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Published on: July 5, 2017
Short-term metformin and exercise training effects on strength, aerobic capacity, glycemic control, and mitochondrial
Eric Rivas1,2,3, David N Herndon1,2, Craig Porter1,2
1Shriners Hospitals for Children, Galveston, Texas.
Insights
Combining metformin with exercise in burned children did not enhance strength or aerobic capacity more than exercise alone. Exercise alone improved glucose control and reduced resting heart rate, with no added benefit from metformin.
Area of Science:
- Pediatric critical care
- Metabolic medicine
- Exercise physiology
Background:
- Severely burned children exhibit chronic sympathetic nervous system activation, leading to hypermetabolism, cardiac stress, and muscle wasting.
- Metformin is a diabetes medication that controls hyperglycemia, while exercise improves strength and aerobic capacity post-burn.
- The combined effects of exercise and metformin on glycemic control and muscle function in burned children are not well understood.
Purpose of the Study:
- To test if a 6-week exercise program with metformin (E + M) improves exercise capacity and muscle function more than exercise with placebo (E).
- To evaluate the impact of combined therapy on glucose tolerance and metabolic function.
- To compare the efficacy of exercise alone versus exercise plus metformin in burned children.
Main Methods:
- A 6-week exercise program was administered to severely burned children, with one group receiving metformin (E + M) and the other a placebo (E).
- Measurements included mitochondrial respiration, strength, peak oxygen consumption (V̇o2peak), fasting glucose, and glucose area under the curve (AUC) via oral glucose tolerance test.
- Resting energy expenditure and resting heart rate were also assessed.
Main Results:
- Metformin alone attenuated mitochondrial respiration compared to placebo before exercise.
- Exercise training in the E + M group increased mitochondrial respiration to levels comparable to the E group.
- Both groups showed similar improvements in strength, V̇o2peak, fasting glucose, and glucose AUC. Exercise reduced resting energy expenditure in the E + M group but not the E group.
Conclusions:
- Short-term metformin administration combined with exercise offers no additional benefits over exercise alone for improving strength, exercise capacity, or glycemic control in burned children.
- Exercise alone effectively improves glucose tolerance and reduces resting heart rate in this population.
- Metformin's impact on mitochondrial function in burned children warrants further investigation, especially in the context of exercise interventions.
Abstract:
Severely burned children experience a chronic state of sympathetic nervous system activation that is associated with hypermetabolic/cardiac stress and muscle wasting. Metformin, a diabetes medication, helps control hyperglycemia in obese diabetic populations, and exercise has been shown to improve exercise strength and aerobic exercise capacity after severe burns. However, whether exercise improves glycemic control in burned children and whether combining exercise and metformin improves outcomes to a greater degree than exercise alone are unknown. We tested the hypothesis that a 6-wk exercise program combined with short-term metformin administration (E + M) improves aerobic and strength exercise capacity to a greater degree than exercise and placebo (E), while improving glucose tolerance and muscle metabolic function. We found that, before exercise training, the metformin group compared with the placebo group had attenuated mitochondrial respiration (pmol·s-1·mg-1) for each state: state 2 (-22.5 ± 3), state 3 (-42.4 ± 13), and oxphos (-58.9 ± 19) ( P ≤ 0.02, M vs. E + M group for each state). However, in the E + M group, exercise increased mitochondrial respiration in each state ( P ≤ 0.05), with respiration being comparable to that in the E group (each P > 0.05). In both groups, exercise induced comparable improvements in strength (change from preexercise, Δ1.6 ± 0.6 N-M·kgLBM) and V̇o2peak (Δ9 ± 7 mlO2·kgLBM) as well as fasting glucose (Δ19.3 ± 13 mg·dl) and glucose AUC (Δ3402 ± 3674 mg·dl-1·min-1), as measured by a 75-g OGTT (all P ≤ 0.03). Exercise reduced resting energy expenditure in E + M (Δ539 ± 480 kcal/24 h, P < 0.01) but not E subjects ( P = 0.68). Both groups exhibited reduced resting heart rate (Δ30 ± 23 beats/min, P ≤ 0.02). These data indicate that short-term metformin combined with exercise provides no further improvement beyond that of exercise alone for strength, exercise capacity, and glycemic control.
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