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- Michaëlsson, Karl, 1959-, et al.
(author)
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Combined associations of body mass index and adherence to a Mediterranean-like diet with all-cause and cardiovascular mortality : A cohort study
- 2020
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In: PLoS Medicine. - : Public Library of Science (PLoS). - 1549-1277 .- 1549-1676. ; 17:9
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Journal article (peer-reviewed)abstract
- BackgroundIt is unclear whether the effect on mortality of a higher body mass index (BMI) can be compensated for by adherence to a healthy diet and whether the effect on mortality by a low adherence to a healthy diet can be compensated for by a normal weight. We aimed to evaluate the associations of BMI combined with adherence to a Mediterranean-like diet on all-cause and cardiovascular disease (CVD) mortality.Methods and findingsOur longitudinal cohort design included the Swedish Mammography Cohort (SMC) and the Cohort of Swedish Men (COSM) (1997–2017), with a total of 79,003 women (44%) and men (56%) and a mean baseline age of 61 years. BMI was categorized into normal weight (20–24.9 kg/m2), overweight (25–29.9 kg/m2), and obesity (30+ kg/m2). Adherence to a Mediterranean-like diet was assessed by means of the modified Mediterranean-like diet (mMED) score, ranging from 0 to 8; mMED was classified into 3 categories (0 to <4, 4 to <6, and 6–8 score points), forming a total of 9 BMI × mMED combinations. We identified mortality by use of national Swedish registers. Cox proportional hazard models with time-updated information on exposure and covariates were used to calculate the adjusted hazard ratios (HRs) of mortality with their 95% confidence intervals (CIs). Our HRs were adjusted for age, baseline educational level, marital status, leisure time physical exercise, walking/cycling, height, energy intake, smoking habits, baseline Charlson’s weighted comorbidity index, and baseline diabetes mellitus. During up to 21 years of follow-up, 30,389 (38%) participants died, corresponding to 22 deaths per 1,000 person-years. We found the lowest HR of all-cause mortality among overweight individuals with high mMED (HR 0.94; 95% CI 0.90, 0.98) compared with those with normal weight and high mMED. Using the same reference, obese individuals with high mMED did not experience significantly higher all-cause mortality (HR 1.03; 95% CI 0.96–1.11). In contrast, compared with those with normal weight and high mMED, individuals with a low mMED had a high mortality despite a normal BMI (HR 1.60; 95% CI 1.48–1.74). We found similar estimates among women and men. For CVD mortality (12,064 deaths) the findings were broadly similar, though obese individuals with high mMED retained a modestly increased risk of CVD death (HR 1.29; 95% CI 1.16–1.44) compared with those with normal weight and high mMED. A main limitation of the present study is the observational design with self-reported lifestyle information with risk of residual or unmeasured confounding (e.g., genetic liability), and no causal inferences can be made based on this study alone.ConclusionsThese findings suggest that diet quality modifies the association between BMI and all-cause mortality in women and men. A healthy diet may, however, not completely counter higher CVD mortality related to obesity.
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| 2. |
- Michaëlsson, Karl, et al.
(author)
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Serum 25-hydroxyvitamin D is associated with fracture risk only during periods of seasonally high levels in women with a high body mass index
- 2021
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In: Journal of Bone and Mineral Research. - : Wiley. - 0884-0431 .- 1523-4681. ; 36:10, s. 1957-1966
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Journal article (peer-reviewed)abstract
- Serum 25-hydroxyvitamin D (S-25OHD) is used to assess vitamin D status and is known to be affected by season and fat mass. Because these factors are often ignored when interpreting S-25OHD, assessment of vitamin D associations with disease outcomes may be distorted. We aimed to investigate the impact of season of blood draw and fat mass on the association of S25OHD with fracture risk. We enrolled 5000 women, mean ± SD age 68 ± 7 years, with dual-energy x-ray absorptiometry (DXA) scans and blood collection in a population-based cohort. Proportional hazards regression, stratified by season and fat mass, was used to determine hazard ratios (HRs) of fracture according to categories of S-25OHD. Our secondary exposures were serum 1,25-dihydroxycholecalciferol (1,25-(OH)2 D3 ), the most active vitamin D metabolite and plasma parathyroid hormone (P-PTH). During an average of 9.2 years of follow-up, 1080 women had a fracture. Women with S-25OHD <30 nmol/L drawn during sunny months (May-October) had a multivariable-adjusted fracture HR of 2.06 (95% CI, 1.27-3.35) compared with those with S-25OHD >60 nmol/L; those with S-25OHD 30-40 nmol/L had an HR of 1.59 (95% CI, 1.12-2.26). In contrast, S-25OHD drawn during November through April was unrelated to fracture risk. The increased risk with low sunny season S-25OHD was seen only among women with body mass index (BMI) ≥25 kg/m2 or fat mass index (FMI) ≥9.8 kg/m2 . High fat mass and low S-25OHD were independently related to lower S-1,25-dihydroxycholecalciferol, which itself predicted fracture risk with samples collected during the sunny season. Irrespective of season, P-PTH was unrelated to fracture risk. We conclude that S-25OHD is associated with fracture risk only if drawn during periods of seasonally high levels in women with a high BMI. These results have implications for the evaluation of vitamin D status and can explain the lack of effect seen with vitamin D supplementation in many fracture trials. © 2021 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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| 3. |
- Michaëlsson, Madeleine, 1968-, et al.
(author)
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The impact and causal directions for the associations between diagnosis of ADHD, socioeconomic status, and intelligence by use of a bi-directional two-sample Mendelian randomization design
- 2022
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In: BMC Medicine. - : BioMed Central (BMC). - 1741-7015. ; 20:1
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Journal article (peer-reviewed)abstract
- Background Previous studies have reported associations between attention-deficit/hyperactivity disorder (ADHD) and lower socioeconomic status and intelligence. We aimed to evaluate the causal directions and strengths for these associations by use of a bi-directional two-sample Mendelian randomization (MR) design. Methods We used summary-level data from the largest available genome-wide association studies (GWAS) to identify genetic instruments for ADHD, intelligence, and markers of socioeconomic status including the Townsend deprivation index, household income, and educational attainment. Effect estimates from individual genetic variants were combined using inverse-variance weighted regression. Results A genetically predicted one standard deviation (SD) increment in the Townsend deprivation index conferred an odds ratio (OR) of 5.29 (95% confidence interval (CI) 1.89-14.76) for an ADHD diagnosis (p<0.001). A genetically predicted one SD higher education level conferred an OR of 0.30 (95% CI 0.25-0.37) (p<0.001), and a genetically predicted one SD higher family income provided an OR of 0.35 (95% CI 0.25-0.49; p<0.001). The associations remained after adjustment for intelligence whereas the lower odds of an ADHD diagnosis with higher intelligence did not persist after adjustment for liability to greater educational attainment (adjusted OR 1.03, 95% CI 0.68-1.56; p=0.87). The MR analysis of the effect of ADHD on socioeconomic markers found that genetic liability to ADHD was statistically associated with each of them (p<0.001) but not intelligence. However, the average change in the socioeconomic markers per doubling of the prevalence of ADHD corresponded only to 0.05-0.06 SD changes. Conclusions Our results indicate that an ADHD diagnosis may be a direct and strong intelligence-independent consequence of socioeconomic related factors, whereas ADHD appears to lead only to modestly lowered socioeconomic status. Low intelligence seems not to be a major independent cause or consequence of ADHD.
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| 4. |
- Stattin, Karl, et al.
(author)
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Fracture risk across a wide range of physical activity levels, from sedentary individuals to elite athletes.
- 2021
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In: Bone. - : Elsevier. - 8756-3282 .- 1873-2763. ; 153
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Journal article (peer-reviewed)abstract
- OBJECTIVE: To examine how physical activity is associated with risk of different fracture outcomes across the full range of physical activity.METHODS: By combining information from three cohort studies and using generalized structural equation modelling, we estimated a continuous unitless latent variable reflecting physical activity that ranged from sedentary through elite athlete levels. Associations between physical activity and fracture outcomes were assessed with proportional hazards regression using restricted cubic splines with the mean physical activity (corresponding to 20-40 min walking or bicycling/day or 2-3 h exercise/week) as reference.RESULTS: Among 63,980 men and women (49-68 years) and during 13 years of follow-up, 8506 fractures occurred, including 2164 distal forearm, 779 proximal humerus, 346 clinical spine, and 908 hip fractures. Both lower and higher physical activity was associated with higher risk of any fracture compared to the mean. Physical activity at 1 standard deviation (SD) below the mean, corresponding to walking/bicycling <20 min/day or exercising <1-1 h/week, was associated with a lower risk of distal forearm fracture (hazard ratio [HR]: 0.92, 95% confidence interval [CI]: 0.85-0.99) and higher risk of hip fracture (HR: 1.24, 95% CI: 1.13-1.37), but no associations were seen above the mean physical activity level for these fractures. Physical activity was not associated with proximal humerus fracture but had a possible U-shaped association with clinical spine fracture.CONCLUSION: Physical activity was non-linearly associated with fracture risk and the association differed across fracture sites. Up to 2-3 h weekly exercise is beneficial for the prevention of hip fracture but may increase the risk of distal forearm fracture.
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| 5. |
- Titova, Olga E., et al.
(author)
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Comprehensive analyses of circulating cardiometabolic proteins and objective measures of fat mass
- 2023
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In: International Journal of Obesity. - : Springer Nature. - 1476-5497 .- 0307-0565. ; 47:11, s. 1043-1049
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Journal article (peer-reviewed)abstract
- Background: The underlying molecular pathways for the effect of excess fat mass on cardiometabolic diseases is not well understood. Since body mass index is a suboptimal measure of body fat content, we investigated the relationship of fat mass measured by dual-energy X-ray absorptiometry with circulating cardiometabolic proteins. Methods: We used data from a population-based cohort of 4950 Swedish women (55–85 years), divided into discovery and replication samples; 276 proteins were assessed with three Olink Proseek Multiplex panels. We used random forest to identify the most relevant biomarker candidates related to fat mass index (FMI), multivariable linear regression to further investigate the associations between FMI characteristics and circulating proteins adjusted for potential confounders, and principal component analysis (PCA) for the detection of common covariance patterns among the proteins. Results: Total FMI was associated with 66 proteins following adjustment for multiple testing in discovery and replication multivariable analyses. Five proteins not previously associated with body size were associated with either lower FMI (calsyntenin-2 (CLSTN2), kallikrein-10 (KLK10)), or higher FMI (scavenger receptor cysteine-rich domain-containing group B protein (SSC4D), trem-like transcript 2 protein (TLT-2), and interleukin-6 receptor subunit alpha (IL-6RA)). PCA provided an efficient summary of the main variation in FMI-related circulating proteins involved in glucose and lipid metabolism, appetite regulation, adipocyte differentiation, immune response and inflammation. Similar patterns were observed for regional fat mass measures. Conclusions: This is the first large study showing associations between fat mass and circulating cardiometabolic proteins. Proteins not previously linked to body size are implicated in modulation of postsynaptic signals, inflammation, and carcinogenesis.
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| 6. |
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| 7. |
- Zheng, Rui, et al.
(author)
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Metabolites affecting body composition associate with hip fracture risk in elderly women : A large-scale metabolome-wide association study
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Other publication (other academic/artistic)abstract
- Hip fracture is the most devastating fragility fracture and a major threat to individual health. It is known that body composition and changes therein influence hip fracture occurrence but the molecular mechanisms are not fully understood. Few studies have investigated whether circulating metabolites can impact body composition in the context of hip fracture risk. Here, we used untargeted metabolomics to unveil the metabolic interrelationships among bone, muscle, and fat tissues in a cohort of 4886 women (mean age 68 ± 7 years). We discovered and replicated circulating metabolites associated with bone mineral density (BMD), fat and lean mass measured by dual-energy X-ray absorptiometry. Importantly, pyrrolidine and its ethanol derivative, kynurenic acid (KYNA), 3,12-dioxochol-4-en-24-oic acid, and a predicted steroid (ST 22:1;O3;S) were associated with all three measures. The association between leucine or KYNA and body composition was consistent with previous findings. In total 23 metabolites reflecting BMD, fat or lean mass were associated with hip fracture risk; we found the most pronounced association with ST 22:1;O3;S (hazard ratio 0.55 per 1 SD higher level; 95% CI, 0.36 to 0.84). Strong interplay among the three body composition compartments via lysoglycerophospholipids and amino acid derivatives were illustrated by network analysis. The strongest correlations of bone-related clinical biomarkers including circulating 25-hydroxyvitamin D, parathyroid hormone, CrossLaps, osteocalcin and C-reactive protein were found with lipids. Using two-sample Mendelian randomization analysis, genetically-predicted levels of LPC 20:3, gamma-glutamylleucine, leucine and KYNA were causally associated with multiple outcomes, including BMD and 25-hydroxyvitamin D. Our work reveals the importance of several lysoglycerophospholipids and amino acid metabolites in body composition crosstalk and provides potential actionable targets of sarcopenia, osteoporosis, and fracture prevention.
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| 8. |
- Zheng, Rui, et al.
(author)
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Prior loss of body mass index, low body mass index, and central obesity independently contribute to higher rates of fractures in elderly women and men
- 2021
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In: Journal of Bone and Mineral Research. - : John Wiley & Sons. - 0884-0431 .- 1523-4681. ; 36:7, s. 1288-1299
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Journal article (peer-reviewed)abstract
- We aimed to comprehensively evaluate the association of body composition with fracture risk using longitudinal data from a Swedish cohort of 44,366 women and men (mean age of 70 years) and a subcohort of 5022 women. We estimated hazard ratios (HRs) of fracture for baseline body mass index (BMI), BMI change during the prior 12 and 18 years, baseline waist-to-height ratio, total and regional distribution of fat and lean mass, with and without areal bone mineral density (BMD) adjustment. During follow-up (median 8.7 years), 7290 individuals sustained a fracture, including 4279 fragility fractures, of which 1813 were hip fractures. Higher baseline BMI and prior gain in BMI were inversely associated with all types of fracture. Lower fracture rate with higher baseline BMI was seen within every category of prior BMI change, whereas higher prior BMI gain conferred a lower rate of fracture within those with normal baseline BMI. Each standard deviation (SD) higher baseline waist-to-height ratio, after adjustment for BMI, was associated with higher rates of hip fracture in both women and men (HR 1.12; 95% CI, 1.05-1.19). In the subcohort (median follow-up 10 years), higher baseline fat mass index (FMI) and appendicular lean mass index (LMI) showed fracture-protective effects. After BMD adjustment, higher baseline BMI, total LMI, FMI, and higher prior BMI gain were associated with higher fracture rate. Baseline fat distribution also was associated with fracture rate; a 1-SD higher android to gynoid fat mass ratio in prior BMI gainers was associated with BMD-adjusted HRs of 1.16 (95% CI, 1.05-1.28) for any fracture and 1.48 (95% CI, 1.16-1.89) for hip fracture. This pattern was not observed among prior BMI losers. These findings indicate that for optimal fracture prevention, low baseline BMI, prior BMI loss and high baseline central obesity should be avoided in both women and men. © 2021 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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