic fibrosis–related diabetes. He has seen significant achievements in diabetes treatment during his medical career, including improved insulin pumps, more effective insulins, and continuous glucose monitoring. In fact, research by two of his UI colleagues in pediatric endocrinology, Eva Tsalikian and Michael Tansey (98R, 01F), helped drive the clinical application of continuous glucose monitoring devices like the ones the Ivorys use.

Much more work remains, Norris says. Not only are incidence rates for both Type 1 and Type 2 diabetes increasing, Type 2 involves insulin resistance, a complicated condition of the disease that can negatively affect organ systems.

"We don't have good medicines that cure or help insulin resistance," he says. "In Type 1 diabetes, if you can control your blood sugars with insulin, you've taken care of the one problem you have. But we don't yet have the tools to perfectly control blood sugar."

Norris says the energy of his peers in the research center is "palpable." Teams have benefited from $224 million in federal research funds, including a doubling of grants from the National Institute of Diabetes and Digestive and Kidney Diseases in the last year alone.

But competition for federal dollars is increasing, Abel says. To maintain momentum, he is searching for additional means to advance the center's mission, including mining new funding sources and forming a robust collaboration with diabetes researchers at the University of Minnesota.

Abel is at once motivated and patient. His grandmother struggled with diabetes, and he lost a first cousin to the disease.

"Diabetes causes much suffering and expense, and it is not going away—in fact, it's likely to get worse over time. There is a big imperative for us to understand how and why it happens," he says. "While I'm encouraged by our progress, it's a marathon and not a sprint. The more we learn, the more questions arise."

The Von Ahsen Family PHOTO COURTESY THE VON AHSEN FAMILY The Von Ahsen Family

THE BIG IMPACT OF SMALL ADVANCES

Emerson Von Ahsen grimaces slightly as her mother, Morgan, attaches an Omnipod insulin pump to her behind. One click and it's over. The girl bounces up and down and assures those watching the YouTube video she is making that the process is quick and (mostly) painless.

"It's gonna be OK," she sings, "when I change my pump, OK?"

Emerson was diagnosed with Type 1 diabetes just days after her first birthday. Now the kindergartner from rural Williamsburg, Iowa, doesn't know a life without the disease. Her mom and dad were just settling into life as parents when their routine was suddenly disrupted, their days punctuated by multiple insulin injections and blood sugar checks.

"We would check her blood sugar before she ate and give her insulin, and then two hours later we would recheck her sugar," Morgan recalls. "We would set our alarm in the middle of the night, once at midnight and again around 3 a.m., and poke her little toe to check again. She always slept through it, which was the biggest blessing."

Now Emerson wears an insulin pump and a continuous glucose monitor, allowing her parents to check her levels remotely. The disease still requires constant management, however, and Morgan trains Emerson's teachers and day care providers every year. Emerson, for her part, is so unfazed by her treatment regimen that she decided to make video tutorials for kids who may be struggling with it.

Morgan, who brings Emerson to UI Stead Family Children's Hospital for diabetes care, says she feels confident that major advances will occur in Emerson's lifetime—even at Iowa. She stays up to date on recent developments and is encouraged by what she has witnessed during the four years since her daughter's diagnosis.

"I understand that patience is key, but I like to think that someday Emerson will get to live without diabetes." —MORGAN VON AHSEN

"Some advances may seem small, but they can make a big difference. For example, when we first got a continuous glucose monitor, we still had to enter her blood sugar every 12 hours to keep it calibrated. She now wears the newest model, and I can't remember the last time I poked her. I used to wake up in the middle of the night to poke her, and I don't do that now," Morgan says. "I understand that patience is key, but I like to think that someday Emerson will get to live without diabetes. I don't know if that will happen, but I'm not ready to give up hope that it will."

Abel says even if diabetes can't ever fully be cured, his mission is to eradicate the disease—and the suffering it causes—as much as possible. He believes Iowa is well positioned to make that happen.

"There's no question now that diabetes research is one of our institutional crown jewels, in terms of the depth and the breadth of what we are doing and the national and international reputation that we now have in the sphere of diabetes research," he says. "Now we just need more space."


ADVANCING SCIENCE THROUGH MENTORING

Iowa's leading diabetes researcher unlocks the potential of his lab members through a robust mentorship program.
Dr. Dale Abel PHOTO: JUSTIN TORNER Dr. Dale Abel

When diabetes researcher E. Dale Abel was being recruited to the University of Iowa in 2013 to lead the new Fraternal Order of Eagles Diabetes Research Center (FOEDRC), he met individually with each member of his lab at the University of Utah to ask one question:

"Will you join me in Iowa City?"

All 13 said yes.

"I think the fact that everyone came here speaks very highly of Dr. Abel," says Renata Pereira, who followed her mentor to Iowa and now is an assistant professor of internal medicine and a researcher in the FOEDRC. "Not only does he treat me with respect and value my opinions and suggestions, he has allowed me to contribute to his lab technically and conceptually. Meanwhile, he gave me great freedom to foster my own research interests. The more responsibility I'm given, the more I thrive. His mentoring style created a healthy environment for my growth."

Abel credits his own successes to mentoring. "I'm where I am because of people who gave me a chance and opened doors for me," he says.

After earning a medical degree from the University of the West Indies in Jamaica, Abel attended Oxford University as a Rhodes Scholar and later established research labs at Harvard and Utah. One of his priorities at Iowa is to cultivate and inspire young scientists. In fact, the motto of the Abel lab is "pay it forward."

"I'm very committed to giving the same opportunities I had to as many as I can," says Abel, who studies the link between diabetes and heart disease in the FOEDRC and chairs the Department of Internal Medicine in the UI Roy J. and Lucille A. Carver College of Medicine. "We have some amazing undergraduate students at Iowa from all walks of life, many of them first-generation students and minorities who also have aspirations and goals to become doctors or scientists or other health care professionals. I open my lab to them and encourage many of the other folks here to let their labs be a sandbox where students can come and play."

Doing so, Abel wagers, will kindle in them a passion for scientific discovery—and position them to advance knowledge of diseases like diabetes. He actively recruits minority students, helps lab members find project funding and the best conferences for presenting their results, and teaches junior faculty how to mentor undergraduates.

Kevin Kato is a senior biology major from West Des Moines. He knew that experience in a campus research lab would likely boost his medical school applications, but he says the two years he has spent in Abel's lab mean much more than an entry on his résumé.

"In the Abel lab, I get to be around some of the smartest people on campus, and they are open and engaging and kind. Always willing to answer questions," says Kato, who has been working with FOEDRC researcher Yuan Zhang and is an author on a research paper published in 2020 by Nature Metabolism. "I feel like I get special attention."

Mentoring in the Abel lab goes beyond simply offering advice. It's about setting up students for future success, from sharing tips on competitive grant writing to making introductions in key networks to checking in periodically on a more personal level. While undergraduates like Kato are paired with a junior faculty member or postdoctoral fellow for one-on-one mentoring, guidance and direction come from everyone involved with the lab, says recent graduate Margaret Mungai (20BS). Mungai deferred a 2020–21 Fulbright grant to conduct research in Spain due to the pandemic and currently is in Berkeley, California, working on a joint diabetes research project with Iowa and the University of California at Berkeley.

"When I was preparing for one of my first national conferences as an undergraduate, Dr. Abel had me present my research at one of our weekly lab meetings, and then the whole lab went through each slide to make sure the presentation was good," she says. "Dr. Abel was really invested in each one of us, whether we were undergrads, graduate students, or postdocs."

Abel also teaches his mentees how to be good mentors and has them build individual development plans for their students. Antentor O. Hinton Jr., a postdoctoral research fellow who joined Abel's lab in 2016, says being a mentor has made him a better scientist.

"As a postdoc, I'm required to do research, and that's it—but the highlight of the lab is mentoring," says Hinton, who was recognized in 2020 for excellence in mentoring by the Louis Stokes Alliances for Minority Participation. "I am so proud of my students. Working with them makes me better. They challenge me and show me my flaws. That helps them grow, and it helps me grow. It improves my own training and shows me how to run a lab."

Hinton heads to Vanderbilt University in the fall as an assistant professor of molecular physiology and biophysics. While Abel would prefer to keep on campus the young scientists who move through his lab, he says the mentoring they receive and give at Iowa will pay dividends for years to come in the arena that matters most: scientific discovery.

"We can't keep everybody here, but I certainly want us to be known not only as a place for doing innovative and cutting-edge diabetes research but also as a place where people can train to be future investigators," he says. "In doing so, we play an important role in building up the bench."


More from the University of Iowa

Calvin Carter and Sunny Huang Remote Control of Blood Sugar
University of Iowa researchers' unexpected and surprising discovery may have major implications in diabetes care, particularly for patients who find current treatment regimens cumbersome.
Margaret Mungai Daring to Disrupt Disease
As a young girl in Kenya, Margaret Mungai aspired to become a doctor. Now, the University of Iowa biology major not only is poised to attend medical school, she is aiming to advance novel treatments for disease as a physician-scientist.
Eric Ortiz From Patient to Participant
A childhood diagnosis of diabetes helped cement Eric Ortiz's desire to work in health care. After years of seeking medical treatment at the University of Iowa, he eventually enrolled as a premed student. Now, the biology major is researching the disease and is poised to pursue a career in public health.
Iowa Center for Research by Undergraduate Students Undergrads Tackle Pressing Health Problems
In University of Iowa research labs, students learn life lessons and contribute to scientific discovery.

DID YOU KNOW?

  • Some 34 million Americans have diabetes (more than 10% of the population), with 1.5 million diagnosed every year and 88 million considered at risk.
  • Diabetes was the seventh-leading cause of death in the United States in 2017.
  • The national cost of diabetes in the U.S. in 2017 was more than $327 billion, up from $245 billion in 2012.
  • Approximately 225,000 people in Iowa, or 9.3% of the adult population, have been diagnosed with diabetes; an additional 70,000 people in Iowa have diabetes but don't know it, greatly increasing their health risk.
  • There is no cure for diabetes.
Source: American Diabetes Association
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