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.

Acute exercise suppresses ad libitum energy intake, but little is known about the effects of exercise on food reward brain regions. After an overnight fast, 30 (17 men, 13 women), healthy, habitually active (age = 22.2 ± 0.7 yr, body mass index = 23.6 ± 0.4 kg/m(2), Vo(2peak) = 44.2 ± 1.5 ml·kg(-1)·min(-1)) individuals completed 60 min of exercise on a cycle ergometer or 60 min of rest (no-exercise) in a counterbalanced, crossover fashion. After each condition, blood oxygen level-dependent responses to high-energy food, low-energy food, and control visual cues, were measured by functional magnetic resonance imaging. Exercise, compared with no-exercise, significantly (P < 0.005) reduced the neuronal response to food (high and low food) cues vs. control cues in the insula (-0.37 ± 0.13 vs. +0.07 ± 0.18%), putamen (-0.39 ± 0.10 vs. -0.10 ± 0.09%), and rolandic operculum (-0.37 ± 0.17 vs. 0.17 ± 0.12%). Exercise alone significantly (P < 0.005) reduced the neuronal response to high food vs. control and low food vs. control cues in the inferior orbitofrontal cortex (-0.94 ± 0.33%), insula (-0.37 ± 0.13%), and putamen (-0.41 ± 0.10%). No-exercise alone significantly (P < 0.005) reduced the neuronal response to high vs. control and low vs. control cues in the middle (-0.47 ± 0.15%) and inferior occipital gyrus (-1.00 ± 0.23%). Exercise reduced neuronal responses in brain regions consistent with reduced pleasure of food, reduced incentive motivation to eat, and reduced anticipation and consumption of food. Reduced neuronal response in these food reward brain regions after exercise is in line with the paradigm that acute exercise suppresses subsequent energy intake.

Acute exercise suppresses relative energy intake; however, it remains unclear whether this occurs in both men and women exposed to the same relative exercise treatment. Eleven healthy men (22 ± 2 years; 16% ± 6% body fat (BF); 26 ± 4 body mass index (BMI); 42.9 ± 6.5 mL·kg(-1)·min(-1) peak oxygen consumption ([Formula: see text]O(2peak))) and 10 healthy women (21 ± 2 years; 24 ± 2 BMI; 23% ± 3% BF; 39.9 ± 5.5 mL·kg(-1)·min(-1) [Formula: see text]O(2peak)) rested for 60 min or exercised on a cycle ergometer at 70% [Formula: see text]O(2peak) until 30% of total daily energy expenditure was expended (men, expenditure = 975 ± 195 kcal in 82 ± 13 min; women, expenditure = 713 ± 86 kcal in 84 ± 17 min) in a counterbalanced, crossover fashion. Appetite hormones and appetite ratings were assessed in response to each condition. Forty minutes after both conditions, ad libitum total and relative energy intake (energy intake minus energy cost of exercise) were assessed at a buffet meal. There was no significant sex or condition effect in appetite hormones (PYY(3-36), acylated ghrelin, insulin) and appetite ratings (hunger, satisfaction, fullness). Total energy intake in men was significantly higher (P < 0.05) in exercise and rest conditions (1648 ± 950, 1216 ± 633 kcal, respectively) compared with women (591 ± 183, 590 ± 231 kcal, respectively). Relative energy intake was significantly lower (P < 0.05) after exercise compared with rest in men (672 ± 827, 1133 ± 619 kcal, respectively) and women (-121 ± 243, 530 ± 233 kcal, respectively). These data highlight the effectiveness of acute exercise to suppress relative energy intake regardless of sex.

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 tak ing 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) partici pated in a double-blind, placebo-controlled, cross-over design. Peak aerobic capacity was measured twice using a continu ous, 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 ven tilation (-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 (r 2 < 0.20) and not significant. Shortterm 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 re sistance or diabetes who already have some degree of mitochondrial dysfunction remains to be determined.Key words: pre-diabetes, type 2 diabetes, exercise, biguanide.Résumé : Isolément, l'exercice physique et un médicament, la metformine, préviennent ou retardent l'apparition du dia bète de type 2. La metformine inhibe légèrement le complexe I de la chaîne respiratoire et peut avoir un effet sur la capa cité aérobie des individus qui font de l'exercice physique. Le but de cette étude est d'évaluer l'effet de la metformine sur la puissance aérobie maximale d'individus en bonne santé et sans troubles mitochondriaux. Six femmes et 11 hommes en bonne santé et de poids normal participent à une étude expérimentale à double insu avec groupe témoin et inversion des groupes. On mesure deux fois la puissance aérobie de pointe au moyen d'un test d'effort continu d'intensité croissante, une fois après 7 à 9 jours de consommation de metformine (dose terminale, 2 000 mg par jour) et l'autre fois, à sept jours d'écart, après avoir pris un placebo. L'ordre des séances d'évaluation est contrebalancé. Au moyen du programme d'analyse statistique R, on compare par des tests t pour mesures appariées les variables suivantes observées dans les deux conditions : la consommation d'oxygène (VO 2 ) de pointe, la fréquence cardiaque (HR), le débit ventilatoire (VE), le ratio d'échanges gazeux (RER), la p...

IMPORTANCE Postpartum weight retention increases lifetime risk of obesity and related morbidity. Few effective interventions exist for multicultural, low-income women. OBJECTIVE To test whether an internet-based weight loss program in addition to the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC program) for low-income postpartum women could produce greater weight loss than the WIC program alone over 12 months. DESIGN, SETTING, AND PARTICIPANTS A 12-month, cluster randomized, assessor-blind, clinical trial enrolling 371 adult postpartum women at 12 clinics in WIC programs from the California central coast between July 2011 and May 2015 with data collection completed in May 2016.INTERVENTIONS Clinics were randomized to the WIC program (standard care group) or the WIC program plus a 12-month primarily internet-based weight loss program (intervention group), including a website with weekly lessons, web diary, instructional videos, computerized feedback, text messages, and monthly face-to-face groups at the WIC clinics. MAIN OUTCOMES AND MEASURESThe primary outcome was weight change over 12 months, based on measurements at baseline, 6 months, and 12 months. Secondary outcomes included proportion returning to preconception weight and changes in physical activity and diet.RESULTS Participants included 371 women (mean age, 28.1 years; Hispanic, 81.6%; mean weight above prepregnancy weight, 7.8 kg; mean months post partum, 5.2 months) randomized to the intervention group or standard care group; 89.2% of participants completed the study. The intervention group produced greater mean 12-month weight loss compared with the standard care group. More participants in the intervention group than the standard care group returned to preconception weight by 12 months. 12-mo Outcomes Standard Care Group (n=197) Intervention Group (n=174) Between-Group Difference (95% CI) P Value Mean weight change, kg −0.9 (−1.7 to −0.1) −3.2 (−4.1 to −2.4) 2.3 (1.1 to 3.5) <.001 At or below preconception weight, No. (%) 36 (18.6) 57 (32.8) 14.2 (4.7 to 23.5) <.001 Change in physical activity, mean (95% CI), min/d −7.2