Forsyth Institute Study Provides Key Insights into Causes of Unresolved Inflammation in Patients with Type 2 Diabetes
CAMBRIDGE, Mass., December 19, 2016 – New research from The Forsyth Institute explores the way white blood cells regulate inflammation in patients with Type 2 Diabetes (T2D). While inflammation can play a protective role against injury and infection, when prolonged, it can lead to health problems such as obesity, cardiovascular diseases, arthritis, blindness, chronic kidney disease, and periodontal disease. There is major link between T2D and inflammation, which can cause many complications that negatively impact a patient’s overall health and quality of life. Therefore, controlling chronic inflammation in the body leads to healthier outcomes for people with T2D.
In a paper titled “Neutrophil ERVI in Type 2 Diabetes” published in The Journal of Immunology, first author Marcelo Freire, DDS, PhD, and senior researcher Thomas Van Dyke, DDS, PhD, along with Dr. Charles Serhan from Brigham and Women’s Hospital and Jesmond Dalli from Queen Mary University of London dissect the mechanisms through which inflammation and resolution are disrupted in diabetes. Dr. Freire’s research demonstrates that neutrophils, a type of white blood cell responsible for activating inflammation, are unable to perform their regular functions, i.e. phagocytosis, or the disposal of bacteria and dead cells, in patients with T2D. The study suggests that an unbalanced gene and protein expression profile of the resolution receptors ERV-1 and BLT-1 on neutrophils is key to this process.
To determine the cause of this receptor alteration, the researchers used healthy and genetically engineered cells in their investigations. The same diabetic receptor pattern was emulated when inflammatory mediators were added to the cell environment, which led the team to understand potential causes for the influence of inflammation in T2D.
Additionally, Dr. Freire was intrigued with the ability to reverse – i.e. treat – unresolved inflammation in patients with diabetes using personalized therapies. The results of the study show that inflammatory induction is not permanent, and after a dose-dependent concentration of the lipid mediator resolvin (a natural mediator of inflammation found in the body), a patient’s cells can be restored to proper function. This receptor plasticity could potentially help us understand when the bodies’ systems are inflamed or not.
“The traditional focus when managing T2D has been the control of hyperglycemia and insulin, not the resolution of inflammation,” says Dr. Freire. “Our research helps us understand how inflammation is related to diabetes and, potentially, may lead to the development of new diagnostic strategies and treatment therapies. We found that it is possible to treat unresolved inflammation in diabetes using personalized therapies and suggest that resolution markers could potentially be tested as a routine part of Type 2 Diabetes diagnosis and patient management. Our strategy was to dissect disease mechanisms and translate to therapeutic strategies.”
Over the past few decades, the global prevalence of T2D has drastically increased and, according to the International Diabetes Federation, roughly 415 million adults currently have diabetes – a number that is expected to increase in the coming years. This global problem heavily impacts quality of life, lifespan, and overall healthcare costs. Dr. Freire’s interest in chronic inflammation and diabetes led him to a seven year NIH K99/R00 Career Development Award, which helped his transition to faculty. “Because of the impact in global health, it was exciting to work with diabetes during my post-doc and screen biological markers related to inflammation and resolution. As a faculty member at Forsyth, this knowledge is guiding my lab to develop novel therapeutic innovations. I look forward to an increase in research on resolution receptor-ligand interactions within the human immune system and the development of personalized therapies for treating chronic diseases.”
In planned research, The Forsyth Institute researchers will explore the underlying causes of dysregulated inflammation and how it can be controlled, including how hyperglycemia and other metabolic changes can influence this phenomenon. Further understanding of inflammation regulation will be vitally important for innovations in personalized medicine and the development of novel treatment techniques -- not just for TD2 but for the majority of chronic diseases, which are affected by inflammation.
The published findings, titled “Neutrophil ERV1 in Type 2 Diabetes,” are co-authored by Marcelo Freire, Jesmond Dalli, Charles Serhan, and Thomas E. Van Dyke. To read the full paper, visit: http://m.jimmunol.org/content/early/2016/12/16/jimmunol.1601543.
About The Forsyth Institute
Founded in 1910, the Forsyth Institute is the only independent research organization in the United States dedicated to understanding the important connections between oral health and overall wellness. Forsyth scientists are shaping the direction of personalized medicine through pioneering biomedical research and its direct application to new diagnostics, devices and therapies. Forsyth combines its expertise in oral and associated systemic diseases with a relentless drive to ask – and answer – critical questions about how to best alleviate daily health challenges for billions. Forsyth is a not-for-profit organization that is also committed to treating underserved populations in local communities and on a national and global scale. To learn more about Forsyth, visit www.forsyth.org.