Blood sugar control may improve response to exercise training, study finds

News — BOSTON – Exercise has a long list of benefits for everyone. For people with metabolic diseases such as prediabetes, type 1 diabetes, and type 2 diabetes, physical activity can help control blood sugar levels and ward off diabetes-related nerve damage and heart disease. However, people with diabetes have a lower aerobic exercise capacity than people without metabolic disease, i.e. their body does not burn oxygen as efficiently and may also resist improving exercise capacity with training.

In a new study, scientists from the Joslin Diabetes Center Research Division set out to determine whether high blood sugar blunts the body’s response to exercise and whether reducing it can restore the ability to improve aerobic capacity with energy. ‘coaching. The team’s findings, published in the journal Diabetessuggest that a combination of a glucose-lowering drug and exercise may improve exercise capacity in people with hyperglycemia or hyperglycemia.

“As the prevalence of metabolic diseases soars, low exercise capacity associated with high blood sugar has the potential to impact a large and growing proportion of the population,” said Sarah J. Lessard, Ph.D., an assistant researcher in the Clinical, Behavioral, and Outcomes Research Section at the Joslin Diabetes Center and an instructor in medicine at Harvard Medical School. “Determining why some people’s bodies resist increasing exercise capacity even with training will help us design strategies to improve the health and longevity of this population.”

In this two-part study, Lessard and his colleagues first tested a drug called canagliflozin that can lower blood sugar in a mouse model. Mice with induced hyperglycemia were monitored as they voluntarily ran on exercise wheels during the six-week study. When the scientists assessed the animals’ response to physical training, they found a marked improvement in those who received canagliflozin compared to those who did not receive the drug.

By analyzing the animals’ muscle tissue, the researchers were also able to identify specific molecules in skeletal muscle responsible for low exercise capacity in the context of high blood sugar.

Then, using small samples of muscle taken from human study participants before and after exercise sessions, the researchers were able to confirm that the molecules identified in the preclinical experiments may also be relevant in humans.

“We find that having high blood sugar for long periods changes how muscles respond to exercise at the molecular level,” Lessard said. “The good news is that we find that lowering blood sugar in mice with diabetes using the drug canagliflozin can prevent impairments that blunt the improvements in exercise capacity that occur with high blood sugar.”

As a next step, Lessard and his colleagues plan to test whether other glucose-lowering treatments — such as dietary strategies — can be as effective as drug therapies in improving exercise response. They are also investigating in more detail the molecular signaling events in muscles that lead to impaired remodeling and poor response to exercise.

“If we can better understand how hyperglycemia drives these muscle changes, we can develop targeted therapies to restore exercise response,” Lessard said.

Co-authors included Tara L. McDonald, Pattarawan Pattamprapanon, Eileen M. Cooney, Roberto C. Nava, Joanna Mitri, and Samar Hafida of the Joslin Diabetes Center.

This work was supported by the National Institute of Diabetes and Digestive and Kidney Diseases (R01 DK 124258); a pilot price and feasibility; and Diabetes Research Center Central Facilities funded by NIH P30 award number DK036836; an American Heart Association Postdoctoral Fellowship (19POST34381036); a Mary K. Iacocca Senior Fellowship; and a fellowship from the Joslin Diabetes Center NIH Training Fellowship (T32 DK 007260). For the human studies, the authors acknowledge the support of the Joslin Clinical Research Center and thank its philanthropic donors.

The authors declare no conflict of interest.

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About the Joslin Diabetes Center

The Joslin Diabetes Center is recognized worldwide for its great expertise in diabetes treatment and research. Joslin is dedicated to finding a cure for diabetes and ensuring that people with diabetes live long, healthy lives. We develop and deliver innovative therapies for patients and scientific discoveries around the world. Joslin is an independent, nonprofit institution affiliated with Harvard Medical School and one of 16 NIH-designated diabetes research centers in the United States.

Joslin Diabetes Center is part of Beth Israel Lahey Health, a healthcare system that brings together academic medical centers and teaching hospitals, community and specialty hospitals, more than 4,800 physicians and 36,000 employees in a common mission to expand access to quality care and advance the science and practice of medicine through groundbreaking research and education.

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