August 4, 2020

High blood sugar may blunt benefits of aerobic exercise

At a Glance

  • Mice with high blood sugar levels had lower gains from aerobic exercise than normal mice.
  • The results suggest that diet changes may be needed to help people get the most benefit from aerobic exercise. 
Woman running on a park trail The findings suggest that high blood sugar may blunt the benefits of aerobic exercise. lzf / iStock / Getty Images Plus

Aerobic exercise benefits the body in many ways. It helps prevent heart disease and other chronic health problems. People with higher aerobic capacity—the ability of the body to use oxygen—tend to live longer.

However, researchers now know that not everyone gets the same benefits from aerobic exercise. Some people can exercise extensively without seeing improvements in their aerobic capacity. Genetics are thought to play a role in this. But lifestyle factors, such as diet, may also contribute.

A research team led by Dr. Sarah Lessard from the Joslin Diabetes Center previously studied rats bred for a low response to aerobic exercise. These animals tended to have problems with their blood sugar levels. Work from other labs has also suggested that hyperglycemia—or chronically high blood sugar—may play a role in reduced response to aerobic exercise. Hyperglycemia can be a sign of diabetes.

To look more closely at this relationship, Lessard and her colleagues performed further experiments with hyperglycemic mice. They induced hyperglycemia in two different ways. In one, mice were fed a diet high in sugar and saturated fat. In the other, a drug was used to cause prediabetes. Using two different methods increased the likelihood that any effects seen would be due to high blood sugar and not other factors, such as body weight or insulin levels, which affect blood sugar.

The study was funded in part by NIH’s National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). Results were published on July 20, 2020, in Nature Metabolism.

Both hyperglycemic and normal mice were allowed to run freely on a wheel for 6 weeks. All mice ran about the same distance during that time. At the end of the period, all had gained some metabolic benefits, including weight loss in mice that were overweight.

However, the hyperglycemic mice gained significantly less aerobic capacity over the training period. When the researchers looked at their muscles, the hyperglycemic mice had fewer aerobic adaptations, such as new blood vessel growth.

Additional studies showed that hyperglycemic mice accumulated more extracellular matrix in their muscles. This protein matrix provides structure and support for cells. In laboratory experiments, the team found that the extra matrix interfered with new blood vessel formation.

The researchers found that a cell-signaling pathway involving a molecule called c-Jun N-terminal kinase (JNK) was overactive in the muscles of hyperglycemic mice after aerobic exercise. This pathway is linked to the responses that muscle cells normally have to high mechanical stresses, such as lifting weights. Short term changes in blood sugar didn’t directly affect JNK signaling in the mice. Rather, the researchers propose that it is the increase in extracellular matrix caused by chronic hyperglycemia that leads to increased JNK signaling. The extra matrix increases mechanical stress, which activates JNK. This, in turn, signals the muscle cells to bulk up rather than adapt to the aerobic activity.

The team finally looked at JNK signaling in the muscles of 24 human volunteers before and after aerobic exercise. The people with higher blood sugar had increased JNK activity after a workout. They also had lower aerobic capacity overall.

In people with diabetes, hyperglycemia can lead to accumulation of extracellular matrix in organs such as the kidney and heart. More work is needed to understand whether the mechanisms proposed here are at work in people. If so, diet changes in people with high blood sugar might improve their response to aerobic exercise.

“We often think of diet and exercise as separate ways to improve our health,” Lessard says. “But our work shows that there is more interaction between these two lifestyle factors than what was previously known, and suggests that we may want to consider them together in order to maximize the health benefits of aerobic exercise.”

—by Sharon Reynolds

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References: Hyperglycaemia is associated with impaired muscle signalling and aerobic adaptation to exercise. MacDonald TL, Pattamaprapanont P, Pathak P, Fernandez N, Freitas EC, Hafida S, Mitri J, Britton SL, Koch LG, Lessard SJ. Nat Metab. 2020 Jul 20. doi: 10.1038/s42255-020-0240-7. Online ahead of print. PMID: 32694831.

Funding: NIH’s National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Cancer Institute (NCI), and National Institute of Neurological Disorders and Stroke (NINDS); American Heart Association; Iacocca Family Foundation; São Paulo Research Foundation; Joslin Clinical Research Center.