Effects of Sodium Bicarbonate Supplementation on Physical Performance and Cardiovascular Variables in Middle-aged and Elderly Adults With Type 2 Diabetes Mellitus

Effects of Sodium Bicarbonate Supplementation on Physical Performance and Cardiovascular Variables in Middle-aged and Elderly Adults With Type 2 Diabetes Mellitus | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Effects of Sodium Bicarbonate Supplementation on Physical Performance and Cardiovascular Variables in Middle-aged and Elderly Adults With Type 2 Diabetes Mellitus Edher Lucas Antunes, Maria Luiza Rios, Rafael Carlos Sochodolak, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4101653/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract The global epidemic of diabetes mellitus (DM) presents a significant health challenge. Physical exercise is crucial in preventing and treating type 2 DM (T2DM). Supplementation with sodium bicarbonate (SB) may enhance physical performance in T2DM individuals during high-intensity protocols. This study aimed to analyze physical performance, blood glucose, and cardiovascular parameters following acute SB supplementation in middle-aged and elderly adults with T2DM. Thirteen individuals (mean age: 62.15 ± 6.90 years, BMI: 29.14 ± 4.49 kg/m2) with an average disease duration of 5.03 ± 6.64 years participated. They underwent a maximal incremental test (MIT) with either SB or a placebo, administered 60 minutes before the test. Blood pressure (BP), heart rate (HR), and capillary blood glucose were monitored pre- and post-test. Results showed significant differences in MIT duration between the SB and placebo conditions (SB: 481 ± 116.97 seconds, placebo: 439 ± 99.92 seconds, p = 0.005), and in blood glucose levels (p = 0.0001). No significant differences were found in BP, HR, or other cardiovascular variables (p > 0.05). SB supplementation was associated with increased test duration and reduced blood glucose levels, indicating improved physical performance and fatigue reduction. These findings suggest that SB supplementation may be a safe and effective strategy for enhancing physical performance in individuals with T2DM. exercise buffers performance-enhancing substances fatigue Figures Figure 1 Figure 2 INTRODUCTION The epidemic of diabetes mellitus (DM) poses a global health problem. Estimates indicate that over 537 million individuals worldwide have already been diagnosed with the disease, and this number may increase to 783 million by the year 2045 [ 1 ]. Diabetes mellitus (DM) is a metabolic condition characterized by disruptions in the action and regulation of insulin. Type 2 diabetes (T2DM), accounting for approximately 90–95% of cases, results from a combination of gradual and persistent loss of secretion, along with insulin resistance, and predominantly affects middle-aged and elderly individuals [ 2 ]. It is common to observe changes in the central nervous system, such as chronotropic incompetence (CI) and a slower heart rate recovery after exercise [ 3 , 4 ]. Since the autonomic nervous system plays a crucial role in heart rate (HR) recovery after exercise, a delay in this response may indicate autonomic dysfunction, which can be a predictor of disease development and progression [ 5 ]. CI has multifactorial origins, but adopting an active lifestyle has been suggested as a safe and effective approach to prevent or reduce changes in insulin and cardiac autonomic neuropathy in individuals with T2DM [ 6 – 8 ], resulting in significant improvements in quality of life. Additionally, individuals with T2DM may experience acid-base imbalances, especially when the condition is not adequately controlled. Diabetic ketoacidosis (DKA), characterized by hyperglycemia, metabolic acidosis, and ketosis, is a prevalent clinical emergency in type 1 DM, but it is also possible in poorly controlled T2DM [ 9 ]. In this context, regular physical exercise plays a crucial role in improving the risk conditions associated with acid-base imbalances in people with T2DM [ 8 ]. It is important to note that both acute and chronic supplementation of SB do not have substantial effects on DKA parameters. However, supplementation may contribute to an increase in physical performance, providing additional benefits to exercise in this population [ 8 , 9 ]. Physical exercise is recognized as a significant non-pharmacological pillar in the prevention and treatment of T2DM [ 10 , 11 ]. It provides a range of acute and chronic benefits, such as improving metabolic parameters affected by the disease, enhancing physical capacities, and promoting cardiovascular health [ 12 , 13 ]. However, considering the limitations imposed by the disease condition, such as muscle fatigue, the use of additional resources, such as supplementation with sodium bicarbonate (SB), can be a strategy to improve physical performance. There is consistent evidence supporting the benefits of SB in physical performance, resulting from its muscle fatigue-delaying effects through physicochemical buffering mechanisms [ 14 – 16 ]. Extracellular buffering is recognized as the primary mechanism through which SB influences physical performance, particularly during high-intensity activities. This ability is essential to prevent the accumulation of hydrogen ions (H + ) and, consequently, reduce metabolic acidosis, which is one of the main factors contributing to muscle fatigue [ 14 , 17 ]. Studies in other populations have revealed that the BS supplementation strategy promotes positive effects on physical performance [ 18 ], particularly in high-intensity training protocols, which, in turn, have demonstrated numerous benefits in individuals with T2DM [ 19 , 20 ]. Although previous studies have observed performance improvement through BS supplementation in other populations, there is no data on supplementation in physical performance in individuals with T2DM. Thus, the hypothesis of the present research was to observe improvement in physical performance and biochemical and cardiovascular parameters after BS supplementation in middle-aged and elderly adults with T2DM. METHODS PARTICIPANTS The sample consisted of 13 individuals with T2DM, recruited through convenience sampling in clinics, hospitals, and the community via telephone contact and in-person recruitment visits. Volunteers were selected based on their medical history and physical examination. Inclusion criteria for the study were: 1) diagnosis of T2DM; 2) age between 45 and 74 years. Exclusion criteria included: 1) history of proliferative diabetic retinopathy, autonomic or peripheral neuropathy; 2) presence of health conditions that could affect physical performance; 3) recurrent or recent hospitalizations in the six months prior to the study; 4) systolic blood pressure equal to or higher than 160 mmHg or diastolic blood pressure equal to or higher than 105 mmHg; 5) smoking; 6) pregnancy or lactation period; 7) insulin dependence. EXPERIMENTAL DESIGN This is a triple-blind, crossover, placebo-controlled, and randomized experimental study comparing interventions with SB and placebo. The study received approval from the Ethics Committee on Human Research at the State University of Ponta Grossa (UEPG), under approval number: 62650422.9.0000.0105 dated October 10, 2022. Data collection took place at the Physical Assessment and Health Laboratory (LAFISE) of the Department of Physical Education at the UEPG. The experimental protocol was divided into two stages. In the first stage, participants underwent physical assessment and a familiarization process with the physical test. In the second stage, the physical test was conducted under the presence of SB or placebo. Heart rate was recorded before, during, and after the tests. The assessed parameters were a) percentage of chronotropic reserve (CR); b) heart rate recovery (HRR). Supplementation was administered to participants 60 minutes before the experimental sessions, ensuring that both the evaluator and the participants were unaware of the supplement's content. Additionally, participants received specific instructions not to engage in physical exercise and to avoid consuming stimulant foods in the 24 hours preceding the tests to ensure uniformity of conditions before assessments. GLUCOSE MEASUREMENT Capillary blood glucose was measured at rest and after 3 minutes at the end of the physical tests, using the standard collection protocol, which includes local antisepsis with alcohol and the use of disposable materials [ 21 ], through a glucometer (G-Tech Free, Brazil), with a result range of 10 to 600 mg/dL (0.6 to 33.3 mmol/L), and reagent strips (G-Tech Free 1, Brazil). Collection was performed at least 2 hours after the last meal. SODIUM BICARBONATE AND PLACEBO SUPPLEMENTATION For the SB supplementation, a dose of 0.3 g.kg -1 was administered to participants 60 minutes before the test to ensure complete absorption of the supplement [ 18 , 22 ]. The choice of this dosage is grounded in evidence that higher doses do not provide additional benefits and may be associated with a higher incidence of adverse effects [ 18 ]. The placebo solution was administered at a dosage of 3.6 g and ensured the same features of SB supplementation. To assess any gastrointestinal discomfort resulting from supplementation, participants used a 10-point scale, where 0 indicated the absence of symptoms, and 10 represented extreme discomfort [ 23 ]. The dosage for each participant was prepared in 200 ml of chilled carbonated water by an individual not involved in data collection, ensuring the impartiality of the process. SUPPLEMENTATION COMPOSITION The solutions were carefully prepared to ensure uniformity in appearance, taste, smell, and viscosity. The active solution (SB) consisted of 92.78% sodium bicarbonate, 2.4% stevioside, 0.016% green dye, 4% lemon flavoring, and 0.8% micronized silica gel, with a correction factor of 1.077 for the preparation of each participant's individual dose. The isotonic placebo solution was composed of 0.9% sodium chloride, 0.3% stevioside, 0.025% green dye, 1% lemon flavoring, and 0.5% micronized silica gel. ANTHROPOMETRY, BLOOD PRESSURE, AND BODY COMPOSITION Body weight and height measurements were taken using a Welmy W200A digital anthropometric scale, with a capacity of up to 200 kg and precision of 100 g. Height measurement followed the recommendations of Guedes (2006) [ 24 ]. Based on these measurements, the Body Mass Index (BMI) was calculated using the standard formula: [body mass (kg) / height (m)²]. Blood pressure was measured with participants at rest, using a digital device (Omron HEM-7122, Jundiaí, Brazil), following the standard application protocol to ensure accuracy and consistency in measurements. Body composition was assessed using a tetrapolar bioimpedance device (Maltron 906, Rayleigh, England), following the manufacturer's recommended protocol. These procedures were conducted in a standardized manner to ensure the accuracy of anthropometric assessments and body composition evaluations. MAXIMAL INCREMENTAL TEST The test utilized in our research was developed based on a modification of the protocol proposed by Puga et al. (2012) [ 24 ], in which only the treadmill incline was manipulated, aiming for a personalized adaptation to accommodate the specific characteristics of participants, such as the presence of diabetic neuropathy. Participants underwent a maximal incremental treadmill test consisting of 11 stages, each lasting 1 minute. The test began with a constant speed of 5.5 km/h and 0% incline, incrementing by 2% incline at each subsequent stage. The laboratory temperature was controlled and maintained at 23°C during all interventions. Additionally, volunteers performed the tests at the same time of day, with a minimum interval of 72 hours and a maximum of 1 week between tests. To determine participants’ maximum heart rate, the equation by Tanaka et al. (2001) [ 26 ] was used by the following formula: 208 – (0.7 * age in years). Participants' subjective perception of effort was assessed at the end of each stage using the Borg scale [ 27 ]. The test was terminated when the subject exhibited excessive fatigue or exhaustion, along with signs indicating cardiovascular abnormalities. HEART RATE RESPONSE The calculation of the percentage of CR was performed considering three parameters: resting heart rate (HR), reserve HR, and maximum HR. The equation used for CR calculation was CR = (reserve HR / [maximum HR - resting HR]) x 100. CR values below 80% are indicative of chronotropic incompetence [ 28 ], and recovery HR values less than 18 beats per minute (bpm) after 60 seconds are indicative of altered chronotropic response [ 29 ]. HR recovery was measured by observing the difference between HR at 30, 60, 90, and 120 seconds into recovery compared to HR at the point of exhaustion. HR monitoring was conducted using a heart rate monitor (Polar V800, Kempele, Finland). STATISTICAL ANALYSIS To assess the normality of the data, the Shapiro-Wilk test was used. For conditions pre- and post-test within the same condition, analysis of variables such as percentage of CR, test duration, and gastrointestinal discomfort was conducted using paired t-tests. The Mann-Whitney test was used for the variable of peak HR and gastrointestinal discomfort. In evaluations between test conditions, the analysis of blood pressure and blood glucose levels was assessed through repeated measures two-way ANOVA. The chi-square test and Fisher's exact test were used to evaluate the association between supplement consumption and the subject's knowledge of what they were consuming. The significance level for all data was set at p < 0.05. RESULTS The participant characteristics are presented in Table 1 . The mean age was 62.15 ± 6.90 years, with a body mass index (BMI) of 29.14 ± 4.49 kg/m 2 . Body composition varied considerably, with a lean body mass of 63.14 ± 7.60% and a fat percentage of 36.88 ± 7.59%. Additionally, the mean duration of the disease was 5.03 ± 6.64 years and indicated heterogeneity in the diagnosis time among the participants. Table 1 Anthropometric characteristics, body composition, years of disease, and comorbidities (n = 13). Variable Results Women (%) 11 (84.61) Age (years) 62.15 ± 6.90 Body Weight (kg) 73.39 ± 14.19 Height (m) 1.58 ± 0.09 Body Mass Index (kg/m²) 29.14 ± 4.49 Fat-Free Mass (%) 63.14 ± 7.60 Body Fat (%) 36.88 ± 7.59 Resting HR (bpm) 70.23 ± 11.94 Years of Disease Diagnosis 5.03 ± 6.64 Comorbidities Systemic Arterial Hypertension (%) 69.23 (9) Hypothyroidism (%) 23.08 (3) Hypercholesterolemia (%) 7.69 (1) Hypertriglyceridemia (%) 7.69 (1) The data are presented as mean ± standard deviation. HR = heart rate. The results of CR values and maximal incremental test duration are presented in Table 2 and Fig. 2 . The comparison of test duration between conditions was statistically significant (p = 0.005). However, there was no significant difference in CR and gastrointestinal discomfort (p = 0.126; p = 0.066, respectively). Additionally, Fisher's exact test indicates no significant association between supplement consumption and the subject's knowledge of what they are consuming (X² (1) = 1.815; p = 0.371). Table 2 Results of chronotropic reserve values, test duration, and gastrointestinal discomfort between conditions (n = 13). Variable SB Placebo p Test Time (s) 481 ± 116.97 439 ± 99.92 0.005* CR (%) 86.45 ± 20.47 82.93 ± 17.63 0.126 Gastrointestinal Discomfort (0–10) 2.8 ± 4.1 0.1 ± 0.3 0.066 The data are presented as mean ± standard deviation. CR = chronotropic reserve; SB = sodium bicarbonate. The results of clinical monitoring variables are presented in Table 3 . Differences were observed in blood glucose values (p = 0.0001), but not between conditions (p = 0.88). In the SB condition, pre-test blood glucose was 151.31 ± 60.33 mg/dL and significantly decreased to 127.85 ± 57.37 mg/dL post-test (p = 0.002). In the placebo condition, a similar reduction in blood glucose was observed, with pre-test values of 155.85 ± 76.97 mg/dL and post-test values of 131.15 ± 79.78 mg/dL (p = 0.004). However, no statistically significant differences were found in systolic (SBP) and diastolic (DBP) blood pressure values between conditions (p = 0.84, p = 0.34) or over time (p = 0.40, p = 0.47), with no interaction (p = 0.19, p = 0.34, respectively). Table 3 Results of monitoring variables for blood pressure values and capillary blood glucose pre and post-test in active supplementation and placebo conditions (n = 13). Variable SB Placebo p Pre Post Pre Post Condition Time Interaction SBP (mmHg) 126.2 ± 15.47 124.8 ± 15.87 123.6 ± 16.51 129.5 ± 16.48 0.84 0.40 0.19 DBP (mmHg) 76.2 ± 9.58 75.8 ± 5.31 71.8 ± 6.97 74.6 ± 10.35 0.34 0.47 0.34 Blood Glucose (mg/dl) 151.31 ± 60.33 127.85 ± 57.37* 155.85 ± 76.97 131.15 ± 79.78* 0.88 0,0001* 0.88 The data are presented as mean ± standard deviation. SBP = systolic blood pressure; DBP = diastolic blood pressure. The results of peak and recovery HR monitoring variables are shown in Table 4 . The comparison between conditions regarding heart rate revealed that there were no statistically significant differences at various points during the test. Peak HR did not show significant differences between conditions (p = 0.169). Additionally, no differences were observed in HR at 30, 60, 90, and 120 seconds of recovery after the test between conditions (p = 0.472, p = 0.238, p = 0.194, p = 0.147, respectively). These results suggest that both conditions exhibited similar behaviors in terms of heart rate over the assessment period. Table 4 Results of peak heart rate and recovery at 30, 60, 90, and 120 seconds after the end of the maximal incremental test between conditions (n = 13). Heart Rate SB Placebo p Peak 151.08 ± 20.77 147.92 ± 18.10 0.169 30 (s) 140 ± 19.39 134.77 ± 17.02 0.472 60 (s) 126.23 ± 18.03 117.77 ± 17.60 0.238 90 (s) 115.08 ± 20.25 105.08 ± 17.86 0.194 120 (s) 109.46 ± 19.59 99.15 ± 15.23 0.147 The data are presented as mean ± standard deviation. HR = heart rate; SB = sodium bicarbonate; s = seconds. DISCUSSION To the best of our knowledge, this is the first study to examine the effect of BS supplementation during maximal incremental test in individuals with T2DM. The hypothesis of this research was to observe improvement in physical performance and biochemical and cardiovascular parameters after supplementation. A significant increase in test duration was observed in the BS condition. Additionally, both conditions showed significant reductions in blood glucose levels after interventions, indicating comparable efficacy of isolated and/or combined physical exercise with BS in glucose metabolism regulation, but without differences in cardiovascular parameters. These results suggest that while both interventions seem effective in glucose regulation, active BS supplementation may confer an additional benefit to participants' exercise capacity, warranting further investigation in future studies. PHYSICAL PERFORMANCE ANALYSIS Acid-base balance is achieved by the action of physicochemical buffers, which can be improved through supplementation with SB. Studies that evaluated pH during exercise have observed a delay in the onset of intramuscular acidosis and, consequently, better exercise performance [ 18 ]. SB supplementation is often associated with the context of physical training, especially in athletes, due to its potential benefits in sports performance [ 30 ]. In this sense, it is not commonly studied in groups that have some health condition, such as individuals with T2DM. Therefore, our results are relevant in suggesting that supplementation may have beneficial effects on cardiovascular and physical performance parameters in this population. While we did not conduct a comprehensive analysis through laboratory tests to assess the biochemical changes resulting from supplementation, previous studies offer relevant results. The research conducted by Stephens et al. (2002) [ 31 ] observed a significant increase in plasma bicarbonate concentration after ingesting 0.3 g.kg -1 of SB in a maximal incremental test on a cycle ergometer. Kumstat et al. (2018) [ 32 ] research demonstrated that blood pH, bicarbonate concentration, and base excess (BE) increased significantly after supplementation with 0.3 g.kg -1 of SB (p < 0.05) in professional swimmers (20.7 ± 2.1 years old). Similarly, the systematic review and meta-analysis conducted by Miranda et al. (2022) [ 33 ] highlighted a significant effect on increasing blood lactate levels (p = 0.006) in combat athletes undergoing a SB supplementation protocol. This may be attributed to the fact that SB promotes an increase in the efflux of H + ions from muscle cells to the blood, where they are neutralized. This process results in the reduction of intramuscular acidosis, which, in turn, allows for prolonged operation of the glycolytic pathway [ 18 , 30 ]. Additionally, Gurton et al. (2023) [ 34 ] suggested that administering SB in solution form may be more effective than encapsulated supplementation, demonstrating a 2% increase in repeated sprint and Yo-Yo IR2 test performance in the solution supplementation group. They observed that the decline in serum bicarbonate during maximal exercise was more pronounced for SB administered in solution compared to capsules (2.7 ± 2.1 mmol.L kg -1 , p = 0.001), which was the method used in our research. The biochemical changes observed in previous studies may have influenced the results obtained in our research, providing a valuable context for interpreting the findings. The active intervention condition had a mean test time of 481 ± 116.97 seconds, while the placebo condition had a mean time of 439 ± 99.92 seconds, representing an average increase of approximately 9.57% in test time. Carr et al. (2011) [ 35 ] literature review included 38 studies that evaluated performance effects with SB supplementation, which observed a moderate performance improvement of 1.7% (± 2.0%) with a standard dose of 0.3g.kg -1 in a 1-minute sprint test in male athletes, notable but with a lesser effect when compared to our research. Additionally, a moderate correlation (r = 0.33; 90% CI -0.10, 0.65) was observed between test performance and pre-exercise serum bicarbonate values after SB supplementation. Acute and chronic SB intake can lead to diverse outcomes. Durkalec-Michalski et al. (2020) [ 36 ] investigated the effects of acute (0.2 g.kg -1 ) and chronic (8 days with a 25% dosage increase every 2 days, from 0.5 g.kg -1 on days 1 and 2 to 0.2 g.kg -1 on days 7 and 8) SB on the physical performance of hockey athletes. Acute supplementation showed significant improvements in the time of a specific discipline test and in the anaerobic capacity of the Wingate test (939 ± 26 vs. 914 ± 22 s, p = 0.006), while chronic supplementation did not result in substantial improvements. However, Lopes-Silva et al. (2019) [ 37 ] meta-analysis indicated that chronic SB intake (0.5 g.kg -1 for 5 days) promoted significant improvements in peak and mean power in the Wingate test. These results highlight the importance of the present research in the practical evaluation of different supplementation protocols. HIGH-INTENSITY PHYSICAL EXERCISE Our results demonstrated an improvement in physical performance and, consequently, an increase in tolerance to high-intensity activities in subjects with T2DM after SB supplementation. Hwang et al. (2019) [ 20 ] aimed to evaluate high-intensity interval training (HIIT) compared to moderate-intensity continuous training (MICT) in 58 elderly individuals with T2DM (63 ± 1 years old) over 8 weeks of supervised training. Improvements in aerobic fitness were observed, with a 10% increase in peak VO 2 for the HIIT group and 8% for the MICT group. Additionally, there was an increase in maximum exercise tolerance, with additions of 1.8 and 1.3 minutes (p ≤ 0.002 in both groups; p ≥ 0.90 for the comparison between HIIT and MICT). Støa et al. (2017) [ 19 ] investigated the effects of HIIT (85% and 95% of maximum HR) and MICT (70% and 75% of maximum HR) in 38 individuals with T2DM over 12 weeks of supervised training. The results demonstrated a significant 21% increase in maximum VO 2 (from 25.6 to 30.9 ml.kg -1 , p < 0.001) in the HIIT group, accompanied by a -0.58% reduction in HbA1c levels (from 7.78 to 7.20%, p < 0.001). Additionally, there was a 1.9% reduction in body weight (p < 0.01) and BMI. These improvements were statistically significant compared to the group undergoing MICT, with no differences in lactate threshold and blood pressure. Moderate correlations were identified between the change in maximum VO 2 and HbA1c when combined (r = -0.52, p < 0.01). In summary, the results obtained in this investigation corroborate the feasibility, safety, and effectiveness of high-intensity training in individuals with T2DM. These findings are relevant in the context of exercise prescription for this population, as the training methods in question provide comparable benefits, with the additional advantage of a lower time demand associated with HIIT protocols. BLOOD GLUCOSE A significant reduction in glucose levels was observed in both conditions. In the SB condition, there was a reduction of 15.5% (151.31 ± 60.33 to 127.85 ± 57.37 mg/dL; p = 0.002), and in the placebo condition, the reduction was 15.85% (155.85 ± 76.97 to 131.15 ± 79.78 mg/dL; p = 0.004). These results highlight the role of exercise as a strategy in glycemic control and the promotion of metabolic health. Furthermore, the dose-response relationship suggests that higher-intensity activities offer additional benefits for metabolic control [ 38 ]. Physical exercise has acute and chronic impacts on the regulation of glucose uptake and inflammatory processes, resulting in a reduction in blood glucose for up to 48 hours, and increasing glucose uptake by up to 50 times through insulin-dependent and independent mechanisms [ 7 , 38 ]. Hiyane et al. (2008) [ 40 ] study with 10 participants (56.9 ± 11.2 years old) demonstrated a significant reduction in blood glucose up to 90 minutes after two sessions of constant load exercise performed at 90% and 110% of the anaerobic threshold. Furthermore, Munan et al. (2020) [ 41 ] meta-analysis of 23 studies of acute exercise showed a significant decrease in mean glucose concentrations after 24 hours by 9.01 mg/dL (p < 0.001). In Zhang et al. (2020) [ 42 ] research, the HIIT group showed substantial differences in fasting, pre-exercise, and 11-hour post-exercise glucose levels compared to the control (p < 0.05). These results are consistent with our findings, where we identified a significant reduction in blood glucose levels immediately after the test, suggesting that this reduction may be maintained in the short and long term. CHRONOTROPIC INCOMPETENCE CI, assessed through CR, is characterized by the inability of the HR to increase proportionally to the increase in activity or metabolic demand, and plays a significant role in exercise tolerance. Recent studies have shown that CI is associated with cardiovascular dysfunctions in people with T2DM, and these conditions can lead to an increased risk of acute myocardial infarction, stroke, and sudden cardiac death [ 3 , 4 ]. Regarding our results, an average of 86.45 ± 20.47% was observed in CR in the SB condition and 82.93 ± 17.63% in the placebo condition. Although there was no statistically significant difference between these values (p = 0.126), it was observed that 38.46% (n = 5) of the subjects in the SB condition and 46.15% (n = 6) in the placebo condition had values below 85% of CR, which is considered indicative of CI, which can negatively influence performance during exercise. In a study conducted by Hansen et al. (2014) [ 43 ], which investigated the maximum chronotropic response index (CRI) in individuals with T2DM and healthy individuals, a significant difference in maximum CRI was demonstrated between the groups (0.85 ± 0.17 for patients with T2DM and 1.02 ± 0.17 for healthy individuals, p < 0.01). Similar to our study, they identified the presence of CI in 42% of patients with T2DM, while only 6% of healthy individuals had this condition. Furthermore, CI showed an association with other factors, such as obesity, glycemic control, insulin resistance, and level of physical fitness. Therefore, CI can be considered a risk marker in this population, but it is important to note that the origin of this condition is multifactorial and not fully understood [ 3 , 4 ]. Physical exercise not only proves to be effective in the treatment of CI, but also plays a crucial role in the prevention and improvement of associated risk factors. A study conducted by Jin et al. (2017) [ 44 ] investigated the effects of a 12-week aerobic training program in 30 individuals with T2DM with CI, revealing a significant increase in maximum HR by 13% (129.23 ± 16.32 vs. 140.50 ± 13.41 bpm, p < 0.01), a 24% increase in test time (703 ± 196 vs. 873 ± 177 seconds, p < 0.01), and a 26% increase in peak VO 2 (16.99 ± 3.96 vs. 21.40 ± 4.94 ml.kg.min -1 , p < 0.01). HEART RATE RECOVERY Heart rate recovery refers to the decrease in maximum/peak heart rate in the period following exercise. This process reflects the dynamic interaction between the parasympathetic and sympathetic systems and is widely recognized as a non-invasive measure to assess autonomic function, providing information on how the cardiovascular system responds to effort [ 45 ]. Regarding heart rate recovery in the first 30 seconds after the test, the values were 140 ± 19.39 in the SB condition and 134.77 ± 17.02 in the placebo condition, showing no significant difference (p = 0.472). The variations in heart rates between exercise peak and 60 seconds after were 24.85 bpm in the SB and 30.15 bpm in the placebo. Both values exceeded the 18 bpm threshold, an important indicator of altered chronotropic response [ 29 ]. Additionally, no participant had a baseline heart rate above 100 bpm, which, along with a reduction in chronotropic response, is an independent predictor of cardiovascular and all-cause mortality in individuals with T2DM [ 4 ], indicating a lower-risk profile in our sample. Qiu et al. (2017) [ 45 ], meta-analysis including 9,113 participants with an average follow-up period of 8.1 years, revealed a significant association between slower heart rate recovery and a substantial increase in the risk of developing T2DM (HR 1.66, 95% CI 1.16–2.38). Furthermore, Jae et al. (2016) [ 46 ] investigated the relationship between delayed heart rate recovery and the development of T2DM in 2,231 men, over an average follow-up of 5 years. During this period, 90 men (4.0%) developed the disease. The relative risks were significantly higher in the lowest quartiles of heart rate reserve (HR 2.71, 95% CI 1.20–6.11) and heart rate recovery (HR 2.81, 95% CI 1.36–5.78) compared to the highest quartiles. Each 1 bpm increase in heart rate reserve and recovery was associated with a 2–3% reduction in the incidence of T2DM. Delayed heart rate recovery after exercise is directly related to an increased risk of adverse cardiac events, including sudden cardiac death (SCD). Several studies have shown this association between SCD and changes in heart rate recovery. A study by Kurl et al. (2021) [ 47 ] examined 1,967 men (aged 42 to 61 years) over a 25-year period, finding a significant increase in the incidence of SCD among those with a lower heart rate reserve (HR 3.86, 95% CI 2.56–5.80) and slower heart rate recovery (HR 2.86, 95% CI 1.95–4.20). Each 1 bpm increase in heart rate recovery reduced the incidence of SCD by 1–2%. Additionally, Vivekananthan et al. (2003) [ 48 ] emphasized that heart rate recovery can be a prognostic indicator of mortality in six years for patients with coronary artery disease, regardless of the severity of the condition. These results indicate that such programs not only improve participants' quality of life but are also associated with a reduction in hospitalizations related to cardiac conditions and highlight the importance of this analysis as a valuable prognostic indicator in assessing cardiovascular risk. LIMITATIONS This study has some limitations to be considered. Firstly, the diversity in the clinical condition of participants, including hormonal conditions, especially in female subjects, differences in disease duration, the presence and degree of cardiac autonomic neuropathy, and variations in cardiorespiratory fitness. Additionally, the intervention was performed on different days, which could introduce some daily variability in the results, although we took measures to minimize this impact. These limitations should be taken into account when interpreting the results of this study and suggest the need for more comprehensive and controlled future investigations. CONCLUSIONS A significant increase in the test duration was observed in the SB condition, suggesting that active supplementation may have a beneficial effect on physical performance. Although no significant differences were observed in cardiovascular parameters, blood glucose decreased significantly in both test conditions, highlighting the positive impact of exercise. These findings indicate that treatment strategies, such as high-intensity exercise associated with the use of ergogenic resources, may be safe and effective for individuals with T2DM, promoting metabolic benefits and improvements in physical performance. However, further research is needed to fully understand the underlying mechanisms of interventions for this population. DECLARATIONS Conflict of Interest The authors report no conflict of interest. Ethical Approval This study was conducted in accordance with the rec-ommendations from the Declaration of Helsinki. Informed Consent All participants provided informed consent prior to their participation. ACKNOWLEDGEMENTS The authors are grateful to the Coordenação deAperfeiçoamento de Pessoal de Nível Superior - Brasil (CAPES) for the scholarship granted to the post-graduate student participating in the study. Author Contribution M.L.R.: Data collectionR.C.S.: Data collectionN.M.O.: Guidance, data analysis, and writingP.V.F.: Guidance, product and laboratory for supplementation preparation, and writingJ.M.N.: Laboratory and supplementation preparation REFERENCES International Diabetes Federation (IDF). (2021). Diabetes Atlas Tenth Edition. Brussels, Belgium: International Diabetes Federation. Kanaley, J. A., et al. (2022). Exercise/physical activity in individuals with type 2 diabetes: a consensus statement from the American College of Sports Medicine. Med Sci Sports Exerc. Keytsman, C., Dendale, P., & Hansen, D. (2015). Chronotropic incompetence during exercise in type 2 diabetes: a etiology, assessment methodology, prognostic impact and therapy. Sports Med, 45, 985-995. Zafrir, B., et al. (2016). Resting heart rate and measures of effort-related cardiac autonomic dysfunction predict cardiovascular events in asymptomatic type 2 diabetes. Eur J Prev Cardiol, 23(12), 1298-1306. Tabachnikov, V., et al. (2022). Heart rate response to exercise and recovery: independent prognostic measures in patients without known major cardiovascular disease. J Cardiopulm Rehabil Prev, 42(3), E34-E41. Nery, C., et al. (2017). Effectiveness of resistance exercise compared to aerobic exercise without insulin therapy in patients with type 2 diabetes mellitus: a meta-analysis. Braz J Phys Ther, 21(6), 400-415. American Diabetes Association Professional Practice Committee. (2022). Classification and diagnosis of diabetes: Standards of Medical Care in Diabetes - 2022. Diabetes Care, 45(Supplement_1), S17-S38. Pereira, W. V. C., et al. (2023). Position of Brazilian Diabetes Society on exercise recommendations for people with type 1 and type 2 diabetes. Diabetol Metab Syndr, 15(1), 1-20. Dhatariya, K. K., et al. (2020). Diabetic ketoacidosis. Nat Rev Dis Primers, 6(1), 40. Pedersen, B. K., & Saltin, B. (2015). Exercise as medicine–evidence for prescribing exercise as therapy in 26 different chronic diseases. Scand J Med Sci Sports, 25, 1-72. Janssen, S. M., & Connelly, D. M. (2021). The effects of exercise interventions on physical function tests and glycemic control in adults with type 2 diabetes: A systematic review. J Bodyw Mov Ther, 28, 283-293. Gutch, M., et al. (2015). Assessment of insulin sensitivity/resistance. Indian J Endocrinol Metab, 19(1), 160. Pan, B., et al. (2018). Exercise training modalities in patients with type 2 diabetes mellitus: a systematic review and network meta-analysis. Int J Behav Nutr Phys Act, 15(1), 1-14. Heibel, A. B., et al. (2018). Time to optimize supplementation: modifying factors influencing the individual responses to extracellular buffering agents. Front Nutr, 5, 35. Maughan, R. J., et al. (2018). IOC consensus statement: dietary supplements and the high-performance athlete. Int J Sport Nutr Exerc Metab, 28(2), 104-125. Grgic, J., et al. (2020). Effects of sodium bicarbonate supplementation on muscular strength and endurance: a systematic review and meta-analysis. Sports Med, 50(7), 1361-1375. Calvo, J. L., et al. (2021). Effect of sodium bicarbonate contribution on energy metabolism during exercise: a systematic review and meta-analysis. J Int Soc Sports Nutr, 18(1), 1-17. Grgic, J., et al. (2021). International Society of Sports Nutrition position stand: sodium bicarbonate and exercise performance. J Int Soc Sports Nutr, 18(1), 1-37. Støa, E. M., et al. (2017). High-intensity aerobic interval training improves aerobic fitness and HbA1c among persons diagnosed with type 2 diabetes. Eur J Appl Physiol, 117(3), 455-467. Hwang, C., et al. (2019). Effect of all-extremity high-intensity interval training vs. moderate-intensity continuous training on aerobic fitness in middle-aged and older adults with type 2 diabetes: A randomized controlled trial. Exp Gerontol, 116, 46-53. Organização Mundial da Saúde (OMS), et al. (2016). Diretrizes da OMS para a tiragem de sangue: boas práticas em flebotomia. Disponível em: . Carr, J., Hopkins, G., & Gore, J. (2011). Effects of acute alkalosis and acidosis on performance. Sports Med, 41(10), 801-814. Price, M., Moss, P., & Rance, S. (2003). Effects of sodium bicarbonate ingestion on prolonged intermittent exercise. Med Sci Sports Exerc, 35(8), 1303-1308. Guedes, D. P. (2006). Manual prático para avaliação em educação física. Editora Manole Ltda. Puga, G. M., et al. (2012). Aerobic fitness evaluation during walking tests identifies the maximal lactate steady state. The Scientific World Journal, 2012. Tanaka, H., Monahan, K. D., & Seals, D. R. (2001). Age-predicted maximal heart rate revisited. J Am Coll Cardiol, 37(1), 153-156. Borg, G. A. V. (1982). Psychophysical bases of perceived exertion. Med Sci Sports Exerc. Brubaker, P. H., & Kitzman, D. W. (2011). Chronotropic incompetence: causes, consequences, and management. Circulation, 123(9), 1010-1020. Watanabe, J., et al. (2001). Heart rate recovery immediately after treadmill exercise and left ventricular systolic dysfunction as predictors of mortality: the case of stress echocardiography. Circulation, 104(16), 1911-1916. Kerksick, C. M., et al. (2018). ISSN exercise & sports nutrition review update: research & recommendations. J Int Soc Sports Nutr, 15(1), 38. Stephens, T. J., et al. (2002). Effect of sodium bicarbonate on muscle metabolism during intense endurance cycling. Med Sci Sports Exerc, 34(4), 614-621. Kumstát, M. M., et al. (2018). Does sodium citrate cause the same ergogenic effect as sodium bicarbonate on swimming performance? J Hum Kinet, 65, 89. Miranda, W. A. S., et al. (2022). Can Sodium Bicarbonate Supplementation Improve Combat Sports Performance? A Systematic Review and Meta-analysis. Curr Nutr Rep, 11(2), 273-282. Gurton, W. H., et al. (2023). Sodium bicarbonate and time-to-exhaustion cycling performance: a retrospective analysis exploring the mediating role of expectation. Sports Med, 9(1), 65. Carr, A. J., Hopkins, W. G., & Gore, C. J. (2011). Effects of acute alkalosis and acidosis on performance: a meta-analysis. Sports Med, 41, 801-814. Durkalec-Michalski, K., et al. (2020). The influence of progressive-chronic and acute sodium bicarbonate supplementation on anaerobic power and specific performance in team sports: a randomized, double-blind, placebo-controlled crossover study. Nutr Metab, 17, 1-15. Lopes-Silva, J. P., Reale, R., & Franchini, E. (2019). Acute and chronic effect of sodium bicarbonate ingestion on Wingate test performance: a systematic review and meta-analysis. J Sports Sci, 37(7), 762-771. Harrington, D., & Henson, J. (2021). Physical activity and exercise in the management of type 2 diabetes: where to start? Pract Diabetes, 38(5), 35-40b. Sylow, L., et al. (2017). Exercise-stimulated glucose uptake—regulation and implications for glycaemic control. Nat Rev Endocrinol, 13(3), 133-148. Hiyane, W. C., et al. (2008). Blood glucose responses of type-2 diabetics during and after exercise performed at intensities above and below anaerobic threshold. Rev Bras Cineantropom Desempenho Hum, 10(1), 8-11. Munan, M., et al. (2020). Acute and chronic effects of exercise on continuous glucose monitoring outcomes in type 2 diabetes: a meta-analysis. Front Endocrinol, 11, 495. Zhang, Q. Q., et al. (2021). Effects of acute exercise with different intensities on glycemic control in patients with type 2 diabetes mellitus. Acta Endocrinol (Buchar), 17(2), 212. Hansen, D., & Dendale, P. (2014). Modifiable predictors of chronotropic incompetence in male patients with type 2 diabetes. J Cardiopulm Rehabil Prev, 34(3), 202-207. Jin, L., et al. (2017). Exercise training on chronotropic response and exercise capacity in patients with type 2 diabetes mellitus. Exp Ther Med, 13(3), 899-904. Qiu, S. H., et al. (2017). Attenuated heart rate recovery predicts risk of incident diabetes: insights from a meta-analysis. Diabet Med, 34(12), 1676-1683. Jae, S. Y., et al. (2016). Exercise heart rate reserve and recovery as predictors of incident type 2 diabetes. Am J Med, 129(5), 536.e7-536.e12. Kurl, S., et al. (2021). Exercise heart rate reserve and recovery as risk factors for sudden cardiac death. Prog Cardiovasc Dis, 68, 7-11. Vivekananthan, D. P., et al. (2003). Heart rate recovery after exercise is a predictor of mortality, independent of the angiographic severity of coronary disease. J Am Coll Cardiol, 42(5), 831-838. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4101653","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":279863374,"identity":"585fe00f-11bd-4524-9c1e-ab2a772305e0","order_by":0,"name":"Edher Lucas Antunes","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA8UlEQVRIiWNgGAWjYHCDHCCuAGJm5gYCKpmRtZwBCTCSooWxDcQgoIV/dv8x6YKKOgZ+9tyDjyvn1UbztwO1/KjYhlOLxJ3DbNIzzhxmkOx5l2x4dtvx3BmHGRsYe87cxm3NjWQ2ad62AwwGN3LMJBu3HcttAGphZmzDrUUerOVfHYP9jRzzn41zjuXOJ6TFAKylgZnBQCLHjLGxoSZ3AyEthjeSja15jh3mkTjzxliy4diB3I1ALQfx+UXuRuLD2zw1dXL87TmGHxtq6nLnnT988MGPCjzehwIeKH0YTB4gqB4J1JGieBSMglEwCkYIAABeM1ddyIrb/gAAAABJRU5ErkJggg==","orcid":"","institution":"Ponta Grossa State University","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Edher","middleName":"Lucas","lastName":"Antunes","suffix":""},{"id":279863375,"identity":"3d8414f0-620c-44ed-b927-0ab856f9a4bb","order_by":1,"name":"Maria Luiza Rios","email":"","orcid":"","institution":"Ponta Grossa State University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Maria","middleName":"Luiza","lastName":"Rios","suffix":""},{"id":279863376,"identity":"9ca5ea5b-26e2-4b0c-b20e-0ce4035b68de","order_by":2,"name":"Rafael Carlos Sochodolak","email":"","orcid":"","institution":"Ponta Grossa State University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Rafael","middleName":"Carlos","lastName":"Sochodolak","suffix":""},{"id":279863377,"identity":"8a625ffa-1f5f-4b74-be8e-eb10a1e79610","order_by":3,"name":"Jessica Mendes Nadal","email":"","orcid":"","institution":"Ponta Grossa State University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Jessica","middleName":"Mendes","lastName":"Nadal","suffix":""},{"id":279863378,"identity":"72ae18c8-d80d-4ab3-9c6c-2c648efa8e5f","order_by":4,"name":"Paulo Vitor Farago","email":"","orcid":"","institution":"Ponta Grossa State University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Paulo","middleName":"Vitor","lastName":"Farago","suffix":""},{"id":279863379,"identity":"e18c12cb-6d33-4053-b049-a7debb4413a5","order_by":5,"name":"Nilo Massaru Okuno","email":"","orcid":"","institution":"Ponta Grossa State University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Nilo","middleName":"Massaru","lastName":"Okuno","suffix":""}],"badges":[],"createdAt":"2024-03-14 14:27:20","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4101653/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4101653/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":53009101,"identity":"0645e0d8-7d0d-4280-83e8-5a9ff53e4f81","added_by":"auto","created_at":"2024-03-19 15:21:05","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":38940,"visible":true,"origin":"","legend":"\u003cp\u003eExperimental design of the study.\u003c/p\u003e\n\u003cp\u003eBP = blood pressure; HR = heart rate.\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-4101653/v1/13194d469d2d6f08cb254fbb.png"},{"id":53009084,"identity":"01d9ed7f-b96f-4518-9afa-30e24b93919a","added_by":"auto","created_at":"2024-03-19 15:20:59","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":47858,"visible":true,"origin":"","legend":"\u003cp\u003eResults of test time values in the maximum incremental test between conditions.\u003c/p\u003e\n\u003cp\u003eThe data is presented with individual values in test time in seconds. SB = sodium bicarbonate.\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-4101653/v1/705c3e683fc56d10f3715e12.png"},{"id":60621748,"identity":"01ce1c97-3f09-4d84-9667-b957fb4adeb7","added_by":"auto","created_at":"2024-07-18 21:04:03","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":596435,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4101653/v1/44641f6d-3f21-4d93-acca-0c53cf8caad5.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eEffects of Sodium Bicarbonate Supplementation on Physical Performance and Cardiovascular Variables in Middle-aged and Elderly Adults With Type 2 Diabetes Mellitus \u003c/p\u003e","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eThe epidemic of diabetes mellitus (DM) poses a global health problem. Estimates indicate that over 537\u0026nbsp;million individuals worldwide have already been diagnosed with the disease, and this number may increase to 783\u0026nbsp;million by the year 2045 [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eDiabetes mellitus (DM) is a metabolic condition characterized by disruptions in the action and regulation of insulin. Type 2 diabetes (T2DM), accounting for approximately 90\u0026ndash;95% of cases, results from a combination of gradual and persistent loss of secretion, along with insulin resistance, and predominantly affects middle-aged and elderly individuals [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIt is common to observe changes in the central nervous system, such as chronotropic incompetence (CI) and a slower heart rate recovery after exercise [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Since the autonomic nervous system plays a crucial role in heart rate (HR) recovery after exercise, a delay in this response may indicate autonomic dysfunction, which can be a predictor of disease development and progression [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. CI has multifactorial origins, but adopting an active lifestyle has been suggested as a safe and effective approach to prevent or reduce changes in insulin and cardiac autonomic neuropathy in individuals with T2DM [\u003cspan additionalcitationids=\"CR7\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e], resulting in significant improvements in quality of life.\u003c/p\u003e \u003cp\u003eAdditionally, individuals with T2DM may experience acid-base imbalances, especially when the condition is not adequately controlled. Diabetic ketoacidosis (DKA), characterized by hyperglycemia, metabolic acidosis, and ketosis, is a prevalent clinical emergency in type 1 DM, but it is also possible in poorly controlled T2DM [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. In this context, regular physical exercise plays a crucial role in improving the risk conditions associated with acid-base imbalances in people with T2DM [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. It is important to note that both acute and chronic supplementation of SB do not have substantial effects on DKA parameters. However, supplementation may contribute to an increase in physical performance, providing additional benefits to exercise in this population [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e].\u003c/p\u003e \u003cp\u003ePhysical exercise is recognized as a significant non-pharmacological pillar in the prevention and treatment of T2DM [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. It provides a range of acute and chronic benefits, such as improving metabolic parameters affected by the disease, enhancing physical capacities, and promoting cardiovascular health [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. However, considering the limitations imposed by the disease condition, such as muscle fatigue, the use of additional resources, such as supplementation with sodium bicarbonate (SB), can be a strategy to improve physical performance.\u003c/p\u003e \u003cp\u003eThere is consistent evidence supporting the benefits of SB in physical performance, resulting from its muscle fatigue-delaying effects through physicochemical buffering mechanisms [\u003cspan additionalcitationids=\"CR15\" citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Extracellular buffering is recognized as the primary mechanism through which SB influences physical performance, particularly during high-intensity activities. This ability is essential to prevent the accumulation of hydrogen ions (H\u003csup\u003e+\u003c/sup\u003e) and, consequently, reduce metabolic acidosis, which is one of the main factors contributing to muscle fatigue [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eStudies in other populations have revealed that the BS supplementation strategy promotes positive effects on physical performance [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e], particularly in high-intensity training protocols, which, in turn, have demonstrated numerous benefits in individuals with T2DM [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Although previous studies have observed performance improvement through BS supplementation in other populations, there is no data on supplementation in physical performance in individuals with T2DM. Thus, the hypothesis of the present research was to observe improvement in physical performance and biochemical and cardiovascular parameters after BS supplementation in middle-aged and elderly adults with T2DM.\u003c/p\u003e"},{"header":"METHODS","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003ePARTICIPANTS\u003c/h2\u003e \u003cp\u003eThe sample consisted of 13 individuals with T2DM, recruited through convenience sampling in clinics, hospitals, and the community via telephone contact and in-person recruitment visits. Volunteers were selected based on their medical history and physical examination. Inclusion criteria for the study were: 1) diagnosis of T2DM; 2) age between 45 and 74 years. Exclusion criteria included: 1) history of proliferative diabetic retinopathy, autonomic or peripheral neuropathy; 2) presence of health conditions that could affect physical performance; 3) recurrent or recent hospitalizations in the six months prior to the study; 4) systolic blood pressure equal to or higher than 160 mmHg or diastolic blood pressure equal to or higher than 105 mmHg; 5) smoking; 6) pregnancy or lactation period; 7) insulin dependence.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eEXPERIMENTAL DESIGN\u003c/h2\u003e \u003cp\u003eThis is a triple-blind, crossover, placebo-controlled, and randomized experimental study comparing interventions with SB and placebo. The study received approval from the Ethics Committee on Human Research at the State University of Ponta Grossa (UEPG), under approval number: 62650422.9.0000.0105 dated October 10, 2022. Data collection took place at the Physical Assessment and Health Laboratory (LAFISE) of the Department of Physical Education at the UEPG.\u003c/p\u003e \u003cp\u003eThe experimental protocol was divided into two stages. In the first stage, participants underwent physical assessment and a familiarization process with the physical test. In the second stage, the physical test was conducted under the presence of SB or placebo. Heart rate was recorded before, during, and after the tests. The assessed parameters were a) percentage of chronotropic reserve (CR); b) heart rate recovery (HRR).\u003c/p\u003e \u003cp\u003eSupplementation was administered to participants 60 minutes before the experimental sessions, ensuring that both the evaluator and the participants were unaware of the supplement's content. Additionally, participants received specific instructions not to engage in physical exercise and to avoid consuming stimulant foods in the 24 hours preceding the tests to ensure uniformity of conditions before assessments.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eGLUCOSE MEASUREMENT\u003c/h2\u003e \u003cp\u003eCapillary blood glucose was measured at rest and after 3 minutes at the end of the physical tests, using the standard collection protocol, which includes local antisepsis with alcohol and the use of disposable materials [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e], through a glucometer (G-Tech Free, Brazil), with a result range of 10 to 600 mg/dL (0.6 to 33.3 mmol/L), and reagent strips (G-Tech Free 1, Brazil). Collection was performed at least 2 hours after the last meal.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eSODIUM BICARBONATE AND PLACEBO SUPPLEMENTATION\u003c/h2\u003e \u003cp\u003eFor the SB supplementation, a dose of 0.3 g.kg\u003csup\u003e-1\u003c/sup\u003e was administered to participants 60 minutes before the test to ensure complete absorption of the supplement [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. The choice of this dosage is grounded in evidence that higher doses do not provide additional benefits and may be associated with a higher incidence of adverse effects [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. The placebo solution was administered at a dosage of 3.6 g and ensured the same features of SB supplementation. To assess any gastrointestinal discomfort resulting from supplementation, participants used a 10-point scale, where 0 indicated the absence of symptoms, and 10 represented extreme discomfort [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. The dosage for each participant was prepared in 200 ml of chilled carbonated water by an individual not involved in data collection, ensuring the impartiality of the process.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eSUPPLEMENTATION COMPOSITION\u003c/h2\u003e \u003cp\u003eThe solutions were carefully prepared to ensure uniformity in appearance, taste, smell, and viscosity. The active solution (SB) consisted of 92.78% sodium bicarbonate, 2.4% stevioside, 0.016% green dye, 4% lemon flavoring, and 0.8% micronized silica gel, with a correction factor of 1.077 for the preparation of each participant's individual dose. The isotonic placebo solution was composed of 0.9% sodium chloride, 0.3% stevioside, 0.025% green dye, 1% lemon flavoring, and 0.5% micronized silica gel.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eANTHROPOMETRY, BLOOD PRESSURE, AND BODY COMPOSITION\u003c/h2\u003e \u003cp\u003eBody weight and height measurements were taken using a Welmy W200A digital anthropometric scale, with a capacity of up to 200 kg and precision of 100 g. Height measurement followed the recommendations of Guedes (2006) [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. Based on these measurements, the Body Mass Index (BMI) was calculated using the standard formula: [body mass (kg) / height (m)\u0026sup2;]. Blood pressure was measured with participants at rest, using a digital device (Omron HEM-7122, Jundia\u0026iacute;, Brazil), following the standard application protocol to ensure accuracy and consistency in measurements. Body composition was assessed using a tetrapolar bioimpedance device (Maltron 906, Rayleigh, England), following the manufacturer's recommended protocol. These procedures were conducted in a standardized manner to ensure the accuracy of anthropometric assessments and body composition evaluations.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eMAXIMAL INCREMENTAL TEST\u003c/h2\u003e \u003cp\u003eThe test utilized in our research was developed based on a modification of the protocol proposed by Puga et al. (2012) [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e], in which only the treadmill incline was manipulated, aiming for a personalized adaptation to accommodate the specific characteristics of participants, such as the presence of diabetic neuropathy.\u003c/p\u003e \u003cp\u003eParticipants underwent a maximal incremental treadmill test consisting of 11 stages, each lasting 1 minute. The test began with a constant speed of 5.5 km/h and 0% incline, incrementing by 2% incline at each subsequent stage. The laboratory temperature was controlled and maintained at 23\u0026deg;C during all interventions. Additionally, volunteers performed the tests at the same time of day, with a minimum interval of 72 hours and a maximum of 1 week between tests.\u003c/p\u003e \u003cp\u003eTo determine participants\u0026rsquo; maximum heart rate, the equation by Tanaka et al. (2001) [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e] was used by the following formula: 208 \u0026ndash; (0.7 * age in years). Participants' subjective perception of effort was assessed at the end of each stage using the Borg scale [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. The test was terminated when the subject exhibited excessive fatigue or exhaustion, along with signs indicating cardiovascular abnormalities.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003eHEART RATE RESPONSE\u003c/h2\u003e \u003cp\u003eThe calculation of the percentage of CR was performed considering three parameters: resting heart rate (HR), reserve HR, and maximum HR. The equation used for CR calculation was CR = (reserve HR / [maximum HR - resting HR]) x 100. CR values below 80% are indicative of chronotropic incompetence [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e], and recovery HR values less than 18 beats per minute (bpm) after 60 seconds are indicative of altered chronotropic response [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. HR recovery was measured by observing the difference between HR at 30, 60, 90, and 120 seconds into recovery compared to HR at the point of exhaustion. HR monitoring was conducted using a heart rate monitor (Polar V800, Kempele, Finland).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eSTATISTICAL ANALYSIS\u003c/h2\u003e \u003cp\u003eTo assess the normality of the data, the Shapiro-Wilk test was used. For conditions pre- and post-test within the same condition, analysis of variables such as percentage of CR, test duration, and gastrointestinal discomfort was conducted using paired t-tests. The Mann-Whitney test was used for the variable of peak HR and gastrointestinal discomfort. In evaluations between test conditions, the analysis of blood pressure and blood glucose levels was assessed through repeated measures two-way ANOVA. The chi-square test and Fisher's exact test were used to evaluate the association between supplement consumption and the subject's knowledge of what they were consuming. The significance level for all data was set at p\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/p\u003e \u003c/div\u003e"},{"header":"RESULTS","content":"\u003cp\u003eThe participant characteristics are presented in Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e. The mean age was 62.15\u0026thinsp;\u0026plusmn;\u0026thinsp;6.90 years, with a body mass index (BMI) of 29.14\u0026thinsp;\u0026plusmn;\u0026thinsp;4.49 kg/m\u003csup\u003e2\u003c/sup\u003e. Body composition varied considerably, with a lean body mass of 63.14\u0026thinsp;\u0026plusmn;\u0026thinsp;7.60% and a fat percentage of 36.88\u0026thinsp;\u0026plusmn;\u0026thinsp;7.59%. Additionally, the mean duration of the disease was 5.03\u0026thinsp;\u0026plusmn;\u0026thinsp;6.64 years and indicated heterogeneity in the diagnosis time among the participants.\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003ctable id=\"Tab1\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eAnthropometric characteristics, body composition, years of disease, and comorbidities (n\u0026thinsp;=\u0026thinsp;13).\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eVariable\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eResults\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eWomen (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e11 (84.61)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAge (years)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e62.15\u0026thinsp;\u0026plusmn;\u0026thinsp;6.90\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eBody Weight (kg)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e73.39\u0026thinsp;\u0026plusmn;\u0026thinsp;14.19\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eHeight (m)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e1.58\u0026thinsp;\u0026plusmn;\u0026thinsp;0.09\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eBody Mass Index (kg/m\u0026sup2;)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e29.14\u0026thinsp;\u0026plusmn;\u0026thinsp;4.49\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eFat-Free Mass (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e63.14\u0026thinsp;\u0026plusmn;\u0026thinsp;7.60\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eBody Fat (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e36.88\u0026thinsp;\u0026plusmn;\u0026thinsp;7.59\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eResting HR (bpm)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e70.23\u0026thinsp;\u0026plusmn;\u0026thinsp;11.94\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eYears of Disease Diagnosis\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e5.03\u0026thinsp;\u0026plusmn;\u0026thinsp;6.64\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eComorbidities\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSystemic Arterial Hypertension (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e69.23 (9)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eHypothyroidism (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e23.08 (3)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eHypercholesterolemia (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e7.69 (1)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eHypertriglyceridemia (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e7.69 (1)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003ctfoot\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"2\"\u003eThe data are presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation. HR\u0026thinsp;=\u0026thinsp;heart rate.\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tfoot\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eThe results of CR values and maximal incremental test duration are presented in Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e and Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e. The comparison of test duration between conditions was statistically significant (p\u0026thinsp;=\u0026thinsp;0.005). However, there was no significant difference in CR and gastrointestinal discomfort (p\u0026thinsp;=\u0026thinsp;0.126; p\u0026thinsp;=\u0026thinsp;0.066, respectively). Additionally, Fisher's exact test indicates no significant association between supplement consumption and the subject's knowledge of what they are consuming (X\u0026sup2;\u003csub\u003e(1)\u003c/sub\u003e\u0026thinsp;=\u0026thinsp;1.815; p\u0026thinsp;=\u0026thinsp;0.371).\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003ctable id=\"Tab2\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eResults of chronotropic reserve values, test duration, and gastrointestinal discomfort between conditions (n\u0026thinsp;=\u0026thinsp;13).\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eVariable\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eSB\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003ePlacebo\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003ep\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eTest Time (s)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e481\u0026thinsp;\u0026plusmn;\u0026thinsp;116.97\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e439\u0026thinsp;\u0026plusmn;\u0026thinsp;99.92\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.005*\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCR (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e86.45\u0026thinsp;\u0026plusmn;\u0026thinsp;20.47\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e82.93\u0026thinsp;\u0026plusmn;\u0026thinsp;17.63\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.126\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eGastrointestinal Discomfort (0\u0026ndash;10)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e2.8\u0026thinsp;\u0026plusmn;\u0026thinsp;4.1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e0.1\u0026thinsp;\u0026plusmn;\u0026thinsp;0.3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.066\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003ctfoot\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"4\"\u003eThe data are presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation. CR\u0026thinsp;=\u0026thinsp;chronotropic reserve; SB\u0026thinsp;=\u0026thinsp;sodium bicarbonate.\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tfoot\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eThe results of clinical monitoring variables are presented in Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e. Differences were observed in blood glucose values (p\u0026thinsp;=\u0026thinsp;0.0001), but not between conditions (p\u0026thinsp;=\u0026thinsp;0.88). In the SB condition, pre-test blood glucose was 151.31\u0026thinsp;\u0026plusmn;\u0026thinsp;60.33 mg/dL and significantly decreased to 127.85\u0026thinsp;\u0026plusmn;\u0026thinsp;57.37 mg/dL post-test (p\u0026thinsp;=\u0026thinsp;0.002). In the placebo condition, a similar reduction in blood glucose was observed, with pre-test values of 155.85\u0026thinsp;\u0026plusmn;\u0026thinsp;76.97 mg/dL and post-test values of 131.15\u0026thinsp;\u0026plusmn;\u0026thinsp;79.78 mg/dL (p\u0026thinsp;=\u0026thinsp;0.004). However, no statistically significant differences were found in systolic (SBP) and diastolic (DBP) blood pressure values between conditions (p\u0026thinsp;=\u0026thinsp;0.84, p\u0026thinsp;=\u0026thinsp;0.34) or over time (p\u0026thinsp;=\u0026thinsp;0.40, p\u0026thinsp;=\u0026thinsp;0.47), with no interaction (p\u0026thinsp;=\u0026thinsp;0.19, p\u0026thinsp;=\u0026thinsp;0.34, respectively).\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003ctable id=\"Tab3\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eResults of monitoring variables for blood pressure values and capillary blood glucose pre and post-test in active supplementation and placebo conditions (n\u0026thinsp;=\u0026thinsp;13).\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eVariable\u003c/p\u003e\n\u003c/th\u003e\n\u003cth colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eSB\u003c/p\u003e\n\u003c/th\u003e\n\u003cth colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003ePlacebo\u003c/p\u003e\n\u003c/th\u003e\n\u003cth colspan=\"3\" align=\"left\"\u003e\n\u003cp\u003ep\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003ePre\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003ePost\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003ePre\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003ePost\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eCondition\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eTime\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eInteraction\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSBP (mmHg)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e126.2\u0026thinsp;\u0026plusmn;\u0026thinsp;15.47\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e124.8\u0026thinsp;\u0026plusmn;\u0026thinsp;15.87\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e123.6\u0026thinsp;\u0026plusmn;\u0026thinsp;16.51\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e129.5\u0026thinsp;\u0026plusmn;\u0026thinsp;16.48\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.84\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.40\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.19\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eDBP (mmHg)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e76.2\u0026thinsp;\u0026plusmn;\u0026thinsp;9.58\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e75.8\u0026thinsp;\u0026plusmn;\u0026thinsp;5.31\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e71.8\u0026thinsp;\u0026plusmn;\u0026thinsp;6.97\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e74.6\u0026thinsp;\u0026plusmn;\u0026thinsp;10.35\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.34\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.47\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.34\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eBlood Glucose (mg/dl)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e151.31\u0026thinsp;\u0026plusmn;\u0026thinsp;60.33\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e127.85\u0026thinsp;\u0026plusmn;\u0026thinsp;57.37*\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e155.85\u0026thinsp;\u0026plusmn;\u0026thinsp;76.97\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e131.15\u0026thinsp;\u0026plusmn;\u0026thinsp;79.78*\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.88\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0,0001*\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.88\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003ctfoot\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"8\"\u003eThe data are presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation. SBP\u0026thinsp;=\u0026thinsp;systolic blood pressure; DBP\u0026thinsp;=\u0026thinsp;diastolic blood pressure.\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tfoot\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eThe results of peak and recovery HR monitoring variables are shown in Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e. The comparison between conditions regarding heart rate revealed that there were no statistically significant differences at various points during the test. Peak HR did not show significant differences between conditions (p\u0026thinsp;=\u0026thinsp;0.169). Additionally, no differences were observed in HR at 30, 60, 90, and 120 seconds of recovery after the test between conditions (p\u0026thinsp;=\u0026thinsp;0.472, p\u0026thinsp;=\u0026thinsp;0.238, p\u0026thinsp;=\u0026thinsp;0.194, p\u0026thinsp;=\u0026thinsp;0.147, respectively). These results suggest that both conditions exhibited similar behaviors in terms of heart rate over the assessment period.\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003ctable id=\"Tab4\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eResults of peak heart rate and recovery at 30, 60, 90, and 120 seconds after the end of the maximal incremental test between conditions (n\u0026thinsp;=\u0026thinsp;13).\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eHeart Rate\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eSB\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003ePlacebo\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003ep\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePeak\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e151.08\u0026thinsp;\u0026plusmn;\u0026thinsp;20.77\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e147.92\u0026thinsp;\u0026plusmn;\u0026thinsp;18.10\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.169\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e30 (s)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e140\u0026thinsp;\u0026plusmn;\u0026thinsp;19.39\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e134.77\u0026thinsp;\u0026plusmn;\u0026thinsp;17.02\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.472\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e60 (s)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e126.23\u0026thinsp;\u0026plusmn;\u0026thinsp;18.03\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e117.77\u0026thinsp;\u0026plusmn;\u0026thinsp;17.60\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.238\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e90 (s)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e115.08\u0026thinsp;\u0026plusmn;\u0026thinsp;20.25\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e105.08\u0026thinsp;\u0026plusmn;\u0026thinsp;17.86\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.194\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e120 (s)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e109.46\u0026thinsp;\u0026plusmn;\u0026thinsp;19.59\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e99.15\u0026thinsp;\u0026plusmn;\u0026thinsp;15.23\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.147\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003ctfoot\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"4\"\u003eThe data are presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation. HR\u0026thinsp;=\u0026thinsp;heart rate; SB\u0026thinsp;=\u0026thinsp;sodium bicarbonate; s\u0026thinsp;=\u0026thinsp;seconds.\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tfoot\u003e\n\u003c/table\u003e\n\u003c/div\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eTo the best of our knowledge, this is the first study to examine the effect of BS supplementation during maximal incremental test in individuals with T2DM. The hypothesis of this research was to observe improvement in physical performance and biochemical and cardiovascular parameters after supplementation. A significant increase in test duration was observed in the BS condition. Additionally, both conditions showed significant reductions in blood glucose levels after interventions, indicating comparable efficacy of isolated and/or combined physical exercise with BS in glucose metabolism regulation, but without differences in cardiovascular parameters. These results suggest that while both interventions seem effective in glucose regulation, active BS supplementation may confer an additional benefit to participants' exercise capacity, warranting further investigation in future studies.\u003c/p\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003ePHYSICAL PERFORMANCE ANALYSIS\u003c/h2\u003e \u003cp\u003eAcid-base balance is achieved by the action of physicochemical buffers, which can be improved through supplementation with SB. Studies that evaluated pH during exercise have observed a delay in the onset of intramuscular acidosis and, consequently, better exercise performance [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. SB supplementation is often associated with the context of physical training, especially in athletes, due to its potential benefits in sports performance [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. In this sense, it is not commonly studied in groups that have some health condition, such as individuals with T2DM. Therefore, our results are relevant in suggesting that supplementation may have beneficial effects on cardiovascular and physical performance parameters in this population.\u003c/p\u003e \u003cp\u003eWhile we did not conduct a comprehensive analysis through laboratory tests to assess the biochemical changes resulting from supplementation, previous studies offer relevant results. The research conducted by Stephens et al. (2002) [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e] observed a significant increase in plasma bicarbonate concentration after ingesting 0.3 g.kg\u003csup\u003e-1\u003c/sup\u003e of SB in a maximal incremental test on a cycle ergometer. Kumstat et al. (2018) [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e] research demonstrated that blood pH, bicarbonate concentration, and base excess (BE) increased significantly after supplementation with 0.3 g.kg\u003csup\u003e-1\u003c/sup\u003e of SB (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05) in professional swimmers (20.7\u0026thinsp;\u0026plusmn;\u0026thinsp;2.1 years old). Similarly, the systematic review and meta-analysis conducted by Miranda et al. (2022) [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e] highlighted a significant effect on increasing blood lactate levels (p\u0026thinsp;=\u0026thinsp;0.006) in combat athletes undergoing a SB supplementation protocol. This may be attributed to the fact that SB promotes an increase in the efflux of H\u003csup\u003e+\u003c/sup\u003e ions from muscle cells to the blood, where they are neutralized. This process results in the reduction of intramuscular acidosis, which, in turn, allows for prolonged operation of the glycolytic pathway [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAdditionally, Gurton et al. (2023) [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e] suggested that administering SB in solution form may be more effective than encapsulated supplementation, demonstrating a 2% increase in repeated sprint and Yo-Yo IR2 test performance in the solution supplementation group. They observed that the decline in serum bicarbonate during maximal exercise was more pronounced for SB administered in solution compared to capsules (2.7\u0026thinsp;\u0026plusmn;\u0026thinsp;2.1 mmol.L kg\u003csup\u003e-1\u003c/sup\u003e, p\u0026thinsp;=\u0026thinsp;0.001), which was the method used in our research. The biochemical changes observed in previous studies may have influenced the results obtained in our research, providing a valuable context for interpreting the findings.\u003c/p\u003e \u003cp\u003eThe active intervention condition had a mean test time of 481\u0026thinsp;\u0026plusmn;\u0026thinsp;116.97 seconds, while the placebo condition had a mean time of 439\u0026thinsp;\u0026plusmn;\u0026thinsp;99.92 seconds, representing an average increase of approximately 9.57% in test time. Carr et al. (2011) [\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e] literature review included 38 studies that evaluated performance effects with SB supplementation, which observed a moderate performance improvement of 1.7% (\u0026plusmn;\u0026thinsp;2.0%) with a standard dose of 0.3g.kg\u003csup\u003e-1\u003c/sup\u003e in a 1-minute sprint test in male athletes, notable but with a lesser effect when compared to our research. Additionally, a moderate correlation (r\u0026thinsp;=\u0026thinsp;0.33; 90% CI -0.10, 0.65) was observed between test performance and pre-exercise serum bicarbonate values after SB supplementation. Acute and chronic SB intake can lead to diverse outcomes. Durkalec-Michalski et al. (2020) [\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e] investigated the effects of acute (0.2 g.kg\u003csup\u003e-1\u003c/sup\u003e) and chronic (8 days with a 25% dosage increase every 2 days, from 0.5 g.kg\u003csup\u003e-1\u003c/sup\u003e on days 1 and 2 to 0.2 g.kg\u003csup\u003e-1\u003c/sup\u003e on days 7 and 8) SB on the physical performance of hockey athletes. Acute supplementation showed significant improvements in the time of a specific discipline test and in the anaerobic capacity of the Wingate test (939\u0026thinsp;\u0026plusmn;\u0026thinsp;26 vs. 914\u0026thinsp;\u0026plusmn;\u0026thinsp;22 s, p\u0026thinsp;=\u0026thinsp;0.006), while chronic supplementation did not result in substantial improvements. However, Lopes-Silva et al. (2019) [\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e] meta-analysis indicated that chronic SB intake (0.5 g.kg\u003csup\u003e-1\u003c/sup\u003e for 5 days) promoted significant improvements in peak and mean power in the Wingate test. These results highlight the importance of the present research in the practical evaluation of different supplementation protocols.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003eHIGH-INTENSITY PHYSICAL EXERCISE\u003c/h2\u003e \u003cp\u003eOur results demonstrated an improvement in physical performance and, consequently, an increase in tolerance to high-intensity activities in subjects with T2DM after SB supplementation. Hwang et al. (2019) [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e] aimed to evaluate high-intensity interval training (HIIT) compared to moderate-intensity continuous training (MICT) in 58 elderly individuals with T2DM (63\u0026thinsp;\u0026plusmn;\u0026thinsp;1 years old) over 8 weeks of supervised training. Improvements in aerobic fitness were observed, with a 10% increase in peak VO\u003csub\u003e2\u003c/sub\u003e for the HIIT group and 8% for the MICT group. Additionally, there was an increase in maximum exercise tolerance, with additions of 1.8 and 1.3 minutes (p\u0026thinsp;\u0026le;\u0026thinsp;0.002 in both groups; p\u0026thinsp;\u0026ge;\u0026thinsp;0.90 for the comparison between HIIT and MICT). St\u0026oslash;a et al. (2017) [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e] investigated the effects of HIIT (85% and 95% of maximum HR) and MICT (70% and 75% of maximum HR) in 38 individuals with T2DM over 12 weeks of supervised training. The results demonstrated a significant 21% increase in maximum VO\u003csub\u003e2\u003c/sub\u003e (from 25.6 to 30.9 ml.kg\u003csup\u003e-1\u003c/sup\u003e, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) in the HIIT group, accompanied by a -0.58% reduction in HbA1c levels (from 7.78 to 7.20%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Additionally, there was a 1.9% reduction in body weight (p\u0026thinsp;\u0026lt;\u0026thinsp;0.01) and BMI. These improvements were statistically significant compared to the group undergoing MICT, with no differences in lactate threshold and blood pressure. Moderate correlations were identified between the change in maximum VO\u003csub\u003e2\u003c/sub\u003e and HbA1c when combined (r = -0.52, p\u0026thinsp;\u0026lt;\u0026thinsp;0.01). In summary, the results obtained in this investigation corroborate the feasibility, safety, and effectiveness of high-intensity training in individuals with T2DM. These findings are relevant in the context of exercise prescription for this population, as the training methods in question provide comparable benefits, with the additional advantage of a lower time demand associated with HIIT protocols.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec16\" class=\"Section2\"\u003e \u003ch2\u003eBLOOD GLUCOSE\u003c/h2\u003e \u003cp\u003eA significant reduction in glucose levels was observed in both conditions. In the SB condition, there was a reduction of 15.5% (151.31\u0026thinsp;\u0026plusmn;\u0026thinsp;60.33 to 127.85\u0026thinsp;\u0026plusmn;\u0026thinsp;57.37 mg/dL; p\u0026thinsp;=\u0026thinsp;0.002), and in the placebo condition, the reduction was 15.85% (155.85\u0026thinsp;\u0026plusmn;\u0026thinsp;76.97 to 131.15\u0026thinsp;\u0026plusmn;\u0026thinsp;79.78 mg/dL; p\u0026thinsp;=\u0026thinsp;0.004). These results highlight the role of exercise as a strategy in glycemic control and the promotion of metabolic health. Furthermore, the dose-response relationship suggests that higher-intensity activities offer additional benefits for metabolic control [\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e]. Physical exercise has acute and chronic impacts on the regulation of glucose uptake and inflammatory processes, resulting in a reduction in blood glucose for up to 48 hours, and increasing glucose uptake by up to 50 times through insulin-dependent and independent mechanisms [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e]. Hiyane et al. (2008) [\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e] study with 10 participants (56.9\u0026thinsp;\u0026plusmn;\u0026thinsp;11.2 years old) demonstrated a significant reduction in blood glucose up to 90 minutes after two sessions of constant load exercise performed at 90% and 110% of the anaerobic threshold. Furthermore, Munan et al. (2020) [\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e] meta-analysis of 23 studies of acute exercise showed a significant decrease in mean glucose concentrations after 24 hours by 9.01 mg/dL (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). In Zhang et al. (2020) [\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e] research, the HIIT group showed substantial differences in fasting, pre-exercise, and 11-hour post-exercise glucose levels compared to the control (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05). These results are consistent with our findings, where we identified a significant reduction in blood glucose levels immediately after the test, suggesting that this reduction may be maintained in the short and long term.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec17\" class=\"Section2\"\u003e \u003ch2\u003eCHRONOTROPIC INCOMPETENCE\u003c/h2\u003e \u003cp\u003eCI, assessed through CR, is characterized by the inability of the HR to increase proportionally to the increase in activity or metabolic demand, and plays a significant role in exercise tolerance. Recent studies have shown that CI is associated with cardiovascular dysfunctions in people with T2DM, and these conditions can lead to an increased risk of acute myocardial infarction, stroke, and sudden cardiac death [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Regarding our results, an average of 86.45\u0026thinsp;\u0026plusmn;\u0026thinsp;20.47% was observed in CR in the SB condition and 82.93\u0026thinsp;\u0026plusmn;\u0026thinsp;17.63% in the placebo condition. Although there was no statistically significant difference between these values (p\u0026thinsp;=\u0026thinsp;0.126), it was observed that 38.46% (n\u0026thinsp;=\u0026thinsp;5) of the subjects in the SB condition and 46.15% (n\u0026thinsp;=\u0026thinsp;6) in the placebo condition had values below 85% of CR, which is considered indicative of CI, which can negatively influence performance during exercise.\u003c/p\u003e \u003cp\u003eIn a study conducted by Hansen et al. (2014) [\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e], which investigated the maximum chronotropic response index (CRI) in individuals with T2DM and healthy individuals, a significant difference in maximum CRI was demonstrated between the groups (0.85\u0026thinsp;\u0026plusmn;\u0026thinsp;0.17 for patients with T2DM and 1.02\u0026thinsp;\u0026plusmn;\u0026thinsp;0.17 for healthy individuals, p\u0026thinsp;\u0026lt;\u0026thinsp;0.01). Similar to our study, they identified the presence of CI in 42% of patients with T2DM, while only 6% of healthy individuals had this condition. Furthermore, CI showed an association with other factors, such as obesity, glycemic control, insulin resistance, and level of physical fitness. Therefore, CI can be considered a risk marker in this population, but it is important to note that the origin of this condition is multifactorial and not fully understood [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e \u003cp\u003ePhysical exercise not only proves to be effective in the treatment of CI, but also plays a crucial role in the prevention and improvement of associated risk factors. A study conducted by Jin et al. (2017) [\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e] investigated the effects of a 12-week aerobic training program in 30 individuals with T2DM with CI, revealing a significant increase in maximum HR by 13% (129.23\u0026thinsp;\u0026plusmn;\u0026thinsp;16.32 vs. 140.50\u0026thinsp;\u0026plusmn;\u0026thinsp;13.41 bpm, p\u0026thinsp;\u0026lt;\u0026thinsp;0.01), a 24% increase in test time (703\u0026thinsp;\u0026plusmn;\u0026thinsp;196 vs. 873\u0026thinsp;\u0026plusmn;\u0026thinsp;177 seconds, p\u0026thinsp;\u0026lt;\u0026thinsp;0.01), and a 26% increase in peak VO\u003csub\u003e2\u003c/sub\u003e (16.99\u0026thinsp;\u0026plusmn;\u0026thinsp;3.96 vs. 21.40\u0026thinsp;\u0026plusmn;\u0026thinsp;4.94 ml.kg.min\u003csup\u003e-1\u003c/sup\u003e, p\u0026thinsp;\u0026lt;\u0026thinsp;0.01).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec18\" class=\"Section2\"\u003e \u003ch2\u003eHEART RATE RECOVERY\u003c/h2\u003e \u003cp\u003eHeart rate recovery refers to the decrease in maximum/peak heart rate in the period following exercise. This process reflects the dynamic interaction between the parasympathetic and sympathetic systems and is widely recognized as a non-invasive measure to assess autonomic function, providing information on how the cardiovascular system responds to effort [\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e]. Regarding heart rate recovery in the first 30 seconds after the test, the values were 140\u0026thinsp;\u0026plusmn;\u0026thinsp;19.39 in the SB condition and 134.77\u0026thinsp;\u0026plusmn;\u0026thinsp;17.02 in the placebo condition, showing no significant difference (p\u0026thinsp;=\u0026thinsp;0.472). The variations in heart rates between exercise peak and 60 seconds after were 24.85 bpm in the SB and 30.15 bpm in the placebo. Both values exceeded the 18 bpm threshold, an important indicator of altered chronotropic response [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. Additionally, no participant had a baseline heart rate above 100 bpm, which, along with a reduction in chronotropic response, is an independent predictor of cardiovascular and all-cause mortality in individuals with T2DM [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e], indicating a lower-risk profile in our sample.\u003c/p\u003e \u003cp\u003eQiu et al. (2017) [\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e], meta-analysis including 9,113 participants with an average follow-up period of 8.1 years, revealed a significant association between slower heart rate recovery and a substantial increase in the risk of developing T2DM (HR 1.66, 95% CI 1.16\u0026ndash;2.38). Furthermore, Jae et al. (2016) [\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e] investigated the relationship between delayed heart rate recovery and the development of T2DM in 2,231 men, over an average follow-up of 5 years. During this period, 90 men (4.0%) developed the disease. The relative risks were significantly higher in the lowest quartiles of heart rate reserve (HR 2.71, 95% CI 1.20\u0026ndash;6.11) and heart rate recovery (HR 2.81, 95% CI 1.36\u0026ndash;5.78) compared to the highest quartiles. Each 1 bpm increase in heart rate reserve and recovery was associated with a 2\u0026ndash;3% reduction in the incidence of T2DM.\u003c/p\u003e \u003cp\u003eDelayed heart rate recovery after exercise is directly related to an increased risk of adverse cardiac events, including sudden cardiac death (SCD). Several studies have shown this association between SCD and changes in heart rate recovery. A study by Kurl et al. (2021) [\u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e] examined 1,967 men (aged 42 to 61 years) over a 25-year period, finding a significant increase in the incidence of SCD among those with a lower heart rate reserve (HR 3.86, 95% CI 2.56\u0026ndash;5.80) and slower heart rate recovery (HR 2.86, 95% CI 1.95\u0026ndash;4.20). Each 1 bpm increase in heart rate recovery reduced the incidence of SCD by 1\u0026ndash;2%. Additionally, Vivekananthan et al. (2003) [\u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e] emphasized that heart rate recovery can be a prognostic indicator of mortality in six years for patients with coronary artery disease, regardless of the severity of the condition. These results indicate that such programs not only improve participants' quality of life but are also associated with a reduction in hospitalizations related to cardiac conditions and highlight the importance of this analysis as a valuable prognostic indicator in assessing cardiovascular risk.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec19\" class=\"Section2\"\u003e \u003ch2\u003eLIMITATIONS\u003c/h2\u003e \u003cp\u003eThis study has some limitations to be considered. Firstly, the diversity in the clinical condition of participants, including hormonal conditions, especially in female subjects, differences in disease duration, the presence and degree of cardiac autonomic neuropathy, and variations in cardiorespiratory fitness. Additionally, the intervention was performed on different days, which could introduce some daily variability in the results, although we took measures to minimize this impact. These limitations should be taken into account when interpreting the results of this study and suggest the need for more comprehensive and controlled future investigations.\u003c/p\u003e \u003c/div\u003e"},{"header":"CONCLUSIONS","content":"\u003cp\u003eA significant increase in the test duration was observed in the SB condition, suggesting that active supplementation may have a beneficial effect on physical performance. Although no significant differences were observed in cardiovascular parameters, blood glucose decreased significantly in both test conditions, highlighting the positive impact of exercise. These findings indicate that treatment strategies, such as high-intensity exercise associated with the use of ergogenic resources, may be safe and effective for individuals with T2DM, promoting metabolic benefits and improvements in physical performance. However, further research is needed to fully understand the underlying mechanisms of interventions for this population.\u003c/p\u003e"},{"header":"DECLARATIONS","content":"\u003ch2\u003eConflict of Interest\u003c/h2\u003e\n\u003cp\u003eThe authors report no conflict of interest.\u003c/p\u003e\n\u003ch2\u003eEthical Approval\u003c/h2\u003e\n\u003cp\u003eThis study was conducted in accordance with the rec-ommendations from the Declaration of Helsinki.\u003c/p\u003e\n\u003ch2\u003eInformed Consent\u003c/h2\u003e\n\u003cp\u003eAll participants provided informed consent prior to their participation.\u003c/p\u003e\n\u003ch2\u003eACKNOWLEDGEMENTS\u003c/h2\u003e\n\u003cp\u003eThe authors are grateful to the Coordena\u0026ccedil;\u0026atilde;o deAperfei\u0026ccedil;oamento de Pessoal de N\u0026iacute;vel Superior - Brasil (CAPES) for the scholarship granted to the post-graduate student participating in the study.\u003c/p\u003e\n\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\n\u003cp\u003eM.L.R.: Data collectionR.C.S.: Data collectionN.M.O.: Guidance, data analysis, and writingP.V.F.: Guidance, product and laboratory for supplementation preparation, and writingJ.M.N.: Laboratory and supplementation preparation\u003c/p\u003e"},{"header":"REFERENCES","content":"\u003col\u003e\n \u003cli\u003eInternational Diabetes Federation (IDF). 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Heart rate recovery immediately after treadmill exercise and left ventricular systolic dysfunction as predictors of mortality: the case of stress echocardiography. Circulation, 104(16), 1911-1916.\u003c/li\u003e\n \u003cli\u003eKerksick, C. M., et al. (2018). ISSN exercise \u0026amp; sports nutrition review update: research \u0026amp; recommendations. J Int Soc Sports Nutr, 15(1), 38.\u003c/li\u003e\n \u003cli\u003eStephens, T. J., et al. (2002). Effect of sodium bicarbonate on muscle metabolism during intense endurance cycling. Med Sci Sports Exerc, 34(4), 614-621.\u003c/li\u003e\n \u003cli\u003eKumst\u0026aacute;t, M. M., et al. (2018). Does sodium citrate cause the same ergogenic effect as sodium bicarbonate on swimming performance? J Hum Kinet, 65, 89.\u003c/li\u003e\n \u003cli\u003eMiranda, W. A. S., et al. (2022). Can Sodium Bicarbonate Supplementation Improve Combat Sports Performance? A Systematic Review and Meta-analysis. 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Effects of acute exercise with different intensities on glycemic control in patients with type 2 diabetes mellitus. Acta Endocrinol (Buchar), 17(2), 212.\u003c/li\u003e\n \u003cli\u003eHansen, D., \u0026amp; Dendale, P. (2014). Modifiable predictors of chronotropic incompetence in male patients with type 2 diabetes. J Cardiopulm Rehabil Prev, 34(3), 202-207.\u003c/li\u003e\n \u003cli\u003eJin, L., et al. (2017). Exercise training on chronotropic response and exercise capacity in patients with type 2 diabetes mellitus. Exp Ther Med, 13(3), 899-904.\u003c/li\u003e\n \u003cli\u003eQiu, S. H., et al. (2017). Attenuated heart rate recovery predicts risk of incident diabetes: insights from a meta-analysis. Diabet Med, 34(12), 1676-1683.\u003c/li\u003e\n \u003cli\u003eJae, S. Y., et al. (2016). Exercise heart rate reserve and recovery as predictors of incident type 2 diabetes. Am J Med, 129(5), 536.e7-536.e12.\u003c/li\u003e\n \u003cli\u003eKurl, S., et al. (2021). Exercise heart rate reserve and recovery as risk factors for sudden cardiac death. Prog Cardiovasc Dis, 68, 7-11.\u003c/li\u003e\n \u003cli\u003eVivekananthan, D. P., et al. (2003). Heart rate recovery after exercise is a predictor of mortality, independent of the angiographic severity of coronary disease. J Am Coll Cardiol, 42(5), 831-838.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"exercise, buffers, performance-enhancing substances, fatigue","lastPublishedDoi":"10.21203/rs.3.rs-4101653/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4101653/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eThe global epidemic of diabetes mellitus (DM) presents a significant health challenge. Physical exercise is crucial in preventing and treating type 2 DM (T2DM). Supplementation with sodium bicarbonate (SB) may enhance physical performance in T2DM individuals during high-intensity protocols. This study aimed to analyze physical performance, blood glucose, and cardiovascular parameters following acute SB supplementation in middle-aged and elderly adults with T2DM. Thirteen individuals (mean age: 62.15\u0026thinsp;\u0026plusmn;\u0026thinsp;6.90 years, BMI: 29.14\u0026thinsp;\u0026plusmn;\u0026thinsp;4.49 kg/m2) with an average disease duration of 5.03\u0026thinsp;\u0026plusmn;\u0026thinsp;6.64 years participated. They underwent a maximal incremental test (MIT) with either SB or a placebo, administered 60 minutes before the test. Blood pressure (BP), heart rate (HR), and capillary blood glucose were monitored pre- and post-test. Results showed significant differences in MIT duration between the SB and placebo conditions (SB: 481\u0026thinsp;\u0026plusmn;\u0026thinsp;116.97 seconds, placebo: 439\u0026thinsp;\u0026plusmn;\u0026thinsp;99.92 seconds, p\u0026thinsp;=\u0026thinsp;0.005), and in blood glucose levels (p\u0026thinsp;=\u0026thinsp;0.0001). No significant differences were found in BP, HR, or other cardiovascular variables (p\u0026thinsp;\u0026gt;\u0026thinsp;0.05). SB supplementation was associated with increased test duration and reduced blood glucose levels, indicating improved physical performance and fatigue reduction. These findings suggest that SB supplementation may be a safe and effective strategy for enhancing physical performance in individuals with T2DM.\u003c/p\u003e","manuscriptTitle":"Effects of Sodium Bicarbonate Supplementation on Physical Performance and Cardiovascular Variables in Middle-aged and Elderly Adults With Type 2 Diabetes Mellitus","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-03-19 15:20:21","doi":"10.21203/rs.3.rs-4101653/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"e5176f26-db87-424f-8404-941442bfbcd0","owner":[],"postedDate":"March 19th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-07-18T20:55:57+00:00","versionOfRecord":[],"versionCreatedAt":"2024-03-19 15:20:21","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4101653","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4101653","identity":"rs-4101653","version":["v1"]},"buildId":"cBFmMYwuxLRRLfASyISRj","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}