Researchers on the University of Colorado Anschutz Medical Campus have received a substantial federal award that promises to deepen understanding of the roots of the most common form of diabetes.
The five-year, $7 million award from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) funds a Biostatistics Research Center (BRC). The BRC will support DEFINE T2D (Definition, Etiology, Function: Integration to Enhance Type 2 Diabetes treatment), a consortium of four study sites that are probing the processes that drive Type 2 diabetes in tens of millions of adults.
The award is a recognition of the statistical expertise, experience coordinating multi-center studies, and longtime work of diabetes researchers and clinicians on the Anschutz Medical Campus. The campus is home to the Center for Innovative Design and Analysis (CIDA) and Lifecourse Epidemiology of Adiposity & Diabetes (LEAD) Center at Colorado School of Public Health, the National Institutes of Health-funded Colorado Diabetes Research Center, and the Barbara Davis Center for Diabetes at the University of Colorado School of Medicine.
Four researchers from ColoradoSPH and the School of Medicine are PIs for the BRC:
- Katerina Kechris, PhD, professor of Biostatistics and Informatics and Associate Director of Data Science with CIDA, is the contact PI
- Wei Perng, PhD, MPH, associate professor of Epidemiology and deputy director of the LEAD Center
- Leslie Lange, PhD, professor with the Department of Biomedical Informatics at the CU School of Medicine and the Department of Epidemiology at ColoradoSPH
- Ivana Yang, PhD, also professor with the CU Department of Biomedical Informatics and the ColoradoSPH Department of Epidemiology.
The study focuses on Type 2 diabetes in the United States because it is so prevalent and the number of people with it is growing, Dr. Yang said. She added that European researchers have generated significant evidence about the different causes and types of the disease. That work encouraged NIDDK to explore the U.S. population, which has different demographics, environmental factors and determinants of health, Dr. Kechris added.
Taking on a multilayered initiative
The broad expertise of the four PIs and the departments they represent is vital for a complex initiative studying large numbers of Type 2 diabetes patients and finding ways to subtype, or further define, Type 2 diabetes based on the characteristics of their disease, Kechris noted.
“We bring expertise in statistical methods for subtyping, how to deal with large data sets, and experience through the LEAD Center with leading multi-site studies,” she said.
As a faculty member of the “new-ish” Department of Biomedical Informatics, Yang added, “it’s important that we are starting to do these kinds of collaborative projects with other schools and departments.”
The BRC is tasked with organizing and coordinating the analysis of mountains of information generated from a variety of patient cohorts across the study sites, which include two at Massachusetts General Hospital and one each at Vanderbilt University School of Medicine and Wake Forest University School of Medicine.
The Center will also take on the tasks of building consensus among the study site partners about the goals of the project, Kechris said.
“How do we leverage all this information?” Kechris added. “That’s where the BRC comes in.”
Unraveling the mysteries of Type 2 diabetes
The research and analytical work ultimately aims to find more precise ways to prevent, diagnose, treat, and manage Type 2 diabetes than simply measuring blood glucose levels. In reality, the disease is far more complex, said Dr. Perng.
“Type 2 diabetes is a very heterogeneous chronic disease, with multiple, underlying causes,” Perng said.
Perng noted that high blood glucose levels in an individual are a warning sign for diabetes, but they do not themselves explain the underlying cause. For example, a high reading could be the result of insulin resistance or poor insulin secretion caused by the pancreas not functioning properly. The two problems may need to be treated and managed differently, she said.
“With insulin resistance, a recommendation from a primary care provider could be to lose weight and exercise,” Perng said. “But if the issue is poor insulin secretion, losing weight is less likely to help. Diet might be more important in that context.”
Similarly, the hemoglobin A1C (HbA1C) test, which reveals an individual’s average blood glucose levels over a three-month period, “isn’t directly linked to the underlying pathophysiology of diabetes as it is a proxy for average glucose levels over time,” Perng said. Further, the reading could be affected by race and ethnicity; hemoglobin disorders, such as sickle cell anemia; altitude; or poor kidney and liver function, she explained.
“The lack of biomarkers other than blood glucose and HbA1C is part of the impetus for this consortium,” which is to discover new biomarkers for Type 2 diabetes in adults and better understand its causes, as well as risks of complications and comorbidities, Perng said.
She added that she is “especially excited” that the new study incorporates social factors, such as education, income, and access to healthy food, in the data collection and analysis.
“Social factors have been historically overlooked in biomedical sciences, but we are now recognizing that they are [among] the strongest drivers of disease risk and health disparities,” Perng said.
A big step forward for the schools and the campus
As a pivotal player in the consortium, the BRC is helping to usher in a new phase of medical care for people with diabetes, said LEAD director and ColoradoSPH Associate Dean of Research Dana Dabelea, PhD.
“The BRC will help these clinical sites conduct the most appropriate analysis of multiple studies and find subgroups of people with diabetes that might have different [causes] and might respond to different treatments,” she said. “That’s very important in the era of precision medicine. We shouldn’t assume some sort of a blanket approach.”
Perng also noted that the BRC award represents “an important milestone” for the Anschutz Medical Campus as its first National Institutes of Health-funded coordinating center and data analysis core centered on studying Type 2 diabetes.
“[ColoradoSPH] should be poised to become a leader in this area,” Dabelea said. “The grant is definitely a step in the right direction.”
