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In monogenic diabetes research, a story of precision medicine at work
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SAN FRANCISCO — The challenges facing the growing diabetes community today have never been greater, and researchers should look no further than discoveries in monogenic diabetes research for the “clearest example” of how precision medicine can truly transform care, according to a speaker at the American Diabetes Association Scientific Sessions.
Monogenic diabetes, the result of a mutation of a single gene that controls the body’s ability to make insulin, is not as rare a condition as researchers once thought, Louis H. Philipson, MD, PhD, FACP, president of medicine and science for the ADA, said during a plenary presentation here. Although not as common as type 1 or type 2 diabetes, it is estimated that between 250,000 and 500,000 people in the U.S. have the condition. Through genetic testing and taking careful family histories, new breakthroughs led to a discovery that forever changed the lives of people living with this form of the disease — that some of the genetic mutations underlying forms of monogenic diabetes respond to sulfonylurea therapy, or require no therapy at all.
“That is the ultimate promise in precision medicine: Finding an inexpensive drug that fixes a problem to simplify and improve treatment,” said Philipson, who, with Siri Atma Greeley, MD, PhD, Rochelle Naylor, MD and Graeme Bell, PhD, supervised the development of the first registry for people with monogenic diabetes in the United States, funded in part by the ADA. “It’s not a cure ... but it’s spectacularly better than what we had before.”
The road to precision medicine, Philipson said, looks like this: Understanding that insights from studying human islets and organ research, together with population-wide data, can be integrated to target today’s therapies and used to design better, more effective and simpler therapies for prevention and treatment in the future.
Cancer researchers, Philipson said, have traveled this road for some time, advancing groundbreaking discoveries through molecular genetics, high-throughput screening, deep machine learning and artificial intelligence.
“We must think along the same lines for all kinds of diabetes,” said Philipson, also the director of the Kovler Diabetes Center and the James C. Tyree professor of diabetes research and care at the University of Chicago. “There is nothing more rewarding I can think of in my professional life than to tell a person with diabetes that they no longer have to take insulin, no longer have to check their blood sugar, or that we can replace insulin with tablets.”
Thinking genetically
Monogenic diabetes may be “the best example today” of what precision medicine can offer, and could potentially help inform precision medicine for all forms of diabetes, Philipson said.
Monogenic forms of diabetes — syndromic or nonsyndromic, neonatal permanent or maturity-onset diabetes of the young (MODY) — offer the clearest opportunity in precision medicine, in that a single nucleotide change or genetic insertion/deletion can lead to diabetes, Philipson said. Genetic testing, he said, must become a standard of care in diabetes, and not just something described in the ADA Standards of Care.
“If we can’t identify these syndromes, which are not that rare after all, incorporating the other ideas central to precision medicine seem, to me, even more difficult,” Philipson said.
The discoveries from research into monogenic diabetes have helped to illuminate key pathways, receptors and transcription factors that involve insulin, its synthesis and release, Philipson said, allowing researchers to better understand metabolic control systems in humans. Further, many genes show overlap in their contributions to type 1 and type 2 diabetes, as well as monogenic diabetes, he said.
“Are genetic tests the key to precision medicine? No,” Philipson said. “It is just one facet of an individualized approach to diabetes and prediabetes. For example, in type 1 diabetes, we now have the type 1 diabetes risk score that can improve diagnosis.”
Genetics alone “does not and cannot” explain the staggering increase of diabetes around the world, Philipson said. However, a deeper knowledge of the variations in human genetics can illuminate risk factors for the disease, and lead to a better understanding of the interplay between the environment and genetics that is likely behind the growing epidemic.
Start now
New insights from genetic discoveries and large population data sets are leading to improved, targeted care for diabetes, as well as yielding insights for diabetes prevention, Philipson said. But for precision medicine to become reality for all people with diabetes, more research is needed, he said. The ADA’s Pathway to Stop Diabetes program aims to help by providing financial and professional resources for a new generation of scientists to aid them on the road to breakthrough discoveries. Philipson urged attendees to contribute to the program.
“We need even more translational studies from animals to humans in order to weaponize the advances in molecular genetics and biomarkers, and we need ever more sharing of large population data,” Philipson said.
Philipson said clinicians can start implementing several tools right now to make a difference: Make better use of biomarkers, take a thorough family history and genetics to push the use of aspects of precision medicine in diabetes care today.
“I ask you to see every patient with diabetes — every person with diabetes — with new eyes,” Philipson said. “Why does this person in front of me have diabetes? What about the family? Can you incorporate such thinking right now? Starting to incorporate the key elements of precision medicine can be a transformational event for both you and your patients.” – by Regina Schaffer
Reference:
Philipson LH. Precision medicine — addressing the many faces of diabetes. Presented at: American Diabetes Association 79th Scientific Sessions; June 7-11, 2019, San Francisco.
Disclosure: Philipson is the president of medicine and science for the ADA. He reports receiving researcher support from the Jaeb Center for Health Research and Johnson & Johnson.