Effects of exercise, metformin and their combination on glucose metabolism in individuals with abnormal glycaemic control: a systematic review and network meta-analysis.

OBJECTIVE: To compare the efficacy of exercise, metformin and their combination on glucose metabolism in individuals with abnormal glycaemic control. DESIGN: Systematic review and network meta-analysis. DATA SOURCES: Embase, Web of Science, PubMed/MEDLINE and SPORTDiscus. ELIGIBILITY CRITERIA: Randomised controlled trials involving exercise, metformin or their combined treatments in individuals with prediabetes or type 2 diabetes mellitus (T2DM) were included. Outcomes included haemoglobin A1c (HbA1c), 2-hour glucose during oral glucose tolerance test, fasting glucose, fasting insulin and homeostasis model assessment of insulin resistance (HOMA-IR). RESULTS: 407 articles with 410 randomised controlled trials (n=33 802) were included. In prediabetes, the exercise showed greater efficacy than metformin on HbA1c levels (mean difference -0.16%, 95% CI (-0.23 to -0.09) vs -0.10%, 95% CI (-0.21 to 0.02)), 2-hour glucose (-0.68 mmol/L, 95% CI (-0.97 to -0.39) vs 0.01 mmol/L, 95% CI (-0.38 to 0.41)) and HOMA-IR (-0.54, 95% CI (-0.71 to -0.36) vs -0.23, 95% CI (-0.55 to 0.10)), while the efficacy on fasting glucose was comparable (-0.26 mmol/L, 95% CI (-0.32 to -0.19) vs -0.33 mmol/L, 95% CI (-0.45 to -0.21)). In T2DM, metformin was more efficacious than exercise on HbA1c (-0.88%, 95% CI (-1.07 to -0.69) vs -0.48%, 95% CI (-0.58 to -0.38)), 2-hour glucose (-2.55 mmol/L, 95% CI (-3.24 to -1.86) vs -0.97 mmol/L, 95% CI (-1.52 to -0.42)) and fasting glucose (-1.52 mmol/L, 95% CI (-1.73 to -1.31) vs -0.85 mmol/L, 95% CI (-0.96 to -0.74)); exercise+metformin also showed greater efficacy in improving HbA1c (-1.23%, 95% CI (-2.41 to -0.05)) and fasting glucose (-2.02 mmol/L, 95% CI (-3.31 to -0.74)) than each treatment alone. However, the efficacies were modified by exercise modality and metformin dosage. CONCLUSION: Exercise, metformin and their combination are efficacious in improving glucose metabolism in both prediabetes and T2DM. The efficacy of exercise appears to be superior to metformin in prediabetes, but metformin appears to be superior to exercise in patients with T2DM. PROSPERO REGISTRATION NUMBER: CRD42023400622.

Evaluation of the Vmaxpro sensor for assessing movement velocity and load-velocity variables: accuracy and implications for practical use.

We investigated the ecological validity of an inertial measurement unit (IMU) (Vmaxpro) to assess the movement velocity (MV) during a 1-repetition maximum (1RM) test and for the prediction of load-velocity (L-V) variables, as well as the ecological intra- day and inter-day reliability during free-weight bench press (BP) and squat (SQ). Furthermore, we provide recommendations for the practical use of the sensor. Twenty-three strength-trained men completed an incremental 1RM test, whereas seventeen men further participated in another 3 sessions consisting of 3 repetitions with 4 different loads (30, 50, 70 and 90% of 1RM) to assess validity and intra- and inter-day reliability, respectively. The MV was assessed using the Vmaxpro and a 3D motion capture system (MoCap). L-V variables and the 1RM were calculated based on submaximal velocities. The Vmaxpro showed high validity during the 1RM test for BP (r = 0.935) and SQ (r = 0.900), but with decreasing validity at lower MVs. The L-V variables and the 1RM demonstrated high validity for BP (r = 0.808-0.942) and SQ (r = 0.615-0.741) with a systematic overestimation. Coefficients of variance for intra- and inter-day reliability ranged from 2.4% to 9.7% and from 3.2% to 8.6% for BP and SQ, respectively. The Vmaxpro appears valid at high and moderately valid at low MVs. Depending on the required degree of accuracy, the sensor may be sufficient for the prediction of L-V variables and the 1RM. Our data indicate the sensor to be suitable for monitoring changes in MVs within and between training sessions.

Validity and Test-Retest Reliability of the Vmaxpro Sensor for Evaluation of Movement Velocity in the Deep Squat.

ABSTRACT: Feuerbacher, JF, Jacobs, MW, Dragutinovic, B, Goldmann, J-P, Cheng, S, and Schumann, M. Validity and test-retest reliability of the Vmaxpro sensor for evaluation of movement velocity in the deep squat. J Strength Cond Res 37(1): 35-40, 2023-We aimed at assessing the validity and test-retest reliability of the inertial measurement unit-based Vmaxpro sensor compared with a Vicon 3D motion capture system and the T-Force sensor during an incremental 1-repetition maximum (1RM) test and at submaximal loads. Nineteen subjects reported to the laboratory for the 1RM test sessions, whereas 15 subjects carried out another 3 sessions consisting of 3 repetitions with 4 different intensities (30, 50, 70, and 90% of 1RM) to determine the intra- and interday reliability. The Vmaxpro sensor showed high validity (Vicon: R2 = 0.935; T-Force: R2 = 0.968) but an overestimation of the mean velocities (MVs) of 0.06 ± 0.08 m·s-1 and 0.06 ± 0.06 m·s-1 compared with Vicon and T-Force, respectively. Regression analysis indicated a systematic bias that is increasing with higher MVs. The intraclass correlation coefficients (ICCs) for Vmaxpro were moderate to high for intraday (ICC: 0.662-0.938; p ≤ 0.05) and for interday (ICC: 0.568-0.837; p ≤ 0.05) reliability, respectively. The Vmaxpro is a valid and reliable measurement device that can be used to monitor movement velocities within a training session. However, practitioners should be cautious when assessing movement velocities on separate days because of the moderate interday reliability.

Maximal isometric strength indices are associated with the oxygen cost of walking and running in recreationally active men and women.

This study assessed the associations of maximal isometric strength and movement economy in 126 recreationally active men and women. Oxygen consumption was assessed through a graded treadmill test with 4-minute increments (4-12 km∙h-1). Maximal isometric leg extensor, leg flexor and handgrip strength were assessed by isometric dynamometry. Models of best fit for gross oxygen cost and gross caloric unit cost were observed across the majority of velocities when the leg extensor/flexor strength ratio and handgrip strength were combined (R2 = 0.207-0.525 and R2 = 0.152-0.475, respectively). Additionally, the oxygen cost differed statistically for the majority of velocities when participants were split by the median of leg extensor strength (12.3-26.3 ml∙kg-1∙km-1, p < 0.05) and the average of all strength variables (13.9-30.3 ml∙kg-1∙km-1, p < 0.05). Our data underline the importance of maintaining maximal strength in order to perform activities with low to moderate oxygen demands.

Recommendations for determining the validity of consumer wearable heart rate devices: expert statement and checklist of the INTERLIVE Network.

Assessing vital signs such as heart rate (HR) by wearable devices in a lifestyle-related environment provides widespread opportunities for public health related research and applications. Commonly, consumer wearable devices assessing HR are based on photoplethysmography (PPG), where HR is determined by absorption and reflection of emitted light by the blood. However, methodological differences and shortcomings in the validation process hamper the comparability of the validity of various wearable devices assessing HR. Towards Intelligent Health and Well-Being: Network of Physical Activity Assessment (INTERLIVE) is a joint European initiative of six universities and one industrial partner. The consortium was founded in 2019 and strives towards developing best-practice recommendations for evaluating the validity of consumer wearables and smartphones. This expert statement presents a best-practice validation protocol for consumer wearables assessing HR by PPG. The recommendations were developed through the following multi-stage process: (1) a systematic literature review based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses, (2) an unstructured review of the wider literature pertaining to factors that may introduce bias during the validation of these devices and (3) evidence-informed expert opinions of the INTERLIVE Network. A total of 44 articles were deemed eligible and retrieved through our systematic literature review. Based on these studies, a wider literature review and our evidence-informed expert opinions, we propose a validation framework with standardised recommendations using six domains: considerations for the target population, criterion measure, index measure, testing conditions, data processing and the statistical analysis. As such, this paper presents recommendations to standardise the validity testing and reporting of PPG-based HR wearables used by consumers. Moreover, checklists are provided to guide the validation protocol development and reporting. This will ensure that manufacturers, consumers, healthcare providers and researchers use wearables safely and to its full potential.

Muscle and serum metabolomes are dysregulated in colon-26 tumor-bearing mice despite amelioration of cachexia with activin receptor type 2B ligand blockade.

Cancer-associated cachexia reduces survival, which has been attenuated by blocking the activin receptor type 2B (ACVR2B) ligands in mice. The purpose of this study was to unravel the underlying physiology and novel cachexia biomarkers by use of the colon-26 (C26) carcinoma model of cancer cachexia. Male BALB/c mice were subcutaneously inoculated with C26 cancer cells or vehicle control. Tumor-bearing mice were treated with vehicle (C26+PBS) or soluble ACVR2B either before (C26+sACVR/b) or before and after (C26+sACVR/c) tumor formation. Skeletal muscle and serum metabolomics analysis was conducted by gas chromatography-mass spectrometry. Cancer altered various biologically functional groups representing 1) amino acids, 2) energy sources, and 3) nucleotide-related intermediates. Muscle metabolomics revealed increased content of free phenylalanine in cancer that strongly correlated with the loss of body mass within the last 2 days of the experiment. This correlation was also detected in serum. Decreased ribosomal RNA content and phosphorylation of a marker of pyrimidine synthesis revealed changes in nucleotide metabolism in cancer. Overall, the effect of the experimental C26 cancer predominated over blocking ACVR2B ligands in both muscle and serum. However, the level of methyl phosphate, which was decreased in muscle in cancer, was restored by sACVR2B-Fc treatment. In conclusion, experimental cancer affected muscle and blood metabolomes mostly independently of blocking ACVR2B ligands. Of the affected metabolites, we have identified free phenylalanine as a promising biomarker of muscle atrophy or cachexia. Finally, the decreased capacity for pyrimidine nucleotide and protein synthesis in tumor-bearing mice opens up new avenues in cachexia research.

Normal weight obesity and physical fitness in Chinese university students: an overlooked association.

BACKGROUND: The primary aim of this study was to examine the associations of normal weight obesity (NWO) with physical fitness in Chinese university students. As a secondary aim, we assessed whether possible differences in physical fitness between students classified as NWO and normal weight non-obese (NWNO) were mediated by skeletal muscles mass. METHODS: A total of 383 students (205 males and 178 females, aged 18-24 years) from two universities volunteered to participate in this study. Body height and weight were measured by standard procedures and body composition was assessed by bio-impedance analysis (InBody 720). NWO was defined by a BMI of 18.5-23.9 kg/m2 and a body fat percentage of > 20% or > 30% in male and female students, respectively. Physical fitness was measured using a 10-min intermittent endurance running test (Andersen test), countermovement jumps (CMJ) and a 5 × 5 m shuttle run test (5mSR). The level of leisure time physical activity (PA) was assessed by a questionnaire. RESULTS: 13.7% of male and 27.5% of female students were classified as NWO. Compared to NWNO, students classified as NWO showed a significantly poorer performance in the Andersen test (males: 1146 ± 70 m vs. 1046 ± 95 m, females: 968 ± 61 m vs. 907 ± 67 m, p < 0.001), CMJ (males: 55.0 ± 7.6 cm vs. 44.9 ± 7.5 cm, females: 39.8 ± 8.0 cm vs. 33.7 ± 5.9 cm, p < 0.001) and 5mSR (males: 18.7 ± 1.0 s vs. 20.0 ± 0.9 s, females: 21.1 ± 1.1 s vs. 22.4 ± 1.3 s, p < 0.001), respectively. The lower levels of physical fitness in NWO were partially explained by lower skeletal muscle mass (p < 0.001) both in male and female students. CONCLUSIONS: NWO was associated with poorer physical fitness and the relationship was partially mediated by lower skeletal muscle mass. The study indicated that attention should be paid for the potential hidden health risk in university students with normal body mass index but excessive fat mass.

Genetic determinants of heel bone properties: genome-wide association meta-analysis and replication in the GEFOS/GENOMOS consortium.

Quantitative ultrasound of the heel captures heel bone properties that independently predict fracture risk and, with bone mineral density (BMD) assessed by X-ray (DXA), may be convenient alternatives for evaluating osteoporosis and fracture risk. We performed a meta-analysis of genome-wide association (GWA) studies to assess the genetic determinants of heel broadband ultrasound attenuation (BUA; n = 14 260), velocity of sound (VOS; n = 15 514) and BMD (n = 4566) in 13 discovery cohorts. Independent replication involved seven cohorts with GWA data (in silico n = 11 452) and new genotyping in 15 cohorts (de novo n = 24 902). In combined random effects, meta-analysis of the discovery and replication cohorts, nine single nucleotide polymorphisms (SNPs) had genome-wide significant (P < 5 × 10(-8)) associations with heel bone properties. Alongside SNPs within or near previously identified osteoporosis susceptibility genes including ESR1 (6q25.1: rs4869739, rs3020331, rs2982552), SPTBN1 (2p16.2: rs11898505), RSPO3 (6q22.33: rs7741021), WNT16 (7q31.31: rs2908007), DKK1 (10q21.1: rs7902708) and GPATCH1 (19q13.11: rs10416265), we identified a new locus on chromosome 11q14.2 (rs597319 close to TMEM135, a gene recently linked to osteoblastogenesis and longevity) significantly associated with both BUA and VOS (P < 8.23 × 10(-14)). In meta-analyses involving 25 cohorts with up to 14 985 fracture cases, six of 10 SNPs associated with heel bone properties at P < 5 × 10(-6) also had the expected direction of association with any fracture (P < 0.05), including three SNPs with P < 0.005: 6q22.33 (rs7741021), 7q31.31 (rs2908007) and 10q21.1 (rs7902708). In conclusion, this GWA study reveals the effect of several genes common to central DXA-derived BMD and heel ultrasound/DXA measures and points to a new genetic locus with potential implications for better understanding of osteoporosis pathophysiology.

What Makes a 97-Year-Old Man Cycle 5,000 km a Year?

BACKGROUND: The nature versus nurture debate is one of the oldest issues in the study of longevity, health and successful aging. OBJECTIVE: We present a 97-year-old man (I.K.) as an example of the effects of habitual exercise on the aging process. METHODS: Extensive assessments included medical examinations, interviews, musculoskeletal structure, performance characteristics, cognitive function and gut microbiota composition. RESULTS: I.K. suffers from iatrogenic hypogonadism, prostate cancer, hypothyroidism and a history of deep popliteal thrombosis. Notwithstanding, he cycles up to 5,000 km a year and participates in competitive sports. His musculoskeletal properties, athletic performance, cognitive function and gut microbiota are outstanding. Some traits even exceed those seen in middle-aged men. CONCLUSIONS: His long-term physically and intellectually active lifestyles combined with extensive social interactions have most likely contributed to his exercise capacity, despite his medical history.

Associations of disordered sleep with body fat distribution, physical activity and diet among overweight middle-aged men.

This cross-sectional study aimed to investigate whether body fat distribution, physical activity levels and dietary intakes are associated with insomnia and/or obstructive sleep apnea among overweight middle-aged men. Participants were 211 Finnish men aged 30-65 years. Among the 163 overweight or obese participants, 40 had insomnia only, 23 had obstructive sleep apnea only, 24 had comorbid insomnia and obstructive sleep apnea and 76 were without sleep disorder. The remaining 48 participants had normal weight without sleep disorder. Fat mass, levels of physical activity and diet were assessed by dual-energy X-ray densitometry, physical activity questionnaire and 3-day food diary, respectively. Among the overweight participants, we found that: (i) groups with sleep disorders had higher fat mass in trunk and android regions than the group without sleep disorder (P = 0.048-0.004); (ii) the insomnia-only group showed a lower level of leisure-time physical activity (436.9 versus 986.5 MET min week(-1) , P = 0.009) and higher intake of saturated fatty acids (14.8 versus 12.7 E%, P = 0.011) than the group without sleep disorder; and (iii) the comorbid group had a lower level of leisure-time physical activity (344.4 versus 986.5 MET min week(-1) , P = 0.007) and lower folate intake (118.9 versus 152.1 µg, P = 0.002) than the group without sleep disorder, which were independent of body mass index. The results suggest that central obesity is associated with insomnia and/or obstructive sleep apnea. In addition, low levels of leisure-time physical activity and poor dietary intakes are related to insomnia or comorbid insomnia and obstructive sleep apnea among overweight men.

Long-term leisure-time physical activity and serum metabolome.

BACKGROUND: Long-term physical inactivity seems to cause many health problems. We studied whether persistent physical activity compared with inactivity has a global effect on serum metabolome toward reduced cardiometabolic disease risk. METHODS AND RESULTS: Sixteen same-sex twin pairs (mean age, 60 years) were selected from a cohort of twin pairs on the basis of their >30-year discordance for physical activity. Persistently (≥5 years) active and inactive groups in 3 population-based cohorts (mean ages, 31-52 years) were also studied (1037 age- and sex-matched pairs). Serum metabolome was quantified by nuclear magnetic resonance spectroscopy. We used permutation analysis to estimate the significance of the multivariate effect combined across all metabolic measures; univariate effects were estimated by paired testing in twins and in matched pairs in the cohorts, and by meta-analysis over all substudies. Persistent physical activity was associated with the multivariate metabolic profile in the twins (P=0.003), and a similar pattern was observed in all 3 population cohorts with differing mean ages. Isoleucine, α1-acid glycoprotein, and glucose were lower in the physically active than in the inactive individuals (P<0.001 in meta-analysis); serum fatty acid composition was shifted toward a less saturated profile; and lipoprotein subclasses were shifted toward lower very-low-density lipoprotein (P<0.001) and higher large and very large high-density lipoprotein (P<0.001) particle concentrations. The findings persisted after adjustment for body mass index. CONCLUSIONS: The numerous differences found between persistently physically active and inactive individuals in the circulating metabolome together indicate better metabolic health in the physically active than in inactive individuals.

Gut-adipose tissue axis in hepatic fat accumulation in humans.

BACKGROUND & AIMS: Recent evidence suggests that in animals gut microbiota composition (GMC) affects the onset and progression of hepatic fat accumulation. The aim of this study was to investigate in humans whether subjects with high hepatic fat content (HHFC) differ in their GMC from those with low hepatic fat content (LHFC), and whether these differences are associated with body composition, biomarkers and abdominal adipose tissue inflammation. METHODS: Hepatic fat content (HFC) was measured using proton magnetic resonance spectroscopy ((1)H MRS). Fecal GMC was profiled by 16S rRNA fluorescence in situ hybridization and flow cytometry. Adipose tissue gene expression was analyzed using Affymetrix microarrays and quantitative PCR. RESULTS: The HHFC group had unfavorable GMC described by lower amount of Faecalibacterium prausnitzii (FPrau) (p<0.05) and relatively higher Enterobacteria than the LHFC group. Metabolically dysbiotic GMC associated with HOMA-IR and triglycerides (p<0.05 for both). Several inflammation-related adipose tissue genes were differentially expressed and correlated with HFC (p<0.05). In addition, the expression of certain genes correlated with GMC dysbiosis, i.e., low FPrau-to-Bacteroides ratio. CONCLUSIONS: HHFC subjects differ unfavorably in their GMC from LHFC subjects. Adipose tissue inflammation may be an important link between GMC, metabolic disturbances, and hepatic fat accumulation.

Effect of aerobic exercise and low carbohydrate diet on pre-diabetic non-alcoholic fatty liver disease in postmenopausal women and middle aged men--the role of gut microbiota composition: study protocol for the AELC randomized controlled trial.

BACKGROUND: Pre-diabetes and non-alcoholic fatty liver disease (NAFLD) are associated with an unhealthy lifestyle and pose extremely high costs to the healthcare system. In this study, we aim to explore whether individualized aerobic exercise (AEx) and low carbohydrate diet (LCh) intervention affect hepatic fat content (HFC) in pre-diabetes via modification of gut microbiota composition and other post-interventional effects. METHODS/DESIGN: A 6-month randomized intervention with 6-month follow-up is conducted from January 2013 to December 2015. The target sample size for intervention is 200 postmenopausal women and middle-aged men aged 50-65 year-old with pre-diabetes and NAFLD. The qualified subjects are randomized into 4 groups with 50 subjects in each group: 1 = AEx, 2 = LCh, 3 = AEx + LCh, and 4 = control. In addition, two age-matched reference groups (5 = pre-diabetes without NAFLD (n = 50) and 6 = Healthy without pre-diabetes or NAFLD (n = 50)) are included. The exercise program consists of progressive and variable aerobic exercise (intensity of 60 to 75% of initial fitness level, 3-5 times/week and 30-60 min/time). The diet program includes dietary consultation plus supplementation with a special lunch meal (40% of total energy intake/day) which aims to reduce the amount of carbohydrate consumption (30%). The control and reference groups are advised to maintain their habitual habits during the intervention. The primary outcome measures are HFC, serum metabolomics and gut microbiota composition. The secondary outcome measures include body composition and cytokines. In addition, socio-psychological aspects, social support, physical activity and diet will be performed by means of questionnaire and interview. DISCUSSION: Specific individualized exercise and diet intervention in this study offers a more efficient approach for liver fat reduction and diabetes prevention via modification of gut microbiota composition. Besides, the study explores the importance of incorporating fitness assessment and exercise in the management of patients with pre-diabetes and fatty liver disorders. If our program is shown to be effective, it will open new strategies to combat these chronic diseases. TRIAL REGISTRATION: Current Controlled Trials: ISRCTN42622771.

Activity of thigh muscles during static and dynamic stances in stroke patients: a pilot case-control study.

PURPOSE: Impaired postural control is a key characteristic of mobility problems in stroke patients and has great impact on the incidence of falls and on the level of independence in activities of daily living. The role played by the thigh muscles in balance impairment in stroke patients has not been sufficiently investigated. This study investigated the activities of the thigh muscles in stroke patients during standing balance manipulations. METHOD: Ten stroke patients and 15 healthy subjects performed 5 upright standing tasks on a force platform: normal standing with eyes open, normal standing with eyes closed, feet together, semi-tandem standing, and a dynamic measurement along a predefined route. The posturography parameters, normalized muscle activity by maximal voluntary isometric contraction of the thigh muscles, were measured. The Berg Balance Scale was administered to evaluate functional balance. RESULTS: The stroke patients showed excessive postural sway compared with healthy control subjects in all conditions of the static balance tests (P < .05). Muscle activity measured by surface electromyography (sEMG) showed higher normalized average EMG (aEMG) in the vastus medialis, rectus femoris, and biceps femoris on the affected side than that in control subjects during all static balance tests (P < .05). The rectus femoris on the unaffected side showed higher aEMG than that in control subjects in the 4 static standing tasks (P < .05). In dynamic tests, the performance time and excursion of the center of pressure were longer in the stroke patients than in the control subjects (P < .05). The activity of the biceps femoris muscle on the affected side was significantly different from that of the control subjects (P < .01). CONCLUSIONS: The vastus medialis, rectus femoris, and biceps femoris muscles on the affected side and the rectus femoris muscle on the unaffected side of stroke patients are involved in the static balance deficits, while the biceps femoris on the affected side influences dynamic balance control.

A hydrogen generator composed of poly (lactic-co-glycolic acid) nanofibre membrane loaded iron nanoparticles for infectious diabetic wound repair.

Diabetic wound, which is chronic skin disease, poses a significant challenge in clinical practice because of persistent inflammation and impaired angiogenesis. Recently, hydrogen has emerged as a novel therapeutic agent due to its superior antioxidant and anti-inflammatory properties. In this study, we engineered a poly (lactic-co-glycolic acid) (PLGA) electrospun nanofibre membrane loaded with citric acid (CA) and iron (Fe) nanoparticles, referred to as Fe@PLGA + CA. Our in vitro assays demonstrated that the Fe@PLGA + CA membrane continuously generated and released hydrogen molecules via a chemical reaction between Fe and CA in an acidic microenvironment created by CA. We also discovered that hydrogen can ameliorate fibroblast migration disorders by reducing the levels of matrix metalloproteinase 9 (MMP9). Furthermore, we confirmed that hydrogen can scavenge or biochemically neutralise accumulated reactive oxygen species (ROS), inhibit pro-inflammatory responses, and induce anti-inflammatory reactions. This, in turn, promotes vessel formation, wound-healing and accelerates skin regeneration. These findings open new possibilities for using elemental iron in skin dressings and bring us one step closer to implementing hydrogen-releasing biomedical materials in clinical practice.

Responses of the Serum Lipid Profile to Exercise and Diet Interventions in Nonalcoholic Fatty Liver Disease.

BACKGROUND: This study aimed to assess the response patterns of circulating lipids to exercise and diet interventions in nonalcoholic fatty liver disease (NAFLD). METHODS: The 8.6-month four-arm randomized controlled study comprised 115 NAFLD patients with prediabetes who were assigned to aerobic exercise (AEx; n = 29), low-carbohydrate diet (Diet; n = 28), AEx plus low-carbohydrate diet (AED; n = 29), and nonintervention (NI, n = 29) groups. Hepatic fat content (HFC) was quantified by proton magnetic resonance spectroscopy. Serum lipidomic analytes were measured using liquid chromatography-mass spectrometry. RESULTS: After intervention, the total level of phosphatidylcholine (PC) increased significantly in the AEx group ( P = 0.043), whereas phosphatidylethanolamine (PE) and triacylglycerol decreased significantly in the AED group ( P = 0.046 and P = 0.036, respectively), and phosphatidylserine decreased in the NI group ( P = 0.002). Changes of 21 lipid metabolites were significantly associated with changes of HFC, among which half belonged to PC. Most of the molecules related to insulin sensitivity belonged to sphingomyelin (40 of 79). Controlling for the change of visceral fat, the significant associations between lipid metabolites and HFC remained. In addition, baseline serum lipids could predict the response of HFC to exercise and/or diet interventions (PE15:0/18:0 for AED, area under the curve (AUC) = 0.97; PE22:6(4Z,7Z,10Z,13Z,16Z,19Z)/0:0 for AEx, AUC = 0.90; and PC14:1(9Z)/19:1(9Z) for Diet, AUC = 0.92). CONCLUSIONS: Changes of lipidome after exercise and/or diet interventions were associated with HFC reductions, which are independent of visceral fat reduction, particularly in metabolites belonging to PC. Importantly, baseline PE could predict the HFC response to exercise, and PC predicted the response to diet. These results indicate that a circulating metabolomics panel can be used to facilitate clinical implementation of lifestyle interventions for NAFLD management.

Are skeletal muscle FNDC5 gene expression and irisin release regulated by exercise and related to health?

Recently, contradictory findings have been reported concerning the function of irisin and its precursor gene, skeletal muscle FNDC5, in energy homeostasis, and the associated regulatory role of exercise and PGC-1α. We therefore evaluated whether muscle FNDC5 mRNA and serum irisin are exercise responsive and whether PGC-1α expression is associated with FNDC5 expression. The male subjects in the study performed single exercises: (1) 1 h low-intensity aerobic exercise (AE) (middle-aged, n = 17), (2) a heavy-intensity resistance exercise (RE) bout (young n = 10, older n = 11) (27 vs. 62 years), (3) long-term 21 weeks endurance exercise (EE) training alone (twice a week, middle-aged, n = 9), or (4) combined EE and RE training (both twice a week, middle-aged, n = 9). Skeletal muscle mRNA expression was analysed by quantitative PCR and serum irisin by ELISA. No significant changes were observed in skeletal muscle PGC-1α, FNDC5 and serum irisin after AE, EE training or combined EE + RE training. However, a single RE bout increased PGC-1α by 4-fold in young and by 2-fold in older men, while FNDC5 mRNA only increased in young men post-RE, by 1.4-fold. Changes in PGC-1α or serum irisin were not consistently accompanied by changes in FNDC5. In conclusion, for the most part, neither longer-term nor single exercise markedly increases skeletal muscle FNDC5 expression or serum irisin. Therefore their changes in response to exercise are probably random and not consistent excluding the confirmation of any definitive link between exercise and FNDC5 expression and irisin release in humans. Moreover, irisin and FNDC5 were not associated with glucose tolerance and being overweight, or with metabolic disturbances, respectively. Finally, factor(s) other than PGC-1α and transcription may regulate FNDC5 expression.

Exercise precision medicine for type 2 diabetes: Targeted benefit or risk?

Concurrent exercise and metformin administration may reduce the acute and chronic effects of exercise on glucose metabolism in the patients with type 2 diabetes (T2D). However, several studies suggest that combing metformin and exercise treatment may have neither additive effect nor even cause adverse effects in T2D patients. This case report aimed to highlight the challenges associated with prescribing exercise to type 2 diabetes patients undergoing metformin treatment. A 67-years old woman was followed-up for five months, including assessment of the acute and chronic glucose and lactate metabolism induced by concomitant exercise and metformin. The findings were four-fold: 1) During a high-intensity interval training bout, blood glucose systematically decreased, while blood lactate concentrations fluctuated randomly; 2) Basal blood lactate levels were well above 2 mmol/L on days with medication only; 3) Combined exercise and metformin administration induced additive effects on the normalization of glucose and 4) high levels of physical activity had a positive impact on the continuous glucose fluctuations, while decreased levels of physical activity induced a large fluctuation of glucose due to home confinement of an infectious disease caused by the SARS-CoV-2 virus. Our findings showed that when combined with exercise and metformin treatment for T2D patients, exercise may contribute to improving glycemic control while metformin may elevate lactate levels in the long term. The observed results underline the need to prescribe exercise and monitor lactate levels for reducing possible risks associated with metformin treatment and reinforce the importance of tailoring exercise therapy.

Body composition in male lifelong trained strength, sprint and endurance athletes and healthy age-matched controls.

Introduction: Aging involves many physiological processes that lead to decreases in muscle mass and increases in fat mass. While regular exercise can counteract such negative body composition outcomes, masters athletes maintain high levels of exercise throughout their lives. This provides a unique model to assess the impact of inherent aging. The present study compared lean mass and fat mass in young and masters athletes from different sports to age-matched non-athletic individuals. Methods: Participants included young (20-39 years, n = 109) and older (70-89 years, n = 147) competitive male athletes, and 147 healthy age-matched controls (young = 53, older = 94 males). Athletes were separated into strength (e.g., weightlifters, powerlifters), sprint (e.g., sprint runners, jumpers) and endurance (e.g., long-distance runners, cross-country skiers) athletic disciplines. Body composition was assessed by dual-energy x-ray absorptiometry (DXA). Upper and lower limb lean mass was combined for appendicular lean mass as well as appendicular lean mass index (ALMI; kg/m2). Individuals' scores were assessed against established cut-offs for low muscle mass, obesity, and sarcopenic obesity to determine prevalence in each group. Results: ALMI was greater in young strength (0.81-2.36 kg/m2, ∼15% and 1.24-2.74 kg/m2, ∼19%) and sprint (95% CI = 0.51-1.61 kg/m2, ∼11% and 0.96-1.97 kg/m2, ∼15%) athletes than in endurance and controls, respectively (all P < 0.001). In masters athletes, only strength athletes had greater ALMI than endurance athletes, but both older strength and sprint athletes had greater ALMI than older controls (0.42-1.27 kg/m2, ∼9% and 0.73-1.67 kg/m2, ∼13%, respectively, both P < 0.001). Fat mass was significantly lower in sprint and endurance athletes compared to strength athletes and controls in both age-groups. Sarcopenic obesity was identified in one young (2%) and eighteen (19%) older controls, while only two older endurance athletes (3%) and one older strength athlete (2%) were identified. Discussion: Lifelong competitive sport participation leads to lower prevalence of sarcopenic obesity than a recreationally active lifestyle. This is achieved in strength athletes by emphasizing muscle mass, while sprint and endurance athletes demonstrate low fat mass levels. However, all older athlete groups showed higher fat mass than the young groups, suggesting that exercise alone may not be sufficient to manage fat mass.

Bidirectional associations between adiposity and physical activity: a longitudinal study from pre-puberty to early adulthood.

Objective: This study aimed to investigate directional influences in the association between adiposity and physical activity (PA) from pre-puberty to early adulthood. Methods: In the Calex-study, height, weight, body fat and leisure-time physical activity (LTPA) were measured at age11.2-years, 13.2-years and 18.3-years in 396 Finnish girls. Body fat was measured by dual-energy X-ray absorptiometry, calculating fat mass index (FMI) as total fat mass in kilograms divided by height in meters squared. LTPA level was evaluated using a physical activity questionnaire. In the European Youth Heart Study (EYHS), height, weight and habitual PA were measured at age 9.6-years, 15.7-years and 21.8-years in 399 Danish boys and girls. Habitual PA and sedentary behaviour were assessed with an accelerometer. Directional influences of adiposity and PA were examined using a bivariate cross-lagged path panel model. Results: The temporal stability of BMI from pre-puberty to early adulthood was higher than the temporal stability of PA or physical inactivity over the same time period both in girls and boys. In the Calex-study, BMI and FMI at age 11.2-years were both directly associated with LTPA at age 13.2-years (ß = 0.167, p = 0.005 and ß = 0.167, p = 0.005, respectively), whereas FMI at age 13.2-years showed an inverse association with LTPA at age 18.3-years (ß = - 0.187, p = 0.048). However, earlier LTPA level was not associated with subsequent BMI or FMI. In the EYHS, no directional association was found for physical inactivity, light-, moderate-, and vigorous-PA with BMI during the follow-up in girls. In boys, BMI at age 15.7-years was directly associated with moderate PA (ß = 0.301, p = 0.017) at age 21.8-years, while vigorous PA at age 15.7-years showed inverse associations with BMI at age 21.8-years (ß = - 0.185, p = 0.023). Conclusion: Our study indicates that previous fatness level is a much stronger predictor of future fatness than level of leisure-time or habitual physical activity during adolescence. The directional associations between adiposity and physical activity are not clear during adolescence, and may differ between boys and girls depending on pubertal status.