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Carnosine supplementation improves glucose control in adults with pre-diabetes and type 2 diabetes: A randomised controlled trial.
Hariharan, R, Cameron, J, Menon, K, Mesinovic, J, Jansons, P, Scott, D, Lu, ZX, de Courten, M, Feehan, J, de Courten, B
Nutrition, metabolism, and cardiovascular diseases : NMCD. 2024;(2):485-496
Abstract
BACKGROUND AND AIMS Type 2 diabetes (T2DM) is a major cause of morbidity and mortality globally. Carnosine, a naturally occurring dipeptide, has anti-inflammatory, antioxidant, and anti-glycating effects, with preliminary evidence suggesting it may improve important chronic disease risk factors in adults with cardiometabolic conditions. METHODS AND RESULTS In this randomised controlled trial, 43 adults (30%F) living with prediabetes or T2DM consumed carnosine (2 g) or a matching placebo daily for 14 weeks to evaluate its effect on glucose metabolism assessed via a 2-h 75 g oral glucose tolerance test. Secondary outcomes included body composition analysis by dual energy x-ray absorptiometry (DEXA), calf muscle density by pQCT, and anthropometry. Carnosine supplementation decreased blood glucose at 90 min (-1.31 mmol/L; p = 0.02) and 120 min (-1.60 mmol/L, p = 0.02) and total glucose area under the curve (-3.30 mmol/L; p = 0.04) following an oral glucose tolerance test. There were no additional changes in secondary outcomes. The carnosine group results remained significant before and after adjustment for age, sex, and change in weight (all>0.05), and in further sensitivity analyses accounting for missing data. There were no significant changes in insulin levels. CONCLUSION This study provides preliminary support for larger trials evaluating carnosine as a potential treatment for prediabetes and the initial stages of T2DM. Likely mechanisms may include changes to hepatic glucose output explaining the observed reduction in blood glucose without changes in insulin secretion following carnosine supplementation.
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Vitamin D supplementation and exercise for improving physical function, body composition and metabolic health in overweight or obese older adults with vitamin D deficiency: a pilot randomized, double-blind, placebo-controlled trial.
Mesinovic, J, Rodriguez, AJ, Cervo, MM, Gandham, A, Xu, CLH, Glavas, C, de Courten, B, Zengin, A, Ebeling, PR, Scott, D
European journal of nutrition. 2023;62(2):951-964
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Overweight and obese older adults are at increased risk for vitamin D deficiency, which is associated with poor metabolic and musculoskeletal health, unfavourable body composition, and attenuated responses to exercise. The aim of this study was to determine whether, compared with placebo, vitamin D3 supplementation (4000 IU/day) taken prior to and during a 12-week exercise program improves physical function, body composition or metabolic health, in overweight or obese older adults with vitamin D deficiency. This study is a 24-week parallel-group, double-blind, placebo-controlled pilot randomised controlled trial. Fifty overweight or obese participants were enrolled for the study, and randomised to either 4000 IU/day of oral vitamin D3 or identical placebo. Results demonstrated that 4000 IU/day vitamin D3 supplementation: - did not affect gait speed when taken with or without exercise, - helped achieve optimal serum 25-hydroxyvitamin D levels and decreased waist circumference (compared with placebo) following multi-modal exercise. - taken alone without exercise reduced stair climb times. However, vitamin D3 supplementation did not have any beneficial effects on other biochemical, body composition or physical function parameters when taken alone or during exercise. Authors conclude that future studies should focus on populations with moderate or severe vitamin D deficiency as they are more likely to experience therapeutic benefits from vitamin D supplementation.
Abstract
PURPOSE Vitamin D supplementation may have non-skeletal health benefits and enhance exercise responsiveness, particularly in those with low vitamin D levels. We determined whether, compared with placebo, vitamin D supplementation taken prior to and during a 12-week exercise program improves physical function, body composition or metabolic health, in overweight and obese older adults with vitamin D deficiency. METHODS Fifty overweight or obese older adults (mean ± SD age: 60 ± 6 years; BMI 30.6 ± 5.7 kg/m2) with vitamin D deficiency (25-hydroxyvitamin D [25(OH)D] < 50 nmol/L) were recruited. Participants were randomly allocated to receive either vitamin D3 (4000 IU/day) or matching placebo for 24 weeks. Between weeks 12 and 24, all participants completed multi-modal exercise three days per week while continuing with vitamin D/placebo. Mean changes in physical function (primary outcome: gait speed), body composition and biochemical parameters at weeks 12 and 24 were compared between groups. RESULTS Vitamin D supplementation, with or without exercise, had no effect on gait speed. From baseline to week 12, vitamin D supplementation increased serum 25(OH)D levels (placebo: 2.5 ± 14.7 nmol/L; treatment: 43.4 ± 18.4 nmol/L; P < 0.001) and reduced stair climb times (placebo: 0.3 ± 1.0 s; treatment: - 0.2 ± 1.0 s; P = 0.046). From 12 to 24 weeks, vitamin D supplementation combined with exercise decreased waist circumference (placebo: 1.3 ± 7.3 cm; treatment: - 3.0 ± 6.1 cm; P = 0.02) and waist-to-hip ratio (placebo: 0.01 ± 0.05; treatment: - 0.03 ± 0.05; P = 0.01) relative to placebo. Vitamin D supplementation, with or without exercise, had no effect on other physical function, body composition or metabolic health outcomes. CONCLUSION Vitamin D supplementation had no effect on most physical function, body composition or metabolic health parameters when taken alone, or during exercise, in overweight or obese older adults with vitamin D deficiency. Vitamin D-related improvements in stair climb times and waist circumference suggest that future trials should explore the effects of vitamin D on muscle power, and its effects on body composition when combined with exercise, in populations with moderate or severe vitamin D deficiency.
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Type 2 Diabetes Mellitus and Sarcopenia as Comorbid Chronic Diseases in Older Adults: Established and Emerging Treatments and Therapies.
Mesinovic, J, Fyfe, JJ, Talevski, J, Wheeler, MJ, Leung, GKW, George, ES, Hunegnaw, MT, Glavas, C, Jansons, P, Daly, RM, et al
Diabetes & metabolism journal. 2023;(6):719-742
Abstract
Type 2 diabetes mellitus (T2DM) and sarcopenia (low skeletal muscle mass and function) share a bidirectional relationship. The prevalence of these diseases increases with age and they share common risk factors. Skeletal muscle fat infiltration, commonly referred to as myosteatosis, may be a major contributor to both T2DM and sarcopenia in older adults via independent effects on insulin resistance and muscle health. Many strategies to manage T2DM result in energy restriction and subsequent weight loss, and this can lead to significant declines in muscle mass in the absence of resistance exercise, which is also a first-line treatment for sarcopenia. In this review, we highlight recent evidence on established treatments and emerging therapies targeting weight loss and muscle mass and function improvements in older adults with, or at risk of, T2DM and/or sarcopenia. This includes dietary, physical activity and exercise interventions, new generation incretin-based agonists and myostatin-based antagonists, and endoscopic bariatric therapies. We also highlight how digital health technologies and health literacy interventions can increase uptake of, and adherence to, established and emerging treatments and therapies in older adults with T2DM and/or sarcopenia.
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Effects of Moderate- to High-Impact Exercise Training on Bone Structure Across the Lifespan: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
Ng, CA, Gandham, A, Mesinovic, J, Owen, PJ, Ebeling, PR, Scott, D
Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 2023;(11):1612-1634
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Moderate- to high-impact exercise improves bone mineral density (BMD) across the lifespan, but its effects on bone structure, which predicts fracture independent of areal BMD, are unclear. This systematic review and meta-analysis investigated effects of impact exercise on volumetric BMD (vBMD) and bone structure. Four databases (PubMed, Embase, SPORTDiscus, Web of Science) were searched up to March 2022 for randomized controlled trials (RCTs) investigating the effects of impact exercise, with ground reaction forces equal to or greater than running, compared with sham or habitual activity, on bone vBMD and structure. Bone variables were measured by quantitative computed tomography or magnetic resonance imaging at the tibia, radius, lumbar spine, and femur. Percentage changes in bone variables were compared among groups using mean differences (MD) and 95% confidence intervals (CI) calculated via random effects meta-analyses. Subgroup analyses were performed in children/adolescents (<18 years), adults (18-50 years), postmenopausal women, and older men. Twenty-eight RCTs (n = 2985) were included. Across all studies, impact exercise improved trabecular vBMD at the distal tibia (MD = 0.54% [95% CI 0.17, 0.90%]), total vBMD at the proximal femur (3.11% [1.07, 5.14%]), and cortical thickness at the mid/proximal radius (1.78% [0.21, 3.36%]). There was no effect on vBMD and bone structure at the distal radius, femoral shaft, or lumbar spine across all studies or in any subgroup. In adults, impact exercise decreased mid/proximal tibia cortical vBMD (-0.20% [-0.24, -0.15%]). In postmenopausal women, impact exercise improved distal tibia trabecular vBMD (0.79% [0.32, 1.25%]). There was no effect on bone parameters in children/adolescents in overall analyses, and there were insufficient studies in older men to perform meta-analyses. Impact exercise may have beneficial effects on bone structure and vBMD at various skeletal sites, but additional high-quality RCTs in different age and sex subgroups are needed to identify optimal exercise protocols for improving bone health across the lifespan. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
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Medication and bone health in multiple sclerosis: A systematic review and meta-analysis.
Cahyadi, M, Mesinovic, J, Chim, ST, Ebeling, P, Zengin, A, Grech, L
Journal of managed care & specialty pharmacy. 2023;(12):1331-1353
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BACKGROUND People with multiple sclerosis (MS) are often prescribed medications associated with adverse effects on bone health. However, it is unclear whether these medications incur decreases in areal bone mineral density (aBMD) and higher fracture risk in this population. OBJECTIVE To investigate the effects of commonly used medications on aBMD and fracture risk among people with MS. METHODS MEDLINE, Embase, Scopus, CINAHL, and Web of Science were searched from their inception until February 5, 2023. We included randomized controlled trials as well as cross-sectional, retrospective, and prospective studies investigating whether glucocorticoids, immunomodulators, antidepressants, anticonvulsants, anxiolytics, opioids, or antipsychotics influenced aBMD or fracture risk in people with MS. Data were pooled using random effects meta-analyses to determine hazard ratios (HRs) and 95% CIs. RESULTS We included 22 studies (n = 18,193). Six studies were included in the meta-analyses of glucocorticoid use and aBMD, whereas 2 studies were included in the medication use and fracture risk meta-analyses. No studies assessed the effect of antidepressants, anxiolytics, anticonvulsants, opioids, and antipsychotics on aBMD, and no studies assessed the effect of immunomodulators on fracture risk. Glucocorticoid use was significantly negatively associated with femoral neck aBMD (correlation = -0.21 [95% CI = -0.29 to -0.13]), but not with lumbar spine aBMD (correlation = -0.21 [95% CI = -0.50 to 0.12]). There were no differences in fracture risk between users of glucocorticoids (HR = 1.71 [95% CI = 0.04 to 76.47]), antidepressants (HR = 1.84 [95% CI = 0.09 to 38.49]), or anxiolytics (HR = 2.01 [95% CI = 0.06 to 64.22]), compared with nonusers. CONCLUSIONS The available evidence is insufficient to support a relationship between greater fracture risk for people with MS taking glucocorticoid, antidepressant, or anxiolytic medication, compared with nonusers, and it is unclear whether these medications are associated with bone loss in people with MS, beyond that in the general population. Additional high-quality studies with homogenous methodology exploring how medications influence aBMD and fracture risk in people with MS are required.
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The authors' reply: 'Comment on: "Effect of vitamin D monotherapy on indices of sarcopenia in community-dwelling older adults: a systematic review and meta-analysis" by Prokopidis et al.'.
Prokopidis, K, Giannos, P, Katsikas Triantafyllidis, K, Kechagias, KS, Mesinovic, J, Witard, OC, Scott, D
Journal of cachexia, sarcopenia and muscle. 2022;(6):2757-2758
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Effect of vitamin D monotherapy on indices of sarcopenia in community-dwelling older adults: a systematic review and meta-analysis.
Prokopidis, K, Giannos, P, Katsikas Triantafyllidis, K, Kechagias, KS, Mesinovic, J, Witard, OC, Scott, D
Journal of cachexia, sarcopenia and muscle. 2022;(3):1642-1652
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BACKGROUND Vitamin D supplementation is proposed as a potentially effective nutritional intervention to mitigate the risk of sarcopenia. The aim of this systematic review and meta-analysis was to investigate the impact of vitamin D supplementation monotherapy on indices of sarcopenia in community-dwelling older adults. METHODS A comprehensive search of the literature was conducted in PubMed, Web of Science, Scopus, and Cochrane Library. Eligible randomized controlled trials (RCTs) compared the effect of vitamin D supplementation (as monotherapy) with placebo on indices of sarcopenia in older (>50 years) adults. Using the random effects inverse-variance model, we calculated the mean difference (MD) in handgrip strength (HGS), short physical performance battery (SPPB), timed up and go (TUG), and appendicular lean mass (ALM) between groups. We also calculated the standardized mean difference (SMD) in general muscle strength and general physical performance (composite plot of all muscle strength and physical performance outcomes, respectively) between groups. RESULTS Ten RCTs were included in the meta-analysis. A significant decrease in SPPB scores was observed with vitamin D supplementation compared with placebo (MD: -0.23; 95% CI -0.40 to -0.06; I2 = 0%; P = 0.007). Vitamin D supplementation conferred no effect on HGS (MD: -0.07 kg; 95% CI -0.70 to 0.55; I2 = 51%, P = 0.82), TUG (MD: 0.07 s; 95% CI -0.08 to 0.22; I2 = 0%, P = 0.35), ALM (MD: 0.06 kg/m2 ; 95% CI: -0.32 to 0.44; I2 = 73%, P = 0.77), general muscle strength (SMD: -0.01; 95% CI -0.17 to 0.15; I2 = 42%, P = 0.90), or general physical performance (SMD: -0.02; 95% CI -0.23 to 0.18; I2 = 71%, P = 0.83). CONCLUSIONS Vitamin D supplementation did not improve any sarcopenia indices in community-dwelling older adults and may compromise some aspects of physical performance. Future studies are warranted to investigate the impact of vitamin D supplementation on individual indices of SPPB, including mobility and balance, in older adults.
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Body composition changes at 12 months following different surgical weight loss interventions in adults with obesity: A systematic review and meta-analysis of randomized control trials.
Sylivris, A, Mesinovic, J, Scott, D, Jansons, P
Obesity reviews : an official journal of the International Association for the Study of Obesity. 2022;(7):e13442
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To determine relative lean mass and fat mass changes in adults with obesity following surgical weight loss interventions, a systematic review and meta-analysis was conducted. The Cochrane Central Register of Controlled Trials, PubMed, Web of Science, EMBASE, and Scopus were screened for eligible studies. Inclusion criteria included randomized controlled trials (RCTs) performed in populations with obesity (body mass index ≥30 kg/m2 ) aged over 18 years, who underwent any type of bariatric surgery and reported body composition measures via dual-energy X-ray absorptiometry or bio-electrical impedance analysis. Authors conducted full text screening and determined that there were six RCTs eligible for inclusion, with data extracted at 12 months post-surgery. Meta-analysis revealed that, relative to gastric banding, Roux-en-Y gastric bypass (RYGB) led to greater total body mass loss (mean difference [MD]: -9.33 kg [95% CI: -12.10, -6.56]) and greater fat mass loss (MD: -8.86 kg [95% CI: -11.80, -5.93], but similar lean mass loss (MD: -0.55 kg [95% CI: -3.82, 2.71]. RYGB also led to similar changes in total body mass, fat mass, and lean mass compared with sleeve gastrectomy. RYGB results in greater 12-month weight and fat loss, but similar changes in lean mass, compared with gastric banding. Further RCTs comparing body composition changes following different bariatric surgery procedures are required.
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Falls, fractures, and areal bone mineral density in older adults with sarcopenic obesity: A systematic review and meta-analysis.
Gandham, A, Mesinovic, J, Jansons, P, Zengin, A, Bonham, MP, Ebeling, PR, Scott, D
Obesity reviews : an official journal of the International Association for the Study of Obesity. 2021;(5):e13187
Abstract
Sarcopenia and obesity are common conditions in older adults that may have differing effects on falls and fracture risk. This systematic review and meta-analysis aimed to determine whether older adults with sarcopenic obesity have increased risk of falls and fractures or lower bone mass compared with older adults with sarcopenia, obesity, or neither condition. Twenty-six studies (n = 37,124) were included in the systematic review and 17 (n = 31,540) were included in the meta-analysis. Older adults with sarcopenic obesity had lower femoral neck areal bone mineral density (aBMD) compared with those with obesity alone but had higher femoral neck aBMD compared with counterparts with sarcopenia alone (both P < 0.05). Older adults with sarcopenic obesity had higher nonvertebral fracture rates (incidence rate ratio: 1.88; 95% confidence intervals: 1.09, 3.23; based on two studies), compared with those with sarcopenia alone, and also had higher falls risk compared with controls (risk ratio: 1.30; 95% confidence intervals: 1.10, 1.54) and obesity alone (risk ratio: 1.17; 95% confidence intervals: 1.01, 1.36). In conclusion, this systematic review and meta-analysis has demonstrated that older adults with sarcopenic obesity are at increased risk of adverse musculoskeletal outcomes compared with individuals with obesity, sarcopenia, or neither condition. These data support the need for developing interventions to improve bone health and physical function in this population.
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The effects of acute exercise on bone turnover markers in middle-aged and older adults: A systematic review.
Smith, C, Tacey, A, Mesinovic, J, Scott, D, Lin, X, Brennan-Speranza, TC, Lewis, JR, Duque, G, Levinger, I
Bone. 2021;:115766
Abstract
BACKGROUND Bone turnover is the cellular machinery responsible for bone integrity and strength and, in the clinical setting, it is assessed using bone turnover markers (BTMs). Acute exercise can induce mechanical stress on bone which is needed for bone remodelling, but to date, there are conflicting results in regards to the effects of varying mechanical stimuli on BTMs. OBJECTIVES This systematic review examines the effects of acute aerobic, resistance and impact exercises on BTMs in middle and older-aged adults and examines whether the responses are determined by the exercise mode, intensity, age and sex. METHODS We searched PubMed, SCOPUS, Web of Science and EMBASE up to 22nd April 2020. Eligibility criteria included randomised controlled trials (RCTs) and single-arm studies that included middle-aged (50 to 65 years) and older adults (>65 years) and, a single-bout, acute-exercise (aerobic, resistance, impact) intervention with measurement of BTMs. PROSPERO registration number CRD42020145359. RESULTS Thirteen studies were included; 8 in middle-aged (n = 275, 212 women/63 men, mean age = 57.9 ± 1.5 years) and 5 in older adults (n = 93, 50 women/43 men, mean age = 68.2 ± 2.2 years). Eleven studies included aerobic exercise (AE, 7 middle-aged/4 older adults), and two included resistance exercise (RE, both middle-aged). AE significantly increased C-terminal telopeptide (CTX), alkaline phosphatase (ALP) and bone-ALP in middle-aged and older adults. AE also significantly increased total osteocalcin (tOC) in middle-aged men and Procollagen I Carboxyterminal Propeptide and Cross-Linked Carboxyterminal Telopeptide of Type I Collagen in older women. RE alone decreased ALP in older adults. In middle-aged adults, RE with impact had no effect on tOC or BALP, but significantly decreased CTX. Impact (jumping) exercise alone increased Procollagen Type 1 N Propeptide and tOC in middle-aged women. CONCLUSION Acute exercise is an effective tool to modify BTMs, however, the response appears to be exercise modality-, intensity-, age- and sex-specific. There is further need for higher quality and larger RCTs in this area.