The North Carolina Diabetes Research Center (NCDRC) is a shining example of an academic learning health system—a mechanism that advances basic science into better diagnostics, treatments and cures for human disease while simultaneously taking data from humans back to the laboratory—taking knowledge from the laboratory bench to the bedside and back again.
“It’s not the dollars themselves, it’s a mechanism. It’s the culture created that is the real winner,” says Donald McClain, MD, PhD, director of Wake Forest School of Medicine’s Center on Diabetes, Obesity and Metabolism, describing the NCDRC, which he also directs. “The Center takes advantage of our complementary strengths and helps investigators, particularly early career ones, tackle the entire realm of issues related to diabetes, from molecular mechanisms to human physiology to population and health equity concerns.”
The NCDRC is a partnership formed in 2020 with a $5.7 million grant from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), part of the National Institutes of Health (NIH), to consolidate the myriad of diabetes research resources offered by Wake Forest School of Medicine, Duke University School of Medicine, the University of North Carolina School of Medicine, and North Carolina Agricultural and Technical State University (NC A&T). The NCDRC is one of just 18 Diabetes Research Centers in the U.S. McClain is joined by fellow Principal Investigators John Buse, MD, PhD, from UNC, David D’Alessio, MD, from Duke, and Elimelda Ongeri, PhD, from NC A&T.
The Center was formed to create an interactive regional scientific network to support innovative diabetes research by connecting investigators to each other and by providing access to powerful research technologies. The project’s theme is translation, as the Center supports both basic mechanistic studies and more applied research aimed at directly impacting diabetes patients and caregivers.
The group currently has 269 members spread across the four institutions. One of the Center’s most important goals is to attract both established diabetes researchers and investigators who are new to the field, spawning unique research collaborations among and within the member institutions.
“It is this grand cycle of molecule to clinical trial, to population, to policy…the academic learning health system creates this larger framework and community.” - Donald McClain, MD, PhD
Each of the organizations brings its own particular scientific strengths to the NCDRC project, resulting in synergies that create enhanced efficiency and productivity. McClain explains that Wake Forest, with its Center on Diabetes, Obesity and Metabolism, has a long and impressive tradition of diabetes research.
Duke and UNC are likewise highly accomplished and versatile centers of diabetes and metabolic research. Duke contributes valuable technical resources, while UNC brings additional expertise in clinical trials design and recruitment. NC A&T contributes its considerable experience in community engagement, particularly with populations affected disproportionately by diabetes and obesity.
A Wealth of Resources
The NCDRC provides powerful research resources to member enabling investigators to take advantage of world-class technologies and expertise they would otherwise be unable to access. Each core offers specialized research navigators to help diabetes-focused investigators analyze and interpret results.
The Metabolomics Core is centered at Duke University and offers comprehensive metabolic analysis. The research expertise within the core has a long history of collaborative research and has established a strong and reliable infrastructure for conducting metabolomic measurements for NCDRC investigators. According to McClain, the technology resources available through the core are among the best in the world. The core directors are Christopher Newgard, PhD, and Debbie Muoio, PhD, from Duke.
The Genomics and Proteomics Core (GPC) provides state-of-the-art resources and expertise in genomics, epigenomics and proteomics. It affords access to high-throughput instrumentation and analytical expertise to NCDRC faculty to support the advancement of diabetes research. The GPC coordinates work and data analysis with the Metabolomics Core Lab to deliver the entire suite of genomics, proteomics, metabolomics and lipidomics analyses. The core is co-directed by Michael Olivier, PhD, and Laura Cox, PhD, from Wake Forest.
The Advanced Clinical Study Methods Core, centered at UNC Chapel Hill, helps NCDRC investigators explore study design methodologies, implement advanced statistical and trial design, and enhance stakeholder engagement. It supports NCDRC investigator studies with needs for advanced methodological and statistical approaches. The core director is Til Sturmer, MD, PhD, from UNC.
The NCDRC Enrichment Program is centered at NC A&T. It is designed to create opportunities and provide resources for networking and advanced training and education in diabetes research.
The Enrichment Program spearheads several activities for the Center:
- Annual meetings. The latest was the virtual meeting held May 19, 2021, with 68 attendees.
- Diabetes Seminar Series. Each month, the host institution (rotating among the participating institutions) selects a speaker for the seminar. The series features leading researchers in the diabetes field, presenting their work to their colleagues in the NCDRC.
- Faculty Development Workshop. The February 2022 workshop featured speakers discussing how to launch a career in research, focusing on the complex process for procuring NIH funding.
- Targeted outreach to hard-to-reach populations. The NCDRC works with a Community Advisory Board to inform culturally appropriate messaging to underrepresented groups, in order to enhance recruiting efforts. The board is composed of key stakeholders, including representatives of the target population.
Planting the Seeds
One of the most important aspects of the Center’s mission is its Pilot and Feasibility (P&F) Program, which provides funding for small, initial studies undertaken by NCDRC members. They are often proof-of-principle or proof-of-concept initiatives, designed to help establish preliminary data prior to application for full NIH funding of larger studies. To be eligible, faculty members at the four NCDRC institutions must fit into one of four categories:
- New investigators with no current or past R01-level NIH research support
- Established investigators new to diabetes research
- Established investigators in diabetes
- Investigators developing new research techniques or novel technologies that could be used in an NCDRC core facility
Successful pilot applicants receive up to $50,000 in direct costs for one year. “It’s a decent budget that really allows a deep dive into the project,” says McClain. “It says ‘I’m going to commit to spending a year working on this,’ and the coin of the realm is to turn it into an independent, NIH-funded grant.”
The program has stimulated extensive interest from investigators in member institutions. As of December 2020, 23 letters of intent had been received, leading to 15 applications for the funding—four from Duke, one from NC A&T, seven from UNC and three from Wake Forest. The applications and topics represented the full spectrum of diabetes research, from early career to established investigators and from basic to translational science.
Nicholette Allred, PhD, from Wake Forest School of Medicine, serves as the P&F Program director.
“Bigger, Better Science”
One of the pilot studies funded by the P&F Program is called Meals for Moms, being conducted by Morgana Mongraw-Chaffin, MPH, PhD, assistant professor of Epidemiology and Prevention. She is recruiting 30 postpartum women who suffered gestational diabetes during their pregnancies and will provide them with medically tailored meals during their early postpartum period. The intervention is designed to positively influence their dietary behaviors to prevent subsequent development of chronic Type 2 diabetes.
“There is a fair bit of support when they are pregnant, but then not a lot when they go home,” says Mongraw-Chaffin. “Anyone who has had a newborn at home knows that it’s a very challenging time.”
Meals for Moms will give them healthy meals for the first three months. Twenty moms will get the meals and 10 will not, serving as a comparison group. The researchers will measure glucose by providing continuous glucose monitors, so that the moms and babies do not need to come to a lab or clinic—everything will be done fully remotely. At the end of the three months, there will be transition materials including cooking and healthy nutrition education, to help encourage lasting improvements.
“If it works and is cost effective, ultimately we would love to be able to show that there is an intervention like this that works so that payers like Medicaid might choose to cover the costs. That would potentially be a huge impact financially on these women’s lives,” says Mongraw-Chaffin. “The people who might need this kind of program and these kinds of interventions are most likely to be un- or under-insured, are likely to be people of color, and often may be struggling with food insecurity. So we are doing our best to recruit a diverse population, including African-American and Hispanic participants.”
“These multi-site collaborations are huge opportunities for people to collaborate who wouldn’t otherwise get to. That can make for bigger, better science.” - Morgana Mongraw-Chaffin, MPH, PhD
Mongraw-Chaffin is enthusiastic about the support she has received from the NCDRC. “The Center has been amazing,” she says. “The budget they give you is a little bit bigger than a lot of other pilot studies. Doing this sort of human subject research takes a lot of work, and it’s a little more expensive. The additional resources have allowed me to have a team, including a specialist who is fantastic at recruiting and interacting with participants.”
She cites the collaborative approach encouraged by the Center as a crucial element in the project’s success. Her collaborators include other epidemiologists, pediatricians, obstetricians, an endocrinologist, a food insecurity researcher and a colleague from the Atrium Health Wake Forest Baptist Weight Management Center. Her community partner, Providence Kitchen, is making and delivering the meals to the moms. “These multi-site collaborations are huge opportunities for people to collaborate who wouldn’t otherwise get to,” she says. “That can make for bigger, better science.”
Feeding the Diabetic Brain
Kylie Kavanagh, DVM, MS, MPH, associate professor of Pathology - Comparative Medicine and Molecular Medicine, leads an NCDRC pilot study focusing on the potential role of diet in the association between diabetes and Alzheimer’s disease. Type 2 diabetics have a two- to four-fold increased risk for developing Alzheimer’s disease. Although the mechanisms linking the diseases are unknown, there is suspicion that diet and metabolism may be a factor.
Prior work in Kavanagh’s lab showed that diabetic brains may use more protein and fat as fuel than normal, indicating increased metabolism. A new pilot study will put the test subjects on strict ketogenic diets to measure the impact on the production of Alzheimer’s proteins in their brains, as seen by brain scans and analysis of brain fluid. With less than 10% of their calories coming from carbohydrates, the researchers will rescan the subjects’ brains after a three-month regimen. The scans will yield data on fat use and glucose uptake in the brain. The information they gather will help determine how brain metabolism has shifted.
“If we can show that this approach reduces changes in Alzheimer’s risk, then you would have more confidence advising that this might be a strategy that could be useful,” says Kavanagh. “If the study meets expectations, we could conclude that this ketogenic diet looks like a rational approach for an older diabetic at risk for Alzheimer’s disease, such as people who have a family history or are showing earlier signs of dementia, if the diet is something that they can tolerate. Once people have clinical signs of Alzheimer’s, it’s too late.”
Kavanagh has found great value in the informational aspect of the Center. “What really stands out to me is the sharing of speakers and knowledge,” she says. “Being able to access the seminar speakers’ presentations has been great. That wouldn’t have happened without the Center and without having everyone enhancing their platforms for remote access.”
The Grand Cycle
McClain notes that the entire energy of the Atrium Health Wake Forest Baptist health system and Wake Forest School of Medicine is dedicated to the academic learning health system ideal.
“It is this grand cycle of molecule to clinical trial, to population, to policy, and meanwhile you’re looping back into molecule, animal model and clinical trial,” he says. “That is the grand picture. The academic learning health system creates this larger framework and community.”
McClain provides an example of the power of this type of collaboration. “A colleague doesn’t have to sit in their yeast biochemistry lab and say, ‘I wonder how I could get this tested in humans?’ No, no, you come to us, and we’ll connect you with someone who will know exactly what to do.”
“We are saying, if you have a good idea in animals, why don’t we just look in health records and see if we can find evidence for that? If we can, you may want to do a clinical trial right off the bat, and we’ll connect you with the regulatory expertise you need to get there, the collaborators you’ll need, the analytic resources, and so on. So, we are able to speed that loop along by creating a community that includes everyone in the entire structure.”