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  • 1.
    Alvehus, Malin
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Burén, Jonas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Sjöström, Michael
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Goedecke, Julia
    Olsson, Tommy
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    The human visceral fat depot has a unique inflammatory profile2010In: Obesity, ISSN 1930-7381, E-ISSN 1930-739X, Vol. 18, no 5, p. 879-883Article in journal (Refereed)
    Abstract [en]

    Obesity can be considered as a low-grade inflammatory condition, strongly linked to adverse metabolic outcomes. Obesity-associated adipose tissue inflammation is characterized by infiltration of macrophages and increased cytokine and chemokine production. The distribution of adipose tissue impacts the outcomes of obesity, with the accumulation of fat in visceral adipose tissue (VAT) and deep subcutaneous adipose tissue (SAT), but not superficial SAT, being linked to insulin resistance. We hypothesized that the inflammatory gene expression in deep SAT and VAT is higher than in superficial SAT. A total of 17 apparently healthy women (BMI: 29.3 +/- 5.5 kg/m2) were included in the study. Body fat (dual-energy X-ray absorptiometry) and distribution (computed tomography) were measured, and insulin sensitivity, blood lipids, and blood pressure were determined. Inflammation-related differences in gene expression(real-time PCR) from VAT, superficial and deep SAT biopsies were analyzed using univariate and multivariate data analyses. Using multivariate discrimination analysis, VAT appeared as a distinct depot in adipose tissue inflammation,while the SAT depots had a similar pattern, with respect to gene expression. A significantly elevated (P < 0.01)expression of the CC chemokine receptor 2 (CCR2) and macrophage migration inhibitory factor (MIF) in VAT contributed strongly to the discrimination. In conclusion, the human adipose tissue depots have unique inflammatory patterns, with CCR2 and MIF distinguishing between VAT and the SAT depots.

  • 2.
    Blomquist, Caroline
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Alvehus, Malin
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Burén, Jonas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Ryberg, Mats
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Larsson, Christel
    Department of Food and Nutrition and Sport Science, University of Gothenburg, Gothenburg, Sweden..
    Lindahl, Bernt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Mellberg, Caroline
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Söderström, Ingegerd
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Chorell, Elin
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Olsson, Tommy
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Attenuated Low-Grade Inflammation Following Long-Term Dietary Intervention in Postmenopausal Women with Obesity2017In: Obesity, ISSN 1930-7381, E-ISSN 1930-739X, Vol. 25, no 5, p. 892-900Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Abdominal fat accumulation after menopause is associated with low-grade inflammation and increased risk of metabolic disorders. Effective long-term lifestyle treatment is therefore needed.

    METHODS: Seventy healthy postmenopausal women (age 60 ± 5.6 years) with BMI 32.5 ± 5.5 were randomized to a Paleolithic-type diet (PD) or a prudent control diet (CD) for 24 months. Blood samples and fat biopsies were collected at baseline, 6 months, and 24 months to analyze inflammation-related parameters.

    RESULTS: Android fat decreased significantly more in the PD group (P = 0.009) during the first 6 months with weight maintenance at 24 months in both groups. Long-term significant effects (P < 0.001) on adipose gene expression were found for toll-like receptor 4 (decreased at 24 months) and macrophage migration inhibitory factor (increased at 24 months) in both groups. Serum interleukin 6 (IL-6) and tumor necrosis factor α levels were decreased at 24 months in both groups (P < 0.001) with a significant diet-by-time interaction for serum IL-6 (P = 0.022). High-sensitivity C-reactive protein was decreased in the PD group at 24 months (P = 0.001).

    CONCLUSIONS: A reduction of abdominal obesity in postmenopausal women is linked to specific changes in inflammation-related adipose gene expression.

  • 3.
    Franks, Paul W.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Lund University, Sweden and Harvard University, USA.
    Body Weight and Risk of Early Death2013In: Obesity, ISSN 1930-7381, E-ISSN 1930-739X, Vol. 21, no 9, p. 1743-1743Article in journal (Other academic)
  • 4.
    Franks, Paul W.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Time to reappraise the use of Body Mass Index in genetic association studies of children?2014In: Obesity, ISSN 1930-7381, E-ISSN 1930-739X, Vol. 22, no 10, p. 2260-2261Article in journal (Other academic)
  • 5. Goedecke, Julia H
    et al.
    Levitt, Naomi S
    Lambert, Estelle V
    Utzschneider, Kristina M
    Faulenbach, Mirjam V
    Dave, Joel A
    West, Sacha
    Victor, Hendriena
    Evans, Juliet
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Olsson, Tommy
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Walker, Brian R
    Seckl, Jonathan R
    Kahn, Steven E
    Differential effects of abdominal adipose tissue distribution on insulin sensitivity in black and white South African women2009In: Obesity, ISSN 1930-7381, E-ISSN 1930-739X, Vol. 17, no 8, p. 1506-1512Article in journal (Refereed)
    Abstract [en]

    Black South African women are more insulin resistant than BMI-matched white women. The objective of the study was to characterize the determinants of insulin sensitivity in black and white South African women matched for BMI. A total of 57 normal-weight (BMI 18-25 kg/m(2)) and obese (BMI > 30 kg/m(2)) black and white premenopausal South African women underwent the following measurements: body composition (dual-energy X-ray absorptiometry), body fat distribution (computerized tomography (CT)), insulin sensitivity (S(I), frequently sampled intravenous glucose tolerance test), dietary intake (food frequency questionnaire), physical activity (Global Physical Activity Questionnaire), and socioeconomic status (SES, demographic questionnaire). Black women were less insulin sensitive (4.4 +/- 0.8 vs. 9.5 +/- 0.8 and 3.0 +/- 0.8 vs. 6.0 +/- 0.8 x 10(-5)/min/(pmol/l), for normal-weight and obese women, respectively, P < 0.001), but had less visceral adipose tissue (VAT) (P = 0.051), more abdominal superficial subcutaneous adipose tissue (SAT) (P = 0.003), lower SES (P < 0.001), and higher dietary fat intake (P = 0.001) than white women matched for BMI. S(I) correlated with deep and superficial SAT in both black (R = -0.594, P = 0.002 and R = 0.495, P = 0.012) and white women (R = -0.554, P = 0.005 and R = -0.546, P = 0.004), but with VAT in white women only (R = -0.534, P = 0.005). In conclusion, body fat distribution is differentially associated with insulin sensitivity in black and white women. Therefore, the different abdominal fat depots may have varying metabolic consequences in women of different ethnic origins.

  • 6. Gustafsson, Stefan
    et al.
    Lind, Lars
    Söderberg, Stefan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Zilmer, Mihkel
    Hulthe, Johannes
    Ingelsson, Erik
    Oxidative Stress and Inflammatory Markers in Relation to Circulating Levels of Adiponectin2013In: Obesity, ISSN 1930-7381, E-ISSN 1930-739X, Vol. 21, no 7, p. 1467-1473Article in journal (Refereed)
    Abstract [en]

    Objective: Previous epidemiological studies together with animal studies have suggested an association between adiponectin and oxidative stress and inflammation, but community-based studies are lacking. Our objective was to investigate the relative importance of oxidative stress and inflammatory markers, representing different pathways in relation to adiponectin. Design and Methods: In a cross-sectional sample of 929 70-year-old individuals (50% women) of the Prospective Investigation of the Vasculature in Uppsala Seniors study, relations between serum adiponectin and oxidative stress [conjugated dienes (CD), homocysteine, total antioxidant capacity, oxidized low-density lipoprotein (OxLDL), OxLDL antibodies, baseline CD of LDL, glutathione (GSH), total glutathione (TGSH), glutathione disulfide], circulation interleukins (IL-6, IL-8), other cytokines [tumor necrosis factor alpha, monocyte chemotactic protein-1 (MCP-1), epidermal growth factor (EGF), vascular endothelial growth factor], cell adhesion molecules (vascular cell adhesion molecule-1, intercellular adhesion molecule-1, E-selectin, P-selectin, L-selectin), and systemic inflammatory markers [C-reactive protein (CRP), leukocyte count] in separate models were investigated. Results: In age- and sex-adjusted, as well as multivariable-adjusted models, adiponectin was significantly and positively associated with GSH, log TGSH, whereas an inverse association was observed for CD and log EGF. An inverse association between adiponectin and MCP-1, log E-selectin, and log CRP was significant in age- and sex-adjusted models, but not in multivariable-adjusted models. Conclusions: Our results imply that higher levels of adiponectin are associated with a more beneficial oxidative stress profile, with higher levels of principal anti-oxidative GSH and total GSH together with lower levels of lipid peroxidation, possibly through shared pathways. Further studies are needed to investigate whether changes in the oxidative stress profile may be a mechanism linking adiponectin with type 2 diabetes and/or cardiovascular disease.

  • 7.
    Lilja, Mikael
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Eliasson, Mats
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Stegmayr, Birgitta
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Olsson, Tommy
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Söderberg, Stefan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Trends in obesity and its distribution: data from the Northern Sweden MONICA survey, 1986–20042008In: Obesity, ISSN 1930-7381, E-ISSN 1930-739X, Vol. 16, no 5, p. 1120-1128Article in journal (Refereed)
    Abstract [en]

    Objective: Obesity, especially abdominal, is a risk factor for many diseases. This study explored trends in theprevalence of general and abdominal obesity, 1986–2004, in northern Sweden.

    Methods and Procedures: Cross-sectional population surveys were performed in 1986, 1990, 1994, 1999, and 2004;250 men and 250 women aged 25−34, 35−44, 45−54, and 55−64 years (from 1994, also 65−74 years) were randomlyselected; the overall participation rate was 77%. Anthropometric data were used.

    Results: Weight and BMI increased in all men, most significantly in men aged 25−64 years (P < 0.0005). Weightincreased in women aged 25−64 years (P < 0.005) and BMI in women aged 25−44 years (P < 0.005). Prevalence ofobesity (BMI≥ 30) increased significantly in men aged 25−44 and 55−74 years (P < 0.005; for men 65−74 years old,P< 0.05) and in women aged 25−44 years (P < 0.005). Waist circumference decreased significantly between 1986and 1990 in all women (P < 0.005) and in men aged 55−64 years (P < 0.05). After 1990 waist circumference increased, most markedly so in women; by 2004 circumference measurements for women, and for men aged 55−64 years, were equal to those of 1986, while for men aged 25−54 years they were higher. Prevalence of abdominal obesity has increased since 1990, most markedly so in women aged 45−64 years (P < 0.0005).

    Discussion: The rapid increase in both general and central obesity raises concern for the future; increasing abdominalobesity in women is particularly alarming.

  • 8.
    Mattsson, Cecilia
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Rask, Eva
    Carlström, Kjell
    Andersson, Jonas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Eliasson, Mats
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Ahrén, Bo
    Söderberg, Stefan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Olsson, Tommy
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Gender-specific links between hepatic 11beta reduction of cortisone and adipokines2007In: Obesity, ISSN 1930-7381, E-ISSN 1930-739X, Vol. 15, no 4, p. 887-894Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Reduction of cortisone to cortisol is mediated by 11beta-hydroxysteroid dehydrogenase type 1 (11betaHSD1), a putative key enzyme in obesity-related complications. Experimental studies suggest that adipokines, notably leptin and tumor necrosis factor-alpha (TNF-alpha), are of importance for 11betaHSD1 activity. We hypothesized that the regulation of hepatic preceptor glucocorticoid metabolism is gender-specific and associated with circulating levels of leptin and TNF-alpha receptors and/or sex hormones. RESEARCH METHODS AND PROCEDURES: A total of 34 males and 38 women (14 premenopausal and 22 postmenopausal) underwent physical examination and fasting blood sampling. Insulin sensitivity was tested by euglycemic hyperinsulinemic clamps, and hepatic 11betaHSD1 enzyme activity was estimated by the conversion of orally-ingested cortisone to cortisol. RESULTS: Hepatic 11betaHSD1 activity was negatively associated with leptin and soluble TNF (sTNF) r1 and sTNFr2 in males. These correlations remained significant after adjustment for age and insulin sensitivity, and for sTNF-alpha receptors also after adjustment of BMI and waist circumference. In contrast, 11beta reduction of cortisone was positively associated to leptin in females after adjustment for BMI and waist circumference. DISCUSSION: Hepatic 11beta reduction shows different links to circulating adipocyte-derived hormones in males and females. This emphasizes the need for further studies on tissue-specific regulation of 11betaHSD1 in both genders.

  • 9. Nyamdorj, Regzedmaa
    et al.
    Qiao, Qing
    Söderberg, Stefan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Pitkäniemi, Janne M
    Zimmet, Paul Z
    Shaw, Jonathan E
    Alberti, K G M M
    Pauvaday, Vassen K
    Chitson, Pierrot
    Kowlessur, Sudhirsen
    Tuomilehto, Jaakko
    BMI compared with central obesity indicators as a predictor of diabetes incidence in Mauritius2009In: Obesity, ISSN 1930-7381, E-ISSN 1930-739X, Vol. 17, no 2, p. 342-348Article in journal (Refereed)
    Abstract [en]

    The aim of the study was to compare BMI with waist circumference (WC), waist-to-hip ratio (WHR), and waist-to-stature ratio (WSR) as a predictor of diabetes incidence. A total of 1,841 men and 2,104 women of Mauritian Indian and Mauritian Creole ethnicity, aged 25-74 years, free of diabetes, hypertension, cardiovascular disease, and gout were seen at baseline in 1987 or 1992, and follow-up in 1992 and/or 1998. At all time points, participants underwent a 2 h 75 g oral glucose tolerance test. Hazard ratios for diabetes incidence were estimated applying an interval-censored survival analysis using age as timescale. Six hundred and twenty-eight individuals developed diabetes during the follow-up period. Multivariable adjusted hazard ratios for diabetes incidence corresponding to a 1 s.d. increase in baseline BMI, WC, WHR, and WSR for Mauritian Indians were 1.49 (1.31-1.71), 1.58 (1.38-1.81), 1.54 (1.37-1.72), and 1.61 (1.41-1.84) in men and 1.33 (1.17-1.51), 1.35 (1.19-1.53), 1.39 (1.24-1.55), and 1.38 (1.21-1.57) in women, respectively; and for Mauritian Creoles they were 1.86 (1.51-2.30), 2.07 (1.68-2.56), 1.92 (1.62-2.26), and 2.17 (1.76-2.69) in men and 1.29 (1.06-1.55), 1.27 (1.04-1.55), 1.24 (1.04-1.48), and 1.27 (1.04-1.55) in women. Paired homogeneity tests showed that there was no difference between BMI and each of the central obesity indicators (all P > 0.05). The relation of BMI with the development of diabetes was as strong as that for indicators of central obesity in this study population.

  • 10. Pan, Qing
    et al.
    Delahanty, Linda M.
    Jablonski, Kathleen A.
    Knowler, William C.
    Kahn, Steven E.
    Florez, Jose C.
    Franks, Paul W.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Harvard University, USA and Lund University, Sweden.
    Variation at the Melanocortin 4 Receptor Gene and Response to Weight-Loss Interventions in the Diabetes Prevention Program2013In: Obesity, ISSN 1930-7381, E-ISSN 1930-739X, Vol. 21, no 9, p. E520-E526Article in journal (Refereed)
    Abstract [en]

    Objective: To assess associations and genotype x treatment interactions for melanocortin 4 receptor (MC4R) locus variants and obesity-related traits.

    Design and Methods: Diabetes prevention program (DPP) participants (N = 3,819, of whom 3,356 were genotyped for baseline and 3,234 for longitudinal analyses) were randomized into intensive lifestyle modification (diet, exercise, weight loss), metformin or placebo control. Adiposity was assessed in a subgroup (n = 909) using computed tomography. All analyses were adjusted for age, sex, ethnicity and treatment.

    Results: The rs1943218 minor allele was nominally associated with short-term (6 month; P = 0.032) and long-term (2 year; P = 0.038) weight change. Eight SNPs modified response to treatment on short-term (rs17066856, rs9966412, rs17066859, rs8091237, rs17066866, rs7240064) or long-term (rs12970134, rs17066866) reduction in body weight, or diabetes incidence (rs17066829) (all P-interaction < 0.05).

    Conclusion: This is the first study to comprehensively assess the role of MC4R variants and weight regulation in a weight loss intervention trial. One MC4R variant was directly associated with obesity-related traits or diabetes; numerous other variants appear to influence body weight and diabetes risk by modifying the protective effects of the DPP interventions.

  • 11. Vimaleswaran, Karani S
    et al.
    Franks, Paul
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Brage, Soren
    Sardinha, Luis B
    Andersen, Lars B
    Wareham, Nicholas J
    Ekelund, Ulf
    Loos, Ruth J F
    Absence of association between the INSIG2 gene polymorphism (rs7566605) and obesity in the European Youth Heart Study (EYHS)2009In: Obesity, ISSN 1930-7381, E-ISSN 1930-739X, Vol. 17, no 7, p. 1453-1457Article in journal (Refereed)
    Abstract [en]

    The first genome-wide association study for BMI identified a polymorphism, rs7566605, 10 kb upstream of the insulin-induced gene 2 (INSIG2) transcription start site, as the most significantly associated variant in children and adults. Subsequent studies, however, showed inconsistent association of this polymorphism with obesity traits. This polymorphism has been hypothesized to alter INSIG2 expression leading to inhibition of fatty acid and cholesterol synthesis. Hence, we investigated the association of the INSIG2 rs7566605 polymorphism with obesity- and lipid-related traits in Danish and Estonian children (930 boys and 1,073 girls) from the European Youth Heart Study (EYHS), a school-based, cross-sectional study of pre- and early pubertal children. The association between the polymorphism and obesity traits was tested using additive and recessive models adjusted for age, age-group, gender, maturity and country. Interactions were tested by including the interaction terms in the model. Despite having sufficient power (98%) to detect the previously reported effect size for association with BMI, we did not find significant effects of rs7566605 on BMI (additive, P = 0.68; recessive, P = 0.24). Accordingly, the polymorphism was not associated with overweight (P = 0.87) or obesity (P = 0.34). We also did not find association with waist circumference (WC), sum of four skinfolds, or with total cholesterol, triglycerides, low-density lipoprotein, or high-density lipoprotein. There were no gender-specific (P = 0.55), age-group-specific (P = 0.63) or country-specific (P = 0.56) effects. There was also no evidence of interaction between genotype and physical activity (P = 0.95). Despite an adequately powered study, our findings suggest that rs7566605 is not associated with obesity-related traits and lipids in the EYHS.Obesity (2009) doi:10.1038/oby.2008.650.

  • 12. Wientzek, Angelika
    et al.
    Tormo Diaz, Maria-Jose
    Huerta Castano, Jose Maria
    Amiano, Pilar
    Arriola, Larraitz
    Overvad, Kim
    Ostergaard, Jane Nautrup
    Charles, Marie-Aline
    Fagherazzi, Guy
    Palli, Domenico
    Bendinelli, Benedetta
    Skeie, Guri
    Borch, Kristin Benjaminsen
    Wendel-Vos, Wanda
    de Hollander, Ellen
    May, Anne M.
    den Ouden, Marjolein E. M.
    Trichopoulou, Antonia
    Valanou, Elissavet
    Söderberg, Stefan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Franks, Paul W.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Brage, Soren
    Vigl, Matthaus
    Boeing, Heiner
    Ekelund, Ulf
    Cross-Sectional Associations of Objectively Measured Physical Activity, Cardiorespiratory Fitness and Anthropometry in European Adults2014In: Obesity, ISSN 1930-7381, E-ISSN 1930-739X, Vol. 22, no 5, p. E127-E134Article in journal (Refereed)
    Abstract [en]

    Objective: To quantify the independent associations between objectively measured physical activity (PA), cardiorespiratory fitness (CRF), and anthropometry in European men and women. Methods: 2,056 volunteers from 12 centers across Europe were fitted with a heart rate and movement sensor at 2 visits 4 months apart for a total of 8 days. CRF (ml/kg/min) was estimated from an 8 minute ramped step test. A cross-sectional analysis of the independent associations between objectively measured PA (m/s(2)/d), moderate and vigorous physical activity (MVPA) (% time/d), sedentary time (% time/d), CRF, and anthropometry using sex stratified multiple linear regression was performed. Results: In mutually adjusted models, CRF, PA, and MVPA were inversely associated with all anthropometric markers in women. In men, CRF, PA, and MVPA were inversely associated with BMI, whereas only CRF was significantly associated with the other anthropometric markers. Sedentary time was positively associated with all anthropometric markers, however, after adjustment for CRF significant in women only. Conclusion: CRF, PA, MVPA, and sedentary time are differently associated with anthropometric markers in men and women. CRF appears to attenuate associations between PA, MVPA, and sedentary time. These observations may have implications for prevention of obesity.

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