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Precision medicine researchers discuss future directions in diabetes care


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3 minutes

Paul W. Franks, PhD
Paul W. Franks, PhD

To date, precision medicine initiatives in diabetes have focused mostly on further understanding the disease, identifying disease-specific biomarkers, and using those biomarkers for diagnosis and to predict treatment response, according to Paul W. Franks, PhD, Co-Chair of the ADA/European Association for the Study of Diabetes (EASD) Precision Medicine in Diabetes Initiative.

“To get from here to clinical implementation, there are several other steps that need to be considered,” said Dr. Franks, Professor and Deputy Director of Lund University Diabetes Center in Sweden, and Adjunct Professor at Harvard School of Public Health. These additional steps include patient engagement, clinician education, and regulatory approval, said Dr. Franks, who led a panel discussion about existing and potential applications of precision medicine during the Joint ADA/EASD Symposium at the Scientific Sessions.

The presentation, Perspectives on the Future of Precision Diabetes Medicine, can be viewed by registered meeting attendees at through September 10, 2020. If you haven’t registered for the Virtual 80th Scientific Sessions, register today to access all of the valuable meeting content.

Andrew T. Hattersley, FRCP, DM
Andrew T. Hattersley, FRCP, DM

Andrew T. Hattersley, FRCP, DM, said monogenic diabetes is one the best examples of the use of precision medicine in diabetes and one of the few examples in medicine where it has become routine. It started with the discovery of monogenic diabetes genes in the 1990s and the stratification of maturity-onset diabetes of the young (MODY) subtypes.

“All of these different genetic subtypes were important because they had a different clinical cause and they had a different optimum treatment,” said Dr. Hattersley, Professor at the University of Exeter Medical School in England.

Researchers found the HNF1A, HNF4A, and ABCC8 genetic subtypes all had progressive severe hyperglycemia as a clinical feature and a sulphonylurea-sensitive treatment response. The HNF1B subtype was characterized by progressive hyperglycemia and renal cysts, and benefitted from insulin treatment. For the glucokinase (GCK) subtype with stable, mild hyperglycemia, pharmaceutical therapy has not proven effective.

Dr. Hattersley, a member of the ADA/EASD Precision Medicine in Diabetes Initiative Steering Committee, stressed the importance of making a diagnosis of GCK MODY to spare the latter group from unnecessary treatment.

“By making a diagnosis, you are defining the etiology,” Dr. Hattersley said.

It’s still not fully understood how to utilize precision medicine in a disease with a wide range of phenotype variations like type 2 diabetes.

Ewan Pearson, PhD
Ewan Pearson, PhD

Another Steering Committee member, Ewan Pearson, PhD, Professor of Diabetic Medicine at the University of Dundee in Scotland and Visiting Professor at the University of Edinburgh and the University of Chinese Academy of Sciences, addressed this conundrum in his presentation on targeting treatment to lower A1C in type 2 diabetes patients.

In diabetes, unlike a cancer, which Dr. Pearson called the “poster child” of precision medicine, there’s not a mutation to target that’s unique to diseased tissue.

“It’s not likely that we’re going to identify single mutations that will have large effects, therefore it’s highly unlikely we’re going to be able to definitively predict response at an individual level,” Dr. Pearson said.

Instead, probabilistic models come into play.

“We will use a response prediction calculator that incorporates phenotype and genotype and biomarkers, and it tells us what is the likelihood of response, which is the drug that’s most likely to be better—not saying absolutely that one drug is better than another for that individual,” Dr. Pearson said.


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