A new study suggests that when blood sugar is elevated, exercise alone may not be enough.
Most of us hear the same advice: move more, eat less fat. Exercise can trim body fat, build muscle, and strengthen the heart. It also raises cardiorespiratory fitness, which is often tracked by how well the body can deliver and use oxygen during activity, a key marker linked with better health over time.
For people living with high blood sugar, though, that oxygen-related boost may be harder to achieve. Hyperglycemia is tied to higher risks of heart and kidney problems, and it can also make it tougher for working muscles to increase oxygen use during training. In other words, the workout can still be “good,” but the body may not adapt as efficiently.
A new study raises an unexpected possibility for this group: under certain conditions, eating more fat, not less, might help restore some of the benefits exercise is supposed to deliver.
A Ketogenic Shift in Metabolism
In research led by exercise medicine scientist Sarah Lessard, published Feb. 25 in Nature Communications, mice with high blood sugar were put on a high-fat ketogenic diet. Their blood sugar dropped, and their bodies responded more strongly to exercise.
“After one week on the ketogenic diet, their blood sugar was completely normal, as though they didn’t have diabetes at all,” said Lessard, associate professor at the Fralin Biomedical Research Institute at VTC Center for Exercise Medicine Research. “Over time, the diet caused remodeling of the mice’s muscles, making them more oxidative and making them react better to aerobic exercise.”
The ketogenic diet is designed to push the body into ketosis, a metabolic state where fat becomes the primary fuel source rather than glucose. That goal is what makes keto so polarizing. It relies on high-fat, very low-carbohydrate eating, which clashes with decades of low-fat messaging in nutrition advice.
Historical and Clinical Context
Despite the controversy, the ketogenic diet has shown promise in certain medical settings. It has been used to help manage epilepsy and has been associated with potential benefits in Parkinson’s disease. In the 1920s, before insulin became available, physicians used it to treat diabetes because it can lower blood sugar levels.
In previous work, Lessard observed that people with high blood sugar tended to have reduced exercise capacity. She questioned whether shifting metabolism through diet could enhance the body’s response to physical activity and improve overall performance.
To explore this idea, researchers fed mice a high-fat, low-carbohydrate diet and gave them access to running wheels. Over time, the animals developed a greater proportion of slow-twitch muscle fibers, which are known to support endurance.
“Their bodies were more efficiently using oxygen, which is a sign of higher aerobic capacity,” Lessard said.
Diet and Exercise: A Combined Effect
According to Lessard, exercise benefits nearly every tissue in the body, including fat tissue. Yet her findings suggest that diet and physical activity should not be viewed as separate strategies.
“What we’re really finding from this study and from our other studies is that diet and exercise aren’t simply working in isolation,” said Lessard, who also holds an appointment in the Department of Human Foods, Nutrition, and Exercise in Virginia Tech’s College of Agriculture and Life Sciences. “There are a lot of combined effects, and so we can get the most benefits from exercise if we eat a healthy diet at the same time.”
She plans to extend the research to human participants to determine whether the same improvements seen in mice can be achieved in people.
Lessard also acknowledged that maintaining a ketogenic diet can be difficult. She suggested that less restrictive approaches, such as the Mediterranean diet, may offer a more practical alternative while still helping control blood sugar. Unlike keto, the Mediterranean pattern includes carbohydrates from unprocessed fruits, vegetables, and whole grains rather than eliminating them entirely.
“Our previous studies have shown that any strategy you and your doctor have arrived at to reduce your blood sugar could work,” she said.
Reference: “A ketogenic diet enhances aerobic exercise adaptation and promotes muscle mitochondrial remodeling in hyperglycemic male mice” by Pattarawan Pattamaprapanont, Roberto C. Nava, Rea Grover, Mia Formato, Eileen M. Cooney, Ana Paula Pinto, Ana B. Alves-Wagner, Anamica Das, Yuntian Guan, Meghana Annambhotla, Saanvi Acharya, Donato A. Rivas and Sarah J. Lessard, 25 February 2026, Nature Communications.
DOI: 10.1038/s41467-026-69349-5
Funding: Diabetes Research Center
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