A panel of experts analyzed the effects of physical activity to identify potential therapeutic interventions for older adults with diabetes at the 83rd Scientific Sessions during Able-Bodied Aging—Physical Activity Considerations for Older Adults with Diabetes.

The session can be viewed on-demand by registered meeting participants at ADA2023.org. If you haven’t registered for the 83rd Scientific Sessions, register today to access the valuable meeting content through August 28.

Physical activity might have a role in preventing diabetes-related complications independent of its effect on glycemic control and the early (but not late) natural history of insulin production preservation, said Bruce A. Perkins, MD, MPH, Professor of Medicine, University of Toronto, Canada.

Dr. Perkins helped lead the Canadian Study of Longevity in Type 1 Diabetes, which studied Canadians with a history of long-standing type 1 diabetes for 50 years or more. He explained that studies of the phenotypes of patients with long-standing type 1 diabetes force researchers to consider therapies to recover surviving insulin-producing cells, treatments that target renal afferent arteriolar tone, and a role for physical activity for neuropathy and neuropathic pain.

“While physical activity has not been a major focus of our studies, or any of these studies, it appears to be at least a marker of many beneficial outcomes,” he said.

Dr. Perkins cited intervention studies for people with pre-diabetic neuropathy using intra-epidermal nerve fiber density and a diabetes prevention program protocol for diet and exercise. After completion, imaging showed improvements in patients’ nerve fibers.

The Environmental Determinants of Diabetes in the Young (TEDDY) study found that increased moderate-to-vigorous activity was associated with higher C-peptide rather than the onset or progression of antibodies.

“Physical activity is causally associated with insulin sensitivity, likely, and its consequent beta-cell reserve rather than this hypothesis that physical activity could alter the autoimmune process in type 1 diabetes or other diseases,” Dr. Perkins explained.

Dr. Perkins’ team reviewed the relationship between physical activity and C-peptide levels among the longstanding cohort and found that while physical activity may have a causal role in beta-cell reserve early in the course of type 1 diabetes, preserved insulin production late in the progression of the disease is likely determined by other factors.

According to Marina Mourtzakis, PhD, Professor of Kinesiology and Health Sciences, University of Waterloo, Canada, physical activity can play a role in preventing and managing sarcopenia.

Strength and aerobic exercises can improve muscle mass, glucose metabolism, insulin sensitivity, and non-contractile protein organization while decreasing fibrotic infiltration. Each of these could contribute to the prevention or management of sarcopenia.

While these benefits are well-established, investigators are still finding the optimal exercise regimen for patients with sarcopenia. Researchers are concerned that strength training could potentially negate the positive effects gained from aerobic exercise or vice versa.

“To prevent or manage sarcopenia with exercise, and I’m also going to highlight with nutrition as well, we need to have a better ability to target its specific mechanisms to make more effective exercise protocols,” Dr. Mourtzakis explained.

These insights could eventually stem from imaging tools, such as ultrasound, which Dr. Mourtzakis prefers because it measures muscle quantity and quality with higher-order texture features that are less affected by technology and the technologist.

The Metformin to Augment Strength Training Effective Response in Seniors (MASTERS) study found that metformin did not enhance muscle and strength development in older adults during progressive resistance training (PRT), explained Philip A. Kern, MD, Professor of Medicine, University of Kentucky.

Researchers hypothesized that metformin would lower inflammation in aging muscle and increase M2 macrophage production and AMP-activated protein kinase (AMPK) activity with PRT. The results ultimately showed that metformin combined with PRT led to no change in inflammation or M2 macrophage production compared to placebo.

Results suggested that metformin blunted an increase in the thigh muscle compared to the placebo group. The drug may also negatively affect muscle quality. PRT alone usually leads to a significant loss of low-density muscle area that correlates with an increase in normal-density muscle. These effects were attenuated when combined with metformin.   

Dr. Kern hypothesized that metformin causes an increase in AMPK activity, which offsets the natural boost individuals usually gain from PRT.

While the original hypothesis of the study was refuted, researchers stumbled upon a potentially consequential discovery related to the interactions of statins and metformin. Participants on statins and metformin saw improved changes in hypertrophy of type 1 fibers, type 2 fibers, and macrophages compared to those only taking metformin.

“It suggested that some of the detrimental effects in the metformin plus PRT group were ameliorated in those taking statins,” Dr. Kern summarized.