Old muscle, new tricks: a clinician perspective on sarcopenia and where to next.

PURPOSE OF REVIEW: This review offers a contemporary clinical approach to the recognition, prevention and management of sarcopenia, and discusses recent clinically relevant advances in the aetiopathogenesis of muscle ageing that may lead to future therapeutic targets. RECENT FINDINGS: The key recent directions for sarcopenia are in the diagnosis, understanding molecular mechanisms and management. Regarding the recognition of the condition, it has become increasingly clear that different definitions hamper progress in understanding. Therefore, the Global Leadership in Sarcopenia has been established in 2022 to develop a universally accepted definition. Moreover, substantial work is occurring to understand the various roles and contribution of inflammation, oxidative stress, mitochondrial dysfunction and metabolic dysregulation on skeletal muscle function and ageing. Finally, the role of resistance-based exercise regimes has been continually emphasised. However, the role of protein supplementation and hormone replacement therapy (HRT) are still under debate, and current clinical trials are underway. SUMMARY: With the global ageing of our population, there is increasing emphasis on maintaining good health. Maintenance of skeletal muscle strength and function are key to preventing frailty, morbidity and death.

Examining the associations between testosterone and biomarkers as men age.

OBJECTIVES: Testosterone concentrations in men decline with advancing age. However, the cause of the decline is yet to be fully elucidated. Therefore, the aims of this study were to examine the associations between chronic diseases such as obesity and type 2 diabetes mellitus (T2DM) with total testosterone (TT) and sex hormone-binding globulin (SHBG), using a large nationally-representative data set (National Health and Nutrition Examination Survey; NHANES). METHODS: NHANES is a cross-sectional survey, physical examination, and laboratory evaluation of a nationally-representative sample of a non-institutionalized United States population. Male participants aged ≥18 years during the NHANES 2013-2014 and NHANES 2015-2016 survey periods were selected for this analysis. The analysis included the following data: body mass index (BMI), oral glucose tolerance test (OGTT), homeostatic model assessment of insulin resistance (HOMA-IR), insulin, glucose, and age. RESULTS: An overweight or obese condition was significantly inversely associated with TT and SHBG, even after adjusting for other variables. Several variables associated with T2DM (OGTT, HOMA-IR, insulin, and glucose) were also inversely associated with TT; however, only the associations between OGTT and insulin with TT remained significant after adjusting for the other variables. Insulin and HOMA-IR levels were significantly inversely associated with SHBG; however, only the association between SHBG and pre-diabetic HOMA-IR levels remained significant after adjusting for the other variables. OGTT became significantly associated with SHBG after adjusting for the other variables. Age was significantly inversely associated with TT, but positively associated with SHBG, even after adjusting for other variables. CONCLUSION: The results of the present study, which is the largest to date, indicate that a marker of obesity, BMI, and some markers of T2DM are both independently and significantly inversely associated with TT and SHBG.

Exercise-induced responses in matrix metalloproteinases and osteopontin are not moderated by exercise format in males with overweight or obesity.

PURPOSE: Matrix metalloproteinase-2 (MMP-2) and -3 (MMP-3), and osteopontin (OPN) are associated with adipose-tissue expansion and development of metabolic disease. The purpose of the current study was to assess the circulating concentration of these markers, along with adiponectin and glucose concentrations, in response to acute exercise in individuals with overweight or obesity. METHODS: Fourteen sedentary males with overweight or obesity (29.0 ± 3.1 kg/m2) completed two separate, 3-day trials in randomised and counterbalanced order. An oral glucose tolerance test (OGTT) was performed on each day of the trial. Day two of each trial consisted of a single 30 min workload-matched bout of either high-intensity interval exercise (HIIE; alternating 100% and 50% of peak pulmonary oxygen uptake, [Formula: see text]O2peak) or continuous moderate intensity (CME; 60% [Formula: see text]O2peak) cycling completed 1 h prior to the OGTT. Glucose and physical activity were continuously monitored, while MMP-2, MMP-3, OPN and adiponectin were measured pre-, 0 h post-, 1 h post- and 25 h post-exercise. RESULTS: Exercise transiently increased MMP-3 and decreased OPN (both p < 0.01), but not MMP-2 or adiponectin. There were no differences in the response of inflammatory markers to the different exercise formats. Exercise increased mean daily glucose concentration and area under the glucose curve during the OGTT on Day 2 and Day 3 (main effect of time; p < 0.05). CONCLUSION: Acute cycling exercise decreased OPN, which is consistent with longer term improvements in cardiometabolic health and increased MMP-3, which is consistent with its role in tissue remodelling. Interestingly, exercise performed prior to the morning OGTT augmented the glucose concentrations in males. TRIAL REGISTRATION: ACTRN12613001086752.

Painful diabetic peripheral neuropathy: Role of oxidative stress and central sensitisation.

AIMS: Diabetic peripheral neuropathy (DPN) occurs in about half of people with diabetes, of whom a quarter may develop chronic pain. Pain may remain for years yet be difficult to treat because the underlying mechanisms remain unclear. There is consensus that processing excessive glucose leads to oxidative stress, interfering with normal metabolism. In this narrative review, we argue that oxidative stress may also contribute to pain. METHODS: We reviewed literature in PubMed published between January 2005 and August 2021. RESULTS AND CONCLUSIONS: In diabetes, hyperglycaemia and associated production of reactive species can directly increase pain signalling and activate sensory neurons; or the effects can be indirect, mediated by mitochondrial damage and enhanced inflammation. Furthermore, pain processing in the central nervous system is compromised in painful DPN. This is implicated in central sensitisation and dysfunctional pain modulation. However, central pain modulatory function is understudied in diabetes. Future research is required to clarify whether central sensitisation and/or disturbances in central pain modulation contribute to painful DPN. Positive results would facilitate early detection and future treatment.

The effect of the inclusion of trunk-strengthening exercises to a multimodal exercise program on physical activity levels and psychological functioning in older adults: secondary data analysis of a randomized controlled trial.

BACKGROUND: Engaging in multimodal exercise program helps mitigate age-related decrements by improving muscle size, muscle strength, balance, and physical function. The addition of trunk-strengthening within the exercise program has been shown to significantly improve physical functioning outcomes. Whether these improvements result in improved psychological outcomes associated with increased physical activity levels requires further investigation. We sought to explore whether the inclusion of trunk-strengthening exercises to a multimodal exercise program improves objectively measured physical activity levels and self-reported psychological functioning in older adults. METHOD: We conducted a secondary analysis within a single-blinded parallel-group randomized controlled trial. Sixty-four healthy older (≥ 60 years) adults were randomly allocated to a 12-week walking and balance exercise program with (n = 32) or without (n = 32) inclusion of trunk strengthening exercises. Each program involved 12 weeks of exercise training, followed by a 6-week walking-only program (identified as detraining). Primary outcome measures for this secondary analysis were physical activity (accelerometry), perceived fear-of-falling, and symptoms of anxiety and depression. RESULTS: Following the 12-week exercise program, no significant between-group differences were observed for physical activity, sedentary behaviour, fear-of-falling, or symptoms of anxiety or depression. Significant within-group improvements (adjusted mean difference [95%CI]; percentage) were observed in moderate-intensity physical activity (6.29 [1.58, 11.00] min/day; + 26.3%) and total number of steps per min/day (0.81 [0.29 to 1.33] numbers or + 16.3%) in trunk-strengthening exercise group by week 12. With respect to within-group changes, participants in the walking-balance exercise group increased their moderate-to-vigorous physical activity (MVPA) (4.81 [0.06 to 9.56] min/day; + 23.5%) and reported reduction in symptoms of depression (-0.26 [-0.49 to -0.04] points or -49%) after 12 weeks of the exercise program. The exercise-induced increases in physical activity levels in the trunk-strengthening exercise group were abolished 6-weeks post-program completion. While improvements in physical activity levels were sustained in the walking-balance exercise group after detraining phase (walking only). CONCLUSIONS: The inclusion of trunk strengthening to a walking-balance exercise program did not lead to statistically significant between-group improvements in physical activity levels or psychological outcomes in this cohort following completion of the 12-week exercise program. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry (ACTRN12613001176752), registered on 28/10/2013.

Effects of diurnal exercise timing on appetite, energy intake and body composition: A parallel randomized trial.

OBJECTIVE: To determine the effect of diurnal exercise timing on appetite, energy intake and body composition in individuals with overweight or obesity. METHODS: Forty sedentary, individuals with overweight or obesity (17 males, 23 females; age: 51 ± 13 years; BMI: 30.9 ± 4.2 kg/m2) were randomly allocated to complete a 12-week supervised multi-modal exercise training program performed either in the morning (amEX) or evening (pmEX). Outcome measures included appetite in response to a standardised test meal, daily energy intake (EI), body weight and body composition. Measures of dietary behaviour were assessed at baseline and post-intervention, along with habitual physical activity, sleep quality and sleep quantity. Significance was set at p ≤ .05 and Hedge's g effect sizes were calculated. RESULTS: Regardless of timing, exercise training increased perceived fullness (AUC; g = 0.82-1.67; both p < .01), decreased daily EI (g = 0.73-0.93; both p < .01) and body-fat (g = 0.29-0.32; both p <. 01). The timing of exercise did not change the daily EI or body-fat response to training (all p ≥ .27), however, perceived fullness increased in the amEX group (p ≤ .01). DISINHIBITION: (g = 0.35-1.95; p ≤ .01) and Hunger (g = 0.05-0.4; p = .02) behaviours decreased following exercise training, with Disinhibition demonstrating greater improvements in the pmEX group (p = .01). Objective and subjective sleep quantity increased with training (all p ≤ .01), but sleep quality was not reported to change. CONCLUSIONS: Multi-modal exercise training improved body composition and some appetite outcomes, although changes were inconsistent and largely independent of exercise-timing. In the absence of dietary manipulation, the effect of diurnal exercise timing on appetite and body composition appear trivial compared to the overall benefits of exercise participation.

Bilingualism Is Associated with a Delayed Onset of Dementia but Not with a Lower Risk of Developing it: a Systematic Review with Meta-Analyses.

Some studies have linked bilingualism with a later onset of dementia, Alzheimer's disease (AD), and mild cognitive impairment (MCI). Not all studies have observed such relationships, however. Differences in study outcomes may be due to methodological limitations and the presence of confounding factors within studies such as immigration status and level of education. We conducted the first systematic review with meta-analysis combining cross-sectional studies to explore if bilingualism might delay symptom onset and diagnosis of dementia, AD, and MCI. Primary outcomes included the age of symptom onset, the age at diagnosis of MCI or dementia, and the risk of developing MCI or dementia. A secondary outcome included the degree of disease severity at dementia diagnosis. There was no difference in the age of MCI diagnosis between monolinguals and bilinguals [mean difference: 3.2; 95% confidence intervals (CI): -3.4, 9.7]. Bilinguals vs. monolinguals reported experiencing AD symptoms 4.7 years (95% CI: 3.3, 6.1) later. Bilinguals vs. monolinguals were diagnosed with dementia 3.3 years (95% CI: 1.7, 4.9) later. Here, 95% prediction intervals showed a large dispersion of effect sizes (-1.9 to 8.5). We investigated this dispersion with a subgroup meta-analysis comparing studies that had recruited participants with dementia to studies that had recruited participants with AD on the age of dementia and AD diagnosis between mono- and bilinguals. Results showed that bilinguals vs. monolinguals were 1.9 years (95% CI: -0.9, 4.7) and 4.2 (95% CI: 2.0, 6.4) older than monolinguals at the time of dementia and AD diagnosis, respectively. The mean difference between the two subgroups was not significant. There was no significant risk reduction (odds ratio: 0.89; 95% CI: 0.68-1.16) in developing dementia among bilinguals vs. monolinguals. Also, there was no significant difference (Hedges' g = 0.05; 95% CI: -0.13, 0.24) in disease severity at dementia diagnosis between bilinguals and monolinguals, despite bilinguals being significantly older. The majority of studies had adjusted for level of education suggesting that education might not have played a role in the observed delay in dementia among bilinguals vs. monolinguals. Although findings indicated that bilingualism was on average related to a delayed onset of dementia, the magnitude of this relationship varied across different settings. This variation may be due to unexplained heterogeneity and different sources of bias in the included studies. Registration: PROSPERO CRD42015019100.

Correction to: Bilingualism Is Associated with a Delayed Onset of Dementia but Not with a Lower Risk of Developing it: a Systematic Review with Meta-Analyses.

The original version of this article unfortunately contained the following mistakes.

Physical education and leisure-time sport reduce overweight and obesity: a number needed to treat analysis.

BACKGROUND: School-based physical education (PE) and organised leisure-time sports participation (LTSP) represent important physical activity opportunities for children. We examined the preventive effect of increased PE as well as LTSP on overweight and obesity (OW/OB) in school children. METHODS: Longitudinal data from children attending 10 primary schools in the Danish municipality of Svendborg, comprising 6 intensive PE (270 min/week) and 4 control (90 min/week) schools were assessed. Age- and sex-specific cut-offs for body mass index (BMI) determined OW/OB status. Associations between OW/OB status and school type (intensive PE or control) or LTSP were investigated using mixed, multilevel logistic regression models. Significant parameter estimates were converted into number needed to treat statistics (NNT). RESULTS: In total, 1009 children (53.3% female; mean age 8.4 ± 1.4 years) were included in the analysis, with 892 children (52% female) being normal weight (NW) at baseline. Eighteen (NNT = 17.1; 95% CI [11.0, 226.1]) children attending an intensive PE school for 2 years, resulted in one fewer case of OW/OB compared with attendance at a normal PE school. For NW children, prevention of one case of OW/OB requires 36 (NNT = 35.8; 95% CI [25.1, 596.3]) children to participate in intensive PE for 2 years in comparison with normal PE. LTSP over 2 years may prevent OW/OB if 15 children participate in one LTSP session/week, 9 in two LTSP sessions/week and 8 in three LTSP sessions/week; for normal weight children, 25 children had to participate in one LTSP session/week, 16 in two LTSP sessions/week and 14 in three LTSP sessions/week. CONCLUSION: We provide the first NNT estimates of school-based PE and LTSP to prevent the onset of OW/OB. PE, and separately, LTSP seem to have both a protective and a treatment effect against OW/OB in children.

Characterizing the plasma metabolome during 14 days of live-high, train-low simulated altitude: A metabolomic approach.

NEW FINDINGS: What is the central question of this study? Does 14 days of live-high, train-low simulated altitude alter an individual's metabolomic/metabolic profile? What is the main finding and its importance? This study demonstrated that ∼200 h of moderate simulated altitude exposure resulted in greater variance in measured metabolites between subject than within subject, which indicates individual variability during the adaptive phase to altitude exposure. In addition, metabolomics results indicate that altitude alters multiple metabolic pathways, and the time course of these pathways is different over 14 days of altitude exposure. These findings support previous literature and provide new information on the acute adaptation response to altitude. ABSTRACT: The purpose of this study was to determine the influence of 14 days of normobaric hypoxic simulated altitude exposure at 3000 m on the human plasma metabolomic profile. For 14 days, 10 well-trained endurance runners (six men and four women; 29 ± 7 years of age) lived at 3000 m simulated altitude, accumulating 196.4 ± 25.6 h of hypoxic exposure, and trained at ∼600 m. Resting plasma samples were collected at baseline and on days 3 and 14 of altitude exposure and stored at -80°C. Plasma samples were analysed using liquid chromatography-high-resolution mass spectrometry to construct a metabolite profile of altitude exposure. Mass spectrometry of plasma identified 36 metabolites, of which eight were statistically significant (false discovery rate probability 0.1) from baseline to either day 3 or day 14. Specifically, changes in plasma metabolites relating to amino acid metabolism (tyrosine and proline), glycolysis (adenosine) and purine metabolism (adenosine) were observed during altitude exposure. Principal component canonical variate analysis showed significant discrimination between group means (P < 0.05), with canonical variate 1 describing a non-linear recovery trajectory from baseline to day 3 and then back to baseline by day 14. Conversely, canonical variate 2 described a weaker non-recovery trajectory and increase from baseline to day 3, with a further increase from day 3 to 14. The present study demonstrates that metabolomics can be a useful tool to monitor metabolic changes associated with altitude exposure. Furthermore, it is apparent that altitude exposure alters multiple metabolic pathways, and the time course of these changes is different over 14 days of altitude exposure.

Trunk exercise training improves muscle size, strength, and function in older adults: A randomized controlled trial.

The aim of this study was to assess the effectiveness of a multimodal exercise program to increase trunk muscle morphology and strength in older individuals, and their associated changes in functional ability. Using a single-blinded parallel-group randomized controlled trial design, 64 older adults (≥60 years) were randomly allocated to a 12-week exercise program comprising walking and balance exercises with or without trunk strengthening/motor control exercises; followed by a 6-week walking-only program (detraining; 32 per group). Trunk muscle morphology (ultrasound imaging), strength (isokinetic dynamometer), and functional ability and balance (6-Minute Walk Test; 30 second Chair Stand Test; Sitting and Rising Test; Berg Balance Scale, Multi-Directional Reach Test; Timed Up and Go; Four Step Square Test) were the primary outcome measures. Sixty-four older adults (mean [SD]; age: 69.8 [7.5] years; 59.4% female) were randomized into two exercise groups. Trunk training relative to walking-balance training increased (mean difference [95% CI]) the size of the rectus abdominis (2.08 [1.29, 2.89] cm2 ), lumbar multifidus (L4/L5:0.39 [0.16, 0.61] cm; L5/S1:0.31 [0.07, 0.55] cm), and the lateral abdominal musculature (0.63 [0.40, 0.85] cm); and increased trunk flexion (29.8 [4.40, 55.31] N), extension (37.71 [15.17, 60.25] N), and lateral flexion (52.30 [36.57, 68.02] N) strength. Trunk training relative to walking-balance training improved 30-second Chair Stand Test (5.90 [3.39, 8.42] repetitions), Sitting and Rising Test (1.23 [0.24, 2.23] points), Forward Reach Test (4.20 [1.89, 6.51] cm), Backward Reach Test (2.42 [0.33, 4.52] cm), and Timed Up and Go Test (-0.76 [-1.40, -0.13] seconds). Detraining led to some declines but all outcomes remained significantly improved when compared to pre-training. These findings support the inclusion of trunk strengthening/motor control exercises as part of a multimodal exercise program for older adults.

Insulin sensitivity is reduced in children with high body-fat regardless of BMI.

PURPOSE: To examine the association between insulin sensitivity and adiposity in children stratified according to their body mass index (BMI: normal weight, NW; overweight or obese, OW/OB) and body-fat percentage (BF%: adipose or NonAdipose), and determine whether cardiorespiratory fitness (CRF) ameliorates any deleterious associations. METHODS: This prospective cohort study comprises a cross-sectional and longitudinal analyses of data collected at baseline and 2 years later on children (7.7-13.4 years) attending public school in Denmark. Levels of CRF were measured using the Andersen test, whereas BF% was measured by dual-energy X-ray absorptiometry (DXA). Fasting plasma glucose and insulin concentrations were measured and the homoeostatic model assessment of insulin resistance (HOMA-IR) used to assess insulin sensitivity. RESULTS: Approximately 8% of children classified as normal weight by BMI had high BF% (NW + Adipose). Children with high BF% had significantly higher insulin (NW + adipose: 32.3%; OW/OB + Adipose: 52.2%) and HOMA-IR scores (NW + Adipose: 32.3%; OW/OB + Adipose: 55.3%) than children classified as NW without high BF% (reference group; NW + NonAdipose). Adjusting for CRF reduced this difference, but did not completely ameliorate these associations. Longitudinally, children with high BF% (OW/OB + Adipose or NW + Adipose) had significantly worse insulin sensitivity 2 years later than NW + NonAdipose children (All p < 0.001). The few children (n = 14) who improved their BMI or BF% during the 2 years follow-up, no longer had significantly worse insulin sensitivity than children with NW + NonAdipose. CONCLUSION: High BF% in children is associated with significantly lower insulin sensitivity even when BMI is considered NW. Longitudinally, insulin sensitivity is lower in children with high BF% with or without high BMI. The CRF was a significant covariate in these models, but CRF did not completely ameliorate the effects of high BF% on insulin sensitivity.

Glucose Ingestion Does Not Improve Maximal Isokinetic Force.

The purpose of this study was to assess maximal isokinetic leg extension force in response to glucose ingestion and to determine whether any performance changes occur in a time-dependent manner. Seventeen young (22.1 ± 3.9 years), lean (%body fat [%BF]: 14.3 ± 8.0; %BF males: 9.7 ± 4.2; %BF females: 23.7 ± 4.2), and recreationally active (>150 min · wk(-1) of physical activity) male (n = 11) and female participants completed the trials. Using a double-blinded crossover design, participants performed sets of 3 maximum isokinetic efforts on a dynamometer (HumacNorm) before and after (5, 15, 30, 45, 60, 75, and 90 minutes after) ingesting either a carbohydrate (75 g glucose) or isovolumic placebo (saccharin-flavored) drink. Blood glucose and electromyography (EMG) were recorded concurrent with force output (max peak force; mean peak force). Despite a significant rise in blood glucose (mean glycemic excursion = 4.01 ± 1.18 mmol · L(-1)), there were no significant interactions in any (absolute or percentage) force (mean peak force: p ≥ 0.683; max peak force: p ≥ 0.567) or EMG (mean peak EMG: p ≥ 0.119; max peak EMG: p ≥ 0.247) parameters measured. The ingestion of glucose resulted in a 3.4% reduction in mean force across subsequent time points (highest: +2.1% at 15 minutes; lowest: -8.6% at 90 minutes after ingestion); however, this effect was small (d < 0.1). The ingestion of glucose does not alter performance of maximal isokinetic efforts in recreationally active young individuals. Additionally, there were no differences in force when assessed as a function of time after glucose ingestion. Consequently, in the absence of fatigue, carbohydrate ingestion is unlikely to present any ergogenic benefits to athletes performing resistance-based exercise.

Comparing the Effectiveness of a Short-Term Vertical Jump vs. Weightlifting Program on Athletic Power Development.

Teo, SYM, Newton, MJ, Newton, RU, Dempsey, AR, and Fairchild, TJ. Comparing the effectiveness of a short-term vertical jump vs. weightlifting program on athletic power development. J Strength Cond Res 30(10): 2741-2748, 2016-Efficient training of neuromuscular power and the translation of this power to sport-specific tasks is a key objective in the preparation of athletes involved in team-based sports. The purpose of this study was to compare changes in center of mass (COM) neuromuscular power and performance of sport-specific tasks after short-term (6-week) training adopting either Olympic-style weightlifting (WL) exercises or vertical jump (VJ) exercises. Twenty-six recreationally active men (18-30 years; height: 178.7 ± 8.3 cm; mass: 78.6 ± 12.2 kg) were randomly allocated to either a WL or VJ training group and performance during the countermovement jump (CMJ), squat jump (SJ), depth jump (DJ), 20-m sprint, and the 5-0-5 agility test-assessed pre and posttraining. Despite the WL group demonstrating larger increases in peak power output during the CMJ (WL group: 10% increase, d = 0.701; VJ group: 5.78% increase, d = 0.328) and SJ (WL group: 12.73% increase, d = 0.854; VJ group: 7.27% increase, d = 0.382), no significant between-group differences were observed in any outcome measure studied. There was a significant main effect of time observed for the 3 VJs (CMJ, SJ, and DJ), 0- to 5-m and 0- to 20-m sprint times, and the 5-0-5 agility test time, which were all shown to improve after the training (all main effects of time p < 0.01). Irrespective of the training approach adopted by coaches or athletes, addition of either WL or VJ training for development of power can improve performance in tasks associated with team-based sports, even in athletes with limited preseason training periods.

Alteration of postprandial glucose and insulin concentrations with meal frequency and composition.

A frequent eating pattern may alter glycaemic control and augment postprandial insulin concentrations in some individuals due to the truncation of the previous postprandial period by a subsequent meal. The present study examined glucose, insulin, C-peptide and glucose-dependent insulinotropic peptide (GIP) responses in obese individuals when meals were ingested in a high-frequency pattern (every 2 h, 6M) or in a low-frequency pattern (every 4 h, 3M) over 12 h. It also examined these postprandial responses to high-frequency, high-protein meals (6MHP). In total, thirteen obese subjects completed three 12 h study days during which they consumed 6276 kJ (1500 kcal): (1) 3M - 15 % protein and 65 % carbohydrate; (2) 6M - 15 % protein and 65 % carbohydrate; (3) 6MHP - 45 % protein and 35 % carbohydrate. Blood samples were collected every 10 min and analysed for glucose, insulin, C-peptide and GIP. Insulin total AUC (tAUC) and peak insulin concentrations (P< 0·05) were higher in the 3M condition than in the 6M condition, but there were no differences in glucose tAUC between the conditions. The 6MHP regimen (glucose: 3569 (se 83) mmol/l × min (64·3 (se 1·5) g/dl × min), insulin: 1·577 (se 0·146) pmol/l (22·7 (se 2·1) µIU/dl) for 12 h) lowered glucose and insulin excursions more so over 12 h than either the 3M regimen (glucose: 3913 (se 78) mmol/l × min (70·5 (se 1·4) g/dl × min), insulin: 2·195 (se 0·146) pmol/l × min (31·6 (se 2·1) µIU/dl × min) for 12 h) or the 6M regimen (glucose: 3902 (se 83) mmol/l × min (70·3 (se 1·5) g/dl × min), insulin: 1·861 (se 0·174) pmol/l × min (26·8 (se 2·5) µIU/dl × min) for 12 h; P< 0·01). Insulin secretion, GIP concentrations and the glucose:insulin ratio were not altered by meal frequency or composition. In obese subjects, ingestion of meals in a low-frequency pattern does not alter glucose tAUC, but increases postprandial insulin responses. The substitution of carbohydrates with protein in a frequent meal pattern results in tighter glycaemic control and reduced postprandial insulin responses.

Hyperglycemia and Central Obesity Disrupt Conditioned Pain Modulation: A Single-Blind Crossover Randomized Controlled Trial.

Hyperglycemia and high adiposity are risk factors for pain in diabetes. To clarify these links with pain, the effects of a glucose load on sensory detection, pain sensitivity, conditioned pain modulation (primary aims), and autonomic and endothelial functions (secondary aims) were examined in 64 pain-free participants: 22 with normal adiposity (determined by dual-energy X-ray absorptiometry), 29 with high adiposity, and 13 with combined high adiposity and elevated glycated hemoglobin (HbA1c; including prediabetes and type 2 diabetes). Participants ingested either 37.5 g glucose or 200 mg sucralose (taste-matched) in the first session and crossed over to the other substance in the second session 1 month later. At baseline, painful temple cooling (the conditioning stimulus) inhibited pressure- and heat-pain in the ipsilateral arm (the test stimuli) immediately after cooling ceased (partial η2's > .32). Glucose ingestion weakened pressure-pain inhibition irrespective of HbA1c levels (partial η2 = .11). However, a larger reduction in pressure-pain inhibition after ingesting glucose was associated with a higher waist/hip ratio (r = .31), suggesting a role of central obesity. Heat-pain inhibition was absent at baseline in unmedicated participants with elevated HbA1c, and these participants reported more occlusion-induced pain after ingesting glucose (partial η2's > .17). Glucose ingestion interfered with parasympathetic activity in all participants (partial η2 = .11) but did not affect endothelial function (measured by reactive hyperemia) or alter other sensations (eg, feet vibration detection). The disruptive effect of hyperglycemia on conditioned pain modulation increases in line with central obesity, which might facilitate pain in diabetes. PERSPECTIVE: Ingesting 37.5 g glucose (approximately 350 mL soft drink) interfered with pain modulation in pain-free adults with normal adiposity or with combined high adiposity and HbA1c levels. The interference was stronger alongside increasing central obesity, suggesting that controlling blood glucose and body fat mass might help preserve pain modulation.

Exploring the efficacy and safety of a novel standardized ashwagandha (Withania somnifera) root extract (Witholytin®) in adults experiencing high stress and fatigue in a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Stress is a state of homeostasis in the body being challenged, resulting in a systemic response. It has become more prevalent in recent years and affects mental and physical health. AIMS: Evaluate the effects of ashwagandha on stress, fatigue, and sex hormones in overweight or mildly obese men and women with self-reported stress and fatigue. METHODS: Two-arm, parallel-group, 12-week, randomized, double-blind, placebo-controlled trial on overweight or mildly obese men and women aged 40-75 years, supplementing with 200 mg of an ashwagandha root extract (Witholytin®) twice daily. RESULTS/OUTCOMES: Supplementation with ashwagandha was associated with a significant reduction in stress levels based on the Perceived Stress Scale (primary outcome); however, the improvements were not significantly different to the placebo group (p = 0.867). Based on the Chalder Fatigue Scale, there was a statistically significant reduction in fatigue symptoms in the ashwagandha group compared to the placebo group (p = 0.016), and participants taking ashwagandha also experienced a significant increase in heart rate variability (p = 0.003). However, there were no significant between-group differences in other self-report outcome measures. In the men taking ashwagandha, there was a significant increase in the blood concentrations of free testosterone (p = 0.048) and luteinizing hormone (p = 0.002) compared to the placebo group. CONCLUSIONS/INTERPRETATION: The results of this study suggest that in overweight middle-to-older age adults experiencing high stress and fatigue, compared to the placebo, ashwagandha did not have a significantly greater impact on perceived stress levels. However, based on secondary outcome measures, it may have anti-fatigue effects. This may be via its impact on the autonomic nervous system. However, further research is required to expand on these current findings.

Temple cooling increases parasympathetic activity and decreases pressure pain on the hand.

BACKGROUND: Applying an ice cube to the temple (the conditioning stimulus) inhibits electrically evoked pain in the forearm. The present study aimed to determine whether temple cooling also inhibits pressure- and heat-pain test stimuli in the upper limb and, if so, to investigate the intra-session test-retest reliability of this response. Additional aims were to establish whether pain inhibition evoked by temple cooling was associated with parasympathetic activity; and to explore sex differences in response. METHODS: The sample consisted of 40 healthy adults (24 females). Heart rate was recorded continuously throughout the session. An ice cube (3 × 4 cm contact area) was applied for 1 min to the temple on the dominant side. Before and immediately afterwards, the pressure pain threshold was measured from the dorsal hand and sensitivity to heat (individually adjusted at baseline to elicit moderate pain) was measured from the ventral forearm. The procedures were repeated 15 min later. RESULTS: Temple cooling inhibited pressure pain on the hand but not heat pain on the forearm. However, test-retest reliability of pressure pain inhibition was poor. Heart rate decreased during temple cooling, consistent with a "diving" reflex. Males had stronger pressure pain inhibition, lower heart rate and higher overall autonomic activity than females. However, cardiac parasympathetic activation during temple cooling was comparable in both sexes and was unrelated to pain inhibition. CONCLUSIONS: These findings indicate that temple cooling evokes pain inhibition that is stronger in males than in females. Cardiac parasympathetic activity does not appear to mediate this response. SIGNIFICANCE: The conditioning stimulus in the conditioned pain modulation paradigm is often applied to the upper or lower limbs. This may confound pain-inhibitory effects in people with peripheral neuropathy who typically have enhanced or diminished sensation in the extremities. Applying an ice cube at the temple area induces pain-inhibitory effects on the upper limb after the ice is removed. Future research examining pain modulation in people with peripheral neuropathy may consider adopting temple cooling as the conditioning stimulus.

High Blood Glucose and Excess Body fat Enhance Pain Sensitivity and Weaken Pain Inhibition in Healthy Adults: A Single-blind Cross-over Randomized Controlled Trial.

To investigate links between blood glucose, body fat mass and pain, the effects of acute hyperglycaemia on pain sensitivity and pain inhibition were examined in healthy adults with normal (n = 24) or excess body fat (n = 20) determined by dual-energy X-ray absorptiometry. Effects of hyperglycaemia on heart rate variability and reactive hyperaemia were also explored. For the overall sample, ingesting 75-g glucose enhanced pain sensitivity during 1-minute cold-water immersion of both feet (conditioning stimulus) and weakened the pain inhibitory effect of cold water on pressure pain thresholds (test stimulus). Exploratory subgroup analyses not adjusted for multiple comparisons suggested that this effect was limited to people with excess fat mass. In addition, acute hyperglycaemia suppressed resting heart rate variability only in people with excess fat mass. Furthermore, regardless of blood glucose levels, people with excess fat mass had weaker pain inhibition for pinprick after cold water and reported more pain during 5-minutes of static blood flow occlusion. Neither high blood glucose nor excess body fat affected pinprick-temporal summation of pain or reactive hyperaemia. Together, these findings suggest that hyperglycaemia and excess fat mass interfere with pain processing and autonomic function. PERSPECTIVE: Ingesting 75-g glucose (equivalent to approximately 2 standard cans of soft drink) interfered with pain-processing and autonomic function, particularly in people with excess body fat mass. As both hyperglycaemia and overweight are risk factors for diabetes, whether these are sources of pain in people with diabetes should be further explored.

Testosterone treatment combined with exercise to improve muscle strength, physical function and quality of life in men affected by inclusion body myositis: A randomised, double-blind, placebo-controlled, crossover trial.

INTRODUCTION: Inclusion body myositis (IBM) is the most commonly acquired skeletal muscle disease of older adults involving both autoimmune attack and muscle degeneration. As exercise training can improve outcomes in IBM, this study assessed whether a combination of testosterone supplementation and exercise training would improve muscle strength, physical function and quality of life in men affected by IBM, more than exercise alone. METHODS: This pilot study was a single site randomised, double-blind, placebo-controlled, crossover study. Testosterone (exercise and testosterone cream) and placebo (exercise and placebo cream) were each delivered for 12 weeks, with a two-week wash-out between the two periods. The primary outcome measure was improvement in quadriceps isokinetic muscle strength. Secondary outcomes included assessment of isokinetic peak flexion force, walk capacity and patient reported outcomes, and other tests, comparing results between the placebo and testosterone arms. A 12-month Open Label Extension (OLE) was offered using the same outcome measures collected at 6 and 12-months. RESULTS: 14 men completed the trial. There were no significant improvements in quadriceps extension strength or lean body mass, nor any of the secondary outcomes. Improvement in the RAND Short Form 36 patient reported outcome questionnaire 'emotional wellbeing' sub-category was reported during the testosterone arm compared to the placebo arm (mean difference [95% CI]: 6.0 points, [95% CI 1.7,10.3]). The OLE demonstrated relative disease stability over the 12-month period but with a higher number of testosterone-related adverse events. CONCLUSIONS: Adding testosterone supplementation to exercise training did not significantly improve muscle strength or physical function over a 12-week intervention period, compared to exercise alone. However, the combination improved emotional well-being over this period, and relative stabilisation of disease was found during the 12-month OLE. A longer duration trial involving a larger group of participants is warranted.