Brooke R. Stephens

Effects of 1 day of inactivity on insulin action in healthy men and women: interaction with energy intake

Prolonged periods of limited muscle activity can reduce insulin action. Acute changes in low muscle activity (ie, sitting) have not been assessed. In addition, unless energy intake is reduced during sitting to match low expenditure, the concurrent energy surplus may explain lower insulin action. The objective of the study was to evaluate the acute effect of sitting, with and without energy surplus, on insulin action. Fourteen young (26.1 ± 4.5 years, mean ± SD), nonobese (23.7% ± 7.1% fat), fit (peak oxygen consumption = 49.1 ± 3.3 mL·kg(-1)·min(-1)) men (n = 7) and women (n = 7) completed three 24-hour conditions: (1) an active, no-sitting condition (high energy expenditure of 2944 ± 124 kcal with energy intake matched to expenditure) = NO-SIT; (2) low energy expenditure (sitting) of 2195 ± 121 kcal with no reduction in energy intake (energy surplus) = SIT; and (3) sitting with energy intake reduced to 2139 ± 118 kcal to match low expenditure (energy balance) = SIT-BAL. Insulin action was measured the following morning during a continuous infusion of [6,6-(2)H]-glucose. Data were analyzed using linear mixed-effects models with planned contrasts. Compared with NO-SIT, insulin action, defined as whole-body rate of glucose disappearance normalized to mean plasma insulin, was reduced by 39% in SIT (P < .001) and by 18% in SIT-BAL (P = .07). Insulin action was higher in SIT-BAL compared with SIT (P = .04). One day of sitting considerably reduced insulin action; this effect was minimized, but not prevented, when energy intake was reduced to match expenditure. Strategies to limit daily sitting may reduce metabolic disease risk.

Effects of exercise on energy-regulating hormones and appetite in men and women.

When previously sedentary men and women follow exercise training programs with ad libitum feeding, men lose body fat, but women do not. The purpose of this study was to evaluate whether this observation could be related to sex differences in the way energy-regulating hormones and appetite perception respond to exercise. Eighteen (9 men, 9 women) overweight/obese individuals completed four bouts of exercise with energy added to the baseline diet to maintain energy balance (BAL), and four bouts without energy added to induce energy deficit (DEF). Concentrations of acylated ghrelin, insulin, and leptin, as well as appetite ratings were measured in response to a meal after a no-exercise baseline and both exercise conditions. In men, acylated ghrelin area under the curve (AUC) was not different between conditions. In women, acylated ghrelin AUC was higher after DEF (+32%) and BAL (+25%), and the change from baseline was higher than men (P < 0.05). In men, insulin AUC was reduced (-17%) after DEF (P < 0.05), but not BAL. In women, insulin AUC was lower (P < 0.05) after DEF (-28%) and BAL (-15%). Leptin concentrations were not different across conditions in either sex. In men, but not in women, appetite was inhibited after BAL relative to DEF. The results indicate that, in women, exercise altered energy-regulating hormones in a direction expected to stimulate energy intake, regardless of energy status. In men, the response to exercise was abolished when energy balance was maintained. The data are consistent with the paradigm that mechanisms to maintain body fat are more effective in women.

Impact of Metformin on Peak Aerobic Capacity

Individually, exercise and the drug metformin have been shown to prevent or delay type 2 diabetes. Metformin mildly inhibits complex I of the electron transport system and may impact aerobic capacity in people exercising while taking metformin. The purpose of the study was to evaluate the effects of metformin on maximal aerobic capacity in healthy individuals without mitochondrial dysfunction. Seventeen healthy, normal-weight men (n=11) and women (n=6) participated in a double-blind, placebo-controlled, cross-over design. Peak aerobic capacity was measured twice using a continuous, incrementally graded protocol; once after 7-9 d of metformin (final dose=2000 mg/d) and once with placebo, with 1 week between tests. The order of the conditions was counterbalanced. Peak oxygen uptake (VO2 peak), heart rate (HR), ventilation (VE), respiratory exchange ratio (RER), rating of perceived exertion (RPE), and test duration were compared across conditions using paired t tests with the R statistical program. VO2 peak (-2.7%), peak heart rate (-2.0%), peak ventilation (-6.2%), peak RER (-3.0%), and exercise duration (-4.1%) were all reduced slightly, but significantly, with metformin (all p<0.05). There was no effect of metformin on RPE or ventilatory breakpoint. Correlations between the decrement in VO2 peak and any of the other outcome variables were weak (r2<0.20) and not significant. Short-term treatment with metformin has statistically significant, but physiologically subtle, effects that reduce key outcomes related to maximal exercise capacity. Whether this small but consistent effect is manifested in people with insulin resistance or diabetes who already have some degree of mitochondrial dysfunction remains to be determined.

The effect of carbohydrate availability following exercise on whole-body insulin action

One bout of exercise enhances insulin-stimulated glucose uptake (insulin action), but the effect is blunted by consumption of carbohydrate-containing food after exercise. The independent roles of energy and carbohydrate in mediating post-exercise insulin action have not been systematically evaluated in humans. The purpose of this study was to determine if varying carbohydrate availability, with energy intake held constant, mediates post-exercise insulin action. Ten young (21 +/- 2 y, overweight (body fat 37% +/- 3%) men and women completed 3 conditions in random order: (i) no-exercise (BASE), (ii) exercise with energy balance but carbohydrate deficit (C-DEF), and (iii) exercise with energy and carbohydrate balance (C-BAL). In the exercise conditions, subjects expended 30% of total daily energy expenditure on a cycle ergometer at 70% VO2 peak. Following exercise, subjects consumed a meal that replaced expended energy (~3000 kJ) and was either balanced (intake = expenditure) or deficient (-100 g) in carbohydrate. Twelve hours later, insulin action was measured by continuous infusion of glucose with stable isotope tracer (CIG-SIT). Changes in insulin action were evaluated using a one-way ANOVA with repeated measures. During CIG-SIT, non-oxidative glucose disposal (i.e., glucose storage) was higher in C-DEF than in BASE (27.2 +/- 3.2 vs. 16.9 +/- 3.5 micromol.L-1.kg-1.min-1, p < 0.05). Conversely, glucose oxidation was lower in C-DEF (8.6 +/- 1.3 micromol.L-1.kg-1.min-1) compared with C-BAL (12.2 +/- 1.2 micromol.L-1.kg-1.min-1), and BASE (17.1 +/- 2.2 micromol.L-1.kg-1.min-1), p < 0.05). Fasting fat oxidation was higher in C-DEF than in BASE (109.8 +/- 10.5 vs. 80.7 +/- 9.6 mg.min-1, p < 0.05). In C-DEF, enhanced insulin action was correlated with the magnitude of the carbohydrate deficit (r = 0.82, p < 0.01). Following exercise, re-feeding expended energy, but not carbohydrate, increased fasting fat oxidation, and shifted insulin-mediated glucose disposal toward increased storage and away from oxidation.

Effect of timing of energy and carbohydrate replacement on post-exercise insulin action

The nutritional environment surrounding an exercise bout modulates post-exercise insulin action. The purpose of this study was to determine how timing energy and carbohydrate replacement proximate to an exercise bout influences exercise-enhanced insulin action. To create an appropriate baseline, sensitivity to insulin was reduced in 9 healthy young men (n=6) and women (n=3) by 2 days of energy surplus and detraining. Then, insulin action (glucose uptake per unit plasma insulin) was assessed by stable isotope dilution during a continuous glucose infusion 12 h after a standardized meal under 4 conditions. In 3 conditions, the meal replaced the energy and carbohydrate expended during an exercise bout (62.9+/-2.8 min cycle ergometry at 65% VO2 peak followed by ten 30 s sprints). The meal was given before (Pre), immediately after (ImmPost), or 3 h after exercise (Delay). The 4th condition was a no-exercise control (Control). Data were analyzed using linear mixed-effects models with planned contrasts. Relative to Control, insulin action increased by 22% in Pre (p=0.05), 44% in ImmPost (p<0.01), and 19% in Delay (p=0.09). Non-oxidative disposal was higher, and oxidative disposal was lower in ImmPost relative to Control and Pre (p<0.05). Hepatic glucose production was suppressed by the infusion to a greater extent in Pre and Delay (76.9%+/-8.8% and 81.2%+/-4.7%) compared with ImmPost (64.7%+/-10.0%). A bout of exercise enhances insulin action even when expended energy and carbohydrate are replaced. Further, timing of energy and carbohydrate consumption subtly modulates the effectiveness of exercise to enhance insulin action.

Impact of nutrient intake timing on the metabolic response to exercise

Effects of nutrient intake timing and exercise on carbohydrate (e.g. insulin sensitivity), protein (muscle protein synthesis), and fat (circulating triacylglycerols) metabolism are reviewed in this paper. Altered nutrient intake timing relative to exercise can modulate the metabolic response, which is relevant for individuals seeking to use exercise to enhance health.