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Short‐term Metformin and Exercise Training Effects on Strength, Aerobic Capacity, Glycemic Control and Mitochondrial Function in Burn Children
Author(s) -
Rivas Eric,
Porter Craig,
Herndon David N.,
Suman Oscar E.
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.715.9
Subject(s) - glycemic , metformin , aerobic capacity , medicine , endocrinology , aerobic exercise , insulin , total body surface area , zoology , biology
Metformin (M) has been shown to attenuate hyperglycemia and exercise (EX) has been shown to improve strength and aerobic exercise capacity in severely burn patients. However, it is unknown if the combination of M+EX can further improve these outcome measures and if EX alone will improve glycemic control in burn populations. This project tested the hypothesis that 6‐weeks of exercise training combined with short‐term administration of metformin (EX+M) compared to exercise alone (EX) would synergistically improve aerobic and strength exercise capacity, while improving mitochondrial respiration and glucose tolerance. Eight burned children (4 male) received EX after discharge while nine burned children (6 male) received M at 72–96 h post‐ admission with EX at discharge. Prior to EX, both groups had similar physical characteristics (means±SD; 15 ± 2y, 157.1±7cm, 50.1±11 kg, 34.7±6 lean body mass, LBM, 46±15% total body surface area burned; P >0.05), peak strength (peak torque 1.6±0.5 N‐M·KgLBM; P >0.05) peak aerobic capacity (VO 2 peak; 34.6±8 mlO2·kgLBM·min; P >0.05) and metabolic characteristics (fasting glucose 110.4±16 mg·dL and insulin 20.6±11 pmol·L, 75g oral glucose tolerance, OGTT, AUC for glucose 17776±3245 mg·dL·min and AUC insulin 8451±6043 pmol·L·min, 1878±151 kcal/24h resting energy expenditure, REE, and resting heart rate, HR 129±13 bpm; P >0.05). At PreEX time, mitochondrial respiration (pmol·sec·mg) was attenuated for each state: leak (−5.9±5) states 2 (−22.5±3) and 3 (−42.4±13), and oxphos (−58.9±19) in the M compared to the EX+M (each, P ≤0.02). Post‐burn injury EX training (started 1.4±0.6 mo postburn ; P =0.33) and completed exercise sessions (30±11 days; P =0.71) was similar between groups. EX improved strength (change from preEX, Δ1.6±0.6 N‐M·KgLBM), VO 2 peak (Δ9±7 mlO2·kgLBM) and reduced fasting glucose (Δ19.3±13 mg·dL) and glucose AUC for the 75g OGTT (Δ3402±3674 mg·dL·min) in both groups (each, P ≤0.03). EX+M significantly reduced REE (Δ539±480 kcal/24h, P <0.01) while E alone did not ( P =0.68). Both, EX+M and EX reduced resting HR (Δ30±23bpm; P ≤0.02). EX+M increased mitochondrial respiration for each state ( P ≤0.05) to similar levels as EX alone (each P >0.05). These data indicate that short‐term metformin combined with exercise provides no further improvement beyond that of exercise alone in terms of strength, exercise capacity, and glycemic control. Most importantly, for the first time we show that short‐term exercise training improved glycemic control in burn patients. However, it remains unknown if a longer (1‐year administration) M treatment is needed to improve the hyperglycemia/insulinemia state in burn patients. Support or Funding Information This study was supported in part or totally by awards from: NIH P50‐GM060338, NIH R01‐GM56687, R01 HD049471, SHC 84080, 71008, 84090, and NIDILRR 90DP0043‐01‐00.