Obesity has emerged as a significant pediatric disorder in the United States (2
). The targeted approaches for improving these trends among children and adolescents have been lifestyle modification (diet, exercise, and behavior) and, more recently, pharmacotherapy, including the insulin-sensitizing drug metformin (22
). We recently reported that 6 months of intensive diet and exercise with metformin resulted in reduced adiposity, and those on diet and exercise alone demonstrated improvements in markers related to inflammation (IL-6, hsCRP), thrombosis (fibrinogen), and IHF contents in obese children with normal glucose tolerance (10
). In these studies, the addition of metformin did not show added benefit compared with lifestyle intervention alone. These improvements were, however, modest, and subjects did not normalize these outcomes as compared with lean age-matched controls.
In the present study, we observed a modest increase in CRF as measured by
in the majority of children (n
= 10 of 16) participating in 6 months of lifestyle modification with dietary counseling and structured exercise. In agreement with our previous findings, the addition of metformin did not have additional effects above lifestyle modification alone on CRF. This suggests that in adolescents with simple obesity (obesity without the presence of IGT, impaired fasting glucose, or type 2 diabetes where the use of metformin is clinically indicated), lifestyle intervention alone could limit the need for metformin, which should have clinical implications because the effect of long-term use of pharmacotherapy at such an early age is unknown. Subjects who increased
during the 6-month intervention had significant reductions in weight, %BF, and BMI, as well as more favorable changes in adiponectin, IL-6, and blood glucose (). It is interesting to note that these favorable changes occurred with an average of only one supervised exercise setting per week.
Exercise training is vital to the prevention of CVD. In adolescence, fitness has been shown to independently predict body fatness (16
) as well as physical activity behavior in adulthood (25
). Moreover, high levels of fitness carried into adulthood are strongly associated with decreased morbidity and mortality attributable to CVD, independent of body fatness (6
). According to National Heath and Nutrition Examination Survey data,
is lower in overweight–obese adolescents age 12–19 yr old compared with their lean counterparts (32
). In agreement with National Heath and Nutrition Examination Survey data, the objectively measured values for
obtained by subjects in the present study are considerably lower than values reported in comparable samples of lean pubertal adolescents (34
). Although we observed an encouraging 12.5% mean increase in
after 6 months of an intensive exercise program, the fitness of the subjects remained relatively low ().
The finding that metformin provided no additional benefits to improving aerobic fitness above and beyond diet and structured exercise alone is not surprising. However, metformin has been shown to have an inhibitory effect on complex I of the electron transport chain (5
), suggesting that maximal exercise capacity may be lower when the drug is taken concomitantly with exercise training. Studies in adults suggest either no effect (21
) or a minor negative effect of metformin on exercise capacity (~3% decrease in
The observed changes in
during the intervention were not likely affected by changes in chronological age. Cross-sectional and longitudinal data from Armstrong and Welsman (1
) suggest that
increases linearly with age in both boys and girls beginning around the age of 10. However, when expressed relative to body mass,
remains fairly constant across age in boys but tends to decrease by ~4.0–5.0 mL·kg−1
in girls during adolescence due in part to an increase in inert fat tissue. These factors probably did not affect our findings, given that the majority of subjects (n
= 10), including pubertal females, increased
by ~4.0 mL·kg−1
during the study.
Improvements in fitness in the present study were associated with decreased adiposity (weight, BMI, and %FM; ), whereas no improvement in
was associated with weight maintenance. The role of physical activity in weight loss is well documented in adults (11
), particularly because aerobic exercise is effective means for inducing a caloric deficit and stimulating fat oxidation both during and after exercise. Although we were not able to quantify exercise intensity, it is plausible that subjects who increased
also performed higher intensity exercise sessions. Compared with low- to moderate-intensity exercise, interventions that incorporate higher intensity exercise bouts seem to lead to greater fat loss, even when sessions are calorically equated (18
Evidence from adult studies suggests a role of physical activity in lowering blood markers related to inflammation. The present study examined the effects of improving fitness on IL-6 and hsCRP and observed a trend for lower concentrations of the proinflammatory cytokine IL-6 but not hsCRP. Few studies have examined the effects of exercise on IL-6 in youth. Cross-sectional data suggest that IL-6 concentrations are higher in sedentary compared with active adolescent girls (19
). Balagopal et al. (3
) reported a significant decrease in IL-6 after a 3-month lifestyle intervention in obese adolescents aged 14–18. Other studies have reported no change in IL-6 after exercise intervention. The interaction between physical activity, IL-6, and adiposity is complex and requires further investigation.
Improved fitness was also associated with a significant increase in adiponectin concentrations as well as a trend for decreased fasting glucose levels. Both outcomes indicate improved insulin sensitivity. It is well known that exercise training results in improved insulin sensitivity but seems to have a transient effect that lasts between 24 and 48 h after the last exercise bout (17
). Adiponectin levels are associated with improved insulin sensitivity in adults, but the role of exercise in modulating circulating adiponectin levels is not clear in children or adolescents. Again, further study will be necessary to elucidate these mechanisms, specifically the manner in which exercise, weight loss, and nontraditional markers of insulin sensitivity (i.e., adiponectin) interact.
The nonsignificant change we observed in IHF during 6 months of DE or DEM may have been a statistical power issue due to such a small sample of adolescents. In our recent randomized controlled trial (10
), which includes a much larger cohort of children (including subjects in the present study), we observed a trend (P
= 0.09) for decreased IHF in the pubertal DE group but not the DEM group.
This study has some limitations: daily physical activity as measured by pedometer step count was not obtained at baseline; the sample size in each group was small, limiting our availability to analyze gender and pubertal age differences; the study was controlled but did not include placebo; and the intervention was of a relatively short duration (6 months). However, it also has important strengths, including the use of a community YMCA exercise program, frequent dietary counseling, and the measurement of body fatness,
, inflammatory factors, and CHO metabolism before and after the intervention.