2.1. Protocol and registration
This systematic review and meta-analysis will be prepared according to the guidelines of the Cochrane Handbook [22]. Regarding the protocol, it will be carried out according to the PRISMA-P statement [18], and the report will be made according to the PRISMA Statement [19]. Finally, it will be registered in PROSPERO: CRD42021275758.
2.2. Eligibility criteria
The acronym PICOTS will be used [23] (P: population/patient/problem, I: intervention, C: comparator or control, O: outcome, T: time/duration, S: study design) to guide the selection of the studies of the as follows:
2.2.1. Participants
Trained and untrained adult women and men (≥ 18 years) diagnosed with MetS [1]–[9], or who meet 3 of the diagnostic criteria for MetS [7]:
Table 1. Harmonizing the Metabolic Syndrome
Measurements / Biomarkers | Categorical cut points |
Men | Women |
Elevated waist circumference | White canadians, americans o europeans: 94cm; people from Asia, Africa or the Middle East, or indigenous people from North or South America: 90cm** | White canadians, americans o europeans: 80cm; people from Asia, Africa or the Middle East, or indigenous people from North or South America: 80cm ** |
Elevated triglycerides (drug treatment for elevated triglycerides is an alternative indicator) | ≥ 150 mg/dL (≥ 1.7 mmol/L) |
Reduced HDL-C (drug treatment for reduced HDL-C is an alternative indicator) | ˂40 mg/dL (˂1.0 mmol/L) | ˂50 mg/dL (˂1.3 mmol/L) |
Elevated blood pressure (treatment with antihypertensive drugs in a patient with a history of hypertension is an alternative indicator) | Systolic ≥ 130 and / or diastolic ≥ 85 mmHg |
Elevated fasting glucose (drug therapy for elevated glucose is an alternative indicator) | ≥ 100 mg / dL (≥ 5.6 mmol/L) |
mg/dL: milligram/deciliter, mmol/L: millimoles per litre, mmHg: millimeter of mercury |
2.2.2. Intervention
Randomized controlled trials (RCTs) on dynamic resistance exercise whose interventions progress greater than or equal to 80% of 1RM will be included. In enunciate 1 details the definition of dynamic resistance exercise.
Enunciate 1. Definition of dynamic resistance exercise
Exercise programs that combine neural and morphological elements, which contain motor unit recruitment and synchronization, muscle cross-sectional area, frequency coding, muscle-tendon stiffness, and neuromuscular inhibition at vigorous relative or absolute intensities, where it is required to exert some type of isometric or dynamic resistance [12], [24], [25] whether with weights, machines, rubber bands, water, or immovable objects and this type of resistance exercise is a combination of dynamic contractions that involve shortening and lengthening of skeletal muscles [13].
2.2.3. Comparator
Aerobic exercise of any type of intensity, usual care or doing nothing.
2.2.4. Primary outcomes
2.2.4.1. Central obesity
Also called abdominal obesity, it is excess fat in and around the abdomen [26]. It is evaluated by measuring the WC. See Table 1 for more details on the waist circumference thresholds.
2.2.4.2. Dyslipidemia
Abnormalities in serum lipid levels, including overproduction or deficiency [27]. For the diagnosis of MetS, it is commonly evaluated by blood sample and TG and HDL values are taken. See Table 1 to expand these values.
2.2.4.3. Fasting glucose
Measure of abnormally elevated free glucose concentration in blood, serum, or blood plasma; It is often called pre-diabetes [28]. The FG it is habitually evaluated by a blood sample. Table 1 shows the categorical cut-off points.
2.2.4.4. Blood pressure
Measurement of the force exerted against the walls of the arteries as the heart pumps blood through the body; this is recorded by two measurements: SBP and DBP [29]. Table 1 reflects these values.
2.2.4.5. Secondary outcomes
2.2.4.5.1. Cardiorespiratory fitness
Measure of the functional capabilities of the heart, lungs, and muscles, relative to the demands of specific exercise routines, such as running or weight lifting [30]. It is evaluated by oxygen consumption tests (VO², VO² Max, VO² peak) [31].
2.2.4.5.2. Quality of life
Generic concept that reflects the concern for the modification and improvement of the attributes of life: physical, mental, social environment, etc., as well as health and disease [32]. Usually, it is evaluated through questionnaires, either generic or specific.
2.2.4.5.3. Adverse events
It is any sign, symptom, laboratory result or unexpected disease with an unfavorable impact, temporarily associated with a treatment, intervention or procedure (therapeutic, prophylactic, anesthetic, surgical or other of a condition), which may or may not be related with these interventions [33].
Table 2
Grades | Name | Comment |
1° | Mild adverse event | Mild or asymptomatic symptoms, clinical or diagnostic observations only and/or intervention not indicated |
2° | Moderate adverse event | Moderate, minimal, local, or non-invasive intervention and/or limitation of age-appropriate activities of daily living is required |
3° | Serious adverse event | Serious or medically significant but not immediately life-threatening, hospitalization and its prolongation, incapacitation and limitation of self-care activities of daily living is indicated |
4° | Adverse event with risk of mortality or disability | Consequences that are life-threatening and require urgent indicated intervention |
5° | Death associated with an adverse event | Death |
On the other hand, these will be grouped as adverse events reported in the study not related to exercise, and/or adverse events associated with exercise that their occurrence was reported during exercise or was a direct result of it. In addition, any withdrawal for health, medical or MetS related reasons will be considered as an adverse event of the disease (Eg. stroke), or if the severity of the event was not reported and this involved the withdrawal of a participant in the study, will be qualified grade 3. On the contrary, withdrawals for reasons not related to health (Eg: travel, time constraints), or that do not report the occurrence of adverse events will not be taken into account as such events [34]. It should be clarified that the RCTs must state in greater detail the reasons for dropouts or withdrawals in the study.
2.2.5. Time
According to primary and secondary studies, statistically significant and clinically relevant effects were found for some clinical biomarkers of MetS by means of dynamic resistance exercise in a minimum duration of 8 weeks [17], [35].
2.2.6. Study design
It will be a systematic review and meta-analysis of RCTs. The systematic reviews collect evidence that meets pre-specified eligibility criteria to answer a specific and well-asked research question, documented a priori with a protocol to produce more reliable results that inform decision-making [18], [22]. On the other hand, RCTs are defined as experimental comparative studies with two groups: control and intervention, where the assignment of the participant to a group is determined by randomization, which provides that all participants have the same probability of be assigned to a group and tends to produce comparable groups [36].
2.2.7. Setting and language
There will be no restrictions on date or language.
2.2.8. Exclusion criteria
Controlled trials in progress and that have performed interventions with pregnant or lactating women will be excluded from this review. RCTs, whose comparators have been nutritional proposals or pharmacology, will not be taken into account. Likewise, RCTs that have compared resistance exercise with medicaments, yoga, tai chi, flexibility and Qigong will not be integrated. Finally, studies that do not clearly present the components of the FITTVP (Frequency, Intensity, Time, Type, Volume and Progression) will not be taken into account for this review.
2.3. Information resources and search strategy
A systematic search will be carried out according to the PRISMA-S [20] in the international electronic databases PubMed, EBSCO, Cochrane Central Register of Controlled Trials (CENTRAL), Ovid, ScienceDirect, Scopus and Clinical Trials. Likewise, studies will be searched in gray literature repositories such as: OpenSIGLE, PsycEXTRA, HMIC (Healthcare Management Information Consortium) and NTIS (The National Technical Information Service). Finally, a manual search of the reference lists provided in the selected articles will be developed, as well as previous systematic reviews and meta-analytic studies to detect potentially eligible studies, between August and September 2021, independently by two blinded reviewers (LP and EP) according to the Cochrane Handbook [22]
The search strategy that will be used in PubMed will be modified to be used in the other databases. All search strategies for each database are reported in the supplementary material. Defined filters based on advanced search guidelines will be applied to each database. Likewise, the list of all potential references and possibly included in the range of the eligibility criteria will be inspected.
2.4. Study selection and data extraction
One reviewer (LP) will export to Rayyan QCRI [37] references, and two independent and blinded reviewers (DH and LP) analyze all retrieved trials according to the eligibility criteria. Also the same pair of reviewers (DH and LP) will be in charge of systematically extracting the relevant data from each study to a computer-programmed spreadsheet. If necessary, it will be considered to contact the authors of the studies in order to clarify or obtain incomplete data. In addition, the participation of the third reviewer (EP) will be involved if there are discrepancies in the process.
The blinded reviewers (DH and LP) will independently extract the following information: characteristics of included studies: first author, country, year of publication, sex, age, sample size, MetS diagnosis, training status, duration of intervention, evaluated outcomes, post-intervention results and comments; components of the dynamic resistance program: FITT-VP (Frequency, Intensity, Time, Type, Volume and Progression) and means
2.5. Risk of bias assessment
Likewise, the group of reviewers (LP and EP) will independently assess the risk of bias with the RoB1 (Revised Cochrane risk-of-bias tool for Randomized Trials) [22] tool, according to the criteria established in the Cochrane Handbook for Systematic Reviews of Health Interventions, through 7 domains: random sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcomes assessment, incomplete outcome data, selective reporting and other bias. Each criterion will be attributed as low, high or unclear risk of bias.
Unclear risk of bias criterion will be distinguished as long as the ability of the reviewers to establish the potential for bias could not be determined through the main study or communication with the author.
2.6. Report of Exercise Interventions in Vigorous Intensity Dynamic Resistance Exercise Programs
The CERT (Consensus on Exercise Reporting Template) [38] tool will be used to assess the completeness of the report of vigorous intensity dynamic resistance exercise interventions. Two reviewers (LP and EP) blinded and independently will use the tool to the included RCTs.
2.7. Statistical analysis
Regarding continuous results: group size, mean values and standard deviations (SD) will be recorded for each group compared in the chosen trials. The pooled effects will be calculated using an inverse variance model and the data will be pooled to generate the post-intervention mean differences with a 95% confidence interval (CI), setting the statistical significance at p < 0.05. A random effects model [39] will be used.
In the event that quality of life has been assessed by 2 or more studies with different assessment instruments, the standardized mean difference (SMD) will be used according to Cohen's guidelines [40] (no effect < 0.2, small effect 0.2 to 0.49, effect moderate 0.5 to 0.79, large effect ≥ 0.80) to inform the magnitude of the effect and help with the interpretation of SMD; if the above described is not presented, this analysis will be reported based on the difference in post-intervention means.
Where possible, assessment of adverse events will be presented as a tally variable, using a Mantel-Haenszel random effects model to pool and compare the total number of adverse events in the dynamic resistance exercise versus usual care, and the risk difference (RD) will be calculated with a 95% CI, with a positive value for RD that favors the safety of exercise, in other words, indicates a lower risk of adverse events with exercise compared to attention. RD will be used as a measure of effect to ensure that RCTs reporting zero adverse events (no difference between exercise and usual care) were not excluded from the meta-analysis. Probably, grade 1 to 2 events are less reported in control groups due to distancing with the investigators, and contain normal physiological responses to exercise (Eg, mild musculoskeletal symptoms), rather than possibly avoidable adverse events [34]. Therefore, only grade 3 or higher adverse events will be included. Finally, all analyzes will be done by a reviewer (LP) using Review Manager version 5.4.1 [41] and an author (EP) will verify them with the extracted data.
Statistical heterogeneity will be assessed with the Higgins test (I2) and classified according to the Cochrane Handbook [22]: insignificant heterogeneity 0–40%, moderate 30–60%, substantial 50–90% and considerable heterogeneity from 75–100%.
Subject to data availability, the following subgroup analyzes [39] will be performed: age, gender, frequency, intensity, duration, means, and training status. Likewise, a sensitivity analysis will be performed, with drawing studies with low methodological quality in the domains of random sequence generation, allocation concealment, and evaluator blinding. Regarding adverse events, subgroup analyzes [39] will be carried out: exercise modality, exercise supervision, duration and quality of the study; in addition, a sensitivity analysis will be performed excluding studies that did not report whether adverse events were measured. Finally, the funnel plot will be used to assess publication bias in in the outcomes presented by 10 or more studies.
2.8. Assessment of the quality of the evidence
The GRADE (Grading of Recommendations, Assessment, Development and Evaluation) [42] approach will be used to assess the certainty and resistance of the evidence in the findings provided by the included RCTs, specifying four levels of quality: high certainty, moderate certainty, low certainty, very low certainty. Finally, the AMSTAR (Assessing the Methodological Quality of Systematic Reviews) [43] tool will be used to assess the quality of this review.