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  • 1
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    Changes in systemic GDF15 across the adult lifespan and their impact on maximal muscle power: the Copenhagen Sarcopenia Study
    Wiley ; 2021
    In:  Journal of Cachexia, Sarcopenia and Muscle Vol. 12, No. 6 ( 2021-12), p. 1418-1427
    Details
    In: Journal of Cachexia, Sarcopenia and Muscle, Wiley, Vol. 12, No. 6 ( 2021-12), p. 1418-1427
    Abstract: Although growth differentiation factor 15 (GDF15) is known to increase with disease and is associated with low physical performance, the role of GDF15 in normal ageing is still not fully understood. Specifically, the influence of circulating GDF15 on impairments in maximal muscle power (a major contributor to functional limitations) and the underlying components has not been investigated. Methods Data from 1305 healthy women and men aged 20 to 93 years from The Copenhagen Sarcopenia Study were analysed. Circulating levels of GDF15 and markers of inflammation (tumor necrosis factor‐alpha, interleukin‐6, and high‐sensitivity C‐reactive protein) were measured by ELISA (R & D Systems) and multiplex bead‐based immunoassays (Bio‐Rad). Relative (normalized to body mass), allometric (normalized to height squared), and specific (normalized to leg muscle mass) muscle power were assessed by the Nottingham power rig [leg extension power (LEP)] and the 30 s sit‐to‐stand (STS) muscle power test. Total body fat, visceral fat, and leg lean mass were assessed by dual energy X‐ray absorptiometry. Leg skeletal muscle index was measured as leg lean mass normalized to body height squared. Results Systemic levels of GDF15 increased progressively as a function of age in women (1.1 ± 0.4 pg·mL −1 ·year −1 ) and men (3.3 ± 0.6 pg·mL −1 ·year −1 ) (both P   〈  0.05). Notably, GDF15 increased at a faster rate from the age of 65 years in women (11.5 ± 1.2 pg·mL −1 ·year −1 , P   〈  0.05) and 70 years in men (19.3 ± 2.3 pg·mL −1 ·year −1 , P   〈  0.05), resulting in higher GDF15 levels in men compared with women above the age of 65 years ( P   〈  0.05). Independently of age and circulatory markers of inflammation, GDF15 was negatively correlated to relative STS power ( P   〈  0.05) but not LEP, in both women and men. These findings were mainly explained by negative associations of GDF15 with specific STS power in women and men (both P   〈  0.05). Conclusions A J‐shaped relationship between age and systemic GDF15 was observed, with men at older age showing steeper increases and elevated GDF15 levels compared with women. Importantly, circulating GDF15 was independently and negatively associated with relative STS power, supporting the potential role of GDF15 as a sensitive biomarker of frailty in older people.
    Type of Medium: Online Resource
    ISSN: 2190-5991 , 2190-6009
    URL: Issue
    URL: Article
    DOI: 10.1002/jcsm.v12.6
    DOI: 10.1002/jcsm.12823
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 2586864-0
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  • 2
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    Multiparametric magnetic resonance imaging: A robust tool to test pathogenesis and pathophysiology behind nephropathy in humans
    Wiley ; 2023
    In:  Clinical Physiology and Functional Imaging Vol. 43, No. 4 ( 2023-07), p. 207-210
    Details
    In: Clinical Physiology and Functional Imaging, Wiley, Vol. 43, No. 4 ( 2023-07), p. 207-210
    Abstract: Chronic kidney disease (CKD) is a major population disease. In diabetes as well as hypertension, kidney disease is one of the most serious complications. Recent research has demonstrated that chronic hypoxia is a key actor in the pathogenesis of CKD. In this review, we focus on how functional magnetic resonance imaging (fMRI) techniques can shed light on pathogenetic mechanisms and monitor new treatments aimed at preventing or ameliorating the disease. Multiparametric MRI techniques can measure changes in renal artery flow, tissue perfusion, and oxygenation repetitively over short time periods, enabling high time resolution. Furthermore, renal fibrosis can be quantified noninvasively by MRI diffusion tensor imaging, and techniques are upcoming to measure renal oxygen consumption. These techniques are all radiation and contrast‐free. We briefly present data, demonstrating that fMRI techniques can play a major role in future research in CKD, and possibly also in daily clinical practice.
    Type of Medium: Online Resource
    ISSN: 1475-0961 , 1475-097X
    URL: Issue
    URL: Article
    DOI: 10.1111/cpf.v43.4
    DOI: 10.1111/cpf.12818
    Language: English
    Publisher: Wiley
    Publication Date: 2023
    detail.hit.zdb_id: 2004626-1
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  • 3
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    TRY plant trait database – enhanced coverage and open access
    Wiley ; 2020
    In:  Global Change Biology Vol. 26, No. 1 ( 2020-01), p. 119-188
    Details
    In: Global Change Biology, Wiley, Vol. 26, No. 1 ( 2020-01), p. 119-188
    Abstract: Plant traits—the morphological, anatomical, physiological, biochemical and phenological characteristics of plants—determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait‐based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits—almost complete coverage for ‘plant growth form’. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait–environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives.
    Type of Medium: Online Resource
    ISSN: 1354-1013 , 1365-2486
    URL: Issue
    URL: Article
    DOI: 10.1111/gcb.v26.1
    DOI: 10.1111/gcb.14904
    Language: English
    Publisher: Wiley
    Publication Date: 2020
    detail.hit.zdb_id: 2020313-5
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  • 4
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    Evaluation of the effects of ezetimibe on albuminuria and kidney fat in individuals with type 2 diabetes and chronic kidney disease
    Wiley ; 2023
    In:  Diabetes, Obesity and Metabolism Vol. 25, No. 9 ( 2023-09), p. 2605-2615
    Details
    In: Diabetes, Obesity and Metabolism, Wiley, Vol. 25, No. 9 ( 2023-09), p. 2605-2615
    Abstract: To investigate the effects of ezetimibe on the urine albumin creatinine ratio (UACR) and kidney parenchyma fat content (kidney‐PF) in individuals with type 2 diabetes (T2D) and early chronic kidney disease. Materials and Methods A randomized, double‐blind, placebo‐controlled study of ezetimibe 10 mg once daily for 16 weeks in individuals with T2D and a UACR of 30 mg/g or higher was conducted. Kidney‐PF was assessed with magnetic resonance spectroscopy. Geometric mean changes from baseline were derived from linear regressions. Results A total of 49 participants were randomized to ezetimibe ( n  = 25) or placebo ( n  = 24). Overall, mean ± standard deviation age was 67 ± 7 years, body mass index was 31 ± 4 kg/m 2 and the proportion of men was 84%. The mean estimated glomerular filtration rate was 76 ± 22 mL/min/1.73m 2 and median (first‐third quartile) UACR was 95 (41‐297) mg/g. Median kidney‐PF was 1.0% (0.3%‐2.1%). Compared with placebo, ezetimibe did not significantly reduce UACR (mean [95% confidence interval] change: −3% [−28%‐31%] ) or kidney‐PF (mean change: −38% [−66%‐14%]). In participants with baseline kidney‐PF above the median, ezetimibe reduced kidney‐PF significantly (mean change: −60% [−84%‐−3%] ) compared with placebo, while the reduction in UACR was not significant (mean change: −28% [−54%‐15%]). Conclusions Ezetimibe did not reduce the UACR or kidney‐PF on top of modern T2D management. However, kidney‐PF was reduced with ezetimibe in participants with high baseline kidney‐PF.
    Type of Medium: Online Resource
    ISSN: 1462-8902 , 1463-1326
    URL: Issue
    URL: Article
    DOI: 10.1111/dom.v25.9
    DOI: 10.1111/dom.15146
    Language: English
    Publisher: Wiley
    Publication Date: 2023
    detail.hit.zdb_id: 2004918-3
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  • 5
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    Episodic and Chronic Cluster Headache: Differences in Family History, Traumatic Head Injury, and Chronorisk
    Wiley ; 2020
    In:  Headache: The Journal of Head and Face Pain Vol. 60, No. 3 ( 2020-03), p. 515-525
    Details
    In: Headache: The Journal of Head and Face Pain, Wiley, Vol. 60, No. 3 ( 2020-03), p. 515-525
    Abstract: The diagnostic criteria of episodic and chronic cluster headache (cCH) were recently modified, yet pathophysiological differences between the two are still unclear. The aim of this cross‐sectional study is to identify and characterize other differences between episodic and cCH. Methods Data from a retrospective, questionnaire‐ and interview‐based study were analyzed with a focus on associated factors including traumatic head injury (THI), familial history, and change of phenotype. Attack patterns were analyzed using Gaussian and spectral modeling. Results 400 patients and 200 controls participated. A positive family history was more prevalent in chronic than episodic cluster headache (eCH) (34/146 (23%) vs 33/253 (13%), respectively, P  = .008). A history of THI was more common in patients than controls (173/400 (43%) vs 51/200 (26%), respectively, P   〈  .0001) and in chronic compared to eCH (77/146 (53%) vs 96/253 (37%), respectively, P  = .004). Patients with a positive family history had a unique diurnal attack pattern with twice the risk of nocturnal attacks as patients who did not report family history. Patients reporting phenotype change had a chronobiological fingerprint similar to the phenotype they had experienced a transition into. A higher attack frequency in chronic patients was the only difference in symptom manifestation across all analyzed subgroups of patients. Conclusions cCH is associated with a positive family history and THI. In familial CH, a peak in nocturnal chronorisk may implicate genes involved in diurnal‐, sleep‐ and homeostatic regulation. The stereotypical nature of the CH attacks themselves is confirmed and differences between subgroups should be sought in other characteristics.
    Type of Medium: Online Resource
    ISSN: 0017-8748 , 1526-4610
    URL: Issue
    URL: Article
    DOI: 10.1111/head.v60.3
    DOI: 10.1111/head.13730
    Language: English
    Publisher: Wiley
    Publication Date: 2020
    detail.hit.zdb_id: 2020316-0
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  • 6
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    Age‐ and sex‐specific changes in visceral fat mass throughout the life‐span
    Wiley ; 2023
    In:  Obesity Vol. 31, No. 7 ( 2023-07), p. 1953-1961
    Details
    In: Obesity, Wiley, Vol. 31, No. 7 ( 2023-07), p. 1953-1961
    Abstract: Visceral fat mass (VFM) is a risk factor for cardiovascular diseases, type 2 diabetes mellitus, and malignancy; however, normative data are limited. The aim of this study was to provide reference data for VFM from a large, apparently healthy Caucasian adult population. Methods Volunteers aged 20 to 93 years from the Copenhagen City Heart Study had a standardized whole‐body dual‐energy x‐ray absorptiometry scan performed using the iDXA (GE Lunar). Total and regional fat mass was measured. VFM was quantified using the CoreScan application. Results A total of 1277 participants were included (708 women, mean [SD], age: 56  [19]  years, height: 1.66 [0.07] m, BMI: 24.64 [4.31]  kg/m 2 ; and 569 men, age: 57 [18] years, height: 1.80 [0.07]  m, BMI: 25.99 [3.86] kg/m 2 ). Increased VFM was positively correlated with age in both sexes. Men had significantly higher VFM in mass (g) after normalization to body size (m 2 ) and total fat mass ( p   〈  0.001). VFM increased more in women with high values of the android/gynoid ratio. Conclusions Normative data of VFM from a large, healthy Danish cohort aged 20 to 93 years are presented. VFM increased with age in both sexes, but men had significantly higher VFM compared with women with the same BMI, body fat percentage, and fat mass index.
    Type of Medium: Online Resource
    ISSN: 1930-7381 , 1930-739X
    URL: Issue
    URL: Article
    DOI: 10.1002/oby.v31.7
    DOI: 10.1002/oby.23779
    Language: English
    Publisher: Wiley
    Publication Date: 2023
    detail.hit.zdb_id: 2027211-X
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  • 7
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    Human renal response to furosemide: Simultaneous oxygenation and perfusion measurements in cortex and medulla
    Wiley ; 2019
    In:  Acta Physiologica Vol. 227, No. 1 ( 2019-09)
    Details
    In: Acta Physiologica, Wiley, Vol. 227, No. 1 ( 2019-09)
    Abstract: Disturbances of renal medullary perfusion and metabolism have been implicated in the pathogenesis of kidney disease and hypertension. Furosemide, a loop diuretic, is widely used to prevent renal medullary hypoxia in acute kidney disease by uncoupling sodium metabolism, but its effects on medullary perfusion in humans are unknown. We performed quantitative imaging of both renal perfusion and oxygenation using Magnetic Resonance Imaging (MRI) before and during furosemide. Based on the literature, we hypothesized that furosemide would increase medullary oxygenation, decrease medullary perfusion, but cause minor changes ( 〈 10%) in renal artery flow (RAF). Methods Interleaved measurements of RAF, oxygenation ( T 2 *) and perfusion by arterial spin labelling in the renal cortex and medulla of 9 healthy subjects were acquired before and after an injection of 20 mg furosemide. They were preceded by measurements made during isometric exercise (5 minutes handgrip bouts), which are known to induce changes in renal hemodynamics, that served as a control for the sensitivity of the hemodynamic MRI measurements. Experiments were repeated on a second day to establish that the measurements and the induced changes were reproducible. Results After furosemide, T 2 * values in the medulla increased by 53% ( P   〈  0.01) while RAF and perfusion remained constant. After hand‐grip exercise, T 2 * values in renal medulla increased by 22% ± 9% despite a drop in medullary perfusion of 7.2% ± 4.7% and a decrease in renal arterial flow of 17.5% ± 1.7% ( P   〈  0.05). Mean coefficients of variation between repeated measurements for all parameters were 7%. Conclusion Furosemide induced the anticipated increase in renal medullary oxygenation, attributable exclusively to a decrease in renal oxygen consumption, since no change of RAF, cortical or medullary perfusion could be demonstrated. All measures and the induced changes were reproducible.
    Type of Medium: Online Resource
    ISSN: 1748-1708 , 1748-1716
    URL: Issue
    URL: Article
    DOI: 10.1111/apha.v227.1
    DOI: 10.1111/apha.13292
    Language: English
    Publisher: Wiley
    Publication Date: 2019
    detail.hit.zdb_id: 2617148-X
    detail.hit.zdb_id: 2219379-0
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  • 8
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    Consensus‐Based Technical Recommendations for Clinical Translation of Renal Phase Contrast MRI
    Wiley ; 2022
    In:  Journal of Magnetic Resonance Imaging Vol. 55, No. 2 ( 2022-02), p. 323-335
    Details
    In: Journal of Magnetic Resonance Imaging, Wiley, Vol. 55, No. 2 ( 2022-02), p. 323-335
    Abstract: Phase‐contrast (PC) MRI is a feasible and valid noninvasive technique to measure renal artery blood flow, showing potential to support diagnosis and monitoring of renal diseases. However, the variability in measured renal blood flow values across studies is large, most likely due to differences in PC‐MRI acquisition and processing. Standardized acquisition and processing protocols are therefore needed to minimize this variability and maximize the potential of renal PC‐MRI as a clinically useful tool. Purpose To build technical recommendations for the acquisition, processing, and analysis of renal 2D PC‐MRI data in human subjects to promote standardization of renal blood flow measurements and facilitate the comparability of results across scanners and in multicenter clinical studies. Study Type Systematic consensus process using a modified Delphi method. Population Not applicable. Sequence Field/Strength Renal fast gradient echo‐based 2D PC‐MRI. Assessment An international panel of 27 experts from Europe, the USA, Australia, and Japan with 6 (interquartile range 4–10) years of experience in 2D PC‐MRI formulated consensus statements on renal 2D PC‐MRI in two rounds of surveys. Starting from a recently published systematic review article, literature‐based and data‐driven statements regarding patient preparation, hardware, acquisition protocol, analysis steps, and data reporting were formulated. Statistical Tests Consensus was defined as ≥75% unanimity in response, and a clear preference was defined as 60–74% agreement among the experts. Results Among 60 statements, 57 (95%) achieved consensus after the second‐round survey, while the remaining three showed a clear preference. Consensus statements resulted in specific recommendations for subject preparation, 2D renal PC‐MRI data acquisition, processing, and reporting. Data Conclusion These recommendations might promote a widespread adoption of renal PC‐MRI, and may help foster the set‐up of multicenter studies aimed at defining reference values and building larger and more definitive evidence, and will facilitate clinical translation of PC‐MRI. Level of Evidence 1 Technical Efficacy Stage 1
    Type of Medium: Online Resource
    ISSN: 1053-1807 , 1522-2586
    URL: Issue
    URL: Article
    DOI: 10.1002/jmri.v55.2
    DOI: 10.1002/jmri.27419
    Language: English
    Publisher: Wiley
    Publication Date: 2022
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  • 9
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    Associations between inflammatory markers, body composition, and physical function: the Copenhagen Sarcopenia Study
    Wiley ; 2021
    In:  Journal of Cachexia, Sarcopenia and Muscle Vol. 12, No. 6 ( 2021-12), p. 1641-1652
    Details
    In: Journal of Cachexia, Sarcopenia and Muscle, Wiley, Vol. 12, No. 6 ( 2021-12), p. 1641-1652
    Abstract: Chronic low‐grade inflammation has been suggested as one of the key elements in the development of sarcopenia, but in contrast to disease‐related loss of muscle mass, the role of chronic low‐grade inflammation in age‐related (primary) sarcopenia is still not clear. The aim of this study was to investigate low‐grade inflammation in relation to age and the potential association between inflammatory biomarkers and body composition, muscle strength and physical performance in a healthy Danish cohort. Methods There were 1160 generally healthy men and women (range: 22–93 years) included. Appendicular lean mass (ALM) and visceral fat normalized to height (kg/m 2 ) was assessed by dual‐energy X‐ray absorptiometry (iDXA, GE Lunar). Muscle strength and physical performance were evaluated by handgrip strength (HGS), 30 s sit‐to‐stand performance, and maximal gait speed (GS). Systemic levels of TNF‐α, IL‐6, IL‐1β, IL‐4, IL‐13, and IFN‐γ were measured using multiplex bead‐based immunoassays (Bio‐Rad). hsCRP was assessed using latex particle‐enhanced immunoturbidimetric assays (Roche Diagnostics). Results With age, ALM/h 2 , HGS, sit‐to‐stand performance and GS decreased, whereas visceral fat/h 2 increased in both men and women ( P   〈  0.05). Systemic levels of hsCRP, TNF‐α, IL‐4, and IFN‐γ increased with age in men and women ( P   〈  0.05), while IL‐1β increased in women only ( P   〈  0.01). Higher levels of hsCRP were associated with lower ALM/h 2 in elderly (≥65 years) men and women ( P   〈  0.001). Higher levels of hsCRP were associated with lower handgrip strength in elderly women ( P   〈  0.05) whereas higher levels of hsCRP was not associated with lower HGS in elderly men ( P  = 0.056). Higher levels of hsCRP were associated with lower GS ( P   〈  0.05), whereas IFN‐γ was positively associated with GS in elderly women ( P   〈  0.05), but not elderly men. Visceral fat index was positively associated with hsCRP in elderly men and women ( P   〈  0.001). Compared with elderly with normal HGS, elderly men and women with low HGS displayed higher levels of TNF‐α and hsCRP ( P   〈  0.05). Conclusions With age, systemic levels of hsCRP, TNF‐α, IL‐4, and IFN‐γ increased, with hsCRP and TNF‐α being especially elevated in more physically frail elderly supporting the association between low‐grade systemic inflammation and poor physical function. In contrast, only high levels of hsCRP were weakly associated with low muscle mass and positively associated with visceral fat and low physical function, suggesting that chronic low‐grade inflammation is not the main driver of age‐related loss of muscle mass as previously suggested.
    Type of Medium: Online Resource
    ISSN: 2190-5991 , 2190-6009
    URL: Issue
    URL: Article
    DOI: 10.1002/jcsm.v12.6
    DOI: 10.1002/jcsm.12832
    Language: English
    Publisher: Wiley
    Publication Date: 2021
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  • 10
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    The Copenhagen Sarcopenia Study: lean mass, strength, power, and physical function in a Danish cohort aged 20–93 years
    Wiley ; 2019
    In:  Journal of Cachexia, Sarcopenia and Muscle Vol. 10, No. 6 ( 2019-12), p. 1316-1329
    Details
    In: Journal of Cachexia, Sarcopenia and Muscle, Wiley, Vol. 10, No. 6 ( 2019-12), p. 1316-1329
    Abstract: Despite no international consensus on the diagnostic criteria for sarcopenia, low lean mass, muscle strength, and physical function are important risk factors for disability, frailty, and mortality in older individuals, as well as in a wide range of patients with muscle loss. Here, we provide a population‐based reference material of total and regional lean body mass, muscle strength/power parameters, and physical function in a healthy cohort of Danish men and women across the lifespan. Methods Volunteers aged 20–93 years from the Copenhagen City Heart Study were invited to establish a Danish reference material (Copenhagen Sarcopenia Study) on lean mass characteristics [appendicular lean mass (ALM), iDXA, GE Lunar], muscle function [handgrip strength (HGS), Jamar dynamometer and leg extension power (LEP), Nottingham Power Rig] , and physical function [30 s sit‐to‐stand test (STS), 10‐m maximal and habitual gait speed (GS)]. Results A total of 1305 participants [729 women (age: 56.4 ± 18.9 years, height: 1.66 ± 0.01 m, body mass index: 24.6 ± 4.3 kg/m 2 and 576 men, age: 57.0 ± 17.5 years, height: 1.80 ± 0.07 m, body mass index: 26.0 ± 3.9 kg/m 2 ] completed all measurements and were included in the present analysis. Lean mass characteristics (TLM, ALM, and ALM/h 2 ) decreased with increasing age in both men and women ( P 〈 0.001). Men demonstrated larger absolute and relative total ALM and higher HGS and LEP compared with women at all age intervals ( P 〈 0.001). HGS and LEP decreased progressively with age in both men and women ( P 〈 0.01); 30 s STS performance, habitual GS, and maximal GS decreased at an accellerated rate of decline with increasing age in both men and women ( P 〈 0.001). Habitual GS was reduced in men and women aged ≥70 years, while maximal GS was reduced from the age of ≥60 years compared with young adults ( P 〈 0.001). Regardless of sex, 30 s STS was reduced from the age of ≥50 years compared with the young reference group ( P 〈 0.001) Conclusions While the power‐based measurements (LEP and 30 s STS) started to decline already at age +50 years, less power‐based parameters (GS and HGS) and lean mass characteristics (TLM, ALM, and ALM/h 2 ) remained unaltered until after the age of +70 years. Notably, the cut‐off thresholds derived in the present study differed from earlier reference data, which underlines the importance of obtaining updated and local reference materials.
    Type of Medium: Online Resource
    ISSN: 2190-5991 , 2190-6009
    URL: Issue
    URL: Article
    DOI: 10.1002/jcsm.v10.6
    DOI: 10.1002/jcsm.12477
    Language: English
    Publisher: Wiley
    Publication Date: 2019
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