Fabiano Trigueiro Amorim

Purpose: We tested the hypotheses that sodium bicarbonate (SB) supplementation improves performance, reduces markers of acute kidney injury (AKI) risk, and increases markers of acute gastrointestinal injury (AGI) during repeated sprints in the heat. Methods: Using a double-blind design, 10 recreationally endurance-trained participants ingested 0.2 g/kg of body weight of SB or placebo before cycling in the heat (dry-bulb: 40 °C, relative humidity: 20%). Exercise bouts included a 22-min warm-up, then 4-sets of 5 × 6-sec maximal-effort standing cycling sprints. Core temperature (Tc) was measured at baseline, end of warm-up, after set two of sprints, and post-exercise bouts. Urine and plasma collected pre-ingestion and pre-, post-, and 1-h post-exercise were analyzed for markers of AKI risk, AGI, and endotoxemia. Results: SB increased peak (average difference between conditions: 21 ± 11 W, condition effect: p = 0.02) and average ( p = 0.03) power across the sprints. Tc increased from pre- to post-exercise (placebo: Δ1.3 ± 0.3 °C, SB: Δ1.4 ± 0.4 °C, time effect: p < 0.001), but there were no effects of condition or interaction. Exercise increased the primary marker of AKI (urinary IGFBP7×TIMP-2, time effect: p = 0.005) but not urinary NGAL. There were no condition or interaction effects for either AKI marker. Plasma I-FABP, a marker of AGI, increased post-exercise bouts (placebo: Δ291 ± 550 pg/mL, SB: Δ397 ± 482 pg/mL, p = 0.03), with no condition or interaction effects. There were no significant effects for markers of endotoxemia (LBP, sCD14). Conclusions: SB supplementation improves repeat sprint performance in the heat without altering Tc, markers of AKI risk, or markers of AGI.

Ad libitum fluid intake, consistent with occupational hydration recommendations, does not attenuate renal oxidative stress, inflammation, or acute kidney injury risk during simulated heat stress. These findings challenge the assumption that current hydration recommendations are protective, suggesting that additional strategies are needed to mitigate heat-induced kidney injury in occupational settings.

Acute kidney injury (AKI) has been observed after prolonged physical activity in the heat. Although a range of strategies to reduce the incidence of AKI have been investigated, sodium bicarbonate (SB) supplementation may mitigate metabolic stress during physical exertion and potentially alleviate renal workload by lowering glomerular filtration demand, reducing bicarbonate reabsorption, and preserving kidney microcirculation. Therefore, the primary objective of this study was to investigate the effect of SB ingestion on markers of AKI. Fourteen healthy men and women (n = 6) completed two (SB & placebo) experimental 2‐hr outdoor work sessions in the heat (~35°C; ~20% humidity) designed to simulate construction tasks. Changes in acid–base balance, markers of kidney injury (NGAL, TIMP2, IGFBP‐7), thermotolerance, and work achieved throughout the experimental trials were analyzed using a linear mixed model with two‐way repeated measures. Despite inducing a significant level of alkalosis in the SB trial (7.40 ± 0.03 vs. 7.45 ± 0.03; p < 0.001), no changes were observed in urinary NGAL, TIMP2, or IGFBP‐7 concentrations (p > 0.27). Core temperature and heart rate were elevated throughout the work session in the SB condition (mean increase of 0.2 ± 0.1°C and 9 ± 3 bpm; p < 0.025), but the rating of perceived effort was lower when compared to placebo (0.3 ± 0.1 au; p = 0.003). Although the environmental and work stress in the present study did not influence markers of acute AKI, participants were less sensitive to increases in thermoregulatory and cardiovascular strain during a state of metabolic alkalosis.

Construction workers are 13 times more likely to die from heat-related illnesses than workers in other job industries. This elevated risk is attributed to excessive heat stress from environmental exposure, metabolic heat generated from physical labor, and the insulating effects of protective clothing. Levels of heat stress may vary across job types, reflecting the diversity of tasks performed and the work environment. Despite elevated risks, heat strain assessed by core temperature (Tcore) in construction workers during summertime in the United States has not been evaluated previously. Thirty-two construction workers (three females) were monitored over 3 summer workdays. Participants were categorized by job type (carpenter, concrete, laborer, roofer) and work environment (covered, uncovered). Heat index (HI), heart rate (HR), and Tcore were measured throughout the workday, while hydration was assessed through pre- and post-shift measurements of urine specific gravity (USG). Peak HI over the 3 days was 27.3, 35.2, and 33.7 °C, indicating the potential for low to moderate heat stress. Roofers experienced a higher peak HI compared to other job types (p < 0.01), but no differences were observed between workers in covered (28.8 ± 3.7 °C) and uncovered (32.1 ± 4.2 °C) areas (p = 0.37). The estimated peak metabolic rate was higher in workers in uncovered areas (868 ± 238 W) compared to covered (632 ± 130 W) (p < 0.01), with no differences among job types (p = 0.23). Forty-three percent of workers had Tcore exceeding 38.0 °C, with 4% exceeding 38.5 °C. Based on USG, 63% of workers began work dehydrated (1.022 ± 0.005), but urine did not become more concentrated during the workday (post-shift USG; 1.022 ± 0.007) (p = 0.78). Forward stepwise regression identified that peak metabolic rate plus post-shift USG were the combined variables most associated with peak Tcore (r² = 0.55, p < 0.01). Construction workers, even in low to moderate environmental heat exposure, experienced significant heat strain, primarily due to an elevated metabolic rate. Environmental heat exposure and metabolic rate vary by job type and work environment.

Background: Bodyweight high-intensity interval training (BW-HIIT) is an effective, time-efficient exercise method that reduces cardiovascular risk factors and improves muscle endurance without requiring external equipment. High mobility group box 1 (HMGB1) is a proinflammatory protein involved in insulin resistance. Previous studies revealed that HMGB1 knockout mice show improved insulin sensitivity and hyperglycemia. This study investigates whether BW-HIIT exercise can reduce proinflammatory markers, such as HMGB1, in individuals with insulin resistance. Methods: In total, 14 adults (2 male/12 female) aged 18 to 55 were subject to six weeks of BW-HIIT. Additionally, 10-week-old mice were subject to exercise conditioning (5 mice per group (all male)) for 4 weeks of treadmill exercise or sedentary. Human and mouse pre- and post-exercise serum/plasma samples were analyzed for lipidomics, hormonal, and cytokine multiplex assays. Cardiometabolic parameters were also performed on human subjects. Results: Post-exercise decreased systolic blood pressure (SBP), cholesterol, triglycerides, high-density lipoprotein (HDL), and cholesterol/HDL ratio in human patients with insulin resistance. Meanwhile, hormones such as amylin, glucagon, and insulin all increased post-BW-HIIT or treadmill exercise in both human and mouse models. Moreover, circulating HMBG1 levels were reduced in insulin-resistant individuals and mice after exercise. Furthermore, treadmill exercise by the animal model increased anti-inflammatory cytokines, including interleukin (IL)-10, IL-12p40, and IL-12p70, and reduced proinflammatory cytokines: eotaxin, IL-2, and macrophage inflammatory protein (MIP)-2 or CXCL2. Conclusions: Six weeks of BW-HIIT exercise can improve cardiometabolic health, anti-inflammatory markers, hormones, and insulin sensitivity in human and mouse models undergoing exercise. Changes in circulating HMBG1 levels following BW-HIIT exercise make HMGB1 a suitable marker for cardiometabolic disease, potentiating its role beyond an alarmin. Further studies are needed to confirm these effects and to elucidate the underlying physiological mechanisms.

Purpose of review: This review examines the effects of occupational heat stress on kidney health. It focuses on the role of hyperthermia in the development of acute kidney injury (AKI) and its potential progression to chronic kidney disease of nontraditional etiology (CKDnt). We highlight the physiological mechanisms by which hyperthermia affects kidney function and discuss emerging preventive strategies. Recent findings: Hyperthermia places the kidneys in a vulnerable state. As body temperature increases, blood flow is directed toward the skin to aid in cooling, diverting it away from internal organs like the kidneys to support blood pressure regulation. At the same time, hyperthermia and dehydration increases energetic demand to promote fluid and electrolyte conservation. Collectively, this can create a localized supply-demand mismatch, resulting in tissue hypoxia that can damage kidney tissues. These findings highlight that heat hyperthermia can lead to subclinical kidney damage, with potential long-term implications for kidney health. Summary: Heat-induced AKI is a growing public health concern. Individuals engaged in manual labor with prolonged exposure are at risk of CKDnt. Interventions aimed to prevent hyperthermia show promise in mitigating the risk of AKI. Further research is necessary to refine these strategies and establish evidence-based guidelines for reducing heat-related kidney injuries.

Background: Type 2 diabetes (T2D) is preceded by prediabetes, and these conditions place a great burden on patients and society. These conditions are significantly associated with poor glycemic control, which is improved by resistance exercise. It has been suggested that resistance exercise should be performed with a high degree of effort to improve glucose metabolism, but this is associated with negative psychological responses that might lead to lower long-term adherence. Objective: This study aimed to investigate the effect of the degree of effort during a resistance exercise session on glycemic control and psychological responses in individuals living with prediabetes or T2D. Methods: This study will be a crossover, 3-arm, randomized controlled trial. A total of 15 participants living with prediabetes or T2D will be thoroughly familiarized with 7 resistance exercises; afterward, they will perform 3 randomized experimental sessions, each lasting approximately 48 hours each, separated by at least 4 washout days. In 2 of these sessions, supervised resistance exercise will be performed, but the sessions will differ in the degree of effort in each set (high vs low) and will be equalized in terms of total weight lifted and session duration. For this, proximity to failure will be manipulated by changing the number of sets per exercise, the number of repetitions per set, and the resting interval between sets and exercises. Participants will also complete a sedentary (control) session, where they will not perform any exercise. In response to each session, psychological responses will be assessed (exertion, affect, enjoyment, self-efficacy, and discomfort). Glycemic control will be assessed by a continuous glucose monitoring device every 5 minutes, throughout the approximately 48 hours of each experimental session. Food and drink will be individually prescribed by a registered dietitian nutritionist and provided to participants, in order to control for the confounding effect of energy intake and diet composition. Physical activity levels will be assessed by accelerometry. Randomization will be done using the opaque, sequentially numbered envelopes technique. Participants and researchers will be blinded for continuous glucose monitoring and accelerometry data, and data will be analyzed by a blinded statistician. Results: This study has been funded, and data collection is expected to take place between June 2024 and May 2025. Final manuscript submission should happen by August 2025. Conclusions: The results of this project might encourage individuals living with prediabetes and T2D to engage in resistance exercise while better informing exercise specialists on how to best incorporate resistance exercise in their client’s or patient’s routine. Trial Registration: ClinicalTrials.gov NCT06208189; https://clinicaltrials.gov/study/NCT06208189 International Registered Report Identifier (IRRID): PRR1-10.2196/63598

Background: Exercise is a fundamental primary standard of care for cardiometabolic health. Body Weight (BW) High-Intensity Interval Training (HIIT) is an effective strategy for reducing cardiometabolic markers in individuals with insulin resistance and Type-2 diabetes (T2D). High-mobility group box 1 (HMGB1), a ubiquitous nuclear factor, plays an ample role beyond an alarmin in T2D development and progression. Our group has described this novel role previously, showing the beneficial effect of whole body HMGB1 silencing in decreasing hyperglycemia in diabetic mice. In the present study we tested the hypothesis that BW-HIIT as an effective exercise training modality will decrease cardiometabolic risk with a concomitant decrease in circulating HMGB1 more prominently in insulin resistant individuals compared to non-insulin resistant individuals contrasting to what we can evidence in a preclinical murine model of insulin resistance; Methods: Human and mouse pre- and post-exercise serum/plasma samples were analyzed for Lipidomics as well as Metabolic and Cytokine Multiplex assays. Standard of care, as well as cardiometabolic parameters, was also performed in human subjects; Results: insulin resistant individuals had the most positive effect, primarily with a decrease in the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR). as an index of insulin resistance as well as decreased HMGB1 post-exercise. Lipidomic analysis illustrated the highly beneficial effect of exercise training using a modified HIIT program, showing an enhanced panel of circulating lipids post-exercise exclusively in insulin resistant individuals. Plasma multiplex revealed significant translational heterogeneity in our studies with distinct metabolic hormone responses to exercise conditioning with a decrease in inflammatory markers in insulin resistant individuals; Conclusions: The current study demonstrated that 6-week BW-HIIT training improves cardiometabolic, anti-inflammatory markers, metabolic hormones, and insulin sensitivity in humans, strongly associated with decreased circulating HMGB1. Overall, these experiments reinforce the potential of HMGB1 as a marker of changes in insulin resistance and the positive effect of exercise training on insulin resistance possibly preventing the development of T2D and associated complications.