Exercise snacks are a time-efficient alternative to moderate-intensity continuous training for improving cardiorespiratory fitness but not maximal fat oxidation in inactive adults: a randomized controlled trial.

The aims of this study were (1) to determine how stair-climbing-based exercise snacks (ES) compared to moderate-intensity continuous training (MICT) for improving cardiorespiratory fitness (CRF), and (2) to explore whether ES could improve maximal fat oxidation rate (MFO) in inactive adults. Healthy, young, inactive adults (n: 42, age: 21.6 ± 2.3 years, BMI: 22.5 ± 3.6 kg·m-2, peak oxygen uptake (VO2peak): 33.6 ± 6.3 mL·kg-1·min-1) were randomly assigned to ES, MICT, or Control. ES (n = 14) and MICT (n = 13) groups performed three sessions per week over 6 weeks, while the control group (n = 15) maintained their habitual lifestyle. ES involved 3 × 30 s "all-out" stair-climbing (6 flight, 126 steps, and 18.9 m total height) bouts separated by >1 h rest, and MICT involved 40 min × 60%-70% HRmax stationary cycling. A significant group × time interaction was found for relative VO2peak (p < 0.05) with ES significantly increasing by 7% compared to baseline (MD = 2.5 mL·kg-1·min-1 (95% CI = 1.2, 3.7), Cohen's d = 0.44), while MICT had no significant effects (MD = 1.0 mL·kg-1·min-1 (-1.1, 3.2), Cohen's d = 0.17), and Control experienced a significant decrease (MD = -1.7 mL·kg-1·min-1 (-2.9, -0.4), Cohen's d = 0.26). MFO was unchanged among the three groups (group × time interaction, p > 0.05 for all). Stair climbing-based ES are a time-efficient alternative to MICT for improving CRF among inactive adults, but the tested ES intervention appears to have limited potential to increase MFO.

A ketone monoester drink reduces postprandial blood glucose concentrations in adults with type 2 diabetes: a randomised controlled trial.

AIMS/HYPOTHESIS: The aim of the present study was to conduct a randomised, placebo-controlled, double-blind, crossover trial to determine whether pre-meal ketone monoester ingestion reduces postprandial glucose concentrations in individuals with type 2 diabetes. METHODS: In this double-blind, placebo-controlled, crossover design study, ten participants with type 2 diabetes (age 59±1.7 years, 50% female, BMI 32±1 kg/m2, HbA1c 54±2 mmol/mol [7.1±0.2%]) were randomised using computer-generated random numbers. The study took place at the Nutritional Physiology Research Unit, University of Exeter, Exeter, UK. Using a dual-glucose tracer approach, we assessed glucose kinetics after the ingestion of a 0.5 g/kg body mass ketone monoester (KME) or a taste-matched non-caloric placebo before a mixed-meal tolerance test. The primary outcome measure was endogenous glucose production. Secondary outcome measures were total glucose appearance rate and exogenous glucose appearance rate, glucose disappearance rate, blood glucose, serum insulin, ß-OHB and NEFA levels, and energy expenditure. RESULTS: Data for all ten participants were analysed. KME ingestion increased mean ± SEM plasma beta-hydroxybutyrate from 0.3±0.03 mmol/l to a peak of 4.3±1.2 mmol/l while reducing 2 h postprandial glucose concentrations by ~18% and 4 h postprandial glucose concentrations by ~12%, predominately as a result of a 28% decrease in the 2 h rate of glucose appearance following meal ingestion (all p<0.05). The reduction in blood glucose concentrations was associated with suppressed plasma NEFA concentrations after KME ingestion, with no difference in plasma insulin concentrations between the control and KME conditions. Postprandial endogenous glucose production was unaffected by KME ingestion (mean ± SEM 0.76±0.15 and 0.88±0.10 mg kg-1 min-1 for the control and KME, respectively). No adverse effects of KME ingestion were observed. CONCLUSIONS/INTERPRETATION: KME ingestion appears to delay glucose absorption in adults with type 2 diabetes, thereby reducing postprandial glucose concentrations. Future work to explore the therapeutic potential of KME supplementation in type 2 diabetes is warranted. TRIAL REGISTRATION: ClinicalTrials.gov NCT05518448. FUNDING: This project was supported by a Canadian Institutes of Health Research (CIHR) Project Grant (PJT-169116) and a Natural Sciences and Engineering Research Council (NSERC) Discovery Grant (RGPIN-2019-05204) awarded to JPL and an Exeter-UBCO Sports Health Science Fund Project Grant awarded to FBS and JPL.

Pharmacist assessments and care to improve adult vaccination rates: A report from project IMPACT vaccine confidence.

BACKGROUND: Neglect of vaccination needs among adults results in a needless burden of hospitalization, suffering, and death. America's community pharmacists deliver a substantial portion of adult vaccinations, yet many Americans still have unmet vaccination needs. OBJECTIVES: This study evaluated rates of vaccine contraindications, acceptance, and willingness to be vaccinated among ambulatory adults. PRACTICE DESCRIPTION: This was a prospective, multisite, multistate, observational study conducted in three waves between October 2021 and August 2023. PRACTICE INNOVATION: Pharmacists conducted comprehensive vaccination need assessments. EVALUATION METHODS: The primary outcomes were numbers of vaccination needs per participant and vaccinations administered, scheduled, or declined. RESULTS: Pharmacists identified a mean of 1.8-2.2 unmet vaccination needs per adult assessed, more than in pilot studies. Participants had already received 61%-74% of vaccinations recommended for them hence 26%-39% of needs were unmet at baseline. The leading vaccination needs were COVID-19, influenza, zoster, tetanus-containing, and pneumococcal vaccines. From a baseline mean of 59.1% for these five vaccinations, pharmacists increased the mean percentage vaccinated to 73.2%. When an option for scheduling future vaccination was added to the process, declinations dropped from 46%-18%. CONCLUSION: This study provides insight into adult vaccine acceptance, willingness, and declination behaviors not described elsewhere. Offering options for future vaccination reduced declination rates. Pharmacists resolved substantial proportions of adult vaccination needs. The signal that apportioning adult vaccines needed, but not received on day of assessment, across several months could help resolve unmet vaccination needs warrants additional research, especially with the rising number of vaccines recommended for adults.

Effect of the ketone beta-hydroxybutyrate on markers of inflammation and immune function in adults with type 2 diabetes.

Pre-clinical and cell culture evidence supports the role of the ketone beta-hydroxybutyrate (BHB) as an immunomodulatory molecule that may inhibit inflammatory signalling involved in several chronic diseases such as type 2 diabetes (T2D), but studies in humans are lacking. Therefore, we investigated the anti-inflammatory effect of BHB in humans across three clinical trials. To investigate if BHB suppressed pro-inflammatory cytokine secretion, we treated LPS-stimulated leukocytes from overnight-fasted adults at risk for T2D with BHB (Study 1). Next (Study 2), we investigated if exogenously raising BHB acutely in vivo by ketone monoester supplementation (KME) in adults with T2D would suppress pro-inflammatory plasma cytokines. In Study 3, we investigated the effect of BHB on inflammation via ex vivo treatment of LPS-stimulated leukocytes with BHB and in vivo thrice-daily pre-meal KME for 14 days in adults with T2D. Ex vivo treatment with BHB suppressed LPS-stimulated IL-1ß, TNF-α, and IL-6 secretion and increased IL-1RA and IL-10 (Study 1). Plasma IL-10 increased by 90 min following ingestion of a single dose of KME in T2D, which corresponded to peak blood BHB (Study 2). Finally, 14 days of thrice-daily KME ingestion did not significantly alter plasma cytokines or leukocyte subsets including monocyte and T-cell polarization (Study 3). However, direct treatment of leukocytes with BHB modulated TNF-α, IL-1ß, IFN-γ, and MCP-1 secretion in a time- and glucose-dependent manner (Study 3). Therefore, BHB appears to be anti-inflammatory in T2D, but this effect is transient and is modulated by the presence of disease, glycaemia, and exposure time.

Impact of fasting & ketogenic interventions on the NLRP3 inflammasome: A narrative review.

Overactivation of the NLRP3 inflammasome is implicated in chronic low-grade inflammation associated with various disease states, including obesity, type 2 diabetes, atherosclerosis, Alzheimer's disease, and Parkinson's disease. Emerging evidence, mostly from cell and animal models of disease, supports a role for ketosis in general, and the main circulating ketone body beta-hydroxybutyrate (BHB) in particular, in reducing NLRP3 inflammasome activation to improve chronic inflammation. As a result, interventions that can induce ketosis (e.g., fasting, intermittent fasting, time-restricted feeding/eating, very low-carbohydrate high-fat ketogenic diets) and/or increase circulating BHB (e.g., exogenous ketone supplementation) have garnered increasing interest for their therapeutic potential. The purpose of the present review is to summarize our current understanding of the literature on how ketogenic interventions impact the NLRP3 inflammasome across human, rodent and cell models. Overall, there is convincing evidence that ketogenic interventions, likely acting through multiple interacting mechanisms in a cell-, disease- and context-specific manner, can reduce NLRP3 inflammasome activation. The evidence supports a direct effect of BHB, although it is important to consider the myriad of other metabolic responses to fasting or ketogenic diet interventions (e.g., elevated lipolysis, low insulin, stable glucose, negative energy balance) that may also impact innate immune responses. Future research is needed to translate promising findings from discovery science to clinical application.

Exercise in the workplace: examining the receptivity of practical and time-efficient stair-climbing "exercise snacks".

In the workplace, people are often sedentary for prolonged time and do not regularly engage in physical activity-two factors independently linked to premature morbidity and mortality. This study aimed to determine the receptivity of incorporating practical stair-climbing "exercise snacks" (Snacks; three isolated bouts of ascending 53-60 stairs performed sporadically throughout the day) into workplace settings compared to more traditional high-intensity interval training (HIIT; performed as three bouts of 53-60 stairs within a structured HIIT workout) and to explore if these exercise strategies could influence sedentary and physical activity behaviour. Fourteen participants (12 women; Mage = 38.9 ± 10.2 years) completed two supervised exercise trials (Snacks and HIIT) followed by 1 week participating in either form of exercise in their workplace. Ratings of perceived exertion (RPE), affective valence, enjoyment, and self-efficacy were measured at the supervised exercise sessions. During the follow-up period, sedentary behaviour and physical activity were measured with an accelerometer. Affective valence was more positive (p = 0.03; η2 p = 0.21) and there was a lower rise in RPE (p = 0.01; η2 p = 0.29) during Snacks than HIIT. Post-exercise enjoyment of, and self-efficacy towards, Snacks and HIIT were high and similar (ps > 0.05). After the supervised trials, 10/14 of the participants preferred Snacks and 4/14 preferred HIIT (p = 0.18). On days when participants chose to perform either exercise modality, the average number of sit-to-stands in a 24 h period was increased (48.3 ± 8.7 to 52.8 ± 7.8; p = 0.03; Hedge's g = 0.73) and moderate-to-vigorous physical activity tended to increase (21.9 ± 18.2 to 38.1 ± 22.1 min; p = 0.06; Hedge's g = 0.60) compared to days when they chose not to exercise. Stair-climbing exercise snacks may be an attractive approach to implement in the workplace setting and has potential to positively impact sedentary behaviour and physical activity metrics.

The effect of acute and 14-day exogenous ketone supplementation on glycemic control in adults with type 2 diabetes: two randomized controlled trials.

Acute ingestion of the exogenous ketone monoester supplement [(R)-3-hydroxybutyl-(R)-3-hydroxybutyrate] lowers blood glucose, suggesting therapeutic potential in individuals with impaired glucose metabolism. However, it is unknown how acute or repeated ingestion of exogenous ketones affects blood glucose control in individuals with type 2 diabetes (T2D). We conducted two randomized, counterbalanced, double-blind, placebo-controlled crossover trials to determine if 1) acute exogenous ketone monoester (0.3 g/kg body mass; N = 18) or 2) 14-day thrice daily premeal exogenous ketone monoester (15 g; N = 15) supplementation could lower blood glucose in individuals living with T2D. A single dose of the ketone monoester supplement elevated blood ß-OHB to ∼2 mM. There were no differences in the primary outcomes of plasma glucose concentration (acutely) or serum fructosamine (glycemic control across 14 days) between conditions. Ketone monoester ingestion acutely increased insulin and lowered nonesterified fatty acid concentrations; plasma metabolomics confirmed a reduction in multiple free fatty acids species and select gluconeogenic amino acids. In contrast, no changes were observed in fasting metabolic outcomes following 14 days of supplementation. In the context of these randomized controlled trials, acute or repeated ketone monoester ingestion in adults with T2D did not lower blood glucose when consumed acutely in a fasted state and did not improve glycemic control following thrice daily premeal ingestion across 14 days. Future studies exploring the mechanistic basis for the (lack of) glucose-lowering effect of exogenous ketone supplementation in T2D and other populations are warranted.NEW & NOTEWORTHY Exogenous ketone supplements can acutely lower blood glucose, suggesting therapeutic potential in individuals with impaired glucose metabolism. However, the effect of exogenous ketones on glucose metabolism in adults with type 2 diabetes has not been investigated in a controlled setting. In adults with type 2 diabetes, ketone monoester ingestion did not lower blood glucose acutely in a fasted state and did not improve glycemic control across thrice daily premeal ingestion across 14 days.

Is low-volume high-intensity interval training a time-efficient strategy to improve cardiometabolic health and body composition? A meta-analysis.

The present meta-analysis aimed to assess the effects of low-volume high-intensity interval training (LV-HIIT; i.e., ≤5 min high-intensity exercise within a ≤15 min session) on cardiometabolic health and body composition. A systematic search was performed in accordance with PRISMA guidelines to assess the effect of LV-HIIT on cardiometabolic health and body composition. Twenty-one studies (moderate to high quality) with a total of 849 participants were included in this meta-analysis. LV-HIIT increased cardiorespiratory fitness (CRF, SMD = 1.19 [0.87, 1.50]) while lowering systolic blood pressure (SMD = -1.44 [-1.68, -1.20]), diastolic blood pressure (SMD = -1.51 [-1.75, -1.27]), mean arterial pressure (SMD = -1.55 [-1.80, -1.30]), MetS z-score (SMD = -0.76 [-1.02, -0.49]), fat mass (kg) (SMD = -0.22 [-0.44, 0.00]), fat mass (%) (SMD = -0.22 [-0.41, -0.02]), and waist circumference (SMD = -0.53 [-0.75, -0.31]) compared to untrained control (CONTROL). Despite a total time-commitment of LV-HIIT of only 14%-47% and 45%-94% compared to moderate-intensity continuous training and HV-HIIT, respectively, there were no statistically significant differences observed for any outcomes in comparisons between LV-HIIT and moderate-intensity continuous training (MICT) or high-volume HIIT. Significant inverse dose-responses were observed between the change in CRF with LV-HIIT and sprint repetitions (ß = -0.52 [-0.76, -0.28]), high-intensity duration (ß = -0.21 [-0.39, -0.02]), and total duration (ß = -0.19 [-0.36, -0.02]), while higher intensity significantly improved CRF gains. LV-HIIT can improve cardiometabolic health and body composition and represent a time-efficient alternative to MICT and HV-HIIT. Performing LV-HIIT at a higher intensity drives higher CRF gains. More repetitions, longer time at high intensity, and total session duration did not augment gains in CRF.

The Effect of Novel Exogenous Ketone Supplements on Blood Beta-Hydroxybutyrate and Glucose.

Exogenous ketone monoesters can raise blood ß-OHB and lower glucose without other nutritional modifications or invasive procedures. However, unpleasant taste and potential gastrointestinal discomfort may make adherence to supplementation challenging. Two novel ketone supplements promise an improved consumer experience but differ in their chemical properties; it is currently unknown how these affect blood ß-OHB and blood glucose compared to the ketone monoester. In a double-blind randomized cross-over pilot study, N=12 healthy individuals (29 ± 5 years, BMI = 25 ± 4 kg/m2, 42% female) participated in three experimental trials with a different ketone supplement providing 10 grams of active ingredient in each; (i) the monoester (R)-3-hydroxybutyl (R)-3-hydroxybutyrate, (ii) D-ß-hydroxybutyric acid with R-1,3-butanediol, and (iii) R-1,3-butanediol. Blood ß-OHB and glucose were measured via finger prick capillary blood samples at baseline and across 240 minutes post-supplementation. Supplement acceptability, hunger, and gastrointestinal distress were assessed via questionnaires. ß-OHB was elevated compared to baseline in all conditions. Total and incremental area under the curve (p < 0.05) and peak ß-OHB (p < 0.001) differed between conditions with highest values seen in the ketone monoester condition. Blood glucose was reduced after consumption of each supplement, with no differences in total and incremental area under the curve across supplements. Supplement acceptability was greatest for D-ß-hydroxybutyric acid with R-1,3-butanediol, with no effect on hunger or evidence of gastrointestinal distress across all supplements. All ketone supplements tested raised ß-OHB with highest values seen after ketone monoester ingestion. Blood glucose was lowered similarly across the assessed time frame with all three supplements.

Effect of Acute and Chronic Ingestion of Exogenous Ketone Supplements on Blood Pressure: A Systematic Review and Meta-Analysis.

Exogenous ketone supplements have been suggested to have potential cardiovascular benefits, but their overall effect on blood pressure is unclear. Our objective was to perform a systematic review and meta-analysis on the effects of exogenous ketone supplements on blood pressure (BP) and concomitant changes in resting heart rate (HR). Five databases were searched on January 27th, 2023, for randomized and non-randomized studies. A random-effects model meta-analysis was performed including all studies jointly and separately for acute and chronic ingestion of ketone supplements. Out of 4012 studies identified in the search, 4 acute and 6 chronic studies with n = 187 participants were included. Pooled results (n = 10) showed no change in systolic (SMD [95% CI]= -0.14 [-0.40; 0.11]; I2= 30%; p = 0.17) or diastolic BP (-0.12 [-0.30; 0.05]; I2= 0%; p = 0.69), with a potential tendency observed toward increased resting heart rate (0.17 [-0.14; 0.47]; I2= 40%; p = 0.10). Similar results for systolic and diastolic BP were observed when assessing separately the effect of acute and chronic ingestion of ketone supplements (p ≥ 0.33). Supplement dosage was found to modulate the increase in resting heart rate (0.019 ± 0.006; p = 0.013; R2=100%), suggesting that higher supplement doses lead to a higher resting heart rate. Based on currently available data, acute or prolonged ingestion of ketone supplements does not seem to modulate BP. However, a tendency for HR to increase after acute ingestion was observed, particularly with higher doses. Higher quality studies with appropriate standardized measurements are needed to confirm these results.

Solutions for Atrial Fibrillation Edvocacy (SAFE): Improving Awareness And Access To Afib Screening For Detection And Referral For Treatment.

Background: Atrial Fibrillation (Afib) can lead to stroke and heart failure, and early detection of Afib is an effective method of preventing these life-threatening conditions. An estimated 2.7 million Americans are living with Afib1, a number that is expected to rise dramatically in the coming years. Methods: The aim of this demonstration project was to create an additional access point in the community at local pharmacies for Afib screening, detection, and referral to physicians for follow-up and initiation of evidence-based therapy when appropriate. This prospective research study was conducted with 14 community pharmacies across the US, in which a total of 650 patients were screened for Afib. Pharmacists conducted SAFEty Risk Assessments that consisted of completion of a Stroke Risk Scorecard and EKG determination utilizing AliveCor's KardiaMobile® 6L device. Results: In 552 (82.5%) of 669 total EKG readings, a "normal" rhythm was detected, and in 117 (17.5%) EKG readings an abnormal detection occurred. A total of 12 out of 650 patients (1.8%) received EKG readings of Afib, which is greater than double the expected prevalence of Afib in the US (0.81%), a statistically significant finding (p < 0.0001). Other notable findings included 42 (6.3%) EKG readings of Wide QRS, and 26 (3.9%) EKG readings of tachycardia. A total of 44 patients were referred to physicians for follow-up on their risk for Afib. Conclusions: Community pharmacies offer a unique, valuable access point for patients to receive Afib screenings. Pharmacists are well positioned to make a significant contribution in the cardiovascular health of their patients and increase the value of team-based health care.

A Perspective on High-Intensity Interval Training for Performance and Health.

Interval training is a simple concept that refers to repeated bouts of relatively hard work interspersed with recovery periods of easier work or rest. The method has been used by high-level athletes for over a century to improve performance in endurance-type sports and events such as middle- and long-distance running. The concept of interval training to improve health, including in a rehabilitative context or when practiced by individuals who are relatively inactive or deconditioned, has also been advanced for decades. An important issue that affects the interpretation and application of interval training is the lack of standardized terminology. This particularly relates to the classification of intensity. There is no common definition of the term "high-intensity interval training" (HIIT) despite its widespread use. We contend that in a performance context, HIIT can be characterized as intermittent exercise bouts performed above the heavy-intensity domain. This categorization of HIIT is primarily encompassed by the severe-intensity domain. It is demarcated by indicators that principally include the critical power or critical speed, or other indices, including the second lactate threshold, maximal lactate steady state, or lactate turnpoint. In a health context, we contend that HIIT can be characterized as intermittent exercise bouts performed above moderate intensity. This categorization of HIIT is primarily encompassed by the classification of vigorous intensity. It is demarcated by various indicators related to perceived exertion, oxygen uptake, or heart rate as defined in authoritative public health and exercise prescription guidelines. A particularly intense variant of HIIT commonly termed "sprint interval training" can be distinguished as repeated bouts performed with near-maximal to "all out" effort. This characterization coincides with the highest intensity classification identified in training zone models or exercise prescription guidelines, including the extreme-intensity domain, anaerobic speed reserve, or near-maximal to maximal intensity classification. HIIT is considered an essential training component for the enhancement of athletic performance, but the optimal intensity distribution and specific HIIT prescription for endurance athletes is unclear. HIIT is also a viable method to improve cardiorespiratory fitness and other health-related indices in people who are insufficiently active, including those with cardiometabolic diseases. Research is needed to clarify responses to different HIIT strategies using robust study designs that employ best practices. We offer a perspective on the topic of HIIT for performance and health, including a conceptual framework that builds on the work of others and outlines how the method can be defined and operationalized within each context.

Can In-Task Affect During Interval and Continuous Exercise Predict 12-Month Physical Activity Behavior? Findings from a Randomized Trial.

BACKGROUND: In-task affective responses to moderate-intensity continuous exercise training (MICT) have been shown to predict future physical activity behavior. However, limited research has investigated whether this affect-behavior relationship is similar for high-intensity interval training (HIIT) and whether it holds true over the longer term. This study aims to determine (1) if in-task affect during 2 weeks of supervised MICT and HIIT predicted changes to unsupervised moderate-to-vigorous physical activity (MVPA) behavior 12 months post-intervention and (2) if this predictive relationship was moderated by exercise type (MICT vs. HIIT). METHOD: Ninety-nine adults (69.7% female; 50.9 ± 9.4 years) who were low active and overweight were randomized to 2 weeks of exercise training of MICT (n = 52) or HIIT (n = 47), followed by 12 months of accelerometry-assessed free-living MVPA. RESULTS: The pooled moderation model was not significant, F(3, 94) = 2.54, p = .07 (R2 = 0.085), with a non-significant group by affect interaction (p = .06). The conditional effect for MICT was significant (B = 17.27, t = 2.17, p = .03), suggesting that 12-month change in MVPA increased by 17.27 min/week for every one-point increase in in-task affect. The conditional effect for HIIT was not significant (p = .85), suggesting that in-task affect was not predictive of 12-month change in MVPA. CONCLUSION: The current findings raise important questions about whether the affect-behavior relationship may vary depending on exercise type. For HIIT-based exercise in particular, additional psychological constructs beyond in-task affect should be considered when attempting to predict future physical activity behavior.

Mild to moderate post-COVID-19 alters markers of lymphocyte activation, exhaustion, and immunometabolic responses that can be partially associated by physical activity level- an observational sub-analysis fit- COVID study.

Aim: This study aimed to evaluate if physical activity is associated with systemic and cellular immunometabolic responses, in young adults after mild-to-moderate COVID-19 infection. Methods: Mild- to- moderate post-COVID-19 patients (70.50 ± 43.10 days of diagnosis; age: 29.4 (21.9- 34.9) years; BMI: 25.5 ± 4.3 kg m2 n = 20) and healthy age-matched controls (age: 29.3 (21.2 - 32.6) years; BMI: 25.4 ± 4.7 kg m2; n = 20) were evaluated. Physical activity levels (PAL), body composition, dietary habits, muscular and pulmonary function, mental health, sleep quality, metabolic parameters, immune phenotypic characterization, stimulated whole blood and PBMC culture (cytokine production), mRNA, and mitochondrial respiration in PBMCs were evaluated. Results: The post-COVID-19 group exhibited lower levels of moderate to vigorous physical activity (MVPA) (p = 0.038); therefore, all study comparisons were performed with adjustment for MVPA. Post-COVID-19 impacted the pulmonary function (FEV1, FEV1%pred, FVC, and FVC %pred) compared with the control (p adjusted by MVPA (p adj) <0.05). Post-COVID-19 exhibited lower levels of serum IL-6 (p adj <0.01), whereas it showed higher serum IL-10, triglyceride, leptin, IgG, ACE activity, TNFRSF1A, and PGE2 (p adj <0.05) levels compared with controls. Post-COVID-19 presented a lower percentage of Treg cells (p adj = 0.03) and altered markers of lymphocyte activation and exhaustion (lower CD28 expression in CD8+ T cells (p adj = 0.014), whereas CD4+T cells showed higher PD1 expression (p adj = 0.037)) compared with the control group. Finally, post- COVID-19 presented an increased LPS-stimulated whole- blood IL-10 concentration (p adj <0.01). When exploring mitochondrial respiration and gene expression in PBMCs, we observed a higher LEAK state value (p adj <0.01), lower OXPHOS activity (complex I) (p adj = 0.04), and expression of the Rev-Erb-α clock mRNA after LPS stimulation in the post-COVID-19 patients than in the control (p adj <0.01). Mainly, PAL was associated with changes in IL-10, triglyceride, and leptin levels in the plasma of post-COVID-19 patients. PAL was also associated with modulation of the peripheral frequency of Treg cells and the expression of PD-1 in CD8+ T cells, although it abrogated the statistical effect in the analysis of TNF-α and IL-6 production by LPS- and PMA-stimulated PBMC of post-COVID-19 patients. Conclusion: Young adults after mild-to-moderate SARS-CoV-2 infection appeared to have lower physical activity levels, which can be associated with clinical and immunometabolic responses in a complex manner.

Sarcopenia and type 2 diabetes: Pathophysiology and potential therapeutic lifestyle interventions.

AIMS: Sarcopenia generally refers to the age-related reduction in muscle strength, functional ability, and muscle mass. Sarcopenia is a multifactorial condition associated with poor glucose disposal, insulin resistance, and subsequently type 2 diabetes (T2D). The pathophysiological connection between sarcopenia and T2D is complex but likely involves glycemic control, inflammation, oxidative stress, and adiposity. METHODS AND RESULTS: Resistance exercise and aerobic training are two lifestyle interventions that may improve glycemic control in older adults with T2D and counteract sarcopenia. Further, there is evidence that dietary protein, Omega-3 fatty acids, creatine monohydrate, and Vitamin D hold potential to augment some of these benefits from exercise. CONCLUSIONS: The purpose of this narrative review is: (1) discuss the pathophysiological link between age-related sarcopenia and T2D, and (2) discuss lifestyle interventions involving physical activity and nutrition that may counteract sarcopenia and T2D.

Saliva insulin tracks plasma insulin across the day following high-carbohydrate and low-carbohydrate meals.

Non-invasive monitoring of insulin could hold promise to identify those with, or at risk for developing, insulin resistance. We aimed to examine saliva insulin responses across the day following high- and low-carbohydrate meals and evaluate whether changes in saliva insulin might accurately reflect changes in plasma insulin. In two randomized crossover studies, young normal weight men (NW; n = 8; Study 1) and adults with overweight/obesity (OO; n = 8; Study 2) completed two 9-h experimental trials in which the participants consumed isocaloric mixed high-carbohydrate (HC) or low-carbohydrate (LC) meals at 0, 3, and 6 h. Plasma and saliva samples were collected at fasted baseline and every 30 min for a total of 19 samples across 9 h. Overall, findings revealed a similar trend for postprandial saliva and plasma insulin responses regardless of the time of the day with a ∼30-45 min lag between saliva and plasma insulin responses. In both NW and OO groups, saliva and plasma insulin area under the curve (AUC) and incremental AUC were significantly higher in HC condition as compared to LC condition (all P ≤ 0.002). Nine-hour plasma and saliva insulin total AUCs were strongly and very strongly correlated in both HC (r = 0.68; P = 0.007) and LC (r = 0.84, P < 0.001) conditions, respectively. Saliva insulin is proportionate to and appears to reasonably track plasma insulin across the day with a ∼30-45 min delay. Saliva insulin shows promise as a non-invasive method to discern between low and high plasma insulin and may have utility in predicting the degree of insulin resistance (NCT03374436).

Effects of ketone supplements on blood ß-hydroxybutyrate, glucose and insulin: A systematic review and three-level meta-analysis.

BACKGROUND: Effects of ketone supplements as well as relevant dose-response relationships and time effects on blood ß-hydroxybutyrate (BHB), glucose and insulin are controversial. OBJECTIVE: This study aimed to summarize the existing evidence and synthesize the results, and demonstrate underlying dose-response relationships as well as sustained time effects. METHODS: Medline, Web of Science, Embase, and Cochrane Central Register of Controlled Trials were searched for relevant randomized crossover/parallel studies published until 25th November 2022. Three-level meta-analysis compared the acute effects of exogenous ketone supplementation and placebo in regulating blood parameters, with Hedge's g used as measure of effect size. Effects of potential moderators were explored through multilevel regression models. Dose-response and time-effect models were established via fractional polynomial regression. RESULTS: The meta-analysis with 327 data points from 30 studies (408 participants) indicated that exogenous ketones led to a significant increase in blood BHB (Hedge's g = 1.4994, 95% CI [1.2648, 1.7340]), reduction in glucose (Hedge's g = -0.3796, 95% CI [-0.4550, -0.3041]), and elevation in insulin of non-athlete healthy population (Hedge's g = 0.1214, 95%CI [0.0582, 0.3011]), as well as insignificant change in insulin of obesity and prediabetes. Nonlinear dose-response relationship between ketone dosage and blood parameter change was observed in some time intervals for BHB (30-60 min; >120 min) and insulin (30-60 min; 90-120 min), with linear relationship observed for glucose (>120 min). Nonlinear associations between time and blood parameter change were found in BHB (>550 mg/kg) and glucose (450-550 mg/kg), with linear relationship observed in BHB (≤250 mg/kg) and insulin (350-550 mg/kg). CONCLUSION: Dose-response relationships and sustained time effects were observed in BHB, glucose and insulin following ketone supplementation. Glucose-lowering effect without increasing insulin load among population of obesity and prediabetes was of remarkable clinical implication. REGISTRY AND REGISTRY NUMBER: PROSPERO (CRD42022360620).

Impact of a Low-Carbohydrate Compared with Low-Fat Breakfast on Blood Glucose Control in Type 2 Diabetes: A Randomized Trial.

BACKGROUND: In type 2 diabetes (T2D), consuming carbohydrates results in a rapid and large increase in blood glucose, particularly in the morning when glucose intolerance is highest. OBJECTIVES: We investigated if a low-carbohydrate (LC) breakfast (∼465 kcal: 25 g protein, 8 g carbohydrates, and 37 g fat) could improve glucose control in people with T2D when compared with a low-fat control (CTL) breakfast (∼450 kcal:20 g protein, 56 g carbohydrates, and 15 g fat). METHODS: Participants with T2D (N = 121, 53% women, mean age 64 y) completed a remote 3-month parallel-group randomized controlled trial comparing a LC with standard low-fat guideline CTL breakfast. The change in HbA1c was the prespecified primary outcome. Continuous glucose monitoring, self-reported anthropometrics, and dietary information were collected for an intention-to-treat analysis. RESULTS: HbA1c was reduced (-0.3%; 95% CI: -0.4%, -0.1%) after 12 wks of a LC breakfast, but the between-group difference in HbA1c was of borderline statistical significance (-0.2; 95% CI: -0.4, 0.0; P = 0.06). Self-reported total daily energy (-242 kcal; 95% CI: -460, -24 kcal; P = 0.03) and carbohydrate (-73 g; 95% CI: -101, -44 g; P < 0.01) intake were lower in the LC group but the significance of this difference is unclear. Mean and maximum glucose, area under the curve, glycemic variability, standard deviation, and time above range were all significantly lower, and time in the range was significantly higher, in the LC group compared with CTL (all P < 0.05). CONCLUSIONS: Advice and guidance to consume a LC breakfast appears to be a simple dietary strategy to reduce overall energy and carbohydrate intake and improve several continuous glucose monitoring variables when compared with a CTL breakfast in persons living with T2D. The trial was registered at clinicaltrials.gov as NCT04550468.