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Short-term metformin and exercise training effects on strength, aerobic capacity, glycemic control, and mitochondrial function in children with burn injury.

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, ?1.6?±?0.6 N-M·kgLBM) and V?o2peak (?9?±?7 mlO2·kgLBM) as well as fasting glucose (?19.3?±?13 mg·dl) and glucose AUC (?3402?±?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 (?539?±?480 kcal/24 h, P < 0.01) but not E subjects ( P = 0.68). Both groups exhibited reduced resting heart rate (?30?±?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.

SUBMITTER: Rivas E

PROVIDER: S-EPMC5899215 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Short-term metformin and exercise training effects on strength, aerobic capacity, glycemic control, and mitochondrial function in children with burn injury.

Rivas Eric E Herndon David N DN Porter Craig C Meyer Walter W Suman Oscar E OE

American journal of physiology. Endocrinology and metabolism 20171114 3

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 ...[more]

PMID: 29138224

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Project description:A low maximal oxygen consumption (VO2max) is a strong risk factor for premature mortality. Supervised endurance exercise training increases VO2max with a very wide range of effectiveness in humans. Discovering the DNA variants that contribute to this heterogeneity typically requires substantial sample sizes. In the present study, we first use RNA expression profiling to produce a molecular classifier that predicts VO2max training response. We then hypothesized that the classifier genes would harbor DNA variants that contributed to the heterogeneous VO2max response. Two independent preintervention RNA expression data sets were generated (n=41 gene chips) from subjects that underwent supervised endurance training: one identified and the second blindly validated an RNA expression signature that predicted change in VO2max ("predictor" genes). The HERITAGE Family Study (n=473) was used for genotyping. We discovered a 29-RNA signature that predicted VO2max training response on a continuous scale; these genes contained approximately 6 new single-nucleotide polymorphisms associated with gains in VO2max in the HERITAGE Family Study. Three of four novel candidate genes from the HERITAGE Family Study were confirmed as RNA predictor genes (i.e., "reciprocal" RNA validation of a quantitative trait locus genotype), enhancing the performance of the 29-RNA-based predictor. Notably, RNA abundance for the predictor genes was unchanged by exercise training, supporting the idea that expression was preset by genetic variation. Regression analysis yielded a model where 11 single-nucleotide polymorphisms explained 23% of the variance in gains in VO2max, corresponding to approximately 50% of the estimated genetic variance for VO2max. In conclusion, combining RNA profiling with single-gene DNA marker association analysis yields a strongly validated molecular predictor with meaningful explanatory power. VO2max responses to endurance training can be predicted by measuring a approximately 30-gene RNA expression signature in muscle prior to training. The general approach taken could accelerate the discovery of genetic biomarkers, sufficiently discrete for diagnostic purposes, for a range of physiological and pharmacological phenotypes in humans.

Dataset Information

Short-term metformin and exercise training effects on strength, aerobic capacity, glycemic control, and mitochondrial function in children with burn injury.

Publications

Short-term metformin and exercise training effects on strength, aerobic capacity, glycemic control, and mitochondrial function in children with burn injury.

Similar Datasets

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