Exercise and Insulin Resistance Markers in Children and Adolescents With Excess Weight: A Systematic Review and Network Meta-Analysis

Antonio García-Hermoso; José Francisco López-Gil; Mikel Izquierdo; Robinson Ramírez-Vélez; Yasmin Ezzatvar

doi:10.1001/jamapediatrics.2023.4038

. 2023 Oct 9;177(12):1276–1284. doi: 10.1001/jamapediatrics.2023.4038

Exercise and Insulin Resistance Markers in Children and Adolescents With Excess Weight

A Systematic Review and Network Meta-Analysis

Antonio García-Hermoso ^1,^✉, José Francisco López-Gil ^1,², Mikel Izquierdo ^1,³, Robinson Ramírez-Vélez ^1,³, Yasmin Ezzatvar ⁴

PMCID: PMC10562991 PMID: 37812414

Key Points

Question

Which type of exercise is most effective in reducing insulin resistance markers, and what is the dose-response association between exercise dose and these markers in children and adolescents with overweight and obesity?

Findings

In this systematic review and network meta-analysis of 55 studies with a total of 3051 children and adolescents, high-intensity interval training alone or combined with resistance training exerted the greatest reduction in insulin resistance markers. In addition, the minimum exercise dosage required to yield clinically meaningful improvements in fasting insulin and homeostatic model assessment for insulin resistance (HOMA-IR) was approximately 900 to 1200 metabolic equivalent of task minutes per week; however, the certainty of evidence varied from low to moderate.

Meaning

These findings suggest that youths with excess weight who engage in a minimum of two to three 60-minute sessions of moderate to vigorous activity per week, preferably through high-intensity interval training alone or combined with resistance training, achieve substantial improvements in fasting insulin and HOMA-IR.

This systematic review and network meta-analysis compares the effectiveness of exercise training modalities in reducing insulin resistance markers and the dose-response association between exercise dose and these markers in children and adolescents with excess weight.

Abstract

Importance

Although benefits have been reported for most exercise modalities, the most effective exercise approaches for reducing insulin resistance in children and adolescents with excess weight and the optimal exercise dose remain unknown.

Objective

To compare exercise training modalities and their association with changes in insulin resistance markers among children and adolescents with excess weight and to establish the optimal exercise dose.

Data Sources

For this systematic review and network meta-analysis, 6 electronic databases (PubMed, EMBASE, Cochrane Central Register of Controlled Trials, Scopus, Web of Science, and CINAHL) were searched for studies from inception to April 1, 2023.

Study Selection

Randomized clinical trials (ie, randomized controlled trials and randomized trials without a control group) were included if they reported outcomes associated with aerobic training, resistance training, high-intensity interval training (HIIT), or a combination of these interventions.

Data Extraction and Synthesis

Data extraction for this systematic review was conducted following a network meta-analysis extension of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guideline. Effect sizes were calculated as the mean difference (MD) with 95% CI using random-effects inverse-variance models with the Hartung-Knapp-Sidik-Jonkman method. The hierarchy of competing interventions was defined using the surface under the cumulative ranking curve. The Cochrane Risk-of-Bias tool, version 2 (RoB2), was used to independently assess the risk of bias of the included studies. The certainty of evidence in consistent networks was assessed using the Grading of Recommendation, Assessment, Development and Evaluation approach. The study protocol was prospectively registered with PROSPERO. Data analyses were conducted between May and June 2023.

Main Outcomes and Measures

The primary outcomes were fasting glucose, insulin, and homeostatic model assessment for insulin resistance (HOMA-IR).

Results

This analysis included 55 studies with a total of 3051 children and adolescents (mean [SD] age, 13.5 [2.3] years; 1537 girls [50.4%] and 1514 boys [49.6%]). Exercise was associated with reductions in fasting insulin (MD, −4.38 μU/mL [95% CI, −5.94 to −2.82 μU/mL]) and HOMA-IR (MD, –0.87 [95% CI, –1.20 to –0.53]). A nonlinear association in both markers was observed, with a required minimal exercise dosage of approximately 900 to 1200 metabolic equivalent of task minutes per week, especially in children and adolescents with insulin resistance at baseline. Combination HIIT and resistance training and concurrent training were the most effective approaches for reducing insulin resistance markers. On average, the certainty of evidence varied from low to moderate.

Conclusions and Relevance

These findings underscore the role of exercise interventions in enhancing insulin resistance markers among children and adolescents with overweight and obesity. It is advisable to include resistance exercises alongside aerobic and HIIT programs for a minimum of two to three 60-minute sessions per week.

Introduction

In both developed and developing countries, childhood obesity remains a major public health challenge in the 21st century.^1,2 The exact causes of childhood obesity are unclear but are believed to involve genetics, physical inactivity, unhealthy eating habits, and psychological factors.³ In children and adolescents, obesity-related insulin resistance and impaired glucose metabolism can increase the risk of developing type 2 diabetes and other metabolic disorders in adolescence and beyond.^4,5

It is crucial to promote healthy habits to prevent and manage childhood obesity,⁶ as this can help reduce the risk of developing the above-mentioned metabolic disorders.⁷ Although diet and physical activity are typically the primary approaches for treating children and adolescents with obesity,⁸ research has shown that increasing physical activity alone, rather than restricting energy intake, can be effective in improving several health outcomes, such as body composition,⁹ cardiometabolic parameters,^10,11 and cardiorespiratory fitness.^10,11 Traditional meta-analysis methods synthesize important overarching questions, but they generally do not include all study information and often ignore or are unable to account for important treatment heterogeneity in design and delivery characteristics.¹² In terms of regulation of glucose metabolism, for example, traditional meta-analysis methods cannot answer important questions about exercise variable dosage (eg, exercise intensity, exercise duration, and type of exercise)^13,14,15,16 because they compare only 2 treatments at a time and do not allow full analysis of trials investigating multiple treatment groups within studies. Therefore, although benefits have been reported for most exercise modalities,¹¹ which exercise approaches are most effective for preventing and reducing insulin resistance in children and adolescents with excess weight, as well as the optimal exercise dose, remains unknown. Network meta-analysis (NMA) methods have the potential to better identify the best approach for exercise interventions to improve insulin resistance in children and adolescents with excess weight.¹⁷

The aim of this study was 3-fold: (1) to determine the association between different exercise modalities and insulin resistance markers (eg, fasting glucose, fasting insulin, and homeostatic model assessment for insulin resistance [HOMA-IR]), (2) to establish which exercise type (eg, aerobic, resistance, high-intensity interval training [HIIT], or their combination) is most effective in reducing insulin resistance markers, and (3) to examine the dose-response association between exercise dose and insulin resistance markers in children and adolescents with excess weight.

Methods

Study Protocol and Registration

The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension Statement for Reporting of Systematic Reviews Incorporating Network Meta-analyses of Health Care Interventions (PRISMA-NMA).¹⁸ The study protocol was prospectively registered with PROSPERO (CRD42023413048).

Eligibility Criteria

Studies were included if they reported the following: (1) a study population composed of children and adolescents (aged 5-18 years) with excess weight (ie, overweight and obesity), as defined by the authors; (2) a study design that either compared 2 or more exercise interventions (categorized as aerobic or endurance, resistance or strength training, concurrent training [combination aerobic and resistance training, regardless of intensity], or HIIT [alternating short bursts of intense physical activity with brief periods of rest or lower-intensity exercise] or their combination) or compared an exercise intervention group with a comparative control group (eg, no treatment or usual care, wait-list control, or education) (ie, a randomized clinical trial [RCT]); (3) supervised exercise interventions with a duration of 4 weeks or more; and (4) a primary outcome of interest of fasting glucose, fasting insulin, and/or homeostatic model assessment (HOMA-IR). Other insulin-resistance parameters, such as quantitative insulin-sensitivity check index, 2-hour glucose, 2-hour insulin, acute insulin response, disposition index, or glycated hemoglobin, were considered as secondary outcomes. Studies that included either a dietary intervention or drug therapy in combination with exercise or participants presenting with other medical conditions (eg, diabetes) were excluded.

Information Sources and Search

The PubMed, EMBASE, Cochrane Central Register of Controlled Trials, Scopus, Web of Science, and CINAHL electronic databases were searched for studies from inception to April 1, 2023. Searches were limited to youths aged 5 to 18 years. Cross-referencing was also performed by examining the reference lists of articles that met the inclusion criteria. A librarian was consulted to supervise the quality of the search. All search strategies are detailed in eMethods 1 in Supplement 1.

Study Selection and Data Collection Process

Two authors (A.G.-H. and Y.E.) carried out the entire process of selecting literature and extracting data independently. If there were any differences in opinions, they were resolved by discussion with a third researcher (J.F.L.-G.).

The variables coded in this study were grouped into 4 major categories: (1) study characteristics, such as the author, journal, and year of publication; (2) participant characteristics, such as age, sex, and body mass index (BMI [calculated as weight in kilograms divided by height in meters squared]); (3) intervention characteristics, such as intervention type, length, frequency, dose (intensity and duration), and compliance; and (4) data for primary and secondary outcomes, including sample sizes and baseline and postexercise means (SDs). If needed, data from figures were extracted using WebPlotDigitizer, version 4.5.¹⁹ Interagreement was assessed with the Cohen κ statistic.

Risk of Bias in Individual Studies

Two reviewers (A.G.-H. and Y.E.) used the Cochrane Risk-of-Bias tool, version 2 (RoB2), to independently assess the risk of bias of the included studies.²⁰ Each study and every domain was judged as “low risk of bias,” “some concerns,” or “high risk of bias.” Any disagreements in quality ratings were solved by discussion. If consensus could not be reached, a third member of the review team (J.F.L.-G.) was consulted.

Statistical Analysis

Stata software, version 17.0 (StataCorp), was used to conduct both the traditional and dose-response meta-analysis. In addition, we employed the Confidence in Network Meta-Analysis (CINeMA) web application to perform the NMA.²¹ Publication bias was assessed using the Luis Furuya-Kanamori (LFK) index.²² Further details are presented in eMethods 2 in Supplement 1.

We assessed the certainty of evidence in consistent networks using the Grading of Recommendation, Assessment, Development and Evaluation approach (GRADE).²³ We considered 4 levels of certainty, ranging from very low to high (indicating a high likelihood of clinically meaningful differences between the true and estimated effect sizes, or a high level of confidence in the similarity between the true and estimated effect sizes, respectively). The assessment considered the risk of bias within comparisons, publication bias, indirectness, imprecision, heterogeneity, and incoherence.

P < .05 (2 tailed) was considered statistically significant. Data analysis was conducted between May and June 2023.

Results

Study Selection

Of the 1495 articles screened after duplicates were removed, 55 met our inclusion criteria (eTable 1 in Supplement 1).^{24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75} Figure 1 illustrates the identification, screening, and inclusion process. The Cohen κ statistic for interrater reliability was 0.84 (95% CI, 0.72 to 0.96). The list of excluded studies is presented in eMethods 3 in Supplement 1.

Study Characteristics

The studies included in this meta-analysis involved a total of 3051 children and adolescents with overweight or obesity (mean [SD] age, 13.5 [2.3] years; 1537 girls [50.4%] and 1514 boys [49.6%]). Baseline characteristics of participants are presented in eTable 1 in Supplement 1. Most studies were RCTs,^{24,25,26,27,28,30,31,34,35,36,37,40,41,42,43,44,45,46,47,48,49,50,51,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69,71,75,76,77,78} but 8 were RCTs with no control group.^{29,32,33,38,39,57,70,74} Although most studies included both boys and girls in their samples, 11 studies included only boys^{42,47,48,54,57,61,62,67,72,74,75} and 9 included only girls.^{25,26,34,49,51,53,64,68,73} The definition of overweight and obesity was mostly based on age and sex-specific BMI cut points. The types of exercise programs analyzed included aerobic, resistance, concurrent training, HIIT, and combination HIIT/resistance training (eTable 1 in Supplement 1).

Risk of Bias Within Studies

The results of the risk of bias analyses are shown in eTable 2 in Supplement 1. All studies were deemed to be at low risk of bias for the “randomization process” domain because we only included randomized studies. Inversely, the “deviations from intended interventions” domain was rated to be at high risk of bias in all studies due to the impossibility of blinding participants and individuals delivering the intervention to group assignment in the exercise interventions. For the rest of the items, most studies were considered to have some concerns regarding risk of bias.

Characteristics of Treatments (Traditional Meta-Analysis)

Compared with the control intervention, physical exercise favored a reduction in fasting insulin (mean difference [MD], −4.38 μU/mL [95% CI, −5.94 to −2.82 μU/mL]; P < .001; I² = 77.8%) and HOMA-IR (MD, –0.87 [95% CI, –1.20 to –0.53]; P < .001; I² = 68.2%) (eFigures 1 and 2 in Supplement 1), but not in fasting glucose (MD, −0.28 mg/dL [95% CI, −0.58 to 0.02 mg/dL]; P = .07; I² = 62.7), 2-hour oral glucose tolerance (MD, −0.57 mg/dL [95% CI, −2.15 to 1.02 mg/dL]; P = .66; I² = 0%), or glycated hemoglobin (MD, −0.04% [95% CI, −0.13% to 0.06%]; P = .41; I² = 4.5%) (eFigures 3-5 in Supplement 1). The effect size of HOMA-IR increased when we analyzed participants with levels of 3.16 or greater at baseline (MD, −1.36 [95% CI, −1.88 to −0.84]; P < .001; I² = 80.1%). A small-study effect size was observed for fasting glucose (LFK = −7.88) and 2-hour oral glucose tolerance (LFK = −6.92), but not for fasting insulin (LFK = −1.07) and HOMA-IR (LFK = 0.45).

In sensitivity analyses, we observed no notable modifications in the results for fasting insulin and HOMA-IR (eFigures 6 and 7 in Supplement 1) after removing 1 study at a time. However, the study of Kelly et al⁷⁶ significantly affected the overall results for 2-hour glucose tolerance (MD, −1.94 mg/dL [95% CI, −3.74 to −0.15 mg/dL]; P = .04) (eFigure 8 in Supplement 1). Similar results were observed for fasting glucose, in which studies by Davis et al⁷⁷ (MD, −0.35 mg/dL [95% CI, −0.69 to −0.01 mg/dL]; P = .045) and Farpour-Lambert et al⁷⁸ (MD, −0.34 mg/dL [95% CI, −0.67 to −0.01 mg/dL]; P = .043) significantly affected the overall results (eFigure 9 in Supplement 1).

Dose-Response Meta-Analysis

Figure 2 presents the nonlinear dose-response associations of exercise dose with fasting insulin and HOMA-IR. For fasting insulin, a minimal exercise dosage of approximately 900 metabolic equivalent of task minutes (MET-min) per week was required to achieve the identified MD of −4.38 μU/mL for fasting insulin, with a flattening effect at around 1500 MET-min/wk (−0.09 μU/mL [95% CI, −0.12 to −0.05 μU/mL] for every 100 MET-min; P < .001 for nonlinearity).

Similarly, for HOMA-IR, a minimal exercise dosage of approximately 1200 MET-min/wk was required to achieve the identified MD of −0.87 (−0.09 [95% CI, −0.12 to −0.06] for every 100 MET-min; P < .001 nonlinearity). Higher doses continued to contribute to marker improvements. After studies that included children and adolescents with a HOMA-IR of 3.16 or greater were selected,⁷⁹ this dose response significantly increased (−0.16 [95% CI, −0.21 to −0.10] for every 100 MET-min; P < .001 for nonlinearity) (eFigure 10 in Supplement 1).

Finally, no association was observed between exercise dose and fasting glucose (−0.13 mg/dL [95% CI, −0.28 to 0.02 mg/dL] for every 100 MET-min; P = .09 for nonlinearity) (eFigure 11 in Supplement 1).

Network Meta-Analysis

Comparisons of associations between different types of exercise and fasting glucose, insulin, and HOMA-IR levels are presented in Figure 3. The NMA estimates (Table) suggested that aerobic training, concurrent training, and combination HIIT/resistance training substantially decreased fasting glucose levels compared with the control intervention. Specifically, the MD was −1.43 mg/dL (95% CI, −2.70 to −0.71 mg/dL) for aerobic training, −2.81 mg/dL (95% CI, −4.80 to −0.93 mg/dL) for concurrent training, and −5.01 mg/dL (95% CI, −8.78 to −1.37 mg/dL) for HIIT/resistance training.

Table. Network Meta-Analyses of the Association Between Exercise and Insulin Resistance Markers in Children and Adolescents With Excess Weight^a.

Marker	Aerobic	Resistance	Concurrent	HIIT	HIIT/resistance
Fasting glucose (mg/dL)
Resistance	−0.55 (−2.86 to 1.77)
Concurrent	−1.26 (−3.48 to 0.77)	0.71 (−1.94 to 3.68)
HIIT	0.16 (−2.16 to 2.64)	−0.72 (−3.92 to 2.46)	1.42 (−1.57 to 4.48)
HIIT/resistance	−3.54 (−7.37 to 0.25)	2.99 (−1.21 to 7.13)	−2.28 (−6.06 to 1.77)	−3.70 (−7.84 to 0.51)
Control	−1.49 (−2.73 to −0.39)^b	−2.04 (−4.30 to 0.21)	−2.75 (−4.95 to −0.79)^b	−1.32 (−3.71 to 0.96)	−5.02 (−8.71 to −1.34)^b
Fasting insulin (μU/mL)
Resistance	−0.58 (−2.98 to 1.61)
Concurrent	−1.28 (−3.47 to 0.72)	0.70 (−2.03 to 3.28)
HIIT	0.29 (−2.04 to 2.53)	−0.86 (−3.90 to 2.21)	1.56 (−1.28 to 4.59)
HIIT/resistance	−3.64 (−7.28 to −0.02)^b	3.06 (−1.08 to 7.13)	−2.37 (−5.97 to 1.46)	−3.93 (−7.72 to 0.15)
Control	−1.48 (−2.72 to −0.32)^b	−2.05 (−4.37 to 0.13)	−2.75 (−4.90 to −0.79)^b	−1.19 (−3.58 to −1.09)	−5.12 (−8.83 to −1.54)^b
HOMA-IR
Resistance	0.18 (−1.20 to 1.51)
Concurrent	−0.33 (−0.96 to 0.28)	0.50 (−0.87 to 1.84)
HIIT	−0.19 (−0.93 to 0.54)	0.37 (−1.12 to 1.78)	0.14 (−0.74 to 0.99)
HIIT/resistance	−0.51 (−1.42 to 0.46)	0.69 (−0.89 to 2.23)	−0.18 (−1.06 to 0.80)	−0.32 (−1.34 to 0.72)
Control	−0.71 (−1.20 to −0.24)^b	−0.53 (−1.84 to 0.72)	−1.03 (−1.57 to −0.52)^b	−0.90 (−1.62 to −0.22)^b	−1.22 (−2.04 to −0.36)^b

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Abbreviations: HIIT, high-intensity interval training; HIIT/resistance, combination HIIT and resistance training; HOMA-IR, homeostasis model assessment of insulin resistance; MD, mean difference.

^{^a}

Data are expressed as the MD (95% CI). Comparisons should be read from left to right. Values correspond to differences in MDs (95% CIs) between column and row; for positive values, the exercise protocol indicated in the column is favored (eg, aerobic training had a mean fasting glucose loss of 0.55 mg/dL compared with resistance training).

^{^b}

P < .05.

Similarly, the NMA estimates suggested that participants in the aerobic training, concurrent training, and HIIT/resistance training groups had substantially decreased fasting insulin levels compared with the control group. The MD was −1.42 μU/mL (95% CI, −2.64 to −0.34 μU/mL) for aerobic training, −2.70 μU/mL (95% CI, −4.74 to −0.82 μU/mL) for concurrent training, and −4.98 μU/mL (95% CI, −8.85 to −1.28 μU/mL) for HIIT/resistance training.

Furthermore, the NMA estimates suggested that aerobic training, concurrent training, HIIT, and HIIT/resistance training substantially diminished HOMA-IR levels compared with the control intervention. The MD was −0.70 (95% CI, −1.17 to −0.26) for aerobic training, −0.87 (95% CI, −1.57 to −0.19) for HIIT, −1.03 (95% CI, −1.58 to −0.56) for concurrent training, and −1.20 (95% CI, −2.09 to −0.41) for HIIT/resistance training.

Intervention Ranking

For fasting glucose levels, combination HIIT/resistance training had the highest surface under cumulative ranking (SUCRA) (93.9%), followed by concurrent training (70.9%). In terms of fasting insulin, HIIT/resistance training had the highest SUCRA (94.7%), followed by concurrent training (72.0%). For HOMA-IR, HIIT/resistance training had the highest SUCRA (95.1%), followed by concurrent training (69.4%) (eFigure 12 in Supplement 1).

Certainty of NMA Evidence

eFigure 13 in Supplement 1 presents the results provided by the CINeMA approach for the NMA. Most comparisons had “some concerns” for the domains within-study bias and reporting bias domains. The incoherence, heterogeneity, and imprecision domains were also assessed as having “some concerns” for most comparisons, which affects confidence in the results. We considered a meaningful clinical difference in fasting glucose, insulin, and HOMA-IR to be −0.28 mg/dL, −4.38 μU/mL, and −0.87, respectively, based on MDs observed in traditional meta-analyses. Overall, only 2 of 15 comparisons for fasting glucose, 5 of 15 for fasting insulin, and 4 of 15 (for HOMA-IR) were considered to have a high confidence rating.

Discussion

The results of this study suggest that exercise was associated with reductions in fasting insulin and HOMA-IR in children and adolescents with overweight and obesity. A notable finding is the nonlinear association of exercise dose with fasting insulin and HOMA-IR, with a minimal dosage requirement of approximately 900 to 1200 MET-min/wk, equivalent to two to three 60-minute sessions of moderate to vigorous activity per week. Furthermore, higher exercise doses contributed to continued improvement in the HOMA-IR marker. Combination HIIT/resistance training and concurrent training were ranked as the best exercise interventions for reducing all insulin resistance markers.

Overall, our results are consistent with previous meta-analyses in this population,^13,14 which reported slightly lower effect sizes in fasting insulin and HOMA-IR. These findings are highly relevant because impaired insulin sensitivity, which may appear prior to glucose dysregulation in youths,⁸⁰ is a major component of obesity and comorbid disease, such as type 2 diabetes and cardiovascular disease. In contrast, our findings related to fasting glucose differ from those reported by García-Hermoso et al,¹³ who observed a reduction in fasting glucose in children and adolescents with obesity. Studies that analyzed 2-hour glucose concentration after glucose tolerance testing, a more robust and valid assessment to determine insulin sensitivity,⁸¹ showed inconsistent results, which are reflected in our meta-analysis.

Another relevant finding is the nonlinear association of exercise dose with fasting insulin and HOMA-IR, with a minimal exercise dose requirement of approximately 900 to 1200 MET-min/wk, equivalent to at least two to three 60-minute sessions of moderate to vigorous activity per week. This finding is consistent with results reported by Davis et al,²⁴ who investigated the association between different doses of aerobic exercise (with no dietary restrictions) and oral glucose tolerance in children with overweight and obesity. Their exercise program was administered 5 days per week, with sessions lasting either 20 minutes (low dose) or 40 minutes (high dose). After 3 months, the researchers noted a trend toward a dose-response association, as reductions in the insulin area under curve were greater in both the high-dose and low-dose exercise groups (adjusted MD, −3.56 and −2.96 μU/mL) compared with the control group. Therefore, these findings suggest that even a modest increase in physical activity per week can yield notable improvements in insulin sensitivity. Therefore, incorporating exercise interventions into the management of overweight and obesity in children and adolescents is a promising strategy for improving insulin resistance and preventing the development of cardiometabolic disease.

Our NMA highlights combination HIIT/resistance training and concurrent training as the most efficient exercise protocols for reducing insulin resistance in this population.¹⁶ Performing HIIT, with or without resistance training, induces metabolic stress on the muscles, leading to increased glucose uptake.⁸² Consequently, insulin sensitivity is improved in this population.²⁵ High-intensity interval training has been demonstrated to enhance insulin sensitivity and glycemic control in several populations, including those with and without cardiometabolic disease.⁸² Therefore, these findings highlight the importance of incorporating muscle strength training into HIIT. For instance, Racil et al²⁶ observed substantial reductions in blood glucose and insulin concentrations in girls with obesity who participated in 12 weeks of HIIT combined with plyometric exercises.

Our finding that concurrent training is the second most efficient exercise protocol for reducing insulin resistance in children and adolescents with overweight or obesity aligns with the study by Kelley et al,¹⁰ which ranked these protocols as the best for reducing fat mass and the percentage of fat in a similar population. In addition, García-Hermoso et al¹⁵ demonstrated that concurrent exercise is more efficient for increasing lean body mass and adiponectin concentration compared with aerobic training alone.

Several mechanisms could explain our results. First, reducing fat mass can decrease inflammation in adipose tissue, thereby improving insulin sensitivity.⁸³ Second, larger muscle mass requires more glucose uptake to support energy demands⁸⁴ and implies a greater quantity of mitochondria present, enhancing muscle capacity to oxidize substrates like glucose and free fatty acids.⁸⁵ Finally, increased adiponectin concentration is associated with increased insulin sensitivity.⁸⁶

Limitations

This study has several limitations. First, our results were limited by the quality of the included evidence, which was judged to have a low to moderate confidence rating for most treatment comparisons. Second, some treatments (eg, HIIT and combination HIIT/resistance training) had limited data, potentially affecting the statistical power to detect clinically meaningful effect sizes. In addition, unexplained heterogeneity persisted despite exploration of multiple populations, exercise types, and methodological characteristics, impacting the confidence in the available evidence. Third, variation in criteria to define overweight and obesity in the included studies may have influenced our findings. Fourth, the study was focused on fasting glucose, fasting insulin, and/or HOMA-IR as primary outcomes, which may have led to a narrow perspective on the association between exercise and insulin resistance, potentially overlooking other critical secondary outcomes. Finally, the estimation of METs could have resulted in deviation from the actual energy expenditure of physical exercise programs.

Conclusions

Our findings in this systematic review and NMA suggest that incorporating resistance exercises alongside aerobic training and HIIT programs may reduce insulin resistance markers in children and adolescents with overweight or obesity. To achieve clinically meaningful improvements in fasting insulin and HOMA-IR, the minimal dosage of exercise is approximately 900 to 1200 MET-min/wk, which corresponds to two to three 60-minute sessions of moderate to vigorous activity per week. However, the certainty of evidence varied from low to moderate. It will be crucial to further investigate and establish minimum physical activity recommendations that effectively address insulin resistance, prevent metabolic syndrome, and reduce type 2 diabetes risk in this specific population.

Supplement 1.

eMethods 1. Electronic Search Strategy

eTable 1. Table of Characteristics

eMethods 2. Data Analysis

eMethods 3. Excluded Studies and Reasons for Exclusion

eTable 2. Results of the Cochrane Risk-of-Bias Tool for Randomized Controlled Trials (RoB-2)

eFigure 1. Effect of Exercise Programs on Fasting Insulin in Children and Adolescents With Excess Weight

eFigure 2. Effect of Exercise Programs on Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) in Children and Adolescents With Excess Weight

eFigure 3. Effect of Exercise Programs on Fasting Glucose in Children and Adolescents With Excess Weight

eFigure 4. Effect of Exercise Programs on 2-Hour Oral Glucose Tolerance in Children and Adolescents With Excess Weight

eFigure 5. Effect of Exercise Programs on Glycated Hemoglobin in Children and Adolescents With Excess Weight

eFigure 6. Sensitivity Analyses Once Each Study Was Excluded for Fasting Insulin

eFigure 7. Sensitivity Analyses Once Each Study Was Excluded for Homeostatic Model Assessment for Insulin Resistance (HOMA-IR)

eFigure 8. Sensitivity Analyses Once Each Study Was Excluded for 2-Hour Oral Glucose Tolerance

eFigure 9. Sensitivity Analyses Once Each Study Was Excluded for Fasting Glucose

eFigure 10. Dose-Response Association Between Metabolic Equivalent of Task Minutes (MET-min) per Week and Differences in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) in Children and Adolescents With Excess Weight and Insulin Resistance (ie, HOMA-IR≥3.16)

eFigure 11. Dose-Response Association Between Metabolic Equivalent of Task Minutes (MET-min) per Week and Differences in Fasting Glucose in Children and Adolescents With Excess Weight

eFigure 12. Rankogram for Each Type of Physical Exercise

eFigure 13. Network Meta-Analysis Confidence Rating for Glucose, Insulin, and Homeostatic Model Assessment for Insulin Resistance Outcomes

eReferences

Click here for additional data file.^{(3.1MB, pdf)}

Supplement 2.

Data Sharing Statement

Click here for additional data file.^{(13.5KB, pdf)}

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