January 25, 2019 — Since 2011, the Foundation for the National Institutes of Health (FNIH) Biomarkers Consortium has been shedding new light on diabetes – a disease that affects more than 30 million people in the United States – by examining the function of the beta cell. Found within the pancreas, the beta cell has the critical role of producing and secreting insulin – an essential hormone necessary for the control of blood sugar and metabolism. In patients with diabetes, the beta cell is attacked or destroyed by the immune system (Type 1 diabetes) or is unable to produce enough insulin to control blood sugar levels (Type 2 diabetes). Over time, uncontrolled blood sugar can cause serious health problems, including heart disease, stroke and kidney disease.

A major challenge in diabetes research is how to best measure the beta cell’s production of insulin. Through the “Identification and Validation of Markers That Predict Long-Term Beta Cell Function and Mass” project, under the direction of the Biomarkers Consortium’s Metabolic Steering Committee, scientists studied research tools to better measure beta cell function in people with Type 2 diabetes and those at risk of diabetes. These tools track important changes that occur as Type 2 diabetes progresses and can help researchers measure how diabetes therapies affect the beta cell. Ultimately, this work will lead to the development of more effective treatments for diabetes patients.

The project team includes leaders from the National Institute of Diabetes and Digestive and Kidney Diseases, U.S. Food and Drug Administration, academia and industry. In the following Q&A, David Fryburg, M.D., Principal Consultant, ROI BioPharma Consulting (and former Global Translational Medicine Leader at Pfizer for Endocrinology and Metabolism), discussed the results of this significant project as it comes to a close. Click here to learn more about the project.

1. Why is examining beta cell function important in clinical studies focused on diabetes?

Ultimately, diabetes mellitus occurs when the ability of the beta cell to produce and secrete insulin drops below that of the body’s needs to keep blood sugar under control. This is a major goal of therapy — to help keep the body’s ability to secrete insulin as good as possible for as long as possible. The ability to measure this with confidence in clinical studies is very important to understanding if a therapy, like a new drug, can affect the course of diabetes.

2. What did the project uncover?

The project was directed to better characterize methods to measure beta cell function in clinical settings. We were interested in both how well they measure beta cell function as well as how easily they can be deployed. Our terrific team, an amalgam of very experienced scientists in academia, industry and government, carefully designed and executed a series of clinical studies to characterize the variability and sensitivity of two techniques to measure beta cell function. Prior to using them, we crafted standardized protocols for each test. The studies found that both tests, the mixed meal tolerance test with minimal modeling, and the arginine stimulation test, had good to excellent reproducibility as well as the ability to discriminate across the glucose tolerance spectrum. They are easier to execute and less expensive to perform compared to current established method, the frequently sampled intravenous glucose tolerance test. For sensitivity to a therapy, the meal tolerance test proved especially useful. We also did additional studies examining the roles of other factors, in beta cell function

3. What is the major impact that this project will have on patients with diabetes?

That the two methods described can be used with confidence in clinical studies. They both are likely not needed — much depends on the questions being asked. They have the advantage of being easier to execute and less expensive to perform compared to the current established method.

4. How will the project outcomes be used by researchers moving forward?

The data from the studies are provided in summary form in publications and the raw data will also be available for investigators to use. These data will allow researchers to have confidence in the use of these methods without having to do all the background or foundational work themselves.

5. Why did you choose to make the data public and how can researchers access it?

Making data publicly available is critical to enabling others to do good work and one of the core missions of the FNIH Biomarkers Consortium. Moreover, it is important to be able to compare new datasets directly — by standardizing the protocols of the tests, it will be possible to compare and perhaps combine data.