Impact of concurrent aerobic and resistance training on body composition, lipid metabolism and physical function in patients with type 2 diabetes and overweight/obesity: a systematic review and meta-analysis

Registration

The study protocol was registered on the Open Science Framework (https://osf.io/evt3w/?view_only=e4b33d370929417ab12c8a3a9e4e9d03).

Literature search strategy

Following a systematic electronic search, articles were gathered from six databases (e.g., PubMed, Scopus, Web of Science, Cochrane Library, Science Direct, and Google Scholar). Four authors (S.B.A.M., A.B.D., H.A., and M.G.) used a combination of keywords and Boolean operators, specifically “OR” and “AND,” to conduct the search until August 7, 2024. The keywords used were (“Diabetes”) AND (“Exercise” OR “Training”), as outlined in Table S1, to retrieve relevant articles. The search strategy was based on keywords related to the PICOS framework (P) Population: T2DM patients with overweight or obesity; (I) Intervention: CART; (C) Comparator: other forms of exercise, non-exercising controls, or standard treatment without exercise; (O) Outcomes: body mass, waist-to-hip ratio, body fat, fat mass, lean body mass, HDL-C, LDL-C, TC, TG, FBG, and physical function; and (S) Study type: randomized controlled trials (RCTs) and controlled clinical trials. A comprehensive examination of the reference lists of the included articles, as well as those of all relevant systematic reviews, was conducted to identify additional articles that met the established inclusion criteria.

Eligibility criteria

The following criteria were used to determine the inclusion of studies in the present analysis: Firstly, the participants were patients diagnosed with T2DM, exhibiting a BMI ranging from 25 to 29.9 kg/m², indicating a state of pre-obesity, or an BMI of 30 kg/m² or higher, categorically designated as obesity. The studies were required to have no specified age limit for participants. The intervention in the studies was required to be CART. The studies were required to investigate at least one of the following primary outcomes in humans: anthropometry (body mass and waist-to-hip ratio), body composition (body fat, fat mass, and lean body mass), lipid metabolism (HDL-C, LDL-C, TC, and TG), and glucose metabolism (FBG). Physical function, as measured by the 6-min walk test and the 30-s sit-to-stand test, was also included as a secondary outcome due to its connection with various cardiometabolic health-related markers. The following criteria were applied to the selection of articles: (v) full-text access was provided, and the articles were published in a peer-reviewed journal from inception until August 7, 2024; (vi) no language restrictions were imposed; and (vii) the studies were RCTs or controlled clinical trials. The following articles were excluded from the analysis: (i) articles that did not assess the relevant outcome measures; (ii) studies involving acute exercise interventions; and (iii) review articles, case reports, studies without a control group, or those with unclear or ambiguous data.

Study selection

Four authors (S.B.A.M., A.B.D., H.A., and M.M.) employed a linear evaluation approach to assess the eligibility criteria. A meticulous examination of the titles, abstracts, and full texts (in instances of uncertainty) was conducted, followed by a thorough evaluation of the remaining articles based on the qualifying criteria. Ultimately, a decision was arrived at. In instances of disagreement or uncertainty, a fifth author (W.S.W.G.) provided assistance by independently implementing the same method. The literature search records were meticulously organized using literature management software (EndNote X9; Clarivate Analytics, Philadelphia, PA, USA).

Data extraction

Two authors (S.B.A.M. and A.B.D.) independently reviewed the full texts of the relevant studies to sample and extract data. The included studies provided substantial data, which was collected and documented, including the first author, publication year, population, gender, sample size, description of the exercise intervention, study length, and outcomes.

Risk of bias assessment

Two authors (S.B.A.M. and A.B.D.) independently evaluated the risk of bias in individual studies following the Cochrane Handbook for Systematic Reviews of Interventions (Higgins et al., 2019). The overall risk of bias for each eligible study was determined according to the following factors: First, the random sequence generation was assessed. Second, the allocation concealment was evaluated. Third, the blinding of participants and personnel was considered. Fourth, the blinding of outcome assessors was examined. Fifth, the completeness of outcome data was assessed. Sixth, the selectivity of outcome reporting was evaluated. Finally, other biases, as described in the Cochrane Handbook for Systematic Reviews of Interventions (Table S2), were considered. The categorization of eligible studies was conducted into three risk levels (high, some concerns, and low) based on the number of factors exhibiting high, unclear, or low risk of bias.

Data analysis

All analyses were conducted using Review Manager 5.4 software (Cochrane Collaboration, https://revman.cochrane.org/info). A random-effects model was employed to present the outcomes, and Cochran’s Q test along with the I² test were used to evaluate heterogeneity. In instances where I² exceeded 50%, a fixed-effects model was implemented to calculate the pooled results, and a subgroup analysis was conducted. The effect size was determined using mean differences (MD) or standardized mean differences (SMD) with 95% confidence intervals (CI). A two-sided p-value of less than 0.05 was considered statistically significant. The GRADEpro methodology (https://www.gradepro.org) was employed to assess the reliability of the evidence, classifying studies as low-, moderate-, or poor-quality evidence (Table S3).

Literature search and selection

From the specified databases, PubMed, Web of Science, Scopus, Science Direct, Cochrane Library, and Google Scholar (Fig. 1), a total of 22,878 studies were obtained. After removing duplicate articles, the number of studies eligible for further evaluation was reduced to 21,195. Through a review of the titles and abstracts based on predetermined inclusion and exclusion criteria, 21,159 studies were excluded. Subsequently, the full text of the remaining 36 articles was carefully examined, excluding 14 articles with reasons. However, two records were subsequent studies of eligible trials included in the present review. Thus, a total of 20 studies were finally included in this review, and data were extracted from 1,289 patients (age: 57.0 ± 7.0; BMI: 31.1 ± 4.6 kg/m²) who met the eligibility criteria (Fig. 1 and Tables S4 and S5).

Literature characteristics

Fourteen out of the 20 studies were from high-income countries (Annibalini et al., 2017; Cuff et al., 2003; Dunstan et al., 1998; Ferrer-García et al., 2011; Gibbs et al., 2012; Hale et al., 2022; Lambers et al., 2008; Loimaala et al., 2003; Magalhães et al., 2019; Maiorana et al., 2002; Scheer et al., 2020; Sigal et al., 2007; Swift et al., 2012; Tessier et al., 2000), two studies, were from upper-middle-income countries (Jorge et al., 2011; Tan, Li & Wang, 2012), and four studies, were from lower-middle-income countries (Motahari Rad et al., 2023; Sabouri et al., 2021; Yavari et al., 2012; Zarei et al., 2021). Only one out of the 20 studies was conducted in a non-clinical setting (home-based intervention). Nine studies conducted short-term exercise interventions lasting 8–12 weeks and 11 studies conducted long-term exercise interventions lasting 16–60 weeks (Table 1).

Risk of bias assessment results

The summary of the risk of bias assessment is shown in Fig. 2. Details of the risk of bias judgment per domain for each study are provided in Fig. 3. Specifically, the large majority of eligible studies showed concerns about the randomization, allocation concealment, blinding of participants/personnel and outcome assessment. On the other side, the majority of studies demonstrated a low risk of bias in missing outcome data and a selective reporting process.

Primary outcomes

Anthropometry

Body mass was reported in 15 trials involving 795 participants, showing no differences between CART and ST (SMD −0.05, 95% CI [−0.66 to 0.56]; I² = 93%; p = 0.94) following either short- (≤16 weeks) or long-term (>16 weeks) interventions (Fig. 4 and Table S3). The waist-to-hip ratio was assessed in six trials (n = 152), demonstrating no meaningful change between CART and ST (SMD −0.26, 95% CI [−0.69 to 0.17]; I² = 41%; p = 0.24) (Fig. 5 and Table S3).

Body composition

Body fat was measured in ten trials (n = 551). CART demonstrated a significant reduction in body fat (SMD −0.42, 95% CI [−0.70 to −0.15]; I² = 56%; p = 0.002) compared to standard treatment, showing low-quality evidence (Fig. 6 and Table S3). Fat mass and lean body mass were included in three trials, involving 168 and 179 participants, respectively. No differences were found in both fat mass (SMD −0.19, 95% CI [−0.50 to 0.11]; I² = 0%; p = 0.22) and lean body mass (SMD −0.02, 95% CI [−0.33 to 0.30]; I² = 0%; p = 0.92) between CART and standard treatment (Figs. 7 and 8, Table S3).

Lipid metabolism

HDL-C, LDL-C, TC and TG were reported in 11 trials, involving 576, 589, 376 and 626 participants, respectively. CART induced a meaningful increase in HDL-C (SMD 0.44, 95% CI [0.05–0.82]; I² = 76%; p = 0.03) compared to standard treatment, showing very low-quality evidence (Fig. 9, Table S3). CART exhibited significant reductions in LDL-C (SMD −0.32, 95% CI [−0.62 to −0.02]; I² = 63%; p = 0.03), TC (SMD −0.35, 95% CI [−0.58 to −0.12]; I² = 16%; p = 0.003), and TG (SMD −0.48, 95% CI [−0.71 to −0.24]; I² = 44%; p < 0.001) with low-quality evidence between CART and standard treatment (Figs. 10–12, Table S3).

Glucose metabolism

FBG reported nine trials involving 387 participants and showing high-quality evidence. CART demonstrated a reduction in FBG (SMD −0.40, 95% CI [−0.70 to −0.10]; I² statistic = 47%; p = 0.009) (Fig. 13 and Table S3) compared to standard treatment.

Secondary outcomes

Physical function

6-min walk test

The 6-min walk test was reported in two trials (n = 60). CART exerted a meaningful increase in cardiorespiratory fitness (SMD 78.78, 95% CI [46.30–111.25]; I² statistic = 0%; p < 0.001 compared to standard treatment, demonstrating moderate-quality evidence (Fig. 14 and Table S3).

30-s sit to stand test

The 30-s sit-to-stand test was used in two trials (n = 84). CART exhibited a significant improvement in lower body muscular strength (SMD 5.19, 95% CI [1.80–8.59]; I² statistic = 59%; p = 0.003) compared to standard treatment, showing low-quality evidence (Fig. 15 and Table S3).

Anthropometry and body composition

Populations with metabolic dysregulation often experience abdominal obesity, which is associated with visceral and ectopic fat, contributing to chronic inflammation that exacerbates insulin resistance (Moore & Shah, 2020). This review suggests that CART improves body fat but does not significantly affect other anthropometric or body composition parameters in individuals with T2DM and overweight/obesity. These findings highlight the need for further investigation into these important variables, as the observed changes remain uncertain. Given that weight management is crucial for individuals with poor metabolic health, our results are particularly relevant for people with T2DM and concomitant overweight/obesity.

CART has been recognized as the most effective form of exercise for improving various anthropometric and body composition measures in individuals with excess weight (Batrakoulis et al., 2018, 2022a; Yapici et al., 2023). Other relevant studies have shown similar effects of CART on anthropometry and body composition in individuals with T2DM and concurrent overweight/obesity (Pan et al., 2018; Zhao et al., 2021). However, further randomized controlled trials (RCTs) are needed to determine whether CART can induce beneficial changes in visceral adiposity, which is linked to higher cardiovascular disease morbidity and mortality risks (Moore & Shah, 2020).

Lipid metabolism

Individuals with T2DM and concurrent overweight/obesity are likely to experience poor lipid profile, promoting cardiovascular complications (Costanzo et al., 2015; Tan et al., 2023). Following the current guidelines published by the American Diabetic Association, it is crucial for these people to maintain normal blood lipid levels, aiming to reduce the risk of developing comorbidities (Colberg et al., 2016). In our review, CART exhibited meaningful improvements in blood lipids. In general, various exercise modes induce favorable alterations in lipid homeostasis in people with T2DM (Kelley & Kelley, 2007; Magalhães et al., 2020), which is an observation aligned with the present results. Such an outcome cannot be explained here; however, the presence of excessive weight in conjunction with T2DM may play some role in the simultaneous control of glucose and lipid metabolism due to a complex, low-grade chronic inflammation. Also, CART appears the best exercise mode for improving lipid profile among individuals with an unhealthy weight (Batrakoulis, 2022a) however, several alternative types of exercise induce positive alterations in blood lipids and lipoproteins among populations with metabolic health impairments and excessive weight (Batrakoulis, 2022a, 2022b, 2022c; Batrakoulis & Fatouros, 2022) promoting time-efficient and positive experiences in this population within real-world gym settings.

Glucose metabolism

Our results indicate that CART significantly reduces FBG in individuals with T2DM and concurrent overweight/obesity. Notably, these reductions in FBG are associated with a decreased risk of developing T2DM-related morbidity and mortality (Moore & Shah, 2020). This finding is consistent with previous meta-analyses that have explored the impact of exercise training on glucose homeostasis in individuals with T2DM, both with and without concurrent overweight/obesity (Zhao et al., 2021). It is important to note that long-term exercise interventions (greater than 12 weeks) appear to be more effective than short-term ones (12 weeks or less), underscoring the enduring benefits of exercise training in glucose control for individuals with T2DM and overweight/obesity (Zou et al., 2016). Moreover, CART has been identified as the most effective exercise modality for improving glycemic management in populations with impaired metabolic health, outperforming other types of exercise like endurance, resistance, or high-intensity interval training (Batrakoulis, Jamurtas & Fatouros, 2021; Batrakoulis et al., 2022a; Zhao et al., 2021). In summary, the positive impact of CART on glucose metabolism may be partly explained by the high prevalence of visceral adiposity in individuals with T2DM and concurrent overweight/obesity (Bays et al., 2008). Consequently, the beneficial changes observed after CART interventions could be linked to the activation of key molecular mechanisms that regulate whole-body glucose homeostasis, particularly those associated with visceral and ectopic fat.

Physical function

Individuals with impaired metabolic health often have low cardiorespiratory fitness and functional capacity, which increases their risk of developing comorbidities (Al-Mhanna et al., 2022a; Colberg et al., 2010; Jensen et al., 2014). In contrast, high cardiorespiratory fitness is linked to a lower risk of cardiovascular disease morbidity and mortality in apparently healthy individuals. This has been identified as a more influential factor for cardiometabolic health than improvements in anthropometrics and body composition (Afolabi et al., 2023; McAuley et al., 2016). Additionally, cardiorespiratory fitness is inversely related to liver fat accumulation and insulin resistance, although no significant differences were found between individuals with T2DM and those without T2DM in terms of cardiorespiratory fitness levels (Sabag et al., 2021). Regarding the positive effects of exercise training on cardiorespiratory fitness, CART has been recognized as the optimal form of exercise for improving aerobic capacity in individuals with overweight/obesity but without comorbidities (Batrakoulis et al., 2022a; O’Donoghue et al., 2021). Notably, exercise protocols combining endurance and resistance training in a single session have proven effective in improving various physical fitness measures in sedentary individuals with excess body weight (Batrakoulis et al., 2018, 2022b, 2021). The significant increase in aerobic capacity may be attributed to the favorable mitochondrial adaptations, increased skeletal muscle capillarization, and enhanced oxidative metabolism induced by CART (Murlasits, Kneffel & Thalib, 2018). However, the findings supporting the positive role of CART in improving cardiorespiratory fitness should be interpreted cautiously, as only two eligible studies were included in the meta-analysis.

With regard to muscular fitness, CART demonstrated a substantial increase in lower body strength. However, the paucity of available data precludes the presentation of compelling evidence regarding the effectiveness of CART on muscular strength and functionality among individuals with T2DM and concurrent overweight/obesity. Nevertheless, this is an important observation given that muscular strength has been documented as a prognosticator of all-cause mortality in adults with no chronic diseases (Carbone et al., 2020). Despite the absence of substantial evidence supporting the pivotal role of muscular fitness in cardiometabolic health among individuals with excessive weight, favorable changes in muscular strength have been associated with a reduced risk of cardiovascular disease in these populations (Carbone et al., 2020). However, CART is in line with the current physical activity guidelines recommending the integration of cardiovascular and neuromuscular stimulus into either a single session or separate sessions weekly (Bull et al., 2020). Interestingly, CART has been reported as a more effective type of exercise for improving musculoskeletal fitness-related parameters compared to aerobic, interval, or resistance training alone (Batrakoulis, 2022a).

The inclusion of the muscle-strengthening component in CART may be the factor that explains the meaningful CART-induced strength increases due to neural adaptations (Strasser, Arvandi & Siebert, 2012), increased muscle fiber activation, mitochondrial biogenesis and glucose transport commonly observed among individuals with metabolic health impairments and excessive weight (Schjerve et al., 2008)

Implications for future research

Although CART appears to be a promising exercise modality for individuals with T2DM and concurrent overweight/obesity, particularly in improving various cardiovascular disease risk factors, there is a lack of strong evidence regarding its effectiveness in real-world settings. Despite recent exercise prescription guidelines for individuals with T2DM (Aschner, 2017; Colberg et al., 2010; Mendes et al., 2016), further studies are needed to determine the optimal training parameters, such as frequency, intensity, and duration. These studies would help guide physicians and exercise professionals in prescribing evidence-based CART programs for individuals with T2DM and overweight/obesity (Batrakoulis, Jamurtas & Fatouros, 2022). Among the 20 eligible RCTs reviewed, the most common CART protocol used either inter- or infra-session formats, typically 2–3 times per week. Circuit-based CART was also widely utilized, combining cardiorespiratory and muscle-strengthening exercises in an efficient manner. Furthermore, additional research should focus on exploring the dose-response relationship between CART and cardiometabolic health parameters, particularly in real-world exercise contexts, as previously suggested (Batrakoulis et al., 2019). Such studies would help optimize the application of CART, determining whether it can serve as the most comprehensive exercise solution for individuals with poor metabolic health in everyday environments.

Limitations

Our meta-analysis has several limitations, and therefore, the results should be interpreted with caution. The included studies displayed inconsistencies in the training parameters used during the interventions, leading to considerable heterogeneity among the studies. Additionally, the present study indicates that beneficial adaptations from CART do not occur in younger individuals, as the mean age of participants was 57 ± 7 years. Therefore, the findings cannot be generalized to younger age groups with T2DM and excess weight. Furthermore, given the outcome measures included, the role of CART in improving cardiometabolic health in this specific population remains unclear, due to the lack of data on factors such as glucose homeostasis, blood pressure, inflammation, and oxidative stress.