| 1. |
- Craddock, Nick, et al.
(författare)
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Genome-wide association study of CNVs in 16,000 cases of eight common diseases and 3,000 shared controls
- 2010
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 464:7289, s. 713-720
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Tidskriftsartikel (refereegranskat)abstract
- Copy number variants (CNVs) account for a major proportion of human genetic polymorphism and have been predicted to have an important role in genetic susceptibility to common disease. To address this we undertook a large, direct genome-wide study of association between CNVs and eight common human diseases. Using a purpose-designed array we typed,19,000 individuals into distinct copy-number classes at 3,432 polymorphic CNVs, including an estimated similar to 50% of all common CNVs larger than 500 base pairs. We identified several biological artefacts that lead to false-positive associations, including systematic CNV differences between DNAs derived from blood and cell lines. Association testing and follow-up replication analyses confirmed three loci where CNVs were associated with disease-IRGM for Crohn's disease, HLA for Crohn's disease, rheumatoid arthritis and type 1 diabetes, and TSPAN8 for type 2 diabetes-although in each case the locus had previously been identified in single nucleotide polymorphism (SNP)-based studies, reflecting our observation that most common CNVs that are well-typed on our array are well tagged by SNPs and so have been indirectly explored through SNP studies. We conclude that common CNVs that can be typed on existing platforms are unlikely to contribute greatly to the genetic basis of common human diseases.
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| 2. |
- Bauer, Juergen M., et al.
(författare)
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Effects of a Vitamin D and Leucine-Enriched Whey Protein Nutritional Supplement on Measures of Sarcopenia in Older Adults, the PROVIDE Study : A Randomized, Double-Blind, Placebo-Controlled Trial
- 2015
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Ingår i: Journal of the American Medical Directors Association. - : Elsevier BV. - 1525-8610 .- 1538-9375. ; 16:9, s. 740-747
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Tidskriftsartikel (refereegranskat)abstract
- Background: Age-related losses of muscle mass, strength, and function (sarcopenia) pose significant threats to physical performance, independence, and quality of life. Nutritional supplementation could positively influence aspects of sarcopenia and thereby prevent mobility disability. Objective: To test the hypothesis that a specific oral nutritional supplement can result in improvements in measures of sarcopenia. Design: A multicenter, randomized, controlled, double-blind, 2 parallel-group trial among 380 sarcopenic primarily independent-living older adults with Short Physical Performance Battery (SPPB; 0-12) scores between 4 and 9, and a low skeletal muscle mass index. The active group (n = 184) received a vitamin D and leucine-enriched whey protein nutritional supplement to consume twice daily for 13 weeks. The control group (n = 196) received an iso-caloric control product to consume twice daily for 13 weeks. Primary outcomes of handgrip strength and SPPB score, and secondary outcomes of chair-stand test, gait speed, balance score, and appendicular muscle mass (by DXA) were measured at baseline, week 7, and week 13 of the intervention. Results: Handgrip strength and SPPB improved in both groups without significant between-group differences. The active group improved more in the chair-stand test compared with the control group, between-group effect (95% confidence interval): -1.01 seconds (-1.77 to -0.19), P = .018. The active group gained more appendicular muscle mass than the control group, between-group effect: 0.17 kg (0.004-0.338), P = .045. Conclusions: This 13-week intervention of a vitamin D and leucine-enriched whey protein oral nutritional supplement resulted in improvements in muscle mass and lower-extremity function among sarcopenic older adults. This study shows proof-of-principle that specific nutritional supplementation alone might benefit geriatric patients, especially relevant for those who are unable to exercise. These results warrant further investigations into the role of a specific nutritional supplement as part of a multimodal approach to prevent adverse outcomes among older adults at risk for disability.
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| 3. |
- Hill, Tom R., et al.
(författare)
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A Vitamin D, Calcium and Leucine-Enriched Whey Protein Nutritional Supplement Improves Measures of Bone Health in Sarcopenic Non-Malnourished Older Adults : The PROVIDE Study
- 2019
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Ingår i: Calcified Tissue International. - : Springer Science and Business Media LLC. - 0171-967X .- 1432-0827. ; 105:4, s. 383-391
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Tidskriftsartikel (refereegranskat)abstract
- Alterations in musculoskeletal health with advanced age contribute to sarcopenia and decline in bone mineral density (BMD) and bone strength. This decline may be modifiable via dietary supplementation. To test the hypothesis that a specific oral nutritional supplement can result in improvements in measures of bone health. Participants (n 380) were participants of the PROVIDE study, a 13-week, multicenter, randomized, controlled, double-blind, 2 parallel-group study among non-malnourished older participants (≥ 65 years) with sarcopenia [determined by Short Physical Performance Battery (SPPB; 0-12) scores between 4 and 9, and a low skeletal muscle mass index (SMI; skeletal muscle mass/BW × 100) ≤ 37% in men and ≤ 28% in women using bioelectric impedance analysis] Supplementation of a vitamin D, calcium and leucine-enriched whey protein drink that comprises a full range of micronutrients (active; 2/day) was compared with an iso-caloric control. Serum 25-hydroxyvitamin D [25(OH)D], parathyroid hormone (PTH), biochemical markers of bone formation (osteocalcin; OC, procollagen type 1 amino-terminal propeptide; P1NP) and resorption (carboxy-terminal collagen crosslinks; CTX), insulin like growth factor 1 (IGF-1) and total-body BMD were analysed pre- and post-intervention. Serum 25(OH)D concentrations increased from 51.1 ± 22.9 nmol/L (mean ± SD) to 78.9 ± 21.1 nmol/L in the active group (p < 0.001 vs. control). Serum PTH showed a significant treatment difference (p < 0.001) with a decline in the active group, and increase in the control group. Serum IGF-1 increased in the active group (p < 0.001 vs. control). Serum CTX showed a greater decline in the active group (p = 0.001 vs. control). There were no significant differences in serum OC or P1NP between groups during the intervention. Total body BMD showed a small (0.02 g/cm2; ~ 2%) but significant increase in the active group after supplementation (p = 0.033 vs. control). Consuming a vitamin D, calcium and leucine-enriched whey protein supplement for 13 weeks improved 25(OH)D, suppressed PTH and had small but positive effects on BMD, indicative of improved bone health, in sarcopenic non-malnourished older adults.
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| 4. |
- Verlaan, Sjors, et al.
(författare)
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Nutritional status, body composition, and quality of life in community-dwelling sarcopenic and non-sarcopenic older adults : A case-control study
- 2017
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Ingår i: Clinical Nutrition. - : Elsevier BV. - 0261-5614 .- 1532-1983. ; 36:1, s. 267-274
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND & AIM: Sarcopenia, the age-related decrease in muscle mass, strength, and function, is a main cause of reduced mobility, increased falls, fractures and nursing home admissions. Cross-sectional and prospective studies indicate that sarcopenia may be influenced in part by reversible factors like nutritional intake. The aim of this study was to compare functional and nutritional status, body composition, and quality of life of older adults between age and sex-matched older adults with and without sarcopenia.METHODS: In a multi-centre setting, non-sarcopenic older adults (n = 66, mean ± SD: 71 ± 4 y), i.e. Short Physical Performance Battery (SPPB): 11-12 and normal skeletal muscle mass index, were recruited to match 1:1 by age and sex to previously recruited adults with sarcopenia: SPPB 4-9 and low skeletal muscle mass index. Health-related quality of life, self-reported physical activity levels and dietary intakes were measured using the EQ-5D scale and index, Physical Activity Scale for the Elderly (PASE), and 3-day prospective diet records, respectively. Concentrations of 25-OH-vitamin D, α-tocopherol (adjusted for cholesterol), folate, and vitamin B-12 were assessed in serum samples.RESULTS: In addition to the defined components of sarcopenia, i.e. muscle mass, strength and function, reported physical activity levels and health-related quality of life were lower in the sarcopenic adults (p < 0.001). For similar energy intakes (mean ± SD: sarcopenic, 1710 ± 418; non-sarcopenic, 1745 ± 513, p = 0.50), the sarcopenic group consumed less protein/kg (-6%), vitamin D (-38%), vitamin B-12 (-22%), magnesium (-6%), phosphorus (-5%), and selenium (-2%) (all p < 0.05) compared to the non-sarcopenic controls. The serum concentration of vitamin B-12 was 15% lower in the sarcopenic group (p = 0.015), and all other nutrient concentrations were similar between groups.CONCLUSIONS: In non-malnourished older adults with and without sarcopenia, we observed that sarcopenia substantially impacted self-reported quality of life and physical activity levels. Differences in nutrient concentrations and dietary intakes were identified, which might be related to the differences in muscle mass, strength and function between the two groups. This study provides information to help strengthen the characterization of this geriatric syndrome sarcopenia and indicates potential target areas for nutritional interventions.
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| 5. |
- Verlaan, Sjors, et al.
(författare)
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Sufficient levels of 25-hydroxyvitamin D and protein intake required to increase muscle mass in sarcopenic older adults - The PROVIDE study
- 2018
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Ingår i: Clinical Nutrition. - : Elsevier. - 0261-5614 .- 1532-1983. ; 37:2, s. 551-557
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Tidskriftsartikel (refereegranskat)abstract
- Background: Inadequate nutritional intake and altered response of aging muscles to anabolic stimuli from nutrients contribute to the development of sarcopenia. Nutritional interventions show inconsistent results in sarcopenic older adults, which might be influenced by their basal nutritional status. Objective: To test if baseline serum 25-hydroxyvitamin D (25(OH)D) concentrations and dietary protein intake influenced changes in muscle mass and function in older adults who received nutritional intervention. Methods and design: Post-hoc analysis was performed in the PROVIDE study that was a randomized controlled, double blind trial among 380 sarcopenic older adults. This study showed that those who received a vitamin D and leucine-enriched whey protein medical nutrition drink for 13 weeks gained more appendicular muscle mass (aMM), and improved lower-extremity function as assessed by the chair stand test compared with controls. To define low and high groups, a baseline serum concentration of 50 nmol/L 25(OH)D and baseline dietary protein intake of 1.0 g/kg/d were used as cut offs. Results: At baseline, participants with lower 25(OH)D concentrations showed lower muscle mass, strength and function compared with participants with a high 25(OH)D, while the group with lower protein intake (g/kg/day) had more muscle mass at baseline compared with the participants with higher protein intake. Participants with higher baseline 25(OH)D concentrations and dietary protein intake had, independent of other determinants, greater gain in appendicular muscle mass, skeletal muscle index (aMM/h(2)), and relative appendicular muscle mass (aMM/body weight x 100%) in response to the nutritional intervention. There was no effect modification of baseline 25(OH)D status or protein intake on change in chair-stand test. Conclusions: Sufficient baseline levels of 25(OH)D and protein intake may be required to increase muscle mass as a result of intervention with a vitamin D and protein supplement in sarcopenic older adults. This suggests that current cut-offs in the recommendations for vitamin D and protein intake could be considered the "minimum" for adults with sarcopenia to respond adequately to nutrition strategies aimed at attenuating muscle loss. (C) 2017 The Author(s). Published by Elsevier Ltd.
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