Sustained improvements in fitness and exercise tolerance in obese adolescents after a 12 week exercise intervention

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Obesity Research & Clinical Practice (2015) xxx, xxx—xxx

ORIGINAL ARTICLE

Sustained improvements in fitness and exercise tolerance in obese adolescents after a 12 week exercise intervention Megan L. Gow a,b,∗, Nancy van Doorn c,d, Carolyn R. Broderick c,d, Louise L. Hardy e, Mandy Ho a,b, Louise A. Baur a,f, Chris T. Cowell a,b,f, Sarah P. Garnett a,b,f,1 a

The Children’s Hospital at Westmead Clinical School, University of Sydney, Westmead, NSW 2145, Australia b Institute of Endocrinology and Diabetes, The Children’s Hospital at Westmead, Westmead, NSW 2145, Australia c School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia d The Children’s Hospital Institute of Sports Medicine, The Children’s Hospital at Westmead, Westmead, NSW 2145, Australia e NSW Physical Activity, Nutrition and Obesity Research Group (PANORG), School of Public Health, University of Sydney, NSW 2006, Australia f Kids Research Institute, The Children’s Hospital at Westmead, Westmead, NSW 2145, Australia Received 14 January 2015 ; received in revised form 30 March 2015; accepted 2 April 2015

KEYWORDS Aerobic fitness; Anaerobic threshold; Exercise tolerance; Adolescents; RESIST

Summary A 12 week exercise program was evaluated for its effect on aerobic fitness, anaerobic threshold, physical activity and sedentary behavior levels in obese insulin resistant adolescents post intervention and at follow up. 111 obese insulin resistant 10—17 year olds were recruited to a 12 month lifestyle intervention, known as RESIST. From months 4 to 6, adolescents participated in supervised exercise sessions twice per week (45—60 min/session). Aerobic fitness and anaerobic threshold were measured by gas analysis at baseline, 6 months (post intervention) and 12 months (follow up). Self-reported physical activity and sedentary behavior was measured using the CLASS questionnaire. At 6 months aerobic fitness and time to

∗ Corresponding author at: The Children’s Hospital at Westmead, Institute of Endocrinology and Diabetes, Locked Bag 4001, Westmead, NSW 2145, Australia. Tel.: +61 2 9845 3119; fax: +61 2 9845 3170. E-mail address: [email protected] (M.L. Gow). 1 Tel.: +61 2 9845 3152; fax: +61 2 9845 3170.

http://dx.doi.org/10.1016/j.orcp.2015.04.001 1871-403X/© 2015 Asian Oceanian Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.

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M.L. Gow et al. reach the anaerobic threshold had improved by 5.8% [95% CI: 0.8—11.3] and 19.7% [95% CI: 10.4—29.0], respectively compared with baseline. These improvements were maintained at 12 months. Compared to baseline, 6 month physical activity levels increased by 19 min/day [95% CI: 5—33] and screen time decreased by 49 min/day [95% CI: 23—74] but returned to baseline levels by 12 months. Improved fitness and anaerobic threshold can be sustained up to 6 months following completion of an exercise program possibly enhancing capacity to perform daily functional tasks. © 2015 Asian Oceanian Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.

Introduction

Methods and procedures

Adolescent obesity is a global public health concern associated with poor aerobic fitness and suboptimal physical activity levels [1,2]. This places obese adolescents at increased risk of cardiometabolic complications, including insulin resistance and type 2 diabetes [3]. Obesity, poor fitness, low physical activity levels and cardiometabolic complications are known to track into adulthood and predict premature death [4,5]. Therefore, effective interventions are necessary to achieve improved long-term health outcomes. Twelve week exercise intervention programs to treat obesity in adolescents have achieved improved aerobic fitness [6—9], weight related outcomes [6,9] and cardiometabolic risk factors [6—8] following the intervention. However, few studies examine the long-term sustainability of physiological improvements associated with an adolescent exercise program [10]. The anaerobic threshold is a useful predictor of aerobic fitness [11] as well as a measure of exercise tolerance [12] and is decreased in obese adolescents [13,14]. Poor exercise tolerance, as indicated by an early anaerobic threshold, is likely to have an effect on an obese adolescent’s ability to perform daily functional tasks. Exercise interventions can lead to improvements in the anaerobic threshold in adults [15]; however, this has not yet been described in adolescents. Hence the aim of this study was to examine the effect and sustainability of a 12 week exercise program on aerobic fitness, anaerobic threshold, physical activity and sedentary behavior in obese insulin resistant adolescents. We hypothesized that aerobic fitness, anaerobic threshold, physical activity and sedentary behavior levels would improve following a 12 week exercise intervention compared with baseline. We also hypothesized that positive effects would be sustained at follow up, 6 months from completion of the exercise intervention.

This paper presents secondary data analyses of a 12 month randomized control trial, known as RESIST, which examined the efficacy of two different diets to improve insulin sensitivity in adolescents with clinical features of insulin resistance and/or pre-diabetes treated with metformin. The study protocol [16] and results reporting weight outcomes at 6 and 12 months [17,18] have been previously published. The study was approved by the Human Research Ethics Committee of The Children’s Hospital at Westmead (07/CHW/12), Sydney South West Area Health, Western Zone (08/LPOOL/195) and Sydney South West Area Health Service, Royal Prince Alfred Hospital (08/RPAH/455). Written informed consent was sought from the parent and assent from the adolescent prior to enrolment in the study.

Participants The RESIST study recruited overweight and obese (International Obesity Task Force age-sex adjusted definitions [19]) 10—17 year olds with pre-diabetes and/or insulin resistance and at least one other clinical feature of insulin resistance [16]. Prediabetes was defined by the American Diabetes Association (impaired fasting glucose >5.6 mmol L−1 and/or impaired glucose tolerance >7.8 mmol L−1 ) [20] and insulin resistance was defined as a fasting insulin (pmol L−1 ) to glucose (mmol L−1 ) ratio greater than 20.

Exercise intervention Fig. 1 outlines the RESIST study exercise intervention timeline conducted at The Children’s Hospital at Westmead, Australia. In phase 1 (0—3 months), adolescents received standard physical activity advice during individual consultations at baseline, 2, 6 and 12 weeks. Advice was consistent with the Australian Government recommendations for children and adolescents which include reducing

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Figure 1 Timeline of RESIST study exercise intervention and measurement of related outcomes.

recreational screen time (ST) to ≤2 h per day and increasing incidental activity and active transport, with the aim of spending ≥60 min per day in moderate-to-vigorous intensity physical activity (MVPA) [21]. During phase 1, all adolescents underwent a pre-participation assessment by a sports physician (CRB) and identified risk factors for injury were addressed prior to commencement of the exercise program. In phase 2 (4—6 months), adolescents completed a 12 week supervised exercise program, which involved two 45—60 min training sessions per week with a qualified personal trainer at either a certified gym or local park at no cost to the families. Exercise programs were arranged in close proximity to the adolescent’s home in small groups of 2—6 study participants where possible or with siblings or friends. Sessions were aimed at familiarizing the adolescents with different types of exercise, including both aerobic and resistance activities of moderateto-vigorous intensity. A set program for sessions was not prescribed, giving the trainers flexibility to tailor activities to appeal to the group and make the sessions enjoyable for the adolescents. In addition, adolescents were encouraged to complete at least one home-based physical activity session per week. In phase 3 (7—12 months; maintenance phase), adolescents received standard physical activity advice consistent with the Australian Government recommendations [21] as in phase 1 and were encouraged to continue to participate in activities learned during the exercise intervention.

Measurements A medical review of each adolescent was conducted by the study physician at baseline, 3, 6, 9 and 12

months. At baseline, the physician collected demographic information (including ethnicity, parental education and income) and family medical history (including diabetes, overweight, polycystic ovarian syndrome, heart disease and hypertension). The physician also completed pubertal staging at baseline and 12 months by clinical examination or self-reports using Tanner drawings. Weight (kg) and height (cm) were measured by study nurses at baseline, 3, 6 and 12 months using standard procedures as previously described [16]. Body mass index (BMI; kg m−2 ) was calculated from age and sex specific reference values and expressed as a percentage of the 95th centile (BMI % 95th centile) [22]. Change in BMI z-score was not used as >86% of the adolescents had a BMI > 97th centile which is beyond the scope of the CDC 2000 reference data [23]. Body composition was measured using dual energy X-ray absorptiometry (DXA) (Prodigy, LunarGE, Madison, WI) equipped with propriety software version 13.6, at baseline, 3 and 12 months. Scans were analyzed using manufacturer recommended techniques. Fat free mass index (FFMI) was calculated (fat free mass height−2 ) [24]. Blood pressure was measured using an automated blood pressure monitor (Dinamap 1846 SX) with adolescents sitting at rest and z-scores were calculated from age, height and sex specific references [25]. An oral glucose tolerance test was performed after an overnight fast at baseline, 3 and 12 months [26] and whole body insulin sensitivity index (ISI) calculated using the Matsuda equation [27]. Fasting blood drawn at baseline, 3, 6 and 12 months was analyzed using standard techniques for glucose, insulin and blood lipids as previously described [16].

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M.L. Gow et al.

Aerobic fitness and anaerobic threshold were measured by an accredited exercise physiologist (NvD) using a Bruce treadmill protocol with gas analysis (Medgraphics CPX/D Breath-by-Breath Exchange system [Medical Graphics Corporation, MN] and the BreezeSuite Version 6.4.1 software program [Medical Graphics Corporation, MN]). Baseline fitness was assessed before the exercise intervention commenced (between 0 and 3 months) and reassessed post intervention (6 months) and at follow up (12 months). Aerobic fitness was recorded as VO2peak and time to fatigue. VO2peak was defined as the peak rate of oxygen consumption during the exercise test expressed relative to body weight (mL kg−1 min−1 ). The anaerobic threshold was defined as the point at which a systemic increase in the ventilatory equivalent for oxygen occurred without an increase in the ventilatory equivalent for carbon dioxide [28]. This point was determined independently by two trained exercise physiologists (NvD/MLG). Both time to reach the anaerobic threshold and relative VO2 (mL kg−1 min−1 ) at the anaerobic threshold were recorded. The exercise test was deemed to be maximal if the respiratory exchange ratio exceeded 1.15 [29], predicted maximal heart rate was reached or the adolescent could not continue due to physical exhaustion. Adolescents self-reported their typical time spent in a range of moderate-to-vigorous physical activities and sedentary behaviors, including ST activities, using the Children’s Leisure Activities Study Survey (CLASS) questionnaire [30] at baseline, 3, 6 and 12 months. From the CLASS questionnaire, total time spent in daily MVPA and ST was calculated and data could be categorized according to national recommendations for daily MVPA (≥60 min) and ST (≤2 h) [30].

Statistical analysis Data were assessed for normality and analyzed using IBM® SPSS Statistics Software for Windows, version 20 (SPSS Inc., Chicago, IL). There were no differences between diet groups at any time point during the study for weight, body composition, cardiometabolic, aerobic fitness, anaerobic threshold, physical activity and sedentary behavior outcomes, therefore results for diet groups were pooled for all analysis. Sex differences between continuous data were examined using independent sample t tests for normally distributed data, Mann—Whitney tests for non-parametric data and Chi-squared tests for categorical data. Correlations between variables were assessed by Pearson’s correlation coefficient,

Spearman’s rho or Kendall’s tau for normally distributed and non-parametric data as appropriate. Consistent with an intention-to-treat approach, all available data for participants as randomly assigned, were retained. Continuous data were assessed using linear mixed models with an unstructured covariance structure and Bonferroni adjusted post hoc tests were used to test for the effect of time (baseline, 3, 6, 12 months) for adolescents with at least one outcome measure. Nonparametric data were log or square root transformed as appropriate. Sex and pubertal status were tested in the model but were not significant for aerobic fitness, physical function, physical activity or sedentary behavior outcomes hence results have been reported as unadjusted models and expressed as estimated marginal means with standard error of the mean for normal data or geometric marginal means with 95% confidence intervals for non-parametric data. Binary data were analyzed using generalized estimating equations with an unstructured correlation structure to test for the effect of time (baseline, 3, 6, 12 months) and expressed as estimated marginal means with standard error of the mean. Completer analysis examining adolescents who had both baseline and 12 month fitness test measurements (n = 81) and subgroup analysis examining adolescents who attended the exercise intervention (n = 100) were also conducted. These results were not different from intention-to-treat analysis therefore results from completer analysis and subgroup analysis are not reported.

Results Baseline characteristics Baseline characteristics of the participants are shown in Table 1. There were no significant differences in baseline aerobic fitness and anaerobic threshold between boys and girls. Baseline ST was significantly higher among boys (mean difference [MD] ± SD: 57.3 ± 27.1 min/day), and only one boy met the recommendation for ST compared with 18 girls. There were more pre-pubertal boys than girls (42% versus 23%) at baseline and boys were taller and heavier. Unadjusted values showed that boys had less total body fat % compared with girls (MD: 4.4 ± 1.0%), while the girls had lower blood pressure and higher ISI compared with the boys. Greater aerobic fitness and anaerobic threshold was associated with lower BMI % 95th centile, blood pressure and body composition outcomes (correlations −0.170 to −0.599), Table 2. Additionally, there was a weak, but significant positive

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Sustained fitness gains in adolescents Table 1

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Baseline characteristics of adolescents in the RESIST study. Boys (n = 45)

Girls (n = 66)

All (n = 111)

13.3 (1.7) 19 (42)

13.0 (2.0) 15 (23)

13.1 (1.9) 34 (31)

0.465 0.033

96.9 (20.1) 166.9 (12.6) 34.5 (4.7) 136.8 (21.1)

86.5 (19.0) 159.4 (9.2) 33.8 (5.7) 129.2 (20.6)

90.7 (20.0) 162.4 (11.3) 34.1 (5.3) 132.3 (21.1)

0.006 0.001 0.483 0.063

Body composition measured by DXAa Total body fat (kg) 43.3 (9.6) Total body fat (%) 44.9 (5.1) Total fat free mass (kg) 50.6 (12.7) Fat free mass index 1.8 (0.3)

42.8 (11.7) 48.9 (4.9) 40.7 (8.1) 1.6 (0.2)

43.0 (10.8) 47.6 (5.3) 44.7 (11.3) 1.7 (0.3)

0.816 <0.001 <0.001 <0.001

Cardiometabolic risk factors SBP z score DBP z score Insulin sensitivity index Triglycerides (mmol L−1 )## HDL-C (mmol L−1 )

(1.22) (0.87) (0.61) [0.98—1.27] (0.22)

0.49 0.73 1.48 1.09 1.05

(1.27) (0.81) (0.69) [0.98—1.21] (0.21)

0.73 0.90 1.38 1.10 1.05

(1.28) (0.86) (0.67) [1.01—1.19] (0.21)

0.014 0.007 0.041 0.742 0.935

Aerobic fitness and anaerobic threshold 24.7 (5.4) VO2peak (mL kg−1 min−1 )b Time to fatigue (min:s)c 8:37 (1:38) 5:35 (2:26) Time to reach AT (min:s)d VO2 at AT 17.8 [16.4—19.2] (mL kg−1 min−1 )d##

23.3 8:07 4:54 17.3

(5.3) (1:44) (2:40) [16.1—18.5]

23.9 8:19 5:11 17.5

(5.4) (1:42) (2:35) [16.6—18.4]

0.174 0.143 0.180 0.499

Age, yr Pre-pubertal (Tanner stage 1—2), n (%) Body weight (kg) Height (cm) BMI (kg/m2 ) BMI % 95th centile

1.09 1.17 1.22 1.12 1.05

Physical activity and sedentary behavior MVPA (min per day)e## 91 [72—113] Met MVPA 32 (71) recommendation ≥ 60 min daily, n (%)e# 4.4 [3.7—5.0] ST (h per day)f## Met ST 1 (2) recommendation ≤ 2 h daily, n (%)f#

75 [64—87] 43 (67)

82 [71—93] 75 (69)

3.3 [2.8—3.9] 18 (28)

3.7 [3.3—4.1] 19 (18)

P-value

0.139 0.667

0.015 <0.001

SBP, systolic blood pressure; DBP, diastolic blood pressure; HDL-C, high density lipoprotein cholesterol; AT, anaerobic threshold; MVPA, moderate to vigorous physical activity; ST, screen time. Mean (SD) presented from independent sample t tests unless otherwise specified. Bold P value indicates significant difference between boys and girls. Missing data: a 1 girl; b 2 boys, 4 girls; c 2 boys, 3 girls; d 2 boys, 7 girls; e 2 girls; and f 1 boy, 2 girls. # Chi squared test. ## Geometric mean [95% CI].

association between both VO2peak and relative VO2 at the anaerobic threshold and ISI, Table 2. ST was inversely correlated with time spent in MVPA (tau = −0.164, P = 0.012) and positively correlated with age (rho = 0.226, P = 0.018), total body fat (rho = 0.209, P = 0.031) and fat free mass (rho = 0.207, P = 0.032).

Weight, body composition and cardiometabolic risk factors Of those who were pre-pubertal at baseline, 42% of boys and 80% of girls had entered puberty by 12 months. BMI % 95th centile and total body fat

% were significantly lower and fat free mass was significantly higher at 12 months compared with baseline, Table 3. There was a small but significant decrease in FFMI in the girls prior to the exercise intervention (baseline, estimated marginal mean ± SE: 1.59 ± 0.03, 3 months: 1.56 ± 0.03, P = 0.015). By 12 months, FFMI was not significantly different to baseline levels in the girls (12 months: 1.60 ± 0.03, P > 0.999) but was significantly higher than baseline in the boys (baseline: 1.79 ± 0.04, 12 months: 1.87 ± 0.04, P < 0.001). ISI improved over the 12 month intervention in both boys and girls. Between baseline and 12 months high density lipoprotein cholesterol (HDL-C) increased and

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SBP, systolic blood pressure; DBP, diastolic blood pressure; AT, anaerobic threshold. r values indicates Pearson’s correlation coefficient for normally distributed data, rho value indicates Spearman’s correlation coefficient for not normally distributed data. * Correlation is significant at the 0.05 level. ** Correlation is significant at the 0.01 level.

0.193* 0.118 0.077 0.201* −0.200* −0.095 −0.106 −0.134 −0.213* −0.221* −0.151 −0.184 −0.222* −0.170* −0.140 −0.200* −0.453** −0.497** −0.317** −0.349** r r r rho

−0.421** −0.495** −0.309** −0.312**

−0.599** −0.558** −0.424** −0.528**

−0.255** −0.141 −0.174 −0.321**

SBP z score Fat free mass index Total body fat (%) BMI % 95th centile

Total body fat (kg)

Total fat free mass (kg)

diastolic blood pressure (DBP) z score decreased. There were no significant differences between baseline and 12 month measures of triglycerides or systolic blood pressure (SBP) z score.

VO2peak (mL kg−1 min−1 ) Time to fatigue (min:s) Time to reach AT (min:s) VO2 at AT (mL kg−1 min−1 )

Table 2

Baseline associations between body composition, cardiometabolic, aerobic fitness and anaerobic threshold measures.

DBP z score

Insulin sensitivity index

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Aerobic fitness Aerobic fitness, expressed as VO2peak (mL kg−1 min−1 ) and time to fatigue, did not differ between boys and girls at baseline or post intervention. Boys were fitter than the girls at follow up (VO2peak , MD [95% CI]: 2.72 [0.02—5.42] mL kg−1 min−1 P = 0.048; exercise time, MD [95% CI]: 1:03 [0:06—2:01] P = 0.029). VO2peak (mL kg−1 min−1 ) and time to fatigue, improved between baseline and 6 months by 5.9% (P = 0.018) and 8.6% (P = 0.015) respectively in all participants and remained significantly improved compared with baseline at 12 months by 6.7% (P = 0.036) and 6.4% (P < 0.001) respectively (Fig. 2A and B). Improved VO2peak (mL kg−1 min−1 ) over the 12 months was inversely correlated with change in total body fat % (r = −0.240, P = 0.030) and positively correlated with time spent in MVPA at 12 months (r = 0.267, P = 0.023). There were no other significant associations between changes in aerobic fitness and changes in weight, body composition, cardiometabolic risk, physical activity or sedentary behavior related outcomes. Maximal heart rate (baseline: 184.6 ± 15.7, 6 month: 185.2 ± 15.7, 12 month: 185.3 ± 14.0) and respiratory exchange ratio at the end of the test (baseline: 1.17 ± 0.13, 6 month: 1.14 ± 0.13, 12 month: 1.18 ± 0.23) did not differ significantly at any time point during the study.

Anaerobic threshold Anaerobic threshold measures did not differ between the boys and girls at baseline or follow up. However, post intervention, boys had an increased anaerobic threshold compared with the girls (VO2 at anaerobic threshold, MD [95% CI]: 2.13 [0.03—4.23] mL kg−1 min−1 P = 0.048; time to reach anaerobic threshold, MD [95% CI]: 1:06 [0:07—2:06] P = 0.028). VO2 (mL kg−1 min−1 ) at the anaerobic threshold and time to reach the anaerobic threshold, improved between baseline and 6 months, by 7.4% (P = 0.026) and 19.7% (P < 0.001), respectively and remained significantly improved compared with baseline at 12 months, by 8.6% (P = 0.009) and 24.1% (P < 0.001) respectively (Fig. 2A and B). VO2 at the anaerobic threshold increased from 73.5% of VO2peak at baseline to 74.8% at 12 months. There were no significant associations between changes

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Table 3 Change in weight, body composition and cardiometabolic outcomes at 3, 6 and 12 months compared with baseline. 3 month (n = 111)

P-value

6 month (n = 111)

BMI % 95th centile

−12.54 (3.03)

<0.001

−16.08 (3.86)

Body composition Total body fat (kg) Total body fat (%) Total fat free mass (kg) Fat free mass index

measured by DXA −1.75 (0.27)

<0.001

—

−1.18 (0.24)

<0.001

−0.11 (0.24) −0.02 (0.01)

Cardiometabolic risk factors SBP z score −0.31 (0.14) DBP z score −0.20 (0.10) Insulin 0.28 (0.08) sensitivity index 1.06 [0.98—1.15] Triglycerides (mmol L−1 )# HDL-C 0.02 (0.02) (mmol L−1 )

P-value

12 month (n = 111)

P-value

−13.77 (3.21)

0.003

—

−0.17 (0.72)

>0.999

—

—

−2.15 (0.51)

<0.001

>0.999

—

—

3.24 (0.37)

<0.001

0.02

—

—

0.04 (0.01)

<0.001

−0.12 (0.12) −0.20 (0.10) 0.21 (0.08)

>0.999 0.323 0.031

0.165 0.312 <0.001

−0.55 (0.12) −0.34 (0.20) —

>0.999

1.09 [1.00—1.19]

>0.999

0.03 (0.02)

0.001

<0.001 0.004 —

>0.999 0.538

1.03 [0.94—1.13] 0.07 (0.02)

>0.999 0.001

SBP, systolic blood pressure; DBP, diastolic blood pressure; HDL-C, high density lipoprotein cholesterol. Mean difference (SEM) based on estimated marginal means from linear mixed models unless otherwise specified. Bold P value indicates significant difference compared with baseline. # Geometric mean [95% CI].

in anaerobic threshold and changes in weight, body composition, cardiometabolic or physical activity related outcomes.

Physical activity and sedentary behavior Daily MVPA significantly increased by 19 min (P = 0.028) and ST significantly decreased by 49 min (P = 0.004) at 6 months compared with baseline; however, these improvements were not sustained at 12 months (Fig. 2C). There were no significant temporal changes in the proportion (approximately 70%) of adolescents meeting the daily recommendation for physical activity (Fig. 2D). However, there was a significant increase in the proportion of those meeting the sedentary behavior recommendation at 3 and 6 months compared with baseline (P = 0.008 and P = 0.007, respectively) but this was not sustained at 12 months.

Discussion Determining the efficacy and sustainability of exercise programs to improve both aerobic fitness and

exercise tolerance in obese adolescents is important. To our knowledge, this is the first study to examine the effect of a short-term exercise intervention on anaerobic threshold, an indicator of exercise tolerance, in obese insulin resistant adolescents. Additionally, this study examines, for the first time in this population, the sustainability of improved fitness and exercise tolerance up to 6 months following completion of the intervention.

Anaerobic threshold Improved anaerobic threshold indicates increased exercise tolerance and suggests that, after completion of the exercise intervention, adolescents were able to perform more work at submaximal levels (i.e. without requiring anaerobic energy sources) before feeling fatigued. Therefore, we speculate that functional tasks, such as walking to the bus stop and climbing stairs at school, should become easier. An increase in exercise tolerance may also facilitate continued or increased participation in physical activity, including school sport, which may assist weight management and improved cardiometabolic outcomes.

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Figure 2 Changes in aerobic fitness, anaerobic threshold, physical activity and sedentary behavior throughout the RESIST study. (A) VO2peak and VO2 at anaerobic threshold at baseline, 6 and 12 months. (B) Time to fatigue and time to reach anaerobic threshold at baseline, 3 and 12 months. (C) Daily minutes spent in moderate to vigorous physical activity and screen time. (D) % meeting physical activity and sedentary behavior recommendations. P values indicate difference compared with baseline.

Aerobic fitness The current study demonstrates improved aerobic fitness following the 12 week exercise intervention, which was sustained 6 months after completion of the intervention. The observed changes in VO2peak , from 23.8 mL kg−1 min−1 at baseline to 25.4 mL kg−1 min−1 at follow up were of a similar magnitude to results from other studies in obese adolescents [6—8]. We also noted a sex difference in aerobic fitness as previously reported [31]; boys had a higher aerobic fitness compared with the girls. Nevertheless, there is a strong indication that the adolescents in the current study had poor baseline aerobic fitness which remained poor throughout the study. Longitudinal studies in young people (6—18 years) suggest that VO2peak is stable in boys at approximately 48 mL kg−1 min−1 but declines with age in girls from 45 to 35 mL kg−1 min−1 [31]. In addition, the estimated thresholds associated with increased cardiovascular risk factor clustering in adolescents are <33.0 mL kg−1 min−1 for girls and <46.0 mL kg−1 min−1 for boys [3]. Greater gains in aerobic fitness than what we observed in this study are likely to be needed for cardiometabolic protection. Alternate strategies such as highintensity interval training may be more successful in

improving aerobic fitness in the short-term as has been observed in adults [32] and adolescents [33]. Additionally, there is evidence that genetic factors play an important role in determining an individual’s response to an exercise program [34,35]. Individual tailoring of exercise interventions depending on genetic suitability may therefore be possible in future studies.

Physical activity and sedentary behavior Self-reported improvements in daily physical activity and sedentary behavior following the exercise intervention were not maintained 6 months after the intervention. Although the health benefits of regular physical activity are well described [1], an improvement in aerobic fitness may be more clinically important. The current study demonstrates that, in the absence of sustained improvements in self-reported physical activity and sedentary behavior, a short-term exercise intervention can lead to sustainable gains in aerobic fitness and exercise tolerance.

Cardiometabolic complications and body composition Poorer fitness levels are associated with increased metabolic risk [3]. However, in our study, aerobic

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Sustained fitness gains in adolescents fitness and anaerobic threshold did not show clear correlations with blood pressure, insulin sensitivity or blood lipids. The lack of association in our study may be due to the severity of obesity and poor fitness among our study cohort. It also highlights the complexity of obesity and related complications. Body composition measures improved in both girls and boys over the 12 month lifestyle intervention. Improved body composition in the boys may be partly attributable to pubertal change [36]; however, girls normally increase their total body fat % during puberty [36], suggesting a beneficial effect of the lifestyle intervention.

Limitations There are a number of limitations to our study including lack of control group and all participants receiving an exercise and dietary intervention with metformin therapy. Due to the importance of an exercise component as part of a lifestyle intervention for obesity treatment, we considered it unethical not to offer the exercise program to all. The dietary intervention and metformin therapy are unlikely to have had a direct effect on aerobic capacity [37] but can result in weight loss [38,39] which may affect relative VO2 measures. Expressing aerobic fitness relative to fat free mass is preferable [40] but was not possible in our study as body composition was not measured post exercise intervention. Nevertheless, the study indicated an increase in time taken to reach VO2peak and time to reach anaerobic threshold, supporting an increase in aerobic capacity in our study cohort. Another limitation was that the exercise intervention was delivered by external contractors and was not standardized; however, this allowed flexibility of the exercise intervention to suit each group. Compliance to the exercise intervention was not measured; anecdotally, attendance varied widely. Motivation to achieve improved results on subsequent exercise tests may have affected results. However, no differences between baseline, post intervention and follow up measures of maximal heart rate or respiratory exchange ratio suggests a consistent level of effort at each test. Finally, the use of self-report assessment to estimate daily physical activity and sedentary behavior has known limitations [41], hence it is possible that physical activity levels were not accurately reported in this study.

Conclusions Our results demonstrate that a 12 week exercise program, can improve aerobic fitness, anaerobic

9 threshold, physical activity and sedentary behavior in obese insulin resistant adolescents. Additionally, gains in aerobic fitness and anaerobic threshold were maintained 6 months following completion of the program. Better anaerobic threshold indicates increased exercise tolerance which may result in improved capacity to undertake activities of daily living. This may lead to greater quality of life and assist in long-term weight management by facilitating further physical activity participation. Aerobic fitness levels, though improved, remained low throughout the study warranting further research into the optimal type, frequency and intensity of exercise interventions to achieve better aerobic fitness gains in obese adolescents.

Conflicts of interest None declared.

Acknowledgements BUPA Foundation Australia Pty Limited, Diabetes Australia Research Trust and Heart Foundation Australia (#G08S3758) funded the RESIST study. MLG is supported by a University of Sydney Australian Postgraduate Award. SPG was supported by an NHMRC Clinical Research Fellowship (#457225) 2007—2010 and an Early Career Research Fellowship, Cancer Institute NSW 2011—2013. We would like to acknowledge FitnessFirst for use of gym facilities, the physical trainers who volunteered their time to train the participants and Alphapharm for providing metformin.

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Please cite this article in press as: Gow ML, et al. Sustained improvements in fitness and exercise tolerance in obese adolescents after a 12 week exercise intervention. Obes Res Clin Pract (2015), http://dx.doi.org/10.1016/j.orcp.2015.04.001