Results from the Diabetes Prevention Program highlight the effectiveness of metformin or regular physical activity in the prevention of type 2 diabetes. Independently, metformin and exercise increase insulin sensitivity, but they have not been studied in combination. To assess the combined effects, insulin-resistant subjects ( n = 9) matched for weight, body fat, and aerobic fitness were studied before any treatment (B), after 2–3 wk of 2,000 mg/day metformin (MET), and after metformin plus 40 min of exercise at 65% V̇o2peak (MET + Ex). A second group ( n = 7) was studied at baseline and after an identical bout of exercise with no metformin (Ex). Biopsies of the vastus lateralis were taken at B, after MET, immediately after MET + Ex ( group 1), or immediately after Ex ( group 2). Insulin sensitivity was assessed 4 h postexercise with a euglycemic hyperinsulinemic (40 mU·m2·min−1) clamp enriched with [6,6-2H]glucose. Insulin sensitivity was 54% higher after Ex ( P < 0.01), but there was no change with Met + Ex. Skeletal muscle AMPKα2 activity was elevated threefold ( P < 0.01) after Ex, but there was no increase with MET + Ex. These findings suggest that the combination of short-term metformin treatment and an acute bout of exercise does not enhance insulin sensitivity, and the addition of metformin may attenuate the well-documented effects of exercise alone.

clinicaltrials.gov Identifier: NCT01408147.

-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 (ϩ32%) and BAL (ϩ25%), and the change from baseline was higher than men (P Ͻ 0.05). In men, insulin AUC was reduced (Ϫ17%) after DEF (P Ͻ 0.05), but not BAL. In women, insulin AUC was lower (P Ͻ 0.05) after DEF (Ϫ28%) and BAL (Ϫ15%). 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. acylated ghrelin; leptin; insulin; physical activity; body fat; food intake EVIDENCE FROM THE NATIONAL WEIGHT CONTROL REGISTRY shows the critical importance of regular aerobic exercise in maintaining lost body weight and body fat (25). On the basis of a strong body of data, the Institute of Medicine indicated that preventing body fat gain over time probably requires 60 min of physical activity per day (4). When previously sedentary individuals begin exercise training programs, however, fat loss is neither inevitable nor consistent across the sexes (11, 36). In general, men lose body fat when they undertake structured exercise training programs with ad libitum eating (9,22,36). In contrast, women do not lose body fat in identical protocols (9,22,36). For example, Donnelly et al. (11) reported that supervised aerobic exercise 5 days/wk for 16 mo lowered body fat and body weight in men who ate ad libitum. In contrast, there were no changes in body fat and body mass in women. These data are corroborated by similar studies showing sex differences in body fat loss or fat oxidation (19,20,36). Taken together, these data suggest that during exercise training, men do not sufficiently increase energy intake to balance their new higher energy expenditure. In contrast, women more precisely match intake with expenditure and therefore maintain body weight and body fat.Sex differences in body fat loss in response to aerobic exercise may result, a...

Prenatal behavioral intervention with partial meal replacement significantly reduced GWG in Hispanic and non-Hispanic women with overweight or obesity. This trial was registered at www.clinicaltrials.gov as NCT01545934.