Cardiovascular, metabolic and hormonal responses to the progressive exercise performed to exhaustion in patients with type 2 diabetes treated with metformin or glyburide

Cunha, Marcus Vinícius da; Silva, M. E. R.; Machado, H. A.; Fukui, Rosa Tsunechiro; Correia, M. R. S.; Santos, R. F.; Wajchenberg, B. L.; Rocha, Dalva Marreiro; Rondon, M. U. P. B.; Negräo, Carlos Eduardo; Ursich, Mileni Josefina Maria

doi:10.1111/j.1463-1326.2006.00690.x

Cited by 11 publications

(8 citation statements)

References 52 publications

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“…We are aware of nonexercise studies that have suggested that metformin may increase glucagon concentrations, but the increases were not statistically significant (24,25). In the nonrandomized exercise studies by Cunha et al (14,15), glucagon concentrations were significantly higher in the participants with type 2 diabetes taking metformin compared with those taking glibenclamide or those with normal glucose tolerance. Although speculative, the glucose-lowering benefits of metformin could be further enhanced by strategies that could help minimize the exercise-induced increased glucagon levels such as exercising after a meal.…”

Section: Discussionmentioning

confidence: 91%

“…Although the combination of metformin and exercise was perceived as safe, interest in this area has reemerged in recent years (4,7,14,15). The current study is unique in that it focused on continuous exercise at several submaximal intensities that are relevant to activity patterns of people with type 2 diabetes and that we examined the interaction between exercise and metformin on the glycemic and hormonal responses to a subsequent meal.…”

Section: Discussionmentioning

confidence: 99%

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Metformin and Exercise in Type 2 Diabetes

et al. 2011

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OBJECTIVETo determine the effect of metformin on the acute metabolic response to submaximal exercise, the effect of exercise on plasma metformin concentrations, and the interaction between metformin and exercise on the subsequent response to a standardized meal.RESEARCH DESIGN AND METHODSTen participants with type 2 diabetes were recruited for this randomized crossover study. Metformin or placebo was given for 28 days, followed by the alternate condition for 28 days. On the last 2 days of each condition, participants were assessed during a nonexercise and a subsequent exercise day. Exercise took place in the morning and involved a total of 35 min performed at three different submaximal intensities.RESULTSMetformin increased heart rate and plasma lactate during exercise (both P ≤ 0.01) but lowered respiratory exchange ratio (P = 0.03) without affecting total energy expenditure, which suggests increased fat oxidation. Metformin plasma concentrations were greater at several, but not all, time points on the exercise day compared with the nonexercise day. The glycemic response to a standardized meal was reduced by metformin, but the reduction was attenuated when exercise was added (metformin × exercise interaction, P = 0.05). Glucagon levels were highest in the combined exercise and metformin condition.CONCLUSIONSThis study reveals several ways by which metformin and exercise therapies can affect each other. By increasing heart rate, metformin could lead to the prescription of lower exercise workloads. Furthermore, under the tested conditions, exercise interfered with the glucose-lowering effect of metformin.

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Section: Discussionmentioning

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Metformin and Exercise in Type 2 Diabetes

et al. 2011

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“…This environment is exacerbated in muscle fibers exposed to high metabolic demand as well as conditions characterized by skeletal muscle hypoxia, such as heart failure (38), type II diabetes (12,35), and aging (37). Therefore, the potential for K ATP channels to contribute significantly to exercise-induced skeletal muscle hyperemia has important implications for characterizing the etiology of blood-muscle O 2 transport decrements in these conditions.…”

Section: Discussionmentioning

confidence: 99%

Acute inhibition of ATP-sensitive K⁺ channels impairs skeletal muscle vascular control in rats during treadmill exercise

Holdsworth

Copp

Ferguson

et al. 2015

American Journal of Physiology-Heart and Circulatory Physiology

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The ATP-sensitive K(+) (KATP) channel is part of a class of inward rectifier K(+) channels that can link local O2 availability to vasomotor tone across exercise-induced metabolic transients. The present investigation tested the hypothesis that if KATP channels are crucial to exercise hyperemia, then inhibition via glibenclamide (GLI) would lower hindlimb skeletal muscle blood flow (BF) and vascular conductance during treadmill exercise. In 27 adult male Sprague-Dawley rats, mean arterial pressure, blood lactate concentration, and hindlimb muscle BF (radiolabeled microspheres) were determined at rest (n = 6) and during exercise (n = 6-8, 20, 40, and 60 m/min, 5% incline, i.e., ~60-100% maximal O2 uptake) under control and GLI conditions (5 mg/kg intra-arterial). At rest and during exercise, mean arterial pressure was higher (rest: 17 ± 3%, 20 m/min: 5 ± 1%, 40 m/min: 5 ± 2%, and 60 m/min: 5 ± 1%, P < 0.05) with GLI. Hindlimb muscle BF (20 m/min: 16 ± 7%, 40 m/min: 30 ± 9%, and 60 m/min: 20 ± 8%) and vascular conductance (20 m/min: 20 ± 7%, 40 m/min: 33 ± 8%, and 60 m/min: 24 ± 8%) were lower with GLI during exercise at 20, 40, and 60 m/min, respectively (P < 0.05 for all) but not at rest. Within locomotory muscles, there was a greater fractional reduction present in muscles comprised predominantly of type I and type IIa fibers at all exercise speeds (P < 0.05). Additionally, blood lactate concentration was 106 ± 29% and 44 ± 15% higher during exercise with GLI at 20 and 40 m/min, respectively (P < 0.05). That KATP channel inhibition reduces hindlimb muscle BF during exercise in rats supports the obligatory contribution of KATP channels in large muscle mass exercise-induced hyperemia.

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“…Some studies suggest that acute and/or short‐term metformin administration promotes fatigue resistance during high‐intensity exercise, while lowering lactate and facilitating carbohydrate oxidation and glucose homeostasis during standardized exercise . Others have reported that metformin decreases peak oxygen uptake, and increases exercise heart rate and lactate, or has no influence on cardiovascular and endocrine responses to exercise . In vitro data suggest high concentrations of metformin inhibit mitochondrial complex I, however, when experiments utilize concentrations of metformin associated with standard doses, mitochondrial respiration is not impaired .…”

Section: Discussionmentioning

confidence: 99%

“…3,20 Others have reported that metformin decreases peak oxygen uptake, 21 and increases exercise heart rate and lactate, 22 or has no influence on cardiovascular and endocrine responses to exercise. 23,24 In vitro data suggest high concentrations of metformin inhibit mitochondrial complex I, [25][26][27] however, when experiments utilize concentrations of metformin associated with standard doses, mitochondrial respiration is not impaired. 28 There are several components of our investigation that warrant discussion.…”

Section: Discussionmentioning

confidence: 99%

Ergogenic properties of metformin in simulated high altitude

Scalzo

Paris

Binns

et al. 2017

Clin Exp Pharma Physio

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Metformin augments glucose/glycogen regulation and may acutely promote fatigue resistance during high-intensity exercise. In hypobaric environments, such as high altitude, the important contribution of carbohydrates to physiological function is accentuated as glucose/glycogen dependence is increased. Because hypoxia/hypobaria decreases insulin sensitivity, replenishing skeletal muscle glycogen in high altitude becomes challenging and subsequent physical performance may be compromised. We hypothesized that in conditions where glycogen repletion was critical to physical outcomes, metformin would attenuate hypoxia-mediated decrements in exercise performance. On three separate randomly ordered occasions, 13 healthy men performed glycogen-depleting exercise and ingested a low-carbohydrate dinner (1200 kcals, <10% carbohydrate). The next morning, in either normoxia or hypoxia (FiO =0.15), they ingested a high-carbohydrate breakfast (1225 kcals, 70% carbohydrate). Placebo (719 mg maltodextrin) or metformin (500 mg BID) was consumed 3 days prior to each hypoxia visit. Subjects completed a 12.5 km cycle ergometer time trial 3.5 hours following breakfast. Hypoxia decreased resting and exercise oxyhemoglobin saturation (P<.001). Neither hypoxia nor metformin affected the glucose response to breakfast (P=.977), however, compared with placebo, metformin lowered insulin concentration in hypoxia 45 minutes after breakfast (64.1±6.6 μU/mL vs 48.5±7.8 μU/mL; mean±SE; P<.001). Post-breakfast, pre-exercise vastus lateralis glycogen content increased in normoxia (+33%: P=.025) and in hypoxia with metformin (+81%; P=.006), but not in hypoxia with placebo (+27%; P=.167). Hypoxia decreased time trial performance compared with normoxia (P<.01). This decrement was similar with placebo (+2.6±0.8 minutes) and metformin (+1.6±0.3 minutes). These results indicate that metformin promotes glycogen synthesis but not endurance exercise performance in healthy men exposed to simulated high altitude.

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Cardiovascular, metabolic and hormonal responses to the progressive exercise performed to exhaustion in patients with type 2 diabetes treated with metformin or glyburide

Cited by 11 publications

References 52 publications

Metformin and Exercise in Type 2 Diabetes

Metformin and Exercise in Type 2 Diabetes

Acute inhibition of ATP-sensitive K⁺ channels impairs skeletal muscle vascular control in rats during treadmill exercise

Ergogenic properties of metformin in simulated high altitude

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Cardiovascular, metabolic and hormonal responses to the progressive exercise performed to exhaustion in patients with type 2 diabetes treated with metformin or glyburide

Cited by 11 publications

References 52 publications

Metformin and Exercise in Type 2 Diabetes

Metformin and Exercise in Type 2 Diabetes

Acute inhibition of ATP-sensitive K+ channels impairs skeletal muscle vascular control in rats during treadmill exercise

Ergogenic properties of metformin in simulated high altitude

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Acute inhibition of ATP-sensitive K⁺ channels impairs skeletal muscle vascular control in rats during treadmill exercise