As he opened his State of the Diabetes Center address for Diabetes Day, an annual event spotlighting research and clinical achievements, Alvin Powers, MD, called this “the most exciting time in diabetes research and patient care.”
“There are new technologies and experimental approaches that are advancing our understanding of the causes of diabetes and diabetes-related complications,” said Powers, Vanderbilt Diabetes Center (VDC) and Vanderbilt Diabetes Research and Training Center (DRTC) director. “In the clinical arena, we have new therapies for individuals with Type 1 and Type 2 diabetes. Plus, there are remarkable efforts to translate new information from the laboratory to the clinic and the community. While there are many great things going on, we have much more to do to reduce the burden and impact of diabetes in Tennessee and around the world.”
There are 17 Diabetes Research Centers and seven Centers for Diabetes Translation Research in the United States, funded by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health (NIH). Vanderbilt was the first diabetes research center funded.
In 1973, the Vanderbilt DRTC began its mission to facilitate the discovery, application and translation of scientific knowledge to improve the lives of people with diabetes. DRCs were created to improve the quality and multidisciplinary nature of research on diabetes and related endocrinology and metabolism research by providing shared access to technical resources and expertise and by creating an environment that supports innovative research.
Today, the Vanderbilt DTRC includes 140 faculty members from 15 departments and three colleges or schools at Vanderbilt and Meharry Medical College who conduct basic, clinical and translational research on the cause, prevention, treatment and complications of diabetes and obesity. Their investigations are supported by more than $78 million in research funding, and in fiscal year 2023, more than 540 publications represented the work of Vanderbilt DRTC members, with half the publications authored by more than one DRTC member.
Two noted visionaries in diabetes research gave plenary lectures during Diabetes Day. Clay Semenkovich, MD, chief of the Division of Endocrinology, Metabolism and Lipid Research and director of the Diabetes Research Center at Washington University, spoke on his laboratory’s work related to diabetes and lipid metabolism, or how the body synthesizes, breaks down, transports and stores lipids or fatty compounds that perform many of the body’s essential functions.
Lipid abnormalities occurring within the context of diabetes are a significant cardiovascular disease risk factor. Understanding the relationship between diabetes and lipid metabolism is crucial for better managing that cardiovascular risk.
Semenkovich’s translational research spans cultured cells, animal models and humans. He presented a review of his lab’s discoveries, including recent findings that are not yet published.
Semenkovich lauded the importance of multidisciplinary events that encourage new collaborations, such as Diabetes Day.
“It’s an honor to be here at Vanderbilt where there has been a Diabetes Research Center and the spirit of multidisciplinary cooperation for more than half a century,” he said. “Vanderbilt has been a leader in decreasing suffering for people with diabetes, specifically because of the innovative, collaborative work catalyzed by Diabetes Day. This event attracts people with multiple different skills – everybody brings something to the table – to help reach the goal of improving the quality of life for people with diabetes and its complications.”
Deborah Wexler, MD, MSc, associate professor of Medicine at Harvard Medical School and chief of the Massachusetts General Hospital (MGH) Diabetes Unit, spoke about lessons learned from major, multicenter diabetes research trials.
Wexler is the MGH site principal investigator and is on the executive committee of the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness (GRADE) Study, an NIH-funded multicenter trial to determine which second hypoglycemic drug, added to metformin, is most effective for patients with Type 2 diabetes. Vanderbilt, under the leadership of Tom Elasy, MD, was a participant in this clinical study.
Wexler also co-leads the PRECIDENTD Trial, a comparative effectiveness trial of SGLT2 inhibitors and GLP-1 receptor agonists substantially supported by Vanderbilt investigators Lindsay Mayberry, PhD, and Lyndsay Nelson, PhD, who lead the project’s stakeholder engagement. Vanderbilt is also a study site led by Leslee Matheny, MD, and Russell L. Rothman, MD, MPP.
Wexler addressed the often-universal challenges faced in recruitment as well as how important studies comparing pharmacological therapies for efficacy can be complicated when the medications are not supplied by pharmaceutical companies.
Wexler told the audience she was impressed by the day’s activities and the success of the Diabetes Research Center at Vanderbilt.
“What’s going on today is really spectacular,” she said. “It fosters new collaborations; it fosters community. We are trying to further strengthen our own DRC, and I’m taking notes.”
Laura Keohane, PhD, associate professor of Health Policy at Vanderbilt University Medical Center, presented findings on the use of insulin as it relates to dementia as well as the initiation of long-term services and supports (LTSS) such as a skilled nursing facility.
Pulling data from the large, prospective Southern Community Cohort Study as well as Medicare and Medicaid claims data, Keohane found that among individuals diagnosed with dementia age 65 and older, 73% were dual eligible for Medicare and Medicaid and that 88% had diabetes.
Data also showed that a diabetes diagnosis with insulin use predicts a shorter time until the initiation of LTSS. She reported other factors associated with greater incidence of LTSS initiation including longer length of time living with diabetes, depression, stroke, amputation, or severe hypoglycemia and Alzheimer’s disease and related dementias.
Based on these findings, Keohane emphasized the need for policy and program changes to better support older, insulin-dependent adults with diabetes and the need to improve care coordination between Medicare and Medicaid as diabetes and other co-morbidities are managed.
Derek Claxton, PhD, assistant professor of Molecular Physiology and Biophysics in the Vanderbilt University School of Medicine, shared findings toward predicting and evaluating the pathogenic probability of missense variants in the hepatic glucose-6-phosphatase catalytic subunit (G6PC1). This enzyme is crucial in maintaining normal blood glucose levels between meals. For this work, Claxton and his team used AlphaFold2, a machine learning platform that predicts the three-dimensional structures of proteins.
Knowing the exact structure of a protein can help scientists better understand how it works and the possible mechanisms driving disease caused by amino acid substitutions (missense variants). The Claxton lab aims to determine how missense variants change G6PC1’s activity and stability by combining sophisticated tools in structural biology with laboratory experiments. Claxton hopes this scientifically diverse approach provides a basis for a more integrated understanding of pathologies such diabetes.
Owen P. McGuinness, PhD, professor of Molecular Physiology and Biophysics and director Hormone Assay and Analytical Services Core at Vanderbilt University, spoke about Powers, his friend and colleague of nearly 40 years. In late 2023, Powers announced plans to step down from his roles as VDC director, Vanderbilt DRTC director, and chief of the Vanderbilt Division of Diabetes, Endocrinology and Metabolism at VUMC. He is remaining in these roles until a nationwide search identifies a successor and will continue his research afterwards.
After recounting an extensive list of Powers’ achievements, McGuinness concluded with the sentiment shared by many that he is a “respected colleague, an innovative collaborator, a generous mentor, a fierce advocate, but most importantly, a dear friend.”
Several young investigators were recognized for their outstanding research efforts. These individuals were chosen by the Diabetes Day organizing committee and were nominated by their research mentors. They include:
- Kathryn Snyder, MD, MPH, a resident in the Vanderbilt Medicine-Pediatrics Program, received the Oscar Crofford Scholar in Diabetes Research Award. Snyder presented her research, “The association of SGLT2i versus DPP4i on fracture: a cohort study of veterans with diabetes.”
- Dudley McNitt, PhD, a postdoctoral fellow, received the Daryl Graner Scholar in Diabetes Research Award. McNitt presented his research, “CD4-driven loss of the key germinal center protein, BCL6, presents Type 1 diabetes development.”
- Darian Carroll a graduate student in the Vanderbilt Interdepartmental Graduate Program and the Department of Molecular Physiology and Biophysics, received a Vanderbilt Diabetes Scholar Award. Carroll presented her research, “The effect of maternal diet and metformin consumption on offspring islet function.”
- Emily Hawes, PhD, a postdoctoral fellow, also received a Vanderbilt Diabetes Scholar Award.
Terri Doss, a research assistant at the Vanderbilt Mouse Metabolic Phenotyping Center (VMMPC), received the Robert K. Hall Service Award for her outstanding contributions to the diabetes research community at Vanderbilt.
In addition to the podium presentations, more than 45 young investigators presented a research poster to attendees and to a judging panel. The following individuals were honored for their outstanding posters and presentations: Kashope Anifowshe, Elizabeth Holliday, Yasminye Pettway, Jordyn Dobson, Hannah Waterman, Nelson Chang, Ilkin Safa and Dominque Stephens.
Diabetes Day was sponsored by the Vanderbilt DRTC and supported by the NIDDK.
