The discovery of several new biomarkers in the blood may further our understanding of exactly who’s at risk for diabetes
BETA cells within the pancreas produce and release insulin. Loss of the function of these cells compromises the body’s ability to control blood sugar and underlies the development of diabetes. So, one of the next frontiers of diabetes therapeutics is to change the progression rate of beta cell failure.
Recognizing this as a research priority, the Foundation of the National Institutes of Health (FNIH) Biomarkers Consortium announced Tuesday the launch of a multi-year clinical study to improve tools for measuring the function of insulin-producing beta cells in people with type 2 diabetes mellitus. Researchers hope the initiative will lead to improved techniques for tracking progression of the disease and pave the way for more effective treatments.
The project ‒ “Diabetes Drug Development: Identification and Validation of Markers that Predict Long-Term Beta Cell Function and Mass” ‒ is being managed by the Metabolic Disorders Steering Committee (MDSC) of the FNIH Biomarkers Consortium.
It is a three-year, $5.1 million clinical study to standardize tests for measuring beta cell function in the clinical setting that aims to improve methods for the early prediction of the long-term response to an intervention and for identification of patients at risk for rapid beta cell function deterioration, thereby enabling future clinical studies that examine diabetes progression.
A biomarker is a biochemical feature or facet that can be used to measure the progress of disease or the effects of treatment. So the validation of biomarkers to measure the progression of diabetes will greatly facilitate the development of better medicines to treat and potentially prevent this disease and its often disabling complications.
Experts believe biomarkers will become one of the major driving forces of pharmaceutical research and drug development in the coming years.
Currently, diabetes researchers are working without the benefit of agreed-upon standards for gauging beta cell function and this initiative will give researchers practical tools that can be used to measure beta cell function over time and stimulate research to maintain and improve that function.
The project was developed through a rigorous consensus-building process by a team of experts from across the entire scientific community. The pharmaceutical industry, academic, and government representatives contributed their clinical trials expertise and scientific support to the design and execution of the studies.
Utilizing a collaborative approach, the FNIH Biomarkers Consortium has brought together diabetes experts from the National Institutes of Health (NIH), Food and Drug Administration (FDA), leading academic institutions, the pharmaceutical industry, and non-profit sector to develop the project.
Biomarkers play an integral part in conducting clinical trials and treating patients. In most instances, they help medical practitioners, researchers, and regulatory officials make well-informed, scientifically sound decisions.
However, in clinical studies, there is often uncertainty in how much weight to place on biomarker results versus clinical outcomes. This uncertainty emanates from opposing goals of the drug approval process. On one hand, the process must ensure that all therapeutics tested are safe and that the benefits outweigh the risks. On the other hand, the process should allow therapies to be accessible to patients as quickly as reasonably possible.
Judicious use of biomarkers in the drug development process can bring these goals into alignment. More efficient discovery and use of biomarkers in the development of anti-diabetes drugs will depend on advancing current understanding of the pathogenesis of diabetes and especially its macrovascular (pertaining to the larger blood vessels) complications.
The idea of using biomarkers to predict diabetes is not entirely new. Glycated hemoglobin (HbA1C) values are now routinely being monitored to screen for at-risk patients. A study published in PLoS One last year shows that several new biomarkers in the blood may further our understanding of exactly who’s at risk for diabetes, and increase our knowledge of the etiology of the disease.
Veikko Salomaa and colleagues from the Department of Chronic Disease Prevention at the National Institute for Health and Welfare in Helsinki, Finland, tested nearly 13,000 people and found almost 600 cases of diabetes during routine follow-up exams.
According to the study, low levels of adiponectin, and high levels of apoB, C-reactive protein (CRP), and insulin, increase the chance that a woman will develop diabetes. When these factors were measured, proper diabetes prediction increased by 14% compared to when doctors only use classic risk factors, such as BMI and blood glucose levels, to predict disease.
The biomarkers that best predicted diabetes in men were low adiponectin, and high levels of CRP, interleukin-1 receptor antagonist (IL-1RA), and ferritin. Accounting for these biomarkers led to a 25% increase in correct diabetes detection in the cohort. Adiponectin is a hormone found in the body that modulates a number of metabolic processes, including glucose regulation and fatty acid catabolism.
The use of adiponectin, a hormone derived from fat cells, which is abundant in plasma and easy to measure through commercially available kits, was also confirmed as a robust biomarker predictive of glycemic efficacy in Type 2 diabetes and healthy subjects, after treatment with peroxisome proliferator-activated receptor-agonists (PPAR), but not after treatment with non-PPAR drugs such as metformin by the first project to be completed by the Biomarkers Consortium.
The project conducted a statistical analysis of pooled and blinded pre-existing data from Phase II clinical trials contributed by four pharmaceutical companies and analyzed under the direction of a diverse team of scientists from industry, the National Institutes of Health (NIH), U.S. Food & Drug Administration (FDA), and academic research institutions.
Source: FNIH Biomarker Consortium