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Exercise response, epigenetic profiles key in improving type 2 diabetes interventions
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Investigating exercise resistance mechanisms would lead to better understanding of how training efforts relate to type 2 diabetes and potentially allow targeted and new interventions, according to findings published in The Journal of Clinical Endocrinology & Metabolism.
Through a systematic review of classic and contemporary primary reports, Lauren M. Sparks, PhD, and Natalie A. Stephens, PhD, both of the Translational Research Institute for Metabolism and Diabetes at Florida Hospital in Orlando, said research would improve outcomes for patients at all levels of exercise response.
Lauren M. Sparks
“A lack of metabolic improvement after engaging in an exercise routine should not necessarily be perceived as a lack of effort (on the part of the patient) by practitioners, researchers and the individuals themselves,” Sparks told Endocrine Today.
“Our lab has found that approximately 20% of individuals with type 2 diabetes, or one in five, do not respond favorably to supervised exercise in terms of lowering blood sugar, improving blood sugar control and increasing muscle function, particularly fat and carbohydrate utilization,” she said.
Earlier research has shown that genetics can predict exercise response, Sparks said. The investigators referenced unpublished data from their own previous studies and research from collaborators, examining the genetic and epigenetic components and associations with the exercise response.
Substantial response variations have been seen in glucose homeostasis, insulin sensitivity and muscle mitochondrial density with supervised exercise training, offering evidence for exercise resistance, according to researchers. Approximately 15% to 20% of individuals fail to improve their metabolic health with exercise, they wrote.
Classic genetic studies have shown that the extent of exercise response is largely heritable, but more recent evidence has demonstrated associations between DNA hypomethylation and response in skeletal muscle. The researchers said DNA sequence variation and/or epigenetic changes could dictate the training response.
“Diabetes research is moving in the direction of personalized medicine,” Sparks said. “The implications for these findings could potentially shift the current paradigm such that exercise therapies and lifestyle interventions could be targeted to those most likely to benefit and identify novel approaches to treat those who do not experience metabolic improvements after exercise training.”
Sparks said more supervised exercise interventions in patients with type 2 diabetes, of varied sex, race, ethnicity and age, specifically aimed at performing genetic and epigenetic profiles of individuals before and after the exercise are needed.
“(This will) associate their metabolic improvements, or lack thereof, with certain aspects of their DNA and/or how it is regulated on an epigenetic level in order to find those critical ‘brake’ points that are preventing them from reaping the benefits of their efforts in the gym,” Sparks said.
The traditional clinical approaches to treating diabetes also warrant reexamination, she said.
“We need to understand how the medications that these individuals with type 2 diabetes are taking will influence their exercise response, especially in conjunction with their genetics,” Sparks said. “This area of research is virtually unexplored.” – by Allegra Tiver
For more information:
Lauren M. Sparks, PhD, can be reached at Translational Research Institute for Metabolism and Diabetes, Florida Hospital, 301 E. Princeton St., Orlando, FL 32804; e-mail: lauren.sparks@flhosp.org.
Disclosure: This work was supported by an American Diabetes Association Junior Faculty Award.
Perspective
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Gerald Bernstein, MD, FACP
This is a terrific article because it opens a lot of doors to finding health solutions through exercise. We might expect that those whose metabolic control benefits from exercise follow a bimodal distribution — at one end are a handful of nonresponders, and at the other end, are super responders.
One issue to consider is the consistency of data over a lifetime. Would an exercise nonresponder at age 30 be the same at 60, especially if they exercised for those 30 years anyway? Then there is the epigenetic issue. Can repetitive behavior over many years result in a gene modification a decade or two later?
Regardless, the better part of therapeutic valor would be for everyone at risk for type 2 diabetes to be in an exercise program over his or her lifetime, as we do when we brush and floss our teeth.
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