This study describes a randomized controlled trial protocol aiming at assessing the acute effects of strength exercise volume on insulin sensitivity in obese individuals.
An acute session of strength exercise (SE) ameliorates insulin sensitivity (IS) for several hours; however, the effects of SE volume (i.e., number of sets) have not been studied thoroughly. Although it is intuitive that some SE is better than none, and more is better than some for the improvement of IS, high-volume sessions might be challenging for diseased populations to complete, especially obese adults, for whom even a brisk walk can be challenging. This protocol details a randomized clinical trial to assess the acute effects of SE on IS in obese adults. The inclusion criteria are body mass index >30 kg/m2, central obesity (waist circumference >88 cm and >102 cm for women and men, respectively), and age >40 years. Participants will be familiarized with the SE (7 exercises targeting major muscle groups) and then will perform three sessions in a randomized order: session 1 – high-volume session (3 sets/exercise); session 2 – low-volume session (1 set/exercise); session 3 – control session (no exercise). Diet will be controlled the day before and on the day of the sessions. Sessions will be completed at night, and an oral glucose tolerance test will be performed the next morning, from which several indexes of IS will be derived, such as the area under the curve (AUC) of glucose and insulin, the Matsuda index, the Cederholm index, the muscle IS index, and the Gutt index. Based on pilot studies, we expect ~15% improvement in IS (insulin AUC, and Matsuda and Cederholm indexes) after the high-volume session, and ~8% improvement after the low-volume session compared to the control session. This study will benefit individuals who find high-volume SE sessions challenging but still aim to improve their IS by investing 1/3 of their time and effort.
Although the chronic effects of strength training on insulin sensitivity have been repeatedly shown1,2,3, even an acute session of strength exercise can improve insulin action for up to 48 h4. This effect has been demonstrated in healthy5,6,7,8, obese 9, older10, insulin-resistant individuals4, and type 2 diabetes mellitus patients11. Others have not reported positive effects12,13,14,15,16,17, and it is unclear why these differences occur.
In a recent narrative review18, it was suggested that strength exercise volume (the number of sets per exercise) is essential to improve insulin sensitivity. For instance, a recent systematic review and meta-analysis demonstrated that sessions composed of 21 sets or more led to a greater improvement in insulin action compared to sessions with fewer than 21 sets19. However, only limited evidence from literature directly supports this notion. For example, higher strength exercise volume (30 sets) improved glucose metabolism more than lower volume (10 sets)20. But it is worth noting that this study implemented circuit-style strength exercises, which limits the comparison to traditional strength exercises. In another study, better insulin sensitivity was observed after a 32-set strength exercise protocol compared to an 8-set protocol21. However, the degree of effort after sets was not reported, and it was presumably greater after the high-volume protocol. This is important because the degree of effort (or proximity to concentric muscular failure, characterized as the inability to continue the set due to failure in the concentric movement of a given repetition) has also been considered an important variable to improve insulin and glucose metabolism18. Thus, the limited available studies on the topic, along with their methodological limitations, preclude further inferences regarding the effects of strength exercise volume on insulin sensitivity.
Another interesting point when discussing strength exercise volume is that it is inherently connected to time commitment. A lower exercise volume, by design, means less time spent in the gym. Among the reasons for not adhering to an exercise program, lack of time is at the top of the list22. Thus, a low-volume strength exercise session that effectively improves insulin sensitivity means less time commitment23 and might result in higher long-term adherence. Furthermore, subjective feelings, such as self-efficacy (self-perception of the ability to accomplish something) and the sensations of pleasure and fun (enjoyment), are also related to exercise adherence24,25,26. It is reasonable to speculate that people might feel more confident and enjoy their exercise experience more when they perform a low-volume strength exercise session that translates into health improvement.
To address the gaps in the literature summarized above, we describe a protocol for a randomized, controlled, crossover, clinical trial with the primary aim of assessing the effects of strength exercise volume on insulin sensitivity in obese individuals. As a secondary aim, we assess the effects of strength exercise volume on subjective feelings (self-efficacy, affection, and enjoyment).
The protocol here describes a randomized, controlled, 3-way, crossover, clinical trial. The chronological sequence of the protocol includes: a pre-participation assessment of health history and anthropometric measures (body mass, height, waist circumference, and body composition); an appointment with the team's certified nutritionist; a familiarization period with the strength exercises and subjective feelings questionnaires; strength assessment in each exercise; random allocation of the order of the sessions; performance of the 3 sessions (separated by 7-28 days), that is immediately followed by answering the subjective feelings questionnaires; an oral glucose tolerance test (OGTT) the next morning; and data analysis. Figure 1 delineates the protocol design.
Figure 1: Study design. A flowchart of the trial methodology followed here. 1: Obese (body mass index [BMI] >30 kg/m2; waist circumference >102/88 cm) subjects; 2: Anthropometric assessments and familiarization; random assignment to 3: high-volume strength exercise session (21 sets), 4: low-volume strength exercise session (7 sets), or 5: control day; 6: standard meal following sessions; 7: sleep and overnight fast; 8: oral glucose tolerance test. Please click here to view a larger version of this figure.
Obtain ethical clearance for the study by submitting the study protocol and informed consent document to the local Institutional Review Board (IRB) or local Research Ethics Committee (REC). The study can only begin after IRB or REC approval. The results presented below are from a pilot study, for which subjects signed a written informed consent before enrollment. After IRB or REC approval, prospectively register the protocol in a public repository, like Clinical Trials (https://clinicaltrials.gov). If your country has a national repository, register the protocol there (for example, in Brazil, there is the Brazilian Clinical Trials (https://ensaiosclinicos.gov.br). The present study was approved by the local IRB (certificate number CAAE 63190422.0.0000.5108) and was prospectively registered in a clinical trial registry (ReBEC #RBR-3vj5dc5 https://ensaiosclinicos.gov.br/rg/RBR-3vj5dc5).
1. Selection and preparation of volunteers
2. Measure the participant's body composition
3. Dietary control
4. Familiarization
5. Strength tests (8 repetition maximum)
6. Random session allocation
7. Blind data collection
8. Exercise sessions
9. OGTT and data analysis
10. Statistical analysis
Figure 2 shows representative (from a pilot study) responses for glucose (Figure 2A) and insulin (Figure 2B) during the OGTT. Usually, peaks for glucose and insulin values are observed at 30 min measurement, which is followed by a constant decrease until 120 min measurement. The lower the glucose peak, the better the result, which is indicative of inhibition of hepatic glucose production. The faster the decrease in glucose after the peak, the better the result, which is indicative of faster glucose disposal (usually associated with skeletal muscle glucose uptake). For insulin, lower values indicate that less insulin is needed to be released by pancreatic beta cells for glycemia control. However, this interpretation is only valid for individuals with functional beta cells, as individuals with dysfunctional (or dead) beta cells will have lower insulin response during the OGTT, but higher glycemic response.
Figure 2: Oral glucose tolerance test. Glycemia (A) and insulin (B) responses to oral glucose tolerance test after no exercise (control), 21 sets strength exercises (high-volume), and 7 sets strength exercises (low-volume) protocols in obese adults. Data shown as mean (bars) and standard deviation (error bars). Please click here to view a larger version of this figure.
Figure 3 shows insulin sensitivity indexes derived from the OGTT. The most common are glucose (Figure 3A) and insulin (Figure 3B) AUC. Notice that lower AUC indicates a better result. In other words, individuals that show lower glycemia and insulin concentration after a standard glucose challenge likely have better insulin sensitivity. Other insulin sensitivity indexes can be calculated from the results of the OGTT (Figure 3C-I). As they use different parameters from the OGTT to estimate insulin sensitivity, the results vary among indexes. However, the pattern is similar for most indexes as low- and high-volume strength exercises improve insulin sensitivity, but superior outcomes are observed following the latter condition.
Figure 3. Insulin sensitivity indexes. Oral glucose tolerance test-derived insulin sensitivity (IS) indexes (ISI) responses after no exercise (control), 21 sets strength exercises (high-volume), and 7 sets strength exercises (low-volume) protocols in obese adults. Glucose (A) and insulin (B) area under the curve (AUC), oral glucose (OG) IS (C), Matsuda ISI (D), Cederholm ISI (E), Muscle ISI (F), Gutt ISI (G), Avignon ISI (H), and Stumvoll ISI (I). *p<0.05; ***p<0.001 for Tukey post-hoc test. Data are shown as individual values (plots), mean (bars) and standard deviation (error bars). Please click here to view a larger version of this figure.
This paper detailed the steps for a randomized controlled trial that aimed to assess the effects of strength exercise volume on insulin sensitivity in obese adults. Randomized controlled trials are the best research protocols to establish cause-and-effect of a treatment in an unbiased manner49,50. Specifically, in this study, we will employ a crossover design, which means every subject recruited will perform each condition in a randomized order51 Although crossover studies increase the burden on the subjects and are not ideal for long-term treatment with carry-over effects, this design reduces data variability, and fewer participants are needed to draw conclusions52. As the acute effects of strength exercise on insulin sensitivity do not last longer than 48 h4, the interval between sessions will be at least 7 days, and participants will only complete 3 conditions, we believe the present study design successfully answers the research question.
Some important aspects of the protocol deserve addressing. For instance, some have suggested that multi joint exercises that recruit large muscle masses should be prescribed to observe the positive effects of strength exercise on insulin sensitivity18. In this protocol, 5 of the 7 exercises (deadlift, bench press, leg press, lat pulldown and shoulder press) are multi-joint, and the other 2, although single joint, recruit large muscle masses (leg extension and leg curl). Moreover, it has been suggested that performing sets close to concentric muscular failure is critical for improving glycemic control, as indicated by reduced insulin and glucose levels18. For this reason, the sets in the current protocol were performed to concentric failure. Furthermore, we chose 7 exercises composed of 3 sets each as the results of a systematic review and meta-analyses reported that strength exercise sessions composed of 21 sets or more showed a greater improvement in insulin action compared to sessions with fewer than 21 sets19. The choice for 1 set in the same 7 exercises was based on the premise that a session of 1/3 duration might be more viable to completion by obese subjects and might lead to higher long-term adherence. The long familiarization period we employ in this study is based on the observation that unaccustomed, eccentric-based strength exercise leads to an acute worsening of insulin sensitivity36,37, that is reversed in the follow-up sessions35. Also, in order to have participants safely and effectively perform sets to failure, a thorough familiarization period is required, especially for obese, physically inactive subjects. Finally, it is paramount to exclude the possible effect of food intake on insulin sensitivity53, 54, so we chose to control dietary intake the day before, and the day of each session in the present protocol.
We describe the assessment of insulin sensitivity by calculating indexes derived from the OGTT55. Although the hyperinsulinemic euglycemic clamp is regarded as the gold standard to quantify insulin sensitivity in vivo56, it is a costly and invasive procedure that requires highly trained personnel57. Also, it is argued that the sustained hyperinsulinemia obtained in the procedure does not reproduce normal physiology58, as opposed to the insulinemic response to the ingestion of 75 g of glucose in a meal. Nonetheless, the OGTT-derived indexes described here have a high correlation coefficient with the hyperinsulinemic-euglycemic clamp, varying between 0.61 and 0.9657. Furthermore, it has been shown that the OGTT is a reliable and consistent method for estimating insulin sensitivity over consecutive days59, and is arguably one of the most frequently used methods for assessing the acute effects of strength exercise on glucose metabolism4,7,10,11,12,13,17,20,37,60,61,62. Thus, the OGTT is a commonly used4,7,10,11,12,13,17,20,37,60,61,62, viable57, reproducible59, inexpensive, simple, physiologic method for assessing insulin sensitivity that correlates strongly57 with the gold-standard hyperinsulinemic-euglycemic clamp method.
It is important to highlight that the results shown are from a pilot study conducted in 4 obese individuals. This pilot study is clearly under powered, which precludes a thorough assessment of the effects of strength exercise volume on insulin sensitivity in obese individuals. Nevertheless, the results suggest that low-volume strength exercise might improve insulin sensitivity, albeit not to the same extent as high-volume strength exercise. Considering that the low-volume protocol takes one-third of the time compared to the high-volume (18 min versus 55 min, respectively), and might be associated with better affective and enjoyment responses, we speculate that a low-volume strength exercise protocol might be associated with higher exercise adherence, which likely leads to greater health improvements in the long-term. Thus, we believe the results of this study can be invaluable for the prescription of strength exercise protocols for those that claim not to have enough time to perform exercise regularly, and for those that find high-volume strength exercise challenging or demotivating.
The authors have nothing to disclose.
This study is supported by the National Council for Scientific and Technological Development (CNPQ: Grant#407975/2018-7 and # 402091/2021-3) and by the Minas Gerais State Agency for Research and Development (FAPEMIG: Grant# APQ-00008-22). The funders played no role in this study's design, and do not play any roles in study conduct, interpretation of data, or reporting of results. This study is based at the Federal University of the Jequitinhonha and Mucuri Valleys (Diamantina-MG, Brazil) which provide the equipment and space (DXA, strength training room, strength training equipment, etc.) necessary for conducting the research.
dual-energy X-ray absorptiometry | GE | DXA, Lunar, iDXA Advanced | for assessing body composition |
G*Power program | Heinrich-Heine-Universität Düsseldorf, Germany | version 3.1.9.6 | for calculating sample size |