M ET ABOL I SM CL IN I CA L A N D E XP E RI ME N TAL 6 3 ( 2 0 14 ) 42 2–4 30

Available online at www.sciencedirect.com

Metabolism www.metabolismjournal.com

The one year exercise and lifestyle intervention program KLAKS: Effects on anthropometric parameters, cardiometabolic risk factors and glycemic control in childhood obesity Susann Blüher a,⁎, David Petroff a, b , Antje Wagner c , Katja Warich c , Ruth Gausche d , Thorsten Klemm e , Mario Wagner f , Alexandra Keller d, g a

Leipzig University Medical Center, IFB AdiposityDiseases, Philipp-Rosenthal-Str. 27, 04103 Leipzig, Germany Center for Clinical Studies, University of Leipzig, Härtelstrasse 16 – 18, 04107 Leipzig, Germany c KLAKS e.V., Lessingstrasse 2, 04109 Leipzig, Germany d CrescNet gGmbH, University of Leipzig, Philipp-Rosenthal-Str. 27b, 04103 Leipzig, Germany e MVZ Labor Dr. Reising-Ackermann & Colleagues, Strümpellstraße 40, 04289 Leipzig, 04289, Leipzig, Germany f Gesundheitssportverein Leipzig e.V., Lessingstrasse 2, 04109 Leipzig, Germany g Pediatric Medical Center, Johannisplatz 1, 04103 Leipzig, Germany b

A R T I C LE I N FO Article history:

AB S T R A C T Objective. Regular physical exercise within structured lifestyle programs may improve

Received 4 September 2013

weight status and minimize metabolic risk factors in childhood obesity. The aim of this

Accepted 22 November 2013

study was to evaluate the effect of the one-year combined physical exercise/lifestyle program KLAKS on anthropometric and metabolic parameters and glycemic control in

Keywords:

childhood obesity.

Obesity therapy

Materials and Methods. 142 overweight/obese (BMI > 90th percentile) candidates

KLAKS program

(7–18 years) were enrolled, 115 participants completed the program. Anthropometrics and

Childhood obesity

biochemical parameters were obtained at beginning and completion. An oral glucose

Metabolic syndrome

tolerance test (OGTT) was performed in a subgroup of participants. Course of glucose and

Oral glucose tolerance test

insulin levels within OGTT was correlated with several parameters and is reported here for those who completed the program. Results. The mean standard deviation scores (SDS) decreased significantly for BMI, waist circumference, waist-to-height ratio (WHtR) and percentage body fat (all p ≤ 0.01). Improved metabolic risk markers included mean glucose levels within an OGTT at follow-up compared to baseline (p < 0.0001) and HbA1c (p = 0.05) as well as indications of improvement for gamma-glutamyl-transferase and free fatty acids.

Abbreviations: ALAT, alanine aminotransferase; ASAT, aspartate aminotransferase; BF, body fat; BMI, body mass index; FI, fasting insulin; GGT, gamma glutamyl transferase; HDL, high density lipoprotein cholesterol; HOMA-IR, homeostasis model assessment of insulin resistance; ITT, intend to treat; KLAKS, Concept Leipzig: Adiposity therapy for school aged children; LDL, low density lipoprotein cholesterol; OGTT, oral glucose tolerance test; PP, per protocol; SDS, standard deviation score; SE, standard error; UA, uric acid; WHtR, waist to height ratio; WHR, waist to hip ratio. ⁎ Corresponding author: Leipzig University Medical Center, IFB Adiposity Diseases, Philipp-Rosenthal-Str. 27, 04103 Leipzig, Germany. Tel.: +49 341 97 25 035; fax: +49 341 97 26 329. E-mail address: [email protected] (S. Blüher). 0026-0495/$ – see front matter © 2014 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.metabol.2013.11.016

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Conclusions. The one-year combined exercise/lifestyle program KLAKS significantly improves markers of obesity and glycemic control. Impaired cardiometabolic risk markers, even subclinical, are also favorably influenced by program participation. © 2014 Elsevier Inc. All rights reserved.

1.

Introduction

Childhood overweight and obesity are worldwide health problems [1]. Prevalence rates have reached very high levels during the past decades [2], although there seems to be a trend towards stabilization at a still alarmingly high level [3,4]. Many obese children and adolescents already present with features of the metabolic syndrome, including disturbed glucose metabolism, dyslipidaemia, elevated transaminases, nonalcoholic fatty liver disease and others [5–10]. Especially abdominal obesity, defined as increased waist circumference, is associated with increased risk for cardiometabolic comorbidities and the metabolic syndrome already in childhood [11,12]. Thus, early and effective treatment of childhood obesity and prevention of comorbidities are essential, and regular physical activity and the avoidance of sedentary habits play an important role not only for the stabilization or reduction of body weight but also for the avoidance of associated cardiometabolic comorbidities and for psychosocial well-being [13]. A recent guideline on prevention of type 2 diabetes in adults provides clear recommendations: Even a modest change in lifestyle that includes adopting a healthy diet, increasing physical activity and maintaining a healthy body weight, may effectively prevent the risk for diabetes later in life, and these results have since been the basis for worldwide prevention programs [14]. Current pediatric guidelines recommend at least 60, or preferably 90 and more minutes of physical activity per day, however, this amount is reached only by a small number of children [13]. The optimal therapeutic intervention to reduce (abdominal) obesity and cardiometabolic risk factors in childhood obesity is largely unknown, and available studies that have investigated the impact of different exercise regimens or the “optimal” exercise modality are scarce to date [15]. The aim of the present study is to evaluate the effects of the one year combined exercise/lifestyle intervention (KLAKS program) on anthropometric parameters and body composition, glycemic control and cardiometabolic risk markers in childhood obesity.

2.

Materials and Methods

2.1.

Participants

ipants were also invited to participate in the KLAKS program to facilitate lifestyle changes within the family. Written informed consent was obtained from all parents or guardians. The study protocol was approved by The Medical Review Board (see below). The entire study was conducted in accordance with the Declaration of Helsinki.

2.2.

The intervention program KLAKS (Concept Leipzig: adiposity therapy for school-aged children) is a therapy program for obese children and adolescents. The program has been certified and approved by the German Medical Review Board of the Statutory Health Insurance Funds as well as by the German Association of Childhood Obesity (AGA, [17]). The one year lifestyle intervention is mainly based in increased physical activity (150 min/week) and consists of several modules: - A total of 39 physical exercise sessions per intervention year (90 min/week of supervised exercise by certified trainers and an additional 60 min/week of independent free use of the sports facilities, tailored to three age groups - Classes with diet counseling and on the preparation of healthy meals (60 min each), tailored to three age groups (14 per intervention year) - Classes with psychological coaching/support (90 min each), tailored to three age groups (10 per intervention year) - Classes on medical background of obesity (60 min each), tailored to three age groups (3 per intervention year) - Classes for parents on diet counseling and preparation of healthy meals (60–90 min each, 7 per intervention year) - Classes for parents on physical education and exercise (60–120 min each, 6 per intervention year) - Parent–teacher conferences (7 per intervention year, 60 min each) [18]. The aim of the intervention is to prevent a further increase in BMI-SDS, to improve physical and mental well-being as well as to diminish metabolic and/or cardiovascular co-morbidities within one year of intervention.

2.3.

Children and adolescents aged 7–18 years with overweight (BMI > 90th percentile) and accompanying comorbidities (impaired glucose tolerance, features of the metabolic syndrome or a family history (siblings or parents) for obesity/type 2 diabetes) or obesity (BMI > 97th percentile) according to German reference percentiles [16] were eligible for program participation. In addition, overweight siblings of obese partic-

Intervention

Physical exercise

The physical exercise module within the KLAKS-program consists of a total of 90 mandatory and supervised minutes of physical training per week (see above). The entire exercise training is performed at a local sports center (Gesundheitssportverein Leipzig e.V.). All exercise sessions are by appointment and are directly supervised and guided by licensed physical education instructors. An additional 60 min/week are performed according to the manual. The 39 physical

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exercise sessions per intervention year are divided into resistance and endurance training according to the manual. For endurance exercise, training is performed with treadmills or stationary bikes. Resistance exercise is performed with special equipment for children taller than 125 cm (Gymboy TECA®). Training sessions includes chest press, leg press, leg extension, leg flexion, latissimus dorsi pull down, rowing, biceps curl, triceps extension with stack weight equipment. Participants exercise in circles, aiming to reach 8–12 repetitions each per training session.

2.4.

Measurements

2.4.1.

Clinical and anthropometric data

At baseline and after the intervention year, a detailed medical history was obtained, and a physical examination was performed on all participants to exclude any concomitant disease interfering with program participation. For anthropometric measurements, all children were assessed barefoot and only wearing light underwear. Body height was measured by the digital stadiometer “Dr. Keller III” (Günter, Tauscha, Germany; precision ± 2 mm), and body weight was determined by a digital scale (SECA®-scale, Vogel & Halke, Hamburg, Germany; precision ± 100 g) as previously described [19]. Body mass index (BMI) was calculated by the formula: weight in kilograms divided by the square of height in meters. BMI data were standardized to age and sex of the children applying German reference data [16] and were calculated as BMI-SDS according to the LMS method [20]. The BMI-SDS provides a normalized measurement for the degree of overweight or obesity. By applying the LMS method, it is assumed that BMI data of each age group are normally distributed [20]. A cut off ≥1.28 SDS (90th centile) classifies overweight and a cut off ≥ 1.88 SDS (97th centile) classifies obesity in children [16]. Waist and hip circumferences were measured with a flexible, non-elastic band. Waist circumference was defined as the smallest abdominal girth between the lowest rib and the upper anterior iliac spine, and hip circumference was measured horizontally at the maximal buttock circumference [21]. Waist-to hip ratio (WHR) was calculated by the formula: waist circumference in centimeters divided by hip circumference in centimeters. Waist-to height ratio (WHtR) was calculated by the formula: waist circumference in centimeters divided by body height in centimeters [21]. Percentage of body fat content was calculated based on measurements of skinfolds, all measured in triplicates using a caliper (Holtain skinfold caliper, Crosswell, UK) and averaged. The skinfold thickness equation for boys was: body fat (%) = 0.783 × (subscapularis skinfold thickness + triceps skinfold thickness in mm) + 1.6; for girls: body fat (%) = 0.546 × (subscapularis skinfold thickness + triceps skinfold thickness in mm) + 9.7 [22].

2.4.2.

Biochemical parameters

At beginning and after completion of the program, a fasting blood sample was obtained for analysis of biochemical parameters, including fasting plasma glucose, fasting insulin, transaminases (ALAT, ASAT, GGT), uric acid, triglycerides, cholesterol, HDL-cholesterol and LDL-cholesterol levels, HbA1c as well as to assess thyroid function. Measurements of biochemical parameters were performed applying stan-

dardized methods in a certified laboratory based on the German Medical Association Directive on Quality Assurance of Quantitative Laboratory Tests for Medical Purposes [23]. Glucose, transaminases, lipids, uric acid and thyroid hormones were measured with the system Modular Analytics E170 (Roche Diagnostics, Mannheim, Germany). Insulin was measured utilizing the Liaison® assay based on chemiluminescence (Diasorin, Saluggia, Italy; CVs: 5.25%–6.15%). An oral glucose tolerance test (OGTT) was performed in a subcohort of children and was analyzed for those who completed the program. For the OGTT, blood samples were collected at 0, 30, 60, 90, and 120 min after a glucose load of 1.75 g/kg body weight (maximum of 75 g glucose). Impaired glucose tolerance was defined as a glucose level > 7.8 mmol/l 120 min after the glucose load [24]. To determine insulin sensitivity, the homeostasis model assessment for insulin resistance (HOMA-IR) was applied. HOMA-IR was calculated using the equation HOMA-IR = fasting insulin (μU/mL) × fasting glucose (mmol/l)/22.5 [25]. Blood pressure was obtained by the arithmetic mean of three single measurements by a certified device in the supine position after a rest period.

2.5.

Quality assurance and evaluation

Standardized documentation and quality assurance of obtained data are provided by the APV (Adiposity Patients Registry) database. This registry provides a standardized multicenter database for quality assurance of centers involved in the treatment of childhood obesity from Germany, Austria and Switzerland [26]. Data from participating centres are anonymously transmitted twice per year to the University of Ulm for central analysis, completeness and plausibility check. Additional evaluation and plausibility check are regularly performed at the CrescNet database at the University of Leipzig [3,27].

2.6.

Statistical analyses

A very conservative approach to missing data (based on the intent-to-treat (ITT) approach) was chosen by assuming that the mean change from baseline for the missing items is zero, without however changing the total variance. The somewhat optimistic observed data can then be compared to this overlyconservative estimate from the entire cohort. In tables, the means and standard errors (SE) of the data are presented as well as the 25th, 50th and 75th percentiles. Binominal data are shown as number (n) and percentage (%). A two sample paired t-test between the baseline and the follow up data was performed and p-values are given for ITT as well as per-protocol (PP). Analysis of time series for OGTT was performed using a variant of a repeated measures ANOVA taking into account via appropriate partitioning that the same subjects underwent the OGTT on the two occasions. A post-hoc paired t-test with a Bonferroni–Holm correction was used to identify which time points differed significantly. For correlation analyses, Pearson's linear coefficient, r, was used. All values were considered to be significant at the P ≤ 0.05 level. All analyses and graphs were made applying the software package R version 2.14 [28].

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3.

Results

3.1.

Participants

3.2.

142 participants started the intervention and provided complete anthropometric baseline measurements. Mean age at start of the program was 12.2 ± 0.2 years (72 boys; 51%). Complete anthropometric follow up data were available from 115 candidates. The flow of participants through each stage of the intervention, presented as diagram according to the CONSORT/TREND statement [29], is shown in Fig. 1. Mean age after completion of the program was 13.2 ± 0.2 years (58 boys; 50%), showing that the intervention was in fact completed within the proposed year. Detailed anthropometric and metabolic characteristics at baseline and after completion of the intervention are presented in Tables 1 and 2.

Enrollment

Initially contacted / assessed for eligibility (n = 226) Did not respond (n = 83)

Application for coverage of costs transmitted to local health insurance company

Declined to participate (n = 1)

Allocation

Allocated to intervention: n=142 Received allocated intervention (n = 142) Did not receive allocated intervention (n = 0)

Analysis

Follow up

Lost to follow up : n=2 Reasons: - Did not provide follow up data (n = 2)

Discontinued intervention: n = 25 Reasons: - Lack of time (n = 5) - Lack of motivation (n = 15) - Hospital treatment (n = 2) - Problems within family (n = 3)

Analyzed -

Intent to treat: n=142 Per protocol: n=115

Fig. 1 – Diagram according to the CONSORT/TREND statement [29] showing the flow of participants through each stage of the intervention.

425

Anthropometric parameters

Out of the 142 participants who started the intervention, 27 were overweight and 115 were obese at baseline. However, 20 of the 27 overweight candidates had an initial BMI value between the 95th and 97th percentile, suggesting that the overweight and obese sub-cohorts cannot be expected to have distinct characteristics and analyses of the sub-groups were thus not performed. The program was completed by 115 participants (referred to as PP population). Analyzing the entire study population (ITT), the standard deviation score of body mass index (BMISDS) significantly decreased from 2.33 by − 0.11 (95% CI −0.16 to −0.07, p < 0.0001). For the PP population, the change was − 0.14 (− 0.19 to −0.09, p < 0.0001). Standard deviation score of waist circumference was 1.93 at baseline and decreased by − 0.08 (−0.14 to − 0.01, p = 0.02) in the ITT analysis and by −0.11 (− 0.20, − 0.05, p = 0.01) in the PP analysis. For waist-to-height ratio, standard deviation score was 1.90 at baseline and decreased by − 0.11 (− 0.17 to −0.04, p = 0.003) in the ITT analysis and by − 0.13 (− 0.20, − 0.05, p = 0.001) in the PP analysis. The SDS-score for percentage body fat was 1.79 at baseline and decreased by − 0.08 (−0.17, − 0.01; p = 0.02, ITT) or by − 0.14 (−0.18, − 0.02, p = 0.01, PP), Table 1. According to the current guidelines of the scientific medical association, an obesity intervention program for childhood obesity can be considered successful, if a decline in BMI-SDS of ≥ 0.2 is achieved. This was attained by 37 of the candidates in our program (26% ITT, 32% PP). Combining all participants that achieved stabilization or reduction in BMISDS, the program was successful in 76 candidates (54% ITT, 67% PP), Fig. 2.

3.3.

Metabolic parameters

3.3.1.

Oral glucose tolerance test and glucose homeostasis

The analysis of the OGTT shows clearly that the mean glucose levels over the course of the test are lower at follow-up than at baseline (p = 0.00003), see Fig. 3. A post-hoc analysis then shows that the difference at 120 min is significant (follow up: 6.45 ± 0.20 mmol/l vs. 5.78 ± 0.16 mmol/l, p = 0.02 after Bonferroni–Holm correction). On neither occasion was the glucose level at 120 min correlated with age (rbaseline = 0.08 [−0.2, 0.3], p = 0.6; (rfollow-up = −0.05 [−0.4, 0.3], p = 0.8) thus indicating that the change discussed in the previous sentence cannot be attributed to growth or pubertal development. However, a correlation could not be found between changes in BMI-SDS and in the glucose level at 120 min (r = − 0.09 [− 0.4, 0.3], p = 0.6). In contrast, mean insulin levels of the course of the oral glucose tolerance test did not differ between baseline and follow up (Fig. 3b). HbA1c significantly decreased from 5.5% ± 0.08% at start of the intervention to 5.2 ± 0.05 after completion (p = 0.03). No significant differences in insulin levels could be found between start and completion of the program, neither in the fasting state nor 120 min after a standardized glucose load (Table 2, Fig. 3b). As diagnosed by a standardized OGTT, four out of fifty one participants showed impaired glucose metabolism at the beginningof theprogram (8%) comparedto oneparticipant outofthirty

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Table 1 – Anthropometric parameters of KLAKS participants before and after the intervention. Baseline n Males Age (years) Height (cm) Weight (kg) BMI (kg/m2) BMI-SDS Waist (cm) Waist-SDS WHR WHR-SDS WHtR WHtR-SDS Body fat (%) Body fat-SDS Systolic BP (mmHg) Systolic BP-SDS Diastolic BP (mmHg) Diastolic BP-SDS

Follow-up 25th perc.

72 (51%) 142 10.5 142 148.3 142 56.0 142 25.4 142 1.98 142 80.5 99 1.67 142 0.85 99 1.40 142 0.524 99 1.65 139 37.4 133 1.63 142 105.8 142

−0.12

142

65.0

142

−0.12

Median

12.3 159.2 69.6 27.9 2.34 86.0 1.99 0.90 1.97 0.551 1.94 42.6 1.82 115.3 0.78 69.9 0.74

75th perc.

Mean

14.0 12.2 166.2 157.6 83.5 72.2 31.0 28.5 2.62 2.33 93.8 87.6 2.22 1.93 0.93 0.90 2.49 1.89 0.583 0.556 2.19 1.90 47.1 42.5 2.02 1.79 123.2 115.6 1.33 78.0 1.57

0.65 71.3 0.78

SE

n

25th perc.

0.2 1.1 1.7 0.4 0.04 0.9 0.04 0.01 0.11 0.004 0.04 0.6 0.03 1.1

58 (50%) 115 11.4 115 154.4 115 60.7 115 25.6 115 1.90 115 81.0 91 1.45 115 0.84 91 1.32 115 0.502 91 1.43 102 36.2 102 1.36 113 109.0

0.10

113

0.9

113

67.0

0.12

113

−0.08

0.08

Median

13.3 162.7 73.8 27.7 2.15 86.8 1.83 0.90 2.15 0.542 1.83 40.6 1.71 115.3 0.57 72.3

75th perc.

14.9 13.2 170.8 162.4 88.8 76.1 30.9 28.4 2.60 2.18 93.8 88.7 2.18 1.82 0.95 0.89 2.53 1.94 0.576 0.547 2.10 1.75 47.2 41.5 1.98 1.65 125.0 117.4 1.28 78.3

0.93

Mean

1.66

0.63 72.8 0.86

SE

p-value p-value (ITT) (PP)

0.2 1.2 1.8 0.4 0.06 1.1 0.05 0.01 0.11 0.006 0.06 0.8 0.05 1.1

0.9 – < 0.0001 < 0.0001 0.5 < 0.0001 0.07 0.02 1 0.4 0.08 0.003 0.8 0.02 0.2

– < 0.0001 < 0.0001 0.5 < 0.0001 0.05 0.01 1 0.4 0.06 0.001 0.7 0.01 0.1

0.10

0.8

0.8

0.8

0.4

0.3

0.11

1

1

(BMI: body mass index; SDS: standard deviation score; WHR: waist-to-hip ratio; WHtR: waist-to-height ratio; BP: blood pressure; SE: standard error). Number for participants is smaller for the standardized score (SDS) of some anthropometric parameters, since reference tables were only available for subjects over the age of 11 (waist, WHtR) or 8 (body fat), respectively. The PP estimates for differences in means found in the main text are not based on the raw values in this table, but on the subset of patients that provided data both at baseline and follow-up.

Table 2 – Course of glucose and insulin levels from the oral glucose tolerance test as well as cardiometabolic risk markers of KLAKS participants before and after the intervention. Baseline

Glu 0’ (mmol/l) Glu 30’ Glu 60' Glu 90' Glu 120' Ins 0' (pmol/l) Ins 30' Ins 60' Ins 90' Ins 120' Hba1c (%) HOMA-IR ALAT (μmol/l) ASAT (μmol/l) γGT (μmol/l) FFA (mmol/l) Uric acid (μmol/l) HDL (mmol/l) LDL (mmol/l)

Follow-up

n

25th perc.

Median

75th perc.

Mean

SE

n

25th perc.

Median

75th perc.

Mean

SE

98 48 48 47 50 99 47 44 43 48 42 97 106 105 81 41 97

4.62 6.52 5.62 5.54 5.47 76 573 321 299 287 5.20 2.41 0.32 0.34 0.21 0.55 254

4.97 7.44 6.54 6.01 6.26 118 798 500 426 487 5.40 3.62 0.40 0.43 0.27 0.71 306

5.30 8.20 7.59 6.64 6.91 210 1154 938 736 915 5.50 7.25 0.53 0.54 0.35 0.91 371

4.95 7.46 6.69 6.26 6.20 186 895 673 589 645 5.47 6.17 0.48 0.46 0.32 0.72 314

0.06 0.17 0.24 0.19 0.16 22 76 71 76 69 0.08 0.78 0.03 0.02 0.02 0.03 7

77 31 31 31 34 75 33 30 30 30 30 74 83 81 83 21 72

4.70 5.97 5.11 5.13 5.25 82 418 292 284 287 4.99 2.54 0.27 0.35 0.21 0.45 274

4.99 7.24 6.01 5.39 5.94 124 748 590 476 383 5.16 3.95 0.35 0.43 0.25 0.61 312

5.42 8.05 7.02 6.47 6.34 233 1017 982 698 601 5.36 7.40 0.48 0.48 0.37 0.67 370

5.06 6.90 6.24 5.80 5.85 178 866 773 597 505 5.22 6.07 0.46 0.51 0.31 0.60 326

0.07 0.24 0.25 0.18 0.14 21 105 116 88 76 0.05 0.78 0.05 0.05 0.02 0.04 8

102 101

1.05 1.98

1.27 2.52

1.41 2.93

1.25 2.49

0.03 0.08

82 81

1.07 1.91

1.29 2.37

1.51 2.99

1.29 2.48

0.03 0.09

p-value (ITT)

p-value (PP)

– – – – – – – – – – 0.05 0.8 0.4 0.3 0.07 0.06 0.3

– – – – – – – – – – 0.03 0.8 0.4 0.3 0.05 0.04 0.2

0.5 0.3

0.4 0.3

SE: standard error; Glu: glucose; Ins: insulin; ALAT: alanine-aminotransferase; ASAT: aspartate-aminotransferase; GGT: gamma-glutamyltransferase; FFS: free fatty acids; HOMA-IR: homeostasis model assessment of insulin resistance; HDL: high-density lipoprotein cholesterol; LDL: low-density lipoprotein cholesterol.

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Fig. 2 – Change of BMI-SDS of KLAKS-participants after completion of the intervention. Candidates above the dotted line (n = 76; 68% in total) achieved a stabilization or reduction in BMI-SDS after the intervention. A BMI-SDS reduction of ≥ 0.2 was achieved in 37 participants of the KLAKS program (33%, above dashed line).

four after completion of the program (3%). However, this improvement did not reach statistical significance.

3.3.2.

Cardiometabolic risk markers

GGT significantly decreased between start and completion of the program (0.32 ± 0.02 vs. 0.30 ± 0.02; p = 0.05). A significant decrease could also be observed for free fatty acids (0.72 ± 0.03 vs. 0.60 ± 0.04; p = 0.03) (Table 2).

4.

Discussion

The aim of the present study was to evaluate the impact of a combined exercise/lifestyle intervention on anthropometric parameters and body composition, glycemic control and cardiometabolic risk markers in childhood obesity. The study was performed within the standardized and approved obesity therapy program KLAKS for obese children and adolescents. We show that a standardized obesity therapy program for one year significantly reduces anthropometric parameters of body fat content and body fat distribution in overweight or obese children and adolescents. In addition, cardiometabolic risk markers improved, and mean glucose levels over the course of a standardized glucose tolerance test significantly decreased following the intervention. These data suggest that an outpatient obesity intervention based on increased physical exercise may improve (subclinical) features of the metabolic syndrome and impaired glucose metabolism already at a very early stage of childhood obesity

Fig. 3 – a: Time series for glucose levels during an oral glucose tolerance test before (grey points) and after completion (black points) of the intervention. Data are presented as means ± standard error. b: Time series for insulin levels during an oral glucose tolerance test before (grey points) and after completion (black points) of the intervention. Data are presented as means ± standard error.

and may prevent progression of the disease. The lack of correlation between these improvements and changes in BMI-SDS demonstrate that the mechanisms at work are anything but straightforward and accent the need for more research. Certified or validated outpatient programs for the treatment of childhood obesity are very limited to date. In Germany, such programs include Obeldicks [30] and FITOC [31]. However, these programs were established more than 10 years ago, and a higher number of participants could be evaluated compared to our program. The one year outpatient lifestyle intervention Obeldicks addresses children aged 8 to 16 years, and is – comparable to the KLAKS program – based on nutrition education, physical activity, behavior therapy, and individual psychological care. Although the mean BMISDS reduction was higher than in our study cohort, differences in the trial methods, such the requirement that participants prove their motivation beforehand, make it difficult to compare these trials. Both programs were associated with significant improvements of metabolic risk markers. In addition, it could be shown in the Obeldicks program that the achieved weight loss was sustained even four years after the end of intervention [32]. Although we are

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not yet in the position to provide follow up data of participants, the KLAKS program fulfills the criteria suggested by the AGA for successful BMI-SDS reduction following obesity treatment [17]. We show that a significant decrease or stabilization in BMI-SDS could be achieved by about two thirds of participants, which may be attributable to the interdisciplinary approach, combining diet counseling and instruction on the preparation of healthy meals, psychological coaching/support as well as increased physical exercise as the “main arch” of the intervention. In addition, classes and counseling are provided to both, participants and their parents/caregivers. Especially the concept of involving parents into the intervention has been shown to have long-term effects on weight stabilization of their children [33]. On the other hand, the core of the intervention is mainly based on increased physical exercise, as promotion of physical activity is essential to successfully treat childhood obesity, and enrolment of candidates into structured sports programs is strongly recommended [34]. However, it is unclear to date, which exercise regimen is superior to treat obesity per se or visceral obesity which is associated with increased cardiometabolic risk. In adults, both, endurance and resistance exercise paired with energy restriction may effectively reduce visceral fat mass and risk markers for the metabolic syndrome [35,36]. Our results for the pediatric population are in line with these data from adults, as we could show that increased physical exercise within a structured lifestyle program can significantly decrease BMI-SDS as well as additional anthropometric measures and metabolic risk factors in childhood obesity, such as waist circumference, body fat content, glycemic control and GTT as indicator of the hepatic manifestation of a metabolic syndrome. Only limited studies are available on the effect of combined resistance and endurance exercise within the context of a lifestyle program in childhood obesity. Available studies report a significant increase in fat free mass and BMI and a decrease in fat mass as well as significant reduction of cardiometabolic risk factors [37]. A recreational 12-week controlled training program for obese children, consisting of a combination of circuit-based endurance, strength and resistance exercises, significantly decreases BMI and BMISDS, waist circumference, fat mass, homeostasis model assessment for insulin resistance (HOMA-IR), triglycerides and systolic blood pressure [38]. The strength of our study is that we provide evidence that a combined exercise/lifestyle program may successfully and significantly improve anthropometric parameters, body composition as well as metabolic risk markers and glycemic control in childhood obesity. The effect estimates in this paper are based on those participants who provided data at both time points, meaning they may be somewhat optimistic. Table 1b demonstrates that all the significant changes (apart from GGT which would change from significance (p = 0.05) towards a trend (p = 0.07)) would have remained so even if the data had been available from those who dropped out. There are also some limitations of the study: First, the physical exercise program was performed according to the manual of the KLAKS program, and for this first evaluation, there are no additional parameters available

to test for efficacy of the exercise regimens, such as heart rate or spirometry, as the primary endpoints for this analyses were changes in BMI-SDS and anthropometric/ metabolic markers. Second, quantification of muscle mass in addition to fat mass would have provided additional information, but according to the study protocol, measurement of skinfolds for quantification of percentage body fat had to be performed instead of BIA or DEXA measurements.

5.

Conclusion and translational potential

In summary, we show that regular exericse within a structured lifestyle program for childhood obesity significantly improves marker of the body fat content and body fat distribution as well as metabolic risk markers for the metabolic syndrome. As (subclinical) impairments of glucose homeostatis are also significantly improved, the intervention may beneficial to prevent the development of impaired glucose tolerance or type 2 diabetes in obese children and adolescents. A recent European guideline on prevention of type 2 diabetes in adults suggests – among other factors – an increased level of daily physical activity [14]. Thus, regular physical activity should also form the basis for effective lifestyle intervention programs for childhood obesity to prevent the risk for diabetes and cardiometabolic risk later in life.

Author contribution SB: study design and conduct of the study, data collection and analysis, data interpretation, manuscript writing DP: analysis and interpretation of data, statistical expertise, manuscript writing AW: study design, conduct of the study, revision of the manuscript KW: study concept and design, revision of the manuscript RG: data collection and analyses, revision of the manuscript TK: conduct of analyses for biochemical parameters, interpretation of biochemical data, revision of manuscript MW: physical exercise program; interpretation of data, revision of the manuscript AK: study design and conduct of the study, data collection, data interpretation, critical revision of manuscript for important intellectual content All authors had full access to all of the data in the study and can take responsibility for the integrity of the data and the accuracy of the data analyses.

Funding Part of the work was supported by the Federal Ministry of Education and Research, Germany (Integrated Research and Treatment Center IFB “Adiposity Diseases”, FKZ: 01E01001) as well as by grants from the Roland-Ernst-Stiftung für Gesundheitsförderung, the TANITA Healthy Weight Community Trust as well as the Saxonian Ministry for Social Affairs (to SB).

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Acknowledgments [15]

We would like to thank all persons who are involved in the conduct of the KLAKS program. We are also very grateful to all children, adolescents and their parents who participated in this project.

Conflict of interest

[16]

[17]

The authors have nothing to disclose. [18] REFERENCES

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The one year exercise and lifestyle intervention program KLAKS: Effects on anthropometric parameters, cardiometabolic risk factors and glycemic control in childhood obesity.

Regular physical exercise within structured lifestyle programs may improve weight status and minimize metabolic risk factors in childhood obesity. The...
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