Overview
The Biomarker Consortium’s Diabetes Drug Development: Identification and Validation of Markers That Predict Long-Term Beta Cell Function and Mass (Beta Cell) Project was the first component of a two-stage strategy to characterize beta cell function, with the ultimate aims of using short-term measures to predict long-term beta cell response to interventions and of identifying individuals whose beta cell function may be at risk for rapid deterioration. The Beta Cell Project’s core goal was to evaluate both the Mixed Meal Tolerance Test (MMTT) and Arginine Stimulation Test (AST) against the standard Frequently Sampled Intravenous Glucose Tolerance (FSIGT) Test in a series of clinical studies.
The series of clinical studies proposed in this project provided a foundation for the use of selected methodologies in long-term, multi-center clinical trials in the second stage, a separate project that involved a longitudinal study to qualify short-term markers as predictors of future beta cell function.
Taken together, the work from both stages enabled multiple stakeholders to undertake consistent studies of the pathophysiology and natural history of diabetes, as well as to study therapeutic effects of new interventions more effectively. The Beta Cell Project was a 7-year, $5.1 million project that launched in 2011 and was completed by the end of 2018.
Goals
- Evaluate MMTT and AST as validated methods in the assessment of beta cell function.
- Enable development of biomarkers that assess long-term beta cell function, particularly in response to interventions for diabetes.
Partners
Public-Sector Partners
- National Institute of Diabetes, and Digestive and Kidney Diseases (NIDDK)
- U.S. Food and Drug Administration (FDA)
Private-Sector Partners:
- American Diabetes Association*
- Amylin* / AstraZeneca Pharmeceuticals, LP*
- Eli Lilly and Company*
- Janssen
- Johnson & Johnson*
- JDRF*
- Merck*
- Novartis*
- NovoNordisk*
- Pfizer Inc*
- R-squared Solutions
- ROI BioPharma
- Sanofi*
- Takeda*
- Wright Biomarker
Academic Partners:
- Cedars Sinai
- Joslin Clinic
- Mayo Clinic
- University of Padua
- University of Pennsylvania
- University of Washington
*Provided financial or in-kind support for this program.
FNIH Contact
Helen Heymann, MMSC, Senior Scientific Project Manager, Metabolic Disorders; [email protected]
Results & Accomplishments
Publications
This project has resulted in several peer-reviewed scientific publications as well as the acceptance of multiple abstracts by the American Diabetes Association and the European Association for the Study of Diabetes meetings.
Clinical Studies
This project has resulted in the completion of four clinical studies.
Novel Methods
This project established a novel decision-making method for use in the design of interventional clinical trials using MMTT and AST with confidence across the glucose tolerance spectrum.
In-House MMT and Arginine Stimulation
This project led to in-house utilization of MMT and Arginine Stimulation at multiple partner companies for drug development decision making, which resulted in significant cost reductions and efficiency gains.
Scientific Publications
- Standardized Mixed-Meal Tolerance and Arginine Stimulation Tests Provide Reproducible and Complementary Measures of Beta Cell Function: Results from the Foundation for the National Institutes of Health Biomarkers Consortium Investigative Series. Shankar SS, Vella A, Raymond RH, Staten MA, Calle RA, Bergman RN, Cao C, Chen D, Cobelli C, Dalla Man C, Deeg M, Dong JQ, Lee DS, Polidori D, Robertson RO, Ruetten H, Stefanovski D, Vassileva MT, Weir GC, Fryburg DA. Diabetes Care. Accepted July 2016.
- Arginine is preferred to glucagon for stimulation testing of B-cell function. Robertson, RP, Raymond, RH, Lee, DS, Calle, RA, Ghosh A, Savage, PJ, Shankar, SS, Vassileva, MT, Weir GC, & Fryburg, DA. American Journal of Physiology – Endocrinology and Metabolism. 2014; 307 (8): E720-E727.
- Outpatient Versus Inpatient Mixed Meal Tolerance and Arginine Stimulation Testing Yields Comparable Measures of Variability for Assessment of Beta Cell Function (in press)
- “Mixed Meal and intravenous L-arginine tests both stimulate incretin release across glucose tolerance in man: lack of correlation with β-cell function” Ruetten et al., just accepted in journal “Metabolic Syndrome and Related Disorders”
Media
- Q&A with David Fryburg, M.D., Principal Consultant, ROI BioPharma Consulting: Building Tools to Improve Diabetes Drug Development
- VIDEO: FNIH Biomarkers Consortium Beta Cell Project: A New Tool for Diabetes Research