Li LY, Li SM, Pang BX, Wei JP, Wang QH. Effects of exercise training on glucose metabolism indicators and inflammatory markers in obese children and adolescents: A meta-analysis. World J Diabetes 2024; 15(6): 1353-1366 [PMID: 38983830 DOI: 10.4239/wjd.v15.i6.1353]
Corresponding Author of This Article
Qiu-Hong Wang, MD, Associate Professor, Department of Endocrinology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, No. 5 Beixiange Road, Beijing 100053, China. qiuhongforture@126.com
Research Domain of This Article
Endocrinology & Metabolism
Article-Type of This Article
Meta-Analysis
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Le-Yang Li, Song-Mei Li, Jun-Ping Wei, Qiu-Hong Wang, Department of Endocrinology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China
Bo-Xian Pang, Graduate School, Beijing University of Chinese Medicine, Beijing 100029, China
Co-corresponding authors: Jun-Ping Wei and Qiu-Hong Wang.
Author contributions: Wang QH and Wei JP designed the study; Li LY and Li SM searched databases, performed the selection of studies, and analyzed the data; Pang BX helped perform the data analysis and complete table and figure presentation; Li LY wrote the manuscript. The final version was confirmed by all authors for submission. Wang QH and Wei JP contributed to the revised version. Li LY and Li SM independently completed the process of database search, screening research, data collection and data analysis. They have made crucial and indispensable contributions equally towards the completion of the project and thus qualified as the co-first authors of the paper. Wang QH and Wei JP offered critical insights and design perspectives, contributed equally to the revised version, they are co-corresponding authors for their equal and significant contributions, and there is no conflict of interest between them. We believe that designating Wang QH and Wei JP as co-corresponding authors of is fitting for our manuscript as it accurately reflects our team's collaborative spirit, equal contributions, and diversity. All authors contributed to the article. The final version was confirmed by all authors for submission.
Conflict-of-interest statement: The authors have nothing to disclose.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Qiu-Hong Wang, MD, Associate Professor, Department of Endocrinology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, No. 5 Beixiange Road, Beijing 100053, China. qiuhongforture@126.com
Received: December 30, 2023 Revised: February 7, 2024 Accepted: March 26, 2024 Published online: June 15, 2024 Processing time: 164 Days and 2.5 Hours
Abstract
BACKGROUND
Obesity in children and adolescents is a serious problem, and the efficacy of exercise therapy for these patients is controversial.
AIM
To assess the efficacy of exercise training on overweight and obese children based on glucose metabolism indicators and inflammatory markers.
METHODS
The PubMed, Web of Science, and Embase databases were searched for ran-domized controlled trials related to exercise training and obese children until October 2023. The meta-analysis was conducted using RevMan 5.3 software to evaluate the efficacy of exercise therapy on glucose metabolism indicators and inflammatory markers in obese children.
RESULTS
In total, 1010 patients from 28 studies were included. Exercise therapy reduced the levels of fasting blood glucose (FBG) [standardized mean difference (SMD): -0.78; 95% confidence interval (CI): -1.24 to -0.32, P = 0.0008], fasting insulin (FINS) (SMD: -1.55; 95%CI: -2.12 to -0.98, P < 0.00001), homeostatic model assessment for insulin resistance (HOMA-IR) (SMD: -1.58; 95%CI: -2.20 to -0.97, P < 0.00001), interleukin-6 (IL-6) (SMD: -1.31; 95%CI: -2.07 to -0.55, P = 0.0007), C-reactive protein (CRP) (SMD: -0.64; 95%CI: -1.21 to -0.08, P = 0.03), and leptin (SMD: -3.43; 95%CI: -5.82 to -1.05, P = 0.005) in overweight and obese children. Exercise training increased adiponectin levels (SMD: 1.24; 95%CI: 0.30 to 2.18, P = 0.01) but did not improve tumor necrosis factor-alpha (TNF-α) levels (SMD: -0.80; 95%CI: -1.77 to 0.18, P = 0.11).
CONCLUSION
In summary, exercise therapy improves glucose metabolism by reducing levels of FBG, FINS, HOMA-IR, as well as improves inflammatory status by reducing levels of IL-6, CRP, leptin, and increasing levels of adiponectin in overweight and obese children. There was no statistically significant effect between exercise training and levels of TNF-α. Additional long-term trials should be conducted to explore this therapeutic perspective and confirm these results.
Core Tip: It has been reported that exercise training therapy have a potential role in the development of obesity of children and adolescents. This meta-analysis aimed to resolve some contradictory conclusions in recent related studies.
Citation: Li LY, Li SM, Pang BX, Wei JP, Wang QH. Effects of exercise training on glucose metabolism indicators and inflammatory markers in obese children and adolescents: A meta-analysis. World J Diabetes 2024; 15(6): 1353-1366
Overweight and obesity in children and adolescents have become important global public health issues, placing a heavy burden on individuals, relatives, and society as a whole. From 1975 to 2016, the prevalence of obesity among children and adolescents aged 5-19 worldwide increased from 0.7% to 5.6% in females and from 0.9% to 7.8% in males. The World Obesity Federation estimates that by 2025, 206 million children and adolescents aged 5-19 will suffer from obesity, and by 2030, 254 million will be affected[1]. In China, the latest national prevalence rates from 2015 to 2019 have been estimated to be 6.8% and 3.6% for overweight and obese children under 6 years old, respectively, as well as 11.1% and 7.9% for overweight and obese children and adolescents aged 6-17 years old, respectively (according to Chinese standards)[2].
Obesity in children and adolescents has been demonstrated to be a trigger for various chronic diseases, such as asthma, hypertension, and low self-esteem[3], and it has significant and adverse long-term consequences for physical health, especially for cardiovascular metabolic diseases[4]. Obese children have more than a 50% probability of becoming obese adults and to develop pathologies typical of obese adults, including type 2 diabetes and dyslipidemia[5]. Moreover, obesity can exhibit significant family connections, with children of obese parents being overweight at the age of 6, which is 19 years earlier than children of normal weight parents[6].
Due to the potential side effects and high cost of the long-term use of anti-obesity drugs[7], life interventions, including exercise training, remain the main method for managing obesity. According to the 2020 World Health Organization guidelines on physical activity and sedentary behavior among children and adolescents aged 5-17, it is recommended that children and adolescents should limit sedentary behavior and engage in at least 60 min of moderate intensity aerobic exercise (AT) every day[8]. A published review has called for joint action among multiple members, including schools, communities, childcare, and families, to provide comprehensive interventions for obese and overweight children using behavioral, structural, environmental, policy, and biomedical methods[9].
Several meta-analyses have comprehensively evaluated the effects of exercise intervention on obese children, including effects on adiponectin, carbohydrates, lipid metabolism indicators, homeostatic model assessment for insulin resistance (HOMA-IR), and other body composition parameters. Adipose tissue is an active endocrine organ that can secrete pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), and synthesize cytokine peptides called adipokines[10]. TNF-α and IL-6 participate in the inhibitor kappa B kinase/nuclear factor kappa (NF-κB) pathway and the c-Jun N-terminal kinase/activator protein 1 pathway by activating intracellular kinases to inhibit insulin signaling and to stimulate the production of C-reactive protein (CRP) in the liver[11]. Leptin and adiponectin are mainly produced in white adipose tissue. Leptin is considered an important regulator of metabolism and energy homeostasis, and it has been proven that leptin affects the function of the immune system by increasing the pro-inflammatory effects, including the activation of T lymphocytes, increasing the synthesis and release of IL-6 and TNF-α. Leptin acts directly on the nervous system, regulates food intake, and exerts negative feedback regulation on insulin secretion through its peripheral action. Reducing circulating levels of leptin can result in the improvement in insulin sensitivity[12-14]. In contrast to leptin, adiponectin has the ability to inhibit the phosphorylation of the NF-κB, thus influencing the activity of various pro-inflammatory mediators. As a powerful insulin sensitizer, adiponectin has the anti-diabetic effect[12,14]. A previous systematic review has concluded that AT significantly increases serum adiponectin concentration[15]. Another meta-analysis has reported that exercise training effectively reduces fasting blood glucose (FBG), fasting insulin (FINS), and HOMA-IR in overweight or obese children and adolescents[16]. However, other meta-analyses have reported contradictory results for inflammatory indicators[17,18] and adipokines[18-21]. Therefore, we conducted a systematic review and meta-analysis to analyze relevant randomized controlled trials (RCTs) to evaluate the effects of exercise intervention on glucose metabolism indicators and inflammatory factors in obese children and adolescents.
MATERIALS AND METHODS
Database and search strategies
A literature search was conducted using the PubMed, Web of Science, and Embase electronic databases until October 1, 2023. The search results were limited to English publications only. The following terms, as well as their synonyms and related terms, were used for the database searches: "exercise", "childhood obesity", "children", "adolescents", "glucose metabolism indicators", and "inflammatory markers. The search strategy was adjusted for each database, and the references included in the study were reviewed to ensure the studies met the inclusion criteria. The present study was registered on the PROSPERO website (registration number CRD42023472704).
Inclusion and exclusion criteria
The literature meeting the following inclusion criteria were included in the meta-analysis: (1) Type of study: RCT in design; (2) subjects were children or adolescents (under 20 years old); and (3) the experimental group received exercise training but had the same lifestyle as the control group. The exclusion criteria were as follows: (1) Unable to obtain a complete abstract or text; (2) intervention measures not clearly explained; (3) repeated publication of literature; and (4) reviews and conference papers.
Data extraction and literature quality assessment
The selection of research followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Electronic literature evaluation was conducted independently by two researchers (Li LY and Li SM) to identify studies that met the inclusion criteria. The flowchart for inclusion and exclusion is provided in Figure 1. The data of the included literature were extracted, including first author, publication year, country, sample size, gender, average age, exercise training plan, and main outcomes. In addition, covariates that may contribute to subgroup analysis were also extracted.
Figure 1
Flow diagram of study selection and identification.
The risk of bias assessment was independently performed by two researchers using the Cochrane system evaluation method for inclusion in the study. The risk assessment tool included the following content areas: Random sequence generation; allocation concealment; blinding of participants and personnel; blinding of outcome evaluation; incomplete outcome data; selective reporting; and other biases. There were three options for assessment in each field, namely, low risk, unclear risk, and high risk. Any disagreements were resolved through consensus or consultation with a senior researcher (Wang QH).
Statistical analysis
The meta-analysis was conducted using Review Manager 5.3 software. Due to inconsistent outcome units or measurement methods, the standardized mean difference (SMD) and the 95% confidence interval (CI) were used as the summary measures. The Cochrane Q-test and I2 statistic (degree of heterogeneity) were used to estimate heterogeneity between studies. In each analysis, I2 was divided by 25%, 50%, and 75% as the boundary values, representing low, medium, and high heterogeneity, respectively[22]. Fixed or random effects models were used to determine changes in outcome measures. If the heterogeneity level between studies was low, a fixed effects model was used; otherwise, a random effects model was used. If necessary, subgroup analysis was conducted to analyze the causes of heterogeneity, and sensitivity analysis was performed. To determine the possible causes of heterogeneity, subgroup analysis based on age, gender, and intervention time was conducted, and sensitivity analysis was performed by omitting experiments one by one to determine which RCTs caused heterogeneity and how each RCT contributed to the overall analysis. Funnel plots were utilized to evaluate potential publication bias, and forest plots were used to describe the results. A P-value less than 0.05 was considered statistically significant.
RESULTS
Characteristics of included studies
The screening process is illustrated by a flowchart in Figure 1. After searching keywords in three databases and removing duplicate studies using NoteExpress literature management software, a total of 2921 articles entered the first round of screening. After reading the title and abstract, 74 studies remained for full text review. After reading the full text, a total of 29 studies met the inclusion criteria. Because two of these studies had the same registration trial results[23,24], only data from one of them was used[23]. In total, 28 studies were included in the analysis, and the summary characteristics of the 28 RCTs are shown in Table 1.
Accept a standard, balanced, low-fat, and low-calorie diet. Received 4 to 6 (20-30 min) individual treatments from a nutrition specialist pediatrician within a period of 3 months
These 28 trials were published in English between 2004 and 2023, with sample sizes ranging from 15 to 76 for each individual trial. Of the included studies, 11 studies[23,25-34] were conducted in the United States, 5 studies[35-39] were conducted in Tunisia, 3 studies[40-42] were conducted in Iran, 2 studies[43,44] were conducted in Brazil, 2 studies[45,46] were conducted in China, and 1 study was conducted each in Saudi Arabia[47], Portugal[48], Serbia[49], Australia[50], and South Korea[51]. The RCTs used different exercise training programs as the intervention measures. The intensity of exercise was generally measured by maximum oxygen uptake (VO2 max) or maximum heart rate, and the duration of the intervention varied from 4 wk to 6 months depending on the trial. Based on the intervention plans of each study, the exercise intervention types were divided into the following three categories: AT, resistance exercise (RT), and combined exercise (AT + RT). High-intensity interval training (HIIT) is an enhanced form of interval training involving brief, high-intensity, anaerobic exercise (ranging from 85% to 250% VO2 max for 6 s to 4 min) separated by brief but slightly longer bouts of low-intensity aerobic rest (ranging from 20% to 40% VO2 max for 10 s to 5 min)[52]. In the present analysis, HIIT was classified as a combined exercise type. Although some studies included dietary or psychological interventions, the control group of these studies also maintained the same intervention.
When there were two or more training groups, the group with the higher training intensity was selected for statistical analysis[28,36,37,42,45,49,50]. In the study by Davis et al[30], data from the nutrition group and nutrition plus training group were selected based on the inclusion criteria. For the study by Jeon et al[51], real-time data after completion of the training plan were selected rather than data after a 6-wk hiatus.
Risk of bias and quality assessment of individual studies
Figure 2 summarizes the risk of bias of the included trials based on different quality domains using the Cochrane Collaboration tool. Among the RCTs, seven studies clearly reported methods for random sequence generation. One study had allocation concealment as "high risk", and nine articles explicitly reported allocation concealment. Because exercise intervention methods are impossible to blind, all performance risks of bias of the included studies were classified as high-risk. Blinding of outcome assessors was mentioned in only one study. Dropout rates were clearly reported in all studies, and they were higher in one study. All trials showed a low risk of bias in selective outcome reporting. None of the studies had clear information to assess whether there were other risks of bias.
Figure 2 Quality assessment.
A: Risk of bias graph; B: Summary of the quality assessment of the included studies. Green indicates low risk of bias, red indicates high risk of bias, yellow indicates unclear risk of bias.
Effect on glucose metabolism
A meta-analysis was conducted based on FBG, FINS, and HOMA-IR. In the present meta-analysis, there were 22 RCTs involving 747 patients who were randomly divided into an exercise group (n = 378) and a control group (n = 369), and the results demonstrated the comprehensive effect of exercise therapy on FBG levels in obese children. Compared to the control group, the FBG of the experimental group after exercise decreased (SMD: -0.78; 95%CI: -1.24 to -0.32) (Figure 3). Because these experiments showed a high degree of heterogeneity in the test results (I2 = 88%; P < 0.00001), a random effects model was used for statistical analysis. Subgroup analysis based on exercise type showed that AT (SMD: -0.96; 95%CI: -1.79 to -0.12) and combined aerobic and RT (SMD: -1.12; 95%CI: -1.80 to -0.44) resulted in significantly reduced FBG levels, while the effect of RT alone on FBG lacked statistical significance (SMD: 0.34; 95%CI: -0.19 to 0.86). Subgroup analysis based on gender showed that exercise intervention significantly reduced FBG (SMD: -1.94; 95%CI: -2.87 to -1.01) in obese female children, but statistical significance was lacking in the male subgroup (SMD: -0.32; 95%CI: -1.18 to 0.55) and combined gender subgroup (SMD: -0.08; 95%CI: -0.42 to 0.27). Subgroup analysis based on intervention duration showed that interventions less than 12 wk significantly reduced FBG in subjects (SMD: -1.10; 95%CI: -1.65 to -0.54), while interventions greater than 12 wk did not have this effect (SMD: 0.16; 95%CI: -0.28 to 0.59). Of note, the heterogeneity of the subgroup analysis was high, and these results should be interpreted with caution. Sensitivity analysis indicated that deleting a single experiment did not change the overall effect, and funnel plots suggested that there was no publication bias.
Figure 3 Forest plot of the effects of exercise training versus control on fasting blood glucose.
CI: Confidence interval.
A total of 19 studies, including 615 participants, showed the combined effect of exercise therapy on FINS levels, with 317 participants in the exercise group and 298 participants in the control group. After exercise therapy, FINS levels were significantly decreased (SMD: -1.55, 95%CI: -2.12 to - 0.98) (Figure 4). Moreover, there was significant heterogeneity between studies (I2 = 89%, P < 0.00001). Subgroup analysis using exercise intervention duration showed that interventions lasting longer than 12 wk (SMD: -1.20; 95%CI: -2.34 to -0.05) and shorter than 12 wk (SMD: -1.65; 95%CI: -2.33 to -0.97) reduced FINS levels. Subgroup analysis based on gender showed that exercise therapy had a significant beneficial effect on FINS levels in the male (SMD: -1.39; 95%CI: -1.86 to -0.91), female (SMD: -2.40; 95%CI: -3.48 to -1.32), and gender combination (SMD: -0.64; 95%CI: -1.21 to -0.07) subgroups. Both AT (SMD: -1.32; 95%CI: -2.12 to -0.53) and combined exercise (SMD: -1.91; 95%CI: -2.75 to -1.08) reduced FINS levels, but RT (SMD: -0.72; 95%CI: -2.01 to 0.56) had no effect. No significant publication bias was observed.
Figure 4 Forest plot of the effects of exercise training versus control on fasting insulin.
CI: Confidence interval.
A meta-analysis of 16 trials evaluating HOMA-IR levels among a total of 586 individuals found that there was a statistically significant difference (SMD: -1.58; 95%CI: -2.20 to -0.97) in obese children in the experimental group compared to the control group, with 303 subjects in the exercise group and 283 subjects in the control group (Figure 5). These results indicated that exercise therapy significantly improved insulin resistance (IR) in obese children. Because there was a high degree of heterogeneity between studies (I2 = 90%, P < 0.00001), a random effects model was used for statistical analysis. Subgroup analysis based on intervention duration showed a significant decrease in HOMA-IR levels for the intervention duration less than 12 wk (SMD: -1.81; 95%CI: -2.55 to -1.07), while the intervention duration greater than 12 wk lacked a statistically significant difference in HOMA-IR levels (SMD: -0.75; 95%CI: -1.79 to 0.29). Subgroup analysis based on exercise types showed that AT (SMD: -1.15; 95%CI: -1.70 to -0.60) and combination of aerobic and RT (SMD: -1.98; 95%CI: -2.88 to-1.09) were both effective in reducing HOMA-IR levels. In studies with only males (SMD: -1.47; 95%CI: -2.14 to -0.80) and females (SMD: -2.49; 95%CI: -3.61 to -1.36), exercise intervention had a positive effect, but there was no statistically significant difference in the combined gender group (SMD: -0.38; 95%CI: -0.89 to 0.12). Moreover, funnel plots indicated no significant publication bias.
Figure 5 Forest plot of the effects of exercise training on homeostasis model assessment of insulin resistance.
CI: Confidence interval.
Effect on inflammation biomarkers
A meta-analysis was performed among the studies that reported IL-6, TNF-α, and CRP levels. Six studies, including 264 participants, presented the pooled effect of exercise training on IL-6 levels. Because the trials showed heterogeneity (P < 0.00001; I2 = 85%), a random-effects model was used for statistical analysis. A meta-analysis showed a significant beneficial effect of exercise treatment compared to the control group in decreasing the level of IL-6 (SMD: -1.31; 95%CI: -2.07 to -0.55) (Figure 6).
Figure 6 Forest plot of the effects of exercise training on interleukin-6.
CI: Confidence interval.
Among the six studies reporting IL-6, only the study by Peña et al[25] had a study duration greater than 12 wk. After excluding this study, a meta-analysis was conducted on the remaining five studies (SMD: -1.01; 95%CI: -1.61 to -0.41), which had medium heterogeneity (I2 = 72%, P = 0.007). Only the study by Nambi et al[47] used an AT + RT combination protocol. After excluding this study, a meta-analysis was performed on the remaining five studies (SMD: -1.21; 95%CI: -2.18 to -0.24), but the heterogeneity did not decrease (P < 0.00001; I2 = 87%). Regarding subgroup analysis based on gender, the study by Nambi et al[47] only involved males, while the study by Liu et al[46] only involved females. Both experiments showed that exercise training reduced serum IL-6 concentration. Because the measurement methods of the other four studies were consistent, the mean difference (MD) was combined as the effect size (MD: -0.52; 95%CI: -0.90 to -0.15), and heterogeneity was significantly reduced (I2 = 43%, P = 0.15), which indicated that exercise also had a beneficial effect on reducing IL-6 in studies with a combined gender group.
The impact of exercise therapy on TNF-α in obese children was evaluated in 6 RCTs, including 264 obese children, with 150 subjects in the exercise group and 114 subjects in the control group. Except for the study by Nambi et al[47], the other five studies used AT training. Overall, the meta-analysis showed that exercise intervention had no effect on TNF-α levels in obese and overweight children compared to the control group (SMD: -0.80; 95%CI: -1.77 to 0.18) (Figure 7). Because there was significant heterogeneity among the included studies (I2 = 91%, P < 0.00001), a random effects model was utilized. The sensitivity analysis conducted by deleting individual studies showed that the validity of the results changed when the study by Kelly et al[32] was excluded (SMD: -1.25; 95%CI: -2.05 to -0.45).
Figure 7 Forest plot of the effects of exercise training on tumor necrosis factor alpha.
CI: Confidence interval.
The impact of exercise therapy on CRP levels was evaluated in 6 studies, including 179 participants, all of which were less than 12 wk in duration. Because the heterogeneity between studies was moderate (I2 = 68%, P = 0.008), a random effects model was utilized. The meta-analysis showed that exercise therapy reduced CRP levels in obese and overweight children (SMD: -0.64; 95%CI: -1.21 to -0.08) (Figure 8). Subgroup analysis by gender showed that the CRP levels in two studies with only female patients were significantly reduced (SMD: -1.19; 95%CI: -1.69 to -0.69), and there was no heterogeneity between the studies (I2 = 0, P = 0.44). However, the CRP levels of the four combined gender groups lacked statistical significance (SMD -0.37; 95%CI: -1.09 to 0.35). Subgroup analysis based on exercise type showed that using a combined exercise regimen reduced serum CRP levels (SMD: -1.14; 95%CI: -1.72 to -0.57), and there was no heterogeneity between studies (I2 = 0, P = 0.47). However, an AT regimen had no effect on serum CRP concentration (SMD: -0.39; 95%CI: -1.16 to 0.38). Due to the limited number of included studies, the publication bias of these three outcomes was not evaluated.
Figure 8 Forest plot of the effects of exercise training on C-reactive protein.
CI: Confidence interval.
Effect on adipokines
A meta-analysis was performed to evaluate the effects on leptin and adiponectin. A total of 6 studies reported the effect of exercise training on leptin levels in obese and overweight children, all of which were less than 12 wk long and involved 240 patients. The results showed that exercise therapy significantly reduced leptin levels in obese children (SMD: -3.43; 95%CI: -5.82 to -1.05) (Figure 9). Because the results had high heterogeneity (I2 = 97%, P < 0.00001), a random effects model was utilized. Sensitivity analysis indicated that deleting any study did not affect the validity of the results.
Figure 9 Forest plot of the effects of exercise training on leptin.
CI: Confidence interval.
In a meta-analysis of 10 RCTs (352 individuals), exercise training increased blood adiponectin concentration (SMD: 1.24; 95%CI: 0.30 to 2.18) compared to the control group (Figure 10). The intervention duration of these 10 studies was less than 12 wk, and there was high heterogeneity between the studies (I2 = 92%, P < 0.00001). Sensitivity analysis showed that when the study by Wong et al[23] was removed, the results lost statistical significance. Subgroup analysis based on gender and exercise type showed no statistically significant difference in the results between the single AT group (SMD: 0.10; 95%CI: -0.50 to 0.70) and the combined gender group (SMD: -0.11; 95%CI: -0.72 to 0.49). However, the heterogeneity of these subgroups was high.
Figure 10 Forest plot of the effects of exercise training on adiponectin.
CI: Confidence interval.
DISCUSSION
There have been high-quality studies and reviews on the impact of exercise training on overweight or obese adults[53-55], but few meta-analyses have focused on the impact of exercise therapy on weight management in children. The present study systematically reviewed and analyzed 28 RCTs to evaluate the effects of exercise training on glucose metabolism indicators and inflammatory markers in overweight and obese children. Overall, the present findings indicated that exercise training reduces glucose metabolism indicators (FBG, FINS, and HOMA-IR) and inflammatory markers (IL-6, CRP, and leptin) but increases adiponectin concentration without affecting TNF-α in obese and overweight children compared to the control group without exercise.
The present findings regarding the decrease in levels of glucose metabolism indicators were consistent with the results of a previous analysis by Kazeminasab et al[16], which involved 35 trials of exercise training on IR in overweight or obese children and adolescents, demonstrating that exercise significantly reduces FBG, FINS, and HOMA-IR levels. In addition, Cao et al[56] demonstrated the beneficial effects of HIIT on FBG, FINS, and HOMA-IR. Contrary to the results of this review, a meta-analysis conducted by Zhu et al[57] found that HIIT reduces FINS and HOMA-IR in obese children but has no effect on FBG levels. A meta-analysis by Marson et al[58] showed that physical exercise is generally not associated with a decrease in FBG levels compared to the control group but is associated with a decrease in FINS and HOMA-IR. In terms of FINS indicators, the subgroup analysis by Marson et al[58] showed that aerobic training is effective in reducing FINS, while resistance training has no effect on FINS, agreeing with the results of the present study. However, the lack of an effect on FINS after combined training contradicted the present findings, which may be related to the number of studies included, as the present meta-analysis included more RCTs than the previous meta-analysis.
Regarding the impact of exercise training on inflammatory markers, the present results were consistent with those reported by Sirico et al[19], suggesting that exercise significantly reduces IL-6 and leptin levels but increases serum adiponectin concentrations. Several meta-analyses have reported the effect of exercise training on serum adiponectin concentration. Zhang et al[15] recently conducted a meta-analysis on the impact of AT on serum adiponectin concentration in obese children and adolescents; they reported that aerobic training significantly increases serum adiponectin concentration and that high-intensity AT leads to a greater increase in adiponectin concentration. Similar conclusions have been reported by Yu et al[21]. García-Hermoso et al[59] reported that combined exercise significantly increases adiponectin concentration compared to AT. However, the subgroup analysis in the present study showed that resistance training and combined training increased adiponectin levels, but this result was not observed in AT, which may be related to differences in more specific exercise intervention methods. Another meta-analysis conducted by García-Hermoso et al[20] reported that exercise is significantly associated with an increase in adiponectin levels but that it does not alter leptin levels. A meta-analysis involving 11 RCTs by Han et al[60] found that exercise is significantly associated with a decrease in CRP levels in overweight/obese children and adolescents but has no significant correlation with IL-6 and TNF-α.
Previous studies have shown that obesity is associated with low-grade systemic inflammation, including adipokines, IL-6, and TNF-α, which can lead to adverse vascular outcomes, and exercise and dietary intervention plans can counteract inflammatory and oxidative states to some extent, which may be due to exercise enhancing antioxidant capacity and reducing the production of reactive oxygen species[61]. At present, the first-line treatment for weight management in obese and overweight children mainly involves behavioral interventions to address issues related to diet, physical activity, sedentary behavior, and sleep. Although family participation and parents acting as role models are highly advocated, anti-obesity drugs and metabolic weight loss surgery are still supplementary therapies[1,62]. In addition, a previous study has reported that CRP in obese children is closely related to psychological variables, thus providing insights into the prevention and treatment of childhood obesity through psychological intervention[63].
The advantages of the present study included the systematic literature search, which included the latest research, and the meta-analysis, which provided evidence and recommendations for children and adolescents to engage in exercise training and weight management. However, the present study had several limitations. First, there was high heterogeneity, which may be attributed to differences in age, race, baseline body mass index, exercise intensity, serum testing methods, and other factors in the study population, suggesting that the results should be interpreted with caution. Second, the sample size of some of the included studies was relatively small. Finally, one study[46] did not clearly specify the gender of the included population, resulting in the results could not be included in the gender-based subgroup analysis.
CONCLUSION
In summary, the present meta-analysis indicated that exercise training therapy significantly reduces the levels of glucose metabolism indicators, IL-6, CRP, and leptin but increases the levels of adiponectin in obese or overweight children. Moreover, exercise training has no statistically significant effect on the TNF-α levels. Thus, these results support the beneficial role of exercise therapy in managing children's weight and health. However, larger scale RCTs are needed to determine the efficacy of different exercise regimens (including exercise types and intervention duration) in controlling carbohydrate metabolism and anti-inflammatory effects in overweight and obese children.
Footnotes
Provenance and peer review: Invited article; Externally peer reviewed.
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