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Jiang, X., O'Reilly, P. F., Aschard, H., Hsu, Y.-H., Richards, J. B., Dupuis, J., . . . Kiel, D. P. (2018). Genome-wide association study in 79,366 European-ancestry individuals informs the genetic architecture of 25-hydroxyvitamin D levels. Nature Communications, 9, Article ID 260.
Open this publication in new window or tab >>Genome-wide association study in 79,366 European-ancestry individuals informs the genetic architecture of 25-hydroxyvitamin D levels
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2018 (English)In: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 9, article id 260Article in journal (Refereed) Published
Abstract [en]

Vitamin D is a steroid hormone precursor that is associated with a range of human traits and diseases. Previous GWAS of serum 25-hydroxyvitamin D concentrations have identified four genome-wide significant loci (GC, NADSYN1/DHCR7, CYP2R1, CYP24A1). In this study, we expand the previous SUNLIGHT Consortium GWAS discovery sample size from 16,125 to 79,366 (all European descent). This larger GWAS yields two additional loci harboring genome-wide significant variants (P = 4.7×10−9 at rs8018720 in SEC23A, and P = 1.9×10−14 at rs10745742 in AMDHD1). The overall estimate of heritability of 25-hydroxyvitamin D serum concentrations attributable to GWAS common SNPs is 7.5%, with statistically significant loci explaining 38% of this total. Further investigation identifies signal enrichment in immune and hematopoietic tissues, and clustering with autoimmune diseases in cell-type-specific analysis. Larger studies are required to identify additional common SNPs, and to explore the role of rare or structural variants and gene–gene interactions in the heritability of circulating 25-hydroxyvitamin D levels.

National Category
Medical Genetics
Identifiers
urn:nbn:se:uu:diva-343676 (URN)10.1038/s41467-017-02662-2 (DOI)000422650500011 ()29343764 (PubMedID)
Available from: 2018-03-05 Created: 2018-03-05 Last updated: 2018-03-05Bibliographically approved
Michaëlsson, K., Wolk, A., Warensjö, E., Melhus, H. & Byberg, L. (2018). Intake of milk or fermented milk combined with fruit and vegetable consumption in relation to hip fracture rates: A cohort study of Swedish women.. Journal of Bone and Mineral Research, 33(3), 449-457
Open this publication in new window or tab >>Intake of milk or fermented milk combined with fruit and vegetable consumption in relation to hip fracture rates: A cohort study of Swedish women.
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2018 (English)In: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 33, no 3, p. 449-457Article in journal (Refereed) Published
Abstract [en]

Milk products may differ in pro-oxidant properties and their effects on fracture risk could potentially be modified by the intake of foods with antioxidant activity. In the population-based Swedish Mammography Cohort study, we aimed to determine how milk and fermented milk combined with fruit and vegetable consumption are associated with hip fracture. Women born 1914-1948 (n=61 240) answered food frequency and lifestyle questionnaires in 1987-1990 and 38 071 women contributed with updated information in 1997. During a mean follow-up of 22 years, 5827 women had a hip fracture (ascertained via official register data). Compared with a low intake of milk (<1 glass/day) and a high intake of fruits and vegetables (≥5 servings/day), a high intake of milk (≥3 glasses/day) with a concomitant low intake of fruits and vegetables (<2 servings/day) resulted in a HR of 2.49 (95% CI, 2.03-3.05). This higher hip fracture rate among high consumers of milk was only modestly attenuated with a concomitant high consumption of fruit and vegetables (HR 2.14; 95% CI 1.69-2.71). The combination of fruits and vegetables with fermented milk (yogurt or soured milk) yielded a different pattern with lowest rates of hip fracture in high consumers: HR 0.81 (95% CI, 0.68-0.97) for ≥2 servings/day of fermented milk and ≥5 servings/day of fruits and vegetables compared with low consumption of both fruit and vegetables and fermented milk. We conclude that the amount and type of dairy products as well as fruit and vegetable intake are differentially associated with hip fracture rates in women.

Keywords
dairy, fruit, hip fracture, milk, vegetables
National Category
Orthopaedics
Identifiers
urn:nbn:se:uu:diva-334436 (URN)10.1002/jbmr.3324 (DOI)000426731100011 ()29083056 (PubMedID)
Funder
Swedish Research Council, 2011-2427
Available from: 2017-11-23 Created: 2017-11-23 Last updated: 2018-05-23Bibliographically approved
Michaëlsson, K. & Byberg, L. (2018). Interpretation of milk research results. Osteoporosis International, 29(3), 773-775
Open this publication in new window or tab >>Interpretation of milk research results
2018 (English)In: Osteoporosis International, ISSN 0937-941X, E-ISSN 1433-2965, Vol. 29, no 3, p. 773-775Article in journal (Other academic) Published
National Category
Orthopaedics
Identifiers
urn:nbn:se:uu:diva-334430 (URN)10.1007/s00198-017-4291-x (DOI)000426646900026 ()29147751 (PubMedID)
Available from: 2017-11-23 Created: 2017-11-23 Last updated: 2018-06-08Bibliographically approved
Kaluza, J., Harris, H., Melhus, H., Michaëlsson, K. & Wolk, A. (2018). Questionnaire-Based Anti-Inflammatory Diet Index as a Predictor of Low-Grade Systemic Inflammation.. Antioxidants and Redox Signaling, 28(1), 78-84
Open this publication in new window or tab >>Questionnaire-Based Anti-Inflammatory Diet Index as a Predictor of Low-Grade Systemic Inflammation.
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2018 (English)In: Antioxidants and Redox Signaling, ISSN 1523-0864, E-ISSN 1557-7716, Vol. 28, no 1, p. 78-84Article in journal (Refereed) Published
Abstract [en]

There is accumulating evidence that diet may be associated with markers of inflammation. We have evaluated if an empirically developed questionnaire-based Anti-Inflammatory Diet Index (AIDI) may predict low-grade systemic chronic inflammation in a Nordic population. The AIDI was developed using a 123-item food frequency questionnaire among 3503 women (56-74 years old) with high-sensitivity C-reactive protein (hsCRP) plasma concentration <20 mg/L. Using Spearman correlations, we identified 20 foods (AIDI-20) statistically significantly related to hsCRP. The median (range) of AIDI-20 was 8 (0-17) scores, and the median concentration of hsCRP in the lowest versus the highest quintile of AIDI-20 (≤6 vs. ≥11 scores) varied by 80% (1.8 vs. 1.0 mg/L, respectively). In a multivariable-adjusted linear regression model, women in the highest quintile of AIDI-20 compared with those in the lowest had a 26% (95% confidence interval [CI] 18-33%; p-trend <0.001) lower hsCRP concentration; each 1-score increment in the AIDI-20 was associated with a 0.06 (95% CI 0.04-0.08) mg/L lower hsCRP. The observed association between the AIDI-20 and hsCRP was robust by all hsCRP levels and in subgroups defined by inflammatory-related factors. Our results lead to the hypothesis that the empirically developed questionnaire-based dietary anti-inflammatory index may predict low-grade systemic inflammation. Antioxid. Redox Signal. 28, 78-84.

Keywords
C-reactive protein, anti-inflammatory index, diet, food, inflammation
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-337200 (URN)10.1089/ars.2017.7330 (DOI)000415967200006 ()28877589 (PubMedID)
Funder
Forte, Swedish Research Council for Health, Working Life and Welfare, 2015-00778Swedish Research Council, 2015-05997Swedish Research Council Formas, FR 2016/0004
Available from: 2017-12-21 Created: 2017-12-21 Last updated: 2018-01-17Bibliographically approved
Hållmarker, U., Lindbäck, J., Michaëlsson, K., Ärnlöv, J., Åsberg, S., Wester, P., . . . James, S. K. (2018). Survival and incidence of cardiovascular diseases in participants in a long-distance ski race (Vasaloppet, Sweden) compared to the background population. European Heart Journal - Quality of Care and Clinical Outcomes, 4(2), 91-97
Open this publication in new window or tab >>Survival and incidence of cardiovascular diseases in participants in a long-distance ski race (Vasaloppet, Sweden) compared to the background population
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2018 (English)In: European Heart Journal - Quality of Care and Clinical Outcomes, ISSN 2058-5225, E-ISSN 2058-1742, Vol. 4, no 2, p. 91-97Article in journal (Refereed) Published
Abstract [en]

We studied the relationship between taking part in a long-distance ski race and incidence of cardiovascular diseases (CVDs) to address the hypothesis that lifestyle lowers the incidence. A cohort of 399 630 subjects in Sweden, half were skiers in the world's largest ski race, and half were non-skiers. Non-skiers were frequency matched for sex, age, and year of race. Individuals with severe diseases were excluded. The endpoints were death, myocardial infarction, or stroke. The subjects were followed up for a maximum of 21.8 years and median of 9.8 years. We identified 9399 death, myocardial infarction, or stroke events among non-skiers and 4784 among the Vasaloppet skiers. The adjusted hazard ratios (HRs) comparing skiers and non-skiers were 0.52 [95% confidence interval (CI) 0.49-0.54] for all-cause mortality, 0.56 (95% CI 0.52-0.60) for myocardial infarction and 0.63 (95% CI 0.58-0.67) for stroke and for all three outcomes 0.56 (95% CI 0.54-0.58). The results were consistent across subgroups: age, sex, family status, education, and race year. For skiers, a doubling of race time was associated with a higher age-adjusted risk of 19%, and male skiers had a doubled risk than female skiers, with a HR 2.06 (95% CI 1.89-2.41). The outcome analyses revealed no differences in risk of atrial fibrillation between skiers and non-skiers. This large cohort study provides additional support for the hypothesis that individuals with high level of physical activity representing a healthy lifestyle, as evident by their participation in a long-distance ski race, have a lower risk of CVD or death.

Place, publisher, year, edition, pages
Oxford University Press, 2018
Keywords
Incidence of cardiovascular disease, Physical activity, Lifestyle, Prevention, Cross-country skiing, Epidemiology, Vasaloppet
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-344291 (URN)10.1093/ehjqcco/qcy005 (DOI)000429458200006 ()29390055 (PubMedID)
Available from: 2018-03-06 Created: 2018-03-06 Last updated: 2018-06-11Bibliographically approved
Cornelis, M. C., Gustafsson, S., Ärnlöv, J., Elmståhl, S., Söderberg, S., Sundström, J., . . . Ingelsson, E. (2018). Targeted proteomic analysis of habitual coffee consumption.. Journal of Internal Medicine, 283(2), 200-211
Open this publication in new window or tab >>Targeted proteomic analysis of habitual coffee consumption.
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2018 (English)In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 283, no 2, p. 200-211Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Coffee drinking has been implicated in mortality and a variety of diseases but potential mechanisms underlying these associations are unclear. Large-scale systems epidemiological approaches may offer novel insights to mechanisms underlying associations of coffee with health.

OBJECTIVE: We performed an analysis of known and novel protein markers linked to cardiovascular disease and their association with habitual coffee intake in the Prospective Study of the Vasculature in Uppsala Seniors (PIVUS, n = 816) and followed up top proteins in the Uppsala Longitudinal Study of Adult Men (ULSAM, n = 635) and EpiHealth (n = 2418).

METHODS: In PIVUS and ULSAM, coffee intake was measured by 7-day dietary records whilst a computer-based food frequency questionnaire was used in EpiHealth. Levels of up to 80 proteins were assessed in plasma by a proximity extension assay.

RESULTS: Four protein-coffee associations adjusted for age, sex, smoking and BMI, met statistical significance in PIVUS (FDR < 5%, P < 2.31 × 10(-3) ): leptin (LEP), chitinase-3-like protein 1 (CHI3L), tumour necrosis factor (TNF) receptor 6 and TNF-related apoptosis-inducing ligand. The inverse association between coffee intake and LEP replicated in ULSAM (β, -0.042 SD per cup of coffee, P = 0.028) and EpiHealth (β, -0.025 SD per time of coffee, P = 0.004). The negative coffee-CHI3L association replicated in EpiHealth (β, -0.07, P = 1.15 × 10(-7) ), but not in ULSAM (β, -0.034, P = 0.16).

CONCLUSIONS: The current study supports an inverse association between coffee intake and plasma LEP and CHI3L1 levels. The coffee-CHI3L1 association is novel and warrants further investigation given links between CHI3L1 and health conditions that are also potentially influenced by coffee.

Keywords
biomarkers, coffee, epidemiology, population, proteomics
National Category
Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
urn:nbn:se:uu:diva-334452 (URN)10.1111/joim.12703 (DOI)000425830100008 ()29044854 (PubMedID)
Available from: 2017-11-23 Created: 2017-11-23 Last updated: 2018-05-07Bibliographically approved
Michaëlsson, K., Lohmander, L. S., Turkiewicz, A., Wolk, A., Nilsson, P. & Englund, M. (2017). Association between statin use and consultation or surgery for osteoarthritis of the hip or knee: a pooled analysis of four cohort studies.. Osteoarthritis and Cartilage, 25(11), 1804-1813, Article ID S1063-4584(17)31102-0.
Open this publication in new window or tab >>Association between statin use and consultation or surgery for osteoarthritis of the hip or knee: a pooled analysis of four cohort studies.
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2017 (English)In: Osteoarthritis and Cartilage, ISSN 1063-4584, E-ISSN 1522-9653, Vol. 25, no 11, p. 1804-1813, article id S1063-4584(17)31102-0Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: Experimental findings and previous observational data have suggested lower risk of osteoarthritis (OA) with statin use but results are inconsistent. Large-scale studies with a clinically important outcome are needed. Thus, we aimed to determine whether statin use is associated with a reduced risk of developing clinically-defined hip or knee OA.

DESIGN: Pooled analysis based on time-to-event analysis of four population-based large cohorts, encompassing in total 132,607 persons aged 57-91 years resident in southern and central Sweden. We studied the association between statin use and time to consultation or surgery for OA of the hip or knee by time-dependent exposure analysis and Cox regression.

RESULTS: During 7.5 years of follow-up, we identified 7468 out- or inpatient treated cases of hip or knee OA. Compared with never use, current use of statins conferred no overall reduction in the risk of OA with an adjusted pooled hazard ratio (HR) of 1.04 (95% confidence intervals [95% CI] 0.99-1.10). We found no dose-response relation between duration of current statin use and the risk of OA, with similar HRs among patients with less than 1 year of use (HR 1.09; 95% CI 0.92-1.32) as in patients with use for 3 years or more (HR 1.05; 0.93-1.16). Results were comparable in those with low, medium and high dose of current statin use, without indications of heterogeneity of study results.

CONCLUSION: Statin use is not associated with reduced risk of consultation or surgery for OA of the hip or knee.

Keywords
Cohort, Meta-analysis, Osteoarthritis, Pooled analysis, Statin
National Category
Orthopaedics
Identifiers
urn:nbn:se:uu:diva-334461 (URN)10.1016/j.joca.2017.07.013 (DOI)000413267300009 ()28756279 (PubMedID)
Funder
Swedish Research Council
Available from: 2017-11-23 Created: 2017-11-23 Last updated: 2018-02-21Bibliographically approved
Larsson, S. C., Burgess, S. & Michaëlsson, K. (2017). Association of Genetic Variants Related to Serum Calcium Levels With Coronary Artery Disease and Myocardial Infarction. Journal of the American Medical Association (JAMA), 318(4), 371-380
Open this publication in new window or tab >>Association of Genetic Variants Related to Serum Calcium Levels With Coronary Artery Disease and Myocardial Infarction
2017 (English)In: Journal of the American Medical Association (JAMA), ISSN 0098-7484, E-ISSN 1538-3598, Vol. 318, no 4, p. 371-380Article in journal (Refereed) Published
Abstract [en]

IMPORTANCE Serum calcium has been associated with cardiovascular disease in observational studies and evidence from randomized clinical trials indicates that calcium supplementation, which raises serum calcium levels, may increase the risk of cardiovascular events, particularly myocardial infarction.

OBJECTIVE To evaluate the potential causal association between genetic variants related to elevated serum calcium levels and risk of coronary artery disease (CAD) and myocardial infarction using mendelian randomization.

DESIGN, SETTING, AND PARTICIPANTS The analyses were performed using summary statistics obtained for single-nucleotide polymorphisms (SNPs) identified from a genome-wide association meta-analysis of serum calcium levels (N = up to 61 079 individuals) and from the Coronary Artery Disease Genome-wide Replication and Meta-analysis Plus the Coronary Artery Disease Genetics (CardiogramplusC4D) consortium's 1000 genomes-based genome-wide association meta-analysis (N = up to 184 305 individuals) that included cases (individuals with CAD andmyocardial infarction) and noncases, with baseline data collected from 1948 and populations derived from across the globe. The association of each SNP with CAD andmyocardial infarction was weighted by its association with serum calcium, and estimates were combined using an inverse-variance weighted meta-analysis.

EXPOSURES Genetic risk score based on genetic variants related to elevated serum calcium levels.

MAIN OUTCOMES AND MEASURES Co-primary outcomes were the odds of CAD and myocardial infarction.

RESULTS Among the mendelian randomized analytic sample of 184 305 individuals (60 801 CAD cases [approximately 70% with myocardial infarction] and 123 504 noncases), the 6 SNPs related to serum calcium levels and without pleiotropic associations with potential confounders were estimated to explain about 0.8% of the variation in serum calcium levels. In the inverse-variance weighted meta-analysis (combining the estimates of the 6 SNPs), the odds ratios per 0.5-mg/dL increase (about 1 SD) in genetically predicted serum calcium levels were 1.25 (95% CI, 1.08-1.45; P = .003) for CAD and 1.24 (95% CI, 1.05-1.46; P = .009) for myocardial infarction.

CONCLUSIONS AND RELEVANCE A genetic predisposition to higher serum calcium levels was associated with increased risk of CAD andmyocardial infarction. Whether the risk of CAD associated with lifelong genetic exposure to increased serum calcium levels can be translated to a risk associated with short-term to medium-term calcium supplementation is unknown.

Place, publisher, year, edition, pages
AMER MEDICAL ASSOC, 2017
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-332841 (URN)10.1001/jama.2017.8981 (DOI)000406296700017 ()28742912 (PubMedID)
Available from: 2017-11-09 Created: 2017-11-09 Last updated: 2017-11-09Bibliographically approved
Rosqvist, F., Bjermo, H., Kullberg, J., Johansson, L., Michaëlsson, K., Ahlström, H., . . . Risérus, U. (2017). Fatty acid composition in serum cholesterol esters and phospholipids is linked to visceral and subcutaneous adipose tissue content in elderly individuals: a cross-sectional study. Lipids in Health and Disease, 16, 1-10, Article ID 68.
Open this publication in new window or tab >>Fatty acid composition in serum cholesterol esters and phospholipids is linked to visceral and subcutaneous adipose tissue content in elderly individuals: a cross-sectional study
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2017 (English)In: Lipids in Health and Disease, ISSN 1476-511X, E-ISSN 1476-511X, Vol. 16, p. 1-10, article id 68Article in journal (Refereed) Published
Abstract [en]

Background: Visceral adipose tissue (VAT) and truncal fat predict cardiometabolic disease. Intervention trials suggest that saturated fatty acids (SFA), e. g. palmitic acid, promote abdominal and liver fat storage whereas polyunsaturated fatty acids (PUFA), e. g. linoleic acid, prevent fat accumulation. Such findings require investigation in population-based studies of older individuals. We aimed to investigate the relationships of serum biomarkers of PUFA intake as well as serum levels of palmitic acid, with abdominal and total adipose tissue content.

Methods: In a population-based sample of 287 elderly subjects in the PIVUS cohort, we assessed fatty acid composition in serum cholesterol esters (CE) and phospholipids (PL) by gas chromatography and the amount of VAT and abdominal subcutaneous (SAT) adipose tissue by magnetic resonance imaging (MRI), liver fat by MR spectroscopy (MRS), and total body fat, trunk fat and leg fat by dual-energy X-ray absorptiometry (DXA). Insulin resistance was estimated by HOMA-IR.

Results: VAT and trunk fat showed the strongest correlation with insulin resistance (r = 0.49, P < 0.001). Linoleic acid in both CE and PL was inversely related to all body fat depots (r = -0.24 to -0.33, P < 0.001) including liver fat measured in a sub-group (r = -0.26, P < 0.05, n = 73), whereas n-3 PUFA showed weak inverse (18: 3n-3) or positive (20: 5n-3) associations. Palmitic acid in CE, but not in PL, was directly correlated with VAT (r = 0.19, P < 0.001) and trunk fat (r = 0.18, P = 0.003). Overall, the significant associations remained after adjusting for energy intake, height, alcohol, sex, smoking, education and physical activity. The inverse correlation between linoleic acid and VAT remained significant after further adjustment for total body fat.

Conclusions: Serum linoleic acid is inversely related to body fat storage including VAT and trunk fat whereas palmitic acid was less consistently but directly associated, in line with recent feeding studies. Considering the close link between VAT and insulin resistance, a potential preventive role of plant-based PUFA in VAT accumulation warrants further study.

Keywords
Adipose tissue distribution, Body fat, Fatty acid, Linoleic acid, Palmitic acid, Polyunsaturated fat, Saturated fat, Visceral adipose tissue
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-319605 (URN)10.1186/s12944-017-0445-2 (DOI)000398222200001 ()28372558 (PubMedID)
Funder
Swedish Research Council, K2015-54X-22081-04-3EXODIAB - Excellence of Diabetes Research in SwedenSwedish Diabetes Association
Available from: 2017-04-06 Created: 2017-04-06 Last updated: 2017-11-29Bibliographically approved
Stilling, F., Wallenius, S., Michaëlsson, K., Dalgård, C., Brismar, K. & Wolk, A. (2017). High insulin-like growth factor-binding protein-1 (IGFBP-1) is associated with low relative muscle mass in older women. Metabolism: Clinical and Experimental, 73, 36-42
Open this publication in new window or tab >>High insulin-like growth factor-binding protein-1 (IGFBP-1) is associated with low relative muscle mass in older women
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2017 (English)In: Metabolism: Clinical and Experimental, ISSN 0026-0495, E-ISSN 1532-8600, Vol. 73, p. 36-42Article in journal (Refereed) Published
Abstract [en]

Objective: Skeletal muscles serve several important roles in maintaining good health. Insulin like growth factor-1 (IGF-1) is a promoter of protein synthesis in skeletal muscle. Its binding protein, Insulin-like growth factor-binding protein-1 (IGFBP-1) can be one determinant of IGF-1 activity. In the present study we investigate the association between serum IGFBP-1 and muscle mass.

Design: Cross-sectional analysis of 4908 women, between 55 and 85 years old, participating in the Swedish Mammography Cohort-Clinical.

Methods: We defined low relative muscle mass (LRMM) as an appendicular lean mass divided by height squared of less than 5.45 (kg/m(2)), assessed by dual energy x-ray absorptiometry. IGFBP-1 was measured by radioimmunoassay. Logistic regression was used to calculate odds-ratios of LRMM across quartiles of IGFBP-1.

Results: The odds of LRMM increased across quartiles of IGFBP-1. In the age-adjusted model the odds-ratio (OR) of LRMM was 3.41 (95% CI: 2.55-4.56), comparing the highest to the lowest quartile. This estimate was attenuated in multivariate models (OR: 1.84, 95% CI: 1.34-2.53), mainly due to inclusion of fat mass index.

Conclusion: Women with higher IGFBP-1 were more likely to have a low relative muscle mass. High IGFBP-1 may be a marker of a catabolic state.

Place, publisher, year, edition, pages
W B SAUNDERS CO-ELSEVIER INC, 2017
Keywords
Insulin-like growth factor binding, protein 1, Body composition, Muscle, skeletal, Aged
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-333700 (URN)10.1016/j.metabol.2017.04.013 (DOI)000406984200004 ()28732569 (PubMedID)
Funder
Swedish Research CouncilForte, Swedish Research Council for Health, Working Life and WelfareEU, Horizon 2020, 633589
Available from: 2017-11-21 Created: 2017-11-21 Last updated: 2017-12-21Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0003-2815-1217

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