An Update on Perspectives on Type 1 Diabetes Cures
Highlights from the Rachmiel Levine Diabetes and Obesity Symposium.
By Margaret Nguyen, diaTribe
In March, we had the opportunity to attend the 13th Rachmiel Levine Diabetes and Obesity Symposium in the warm and sunshine-filled Pasadena, CA, from March 13-16. The conference dealt with a variety of topics, and focused on basic science research in type 1 diabetes. The presentations addressed several different approaches to finding a cure, and leading experts discussed how to improve research efforts. One important message we heard was that the cure for type 1 diabetes must not put the patient at risks far outweighing the benefits of a cure. The following are our highlights from the symposium.
Necessary Steps for Greater Success in the Search for a Cure
During the conference, Drs. Richard Insel (JDRF, New York) and David Harlan (Uni-versity of Massachusetts School of Medicine, Worcester, MA) discussed how the aims of research design, methodology, and trials must evolve. Both scientists noted the successes and limitations of what previous cure research has shown us, and the necessary steps to move the field forward.
Dr. Insel explained how to optimize type 1 diabetes clinical trial design. He began his presentation by reviewing some of the successes in the field. He cited the DCCT — a landmark trial that followed people for ten years and demonstrated that greater glycemic control reduces complications — as a very important study that shows the crucial benefits of managing diabetes better. With currently available therapies, people diagnosed with type 1 diabetes today (on average) are able to live close to normal lifespans — a marvelous statement that has been many decades of research and therapy development in the making. However, they remain at risk for developing serious diabetic complications. There are only a limited number of therapies that have provided a reprieve from diabetes care or risk of complications, if only temporarily, in a subsection of people. For instance, cadaver islet transplantation can induce insulin independence for up to five years in over 50% of transplant recipients with current protocols. Additionally, anti-vascular endothelial growth factor therapies, which prevent excess blood vessel growth, can treat diabetic retinopathy and even improve eyesight. However, further refining research designs will be required to make other clinically impactful therapies available more quickly.
Dr. Insel gave a number of recommendations for how to conduct a trial for type 1 diabetes. He noted that trial design needs to better account for the underlying pathogenesis of the disease – how the condition progresses. In addition, we still lack basic insights into the pathogenesis of human type 1 diabetes and need to make improvements on this front as well. Another recommendation was to target both beta cells and the immune system instead of focusing on just one or the other, because there is profound cross-talk between the two systems. He also asked researchers to take into account the heterogeneity of the population with type 1 diabetes and the need to consider a patient's age, duration of diabetes, and genetic background and adopt a precision medicine approach to the disease, which means tailoring medical treatment to individual characteristics of each patient. Last, he spoke of the importance of using biomarkers to identify different aspects of the condition's progression. Biomarkers are proteins, antibodies, or other molecules that give insight into what is happening inside the body. With the right biomarkers, researchers can potentially track if a therapy is showing a positive effect earlier in a trial. They can also determine who in a group of people might respond better to a particular therapy and who might not be a candidate at all. His general guidelines for designing a trial were clear and logical, and we hope that many in the audience were inspired to reevaluate their own projects after the talk.
Dr. Harlan discussed recent-onset trials and echoed Dr. Insel's message that we need to better understand how type 1 diabetes develops and progresses. He noted that there are some basic facts that we are still struggling to determine, such as not knowing how many beta cells a person has before they develop type 1 diabetes. At the same time, he argued, we have made some gains. Historically, it was believed that beta cells are passively destroyed. However, we've now learned that beta cells' response to the immune system's attack might determine how long they survive and therefore how long they can produce insulin. This understanding is influencing therapeutic research today.
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Well maybe not so much a furor as a controversy. The question, bluntly put, is whether or not a single HbA1c reading should be sufficient and adequate to diagnose diabetes — and whether the conditions under which the test was conducted should have any bearing on the diagnostic or non-diagnostic value of the test. The lede from