The Future of Complications Treatments Could Get Personal

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Dr. Doria and Dr. Krowlewski discuss their research into complications

Dr. Doria and Dr. Krowlewski discuss their research into complications

Joslin Diabetes Center has been at the forefront of tailored medical care for more than 100 years. Dr. Eliot P. Joslin himself realized the importance of individualizing diabetes treatment for each patient, and that philosophy continues today with the clinic’s Joslin Care model. But new developments in the laboratories of Joslin’s research department could soon bring personalized diabetes medicine to a whole new level.

Researchers are working out how to delve into the unique biology of each patient to figure out which treatments for diabetes complications will lead to the best outcomes.

“Before we would rely basically on the [medical] history or the physical exam and a few tests. Now we may have a few markers that may tell us what the best approach is in a certain person,” says Alessandro Doria, M.D., Ph.D., M.P.H., Senior Investigator in the Section on Genetics and Epidemiology as well as Co-Director of the Advanced Genomics and Genetics Core at Joslin Diabetes Center. Dr. Doria has recently published research on certain genes in people who have both type 2 diabetes and heart disease that could indicate who will respond better to tight glycemic control.

The study was a follow-up on results from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study, a nationwide clinical trial that tested whether A1C levels of less than 6 percent in people with type 2 diabetes successfully reduced risk for cardiovascular disease. The ACCORD study saw that, in general, while intensive control led to fewer instances of heart attack and other major cardiovascular events, there was an overall increase of death from heart disease.

To understand this paradox, Dr. Doria and his team dug into the genetic code of all the ACCORD patients in the intensive control group. They found two genetic markers that were associated with a threefold increase in cardiovascular disease. They then used these two genes to create a risk assessment test and applied it to all of the participants in the ACCORD trial. Those scoring the lowest saw a large benefit to intensive glycemic control and those scoring the highest fell into the previously noted paradoxical group.

Dr. Doria hopes that, after further confirmation of this finding, this risk assessment could be used to help target treatment for its greatest effect.

“If this holds true,” he says, “you could genotype a person and then you can decide whether you really want to push glycemic control to them because it is 1.) effective and 2.) it doesn’t have a major side effects [in these people with low risk scores]. And instead in the other people you want to be more conservative because you know that this would not be effective and in fact this might be detrimental.”

Dr. Doria’s research represents just one of the many personalized medicine efforts in the works at Joslin. These also include the work of Andrej Krowlewski, M.D., Ph.D., head of the Section on Genetics and Epidemiology at Joslin, who has discovered biomarkers that predict who is at greater risk for developing kidney disease. And Jennifer K. Sun, M.D., M.P.H., Chief of the Center for Clinical Eye Research and Trials of the Beetham Eye Institute at Joslin, is working on a protein found in the eyes of people who seem to have protection against eye disease.

“For complications, personalization is going to be very important,” says George L. King, M.D., Chief Scientific Officer at Joslin Diabetes Center. Not everyone who has diabetes will be affected by each complication. “So if we can develop a battery of tests that could tell us who will develop [these complications] we can maximize our efforts to prevent and treat them,” he says.

On the other hand, if patients are at a low risk of developing a complication or are less likely to respond to a certain treatment then they can avoid intensive interventions that won’t produce positive results and avoid unwanted side effects.

For example, only 50 percent of patients with eye disease respond to the injectable anti-VEGF treatment. If doctors could know ahead of time that the treatment will not be effective, patients could avoid months of fruitless eye injections.

These genetically/ environmentally modified-tailored treatments are promising, with many of these biomarkers are now in clinical trials. In the meantime, Joslin doctors will continue to care for their patients in the personalized way that has its roots in the early days of the clinic. But as more biomarkers are identified and genetic tests are refined, that individualization will become even more precise.

“In the near future,” says Dr. King, “[we will] have a whole variety of treatments that could help diabetic patients.”



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