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- Iggman, David, 1981-, et al.
(author)
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Adipose tissue fatty acids and cardiovascular and all-cause mortality in elderly men : a prospective cohort study
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Other publication (other academic/artistic)abstract
- Background: For several fatty acids, adipose tissue reflects long-term dietary intake and may provide more objective information than self-reported intake. No prospective studies have examined whether adipose tissue fatty acids predict cardiovascular and all-cause mortality.Objective: To investigate associations between adipose tissue fatty acids and cardiovascular and overall mortality in a cohort of elderly men. We hypothesized that polyunsaturated fatty acids (PUFA) could be inversely associated with cardiovascular and all-cause mortality.Methods: In the Swedish community-based cohort study ULSAM, adipose tissue biopsies were taken from the buttocks of 853 men at age 71. Cox regression analyses were performed primarily for four PUFA that were considered to reflect dietary intake (linoleic acid, 18:2n-6, alpha-linolenic acid, 18:3n-3, eicosapentaenoic acid, 20:5n-3, and docosahexaenoic acid, 22:6n-3), and for all other available fatty acids (secondary analyses) analyzed by gas-liquid chromatography.Results: During 20-year follow-up, 605 individuals died of which 251 were cardiovascular deaths. After adjusting for risk factors, none of the four primary fatty acids were associated with cardiovascular mortality (hazard ratios (HR)=0.92-1.05 for each SD increase, P≥0.27). Linoleic acid was inversely associated with mortality (HR=0.90, 95% confidence interval (CI) 0.82-0.99, P=0.03). In secondary analyses, palmitoleic acid, 16:1n-7, (HR=1.11, 95% CI 1.02-1.21, P=0.01), and arachidonic acid, 20:4n-6, (HR=1.09, 95% CI 1.00-1.19, P=0.05) were associated with increased mortality, whereas heptadecanoic acid, 17:0, was inversely associated with mortality (HR=0.89, 95% CI 0.79-1.00, P=0.05).Conclusions: Adipose tissue PUFA was inversely associated with total mortality, but not cardiovascular mortality in elderly men. The mechanisms behind adipose tissue PUFA and longevity warrant further investigation.
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- Iggman, David, et al.
(author)
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Adipose tissue fatty acids and insulin sensitivity in elderly men.
- 2010
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In: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 53:5, s. 850-857
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Journal article (peer-reviewed)abstract
- AIMS/HYPOTHESIS Dietary fatty acids may affect insulin sensitivity. Adipose tissue fatty acid composition partly reflects long-term dietary intake, but data from large studies regarding relationships with insulin sensitivity are lacking. We aimed to determine the association between adipose tissue fatty acids and insulin sensitivity in elderly Swedish men. METHODS In a cross-sectional analysis of the community-based Uppsala Longitudinal Study of Adult Men (n = 795, mean age 71 years), adipose tissue biopsies were obtained and fatty acid composition was determined by gas-liquid chromatography. Insulin sensitivity was measured directly by a euglycaemic clamp. RESULTS Palmitic acid (16:0), the major saturated fatty acid (SFA) in the diet and in adipose tissue, was negatively correlated with insulin sensitivity (r = -0.14), as were 16:1 n-7 (r = -0.15), 20:3 n-6 (r = -0.31), 20:4 n-6 (r = -0.38), 22:4 n-6 (r = -0.37) and 22:5 n-3 (r = -0.24; p < 0.001 for all). Some minor SFAs were positively correlated; 12:0 (r = 0.46), 14:0 (r = 0.32), 17:0 (r = 0.21) and 18:0 (r = 0.41; p < 0.001 for all), as were essential polyunsaturated fatty acids (PUFAs) 18:2 n-6 (r = 0.10, p < 0.01) and 18:3 n-3 (r = 0.16, p < 0.001). Docosahexaenoic acid (22:6 n-3) was negatively correlated (r = -0.11, p < 0.01), whereas eicosapentaenoic acid (20:5 n-3) was not (r = -0.02, NS). Most associations diminished or disappeared in lean individuals, indicating an effect of obesity. CONCLUSIONS/INTERPRETATION Adipose tissue enriched with palmitic acid and depleted of essential PUFAs is associated with insulin resistance. The positive association between minor SFAs and insulin sensitivity merits further investigation.
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- Iggman, David, et al.
(author)
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Association of adipose tissue fatty acids with cardiovascular and all-cause mortality in elderly men
- 2016
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In: JAMA cardiology. - : American Medical Association (AMA). - 2380-6583 .- 2380-6591. ; 1:7, s. 745-753
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Journal article (peer-reviewed)abstract
- Importance: The major polyunsaturated fatty acids in adipose tissue objectively reflect long-term dietary intake, and may provide more reliable information than would self-reported intake. Whether adipose tissue fatty acids predict cardiovascular and all-cause mortality needs investigation.Objective: To investigate associations between adipose tissue fatty acids and cardiovascular and overall mortality in a cohort of elderly men.Design, Setting, and Participants: We hypothesized that polyunsaturated fatty acids reflecting dietary intake, are inversely associated with cardiovascular and all-cause mortality. In the Swedish cohort study Uppsala Longitudinal Cohort of Adult Men, buttock fatty acid composition was analyzed by gas-liquid chromatography in 1992 to 1993 and 2008. The study participants were followed during 11 311 person-years, between 1991 and 2011 (median follow-up, 14.8 years). In this community-based study that took place from 1970 to 1973, all men born in 1920 to 1924 in Uppsala, Sweden, were invited and 2322 (82%) were included (at age 50 years). At the reinvestigation at age 71 years, 1221 (73%) of the 1681 invited men participated. Adipose tissue biopsy specimens were taken in a subsample of 853 men. There was no loss to follow-up.Exposures: Adipose tissue proportions of 4 polyunsaturated fatty acids that were considered to mainly reflect dietary intake (linoleic acid, 18:2n-6; α-linolenic acid, 18:3n-3; eicosapentaenoic acid, 20:5n-3; and docosahexaenoic acid, 22:6n-3) comprised primary analyses, and all other available fatty acids were secondary analyses.Main Outcomes and Measures: Hazard ratios (HRs) for cardiovascular and all-cause mortality using Cox proportional hazards regression analyses, performed in 2015.Results: Among the 853 Swedish men, there were 605 deaths, of which 251 were cardiovascular deaths. After adjusting for risk factors, none of the 4 primary fatty acids were associated with cardiovascular mortality (HR, 0.92-1.05 for each standard deviation increase; P ≥ .27). Linoleic acid was inversely associated with all-cause mortality (HR, 0.90; 95% CI, 0.82-0.98; P = .02) and directly associated with intake (P < .001). In secondary analyses, palmitoleic acid, 16:1n-7 (HR, 1.11; 95% CI, 1.02-1.21; P = .02) was associated with higher all-cause mortality, whereas heptadecanoic acid, 17:0, tended to be associated with lower all-cause mortality (HR, 0.89; 95% CI, 0.79-1.00; P = .05). Arachidonic:linoleic acid ratio was associated with both cardiovascular (HR, 1.15; 95% CI, 1.05-1.31; P = .04) and all-cause (HR, 1.13; 95% CI, 1.04-1.23; P = .005) mortality.Conclusions and Relevance: Adipose tissue linoleic acid was inversely associated with all-cause mortality in elderly men, although not significantly with cardiovascular mortality.
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- Iggman, David, et al.
(author)
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Role of dietary fats in modulating cardiometabolic risk during moderate weight gain : a randomized double-blind overfeeding trial (LIPOGAIN study)
- 2014
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In: Journal of the American Heart Association. - 2047-9980. ; 3:5
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Journal article (peer-reviewed)abstract
- BACKGROUND: Whether the type of dietary fat could alter cardiometabolic responses to a hypercaloric diet is unknown. In addition, subclinical cardiometabolic consequences of moderate weight gain require further study.METHODS AND RESULTS: In a 7-week, double-blind, parallel-group, randomized controlled trial, 39 healthy, lean individuals (mean age of 27±4) consumed muffins (51% of energy [%E] from fat and 44%E refined carbohydrates) providing 750 kcal/day added to their habitual diets. All muffins had identical contents, except for type of fat; sunflower oil rich in polyunsaturated fatty acids (PUFA diet) or palm oil rich in saturated fatty acids (SFA diet). Despite comparable weight gain in the 2 groups, total: high-density lipoprotein (HDL) cholesterol, low-density lipoprotein:HDL cholesterol, and apolipoprotein B:AI ratios decreased during the PUFA versus the SFA diet (-0.37±0.59 versus +0.07±0.29, -0.31±0.49 versus +0.05±0.28, and -0.07±0.11 versus +0.01±0.07, P=0.003, P=0.007, and P=0.01 for between-group differences), whereas no significant differences were observed for other cardiometabolic risk markers. In the whole group (ie, independently of fat type), body weight increased (+2.2%, P<0.001) together with increased plasma proinsulin (+21%, P=0.007), insulin (+17%, P=0.003), proprotein convertase subtilisin/kexin type 9, (+9%, P=0.008) fibroblast growth factor-21 (+31%, P=0.04), endothelial markers vascular cell adhesion molecule-1, intercellular adhesion molecule-1, and E-selectin (+9, +5, and +10%, respectively, P<0.01 for all), whereas nonesterified fatty acids decreased (-28%, P=0.001).CONCLUSIONS: Excess energy from PUFA versus SFA reduces atherogenic lipoproteins. Modest weight gain in young individuals induces hyperproinsulinemia and increases biomarkers of endothelial dysfunction, effects that may be partly outweighed by the lipid-lowering effects of PUFA.CLINICAL TRIAL REGISTRATION URL: http://ClinicalTrials.gov. Unique identifier: NCT01427140.
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- Jobs, Elisabeth, et al.
(author)
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Serum cathepsin S is associated with decreased insulin sensitivity and the development of diabetes type 2 in a community-based cohort of elderly men
- 2012
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In: Diabetes Care. - : American diabetes association. - 0149-5992 .- 1935-5548. ; 36:1, s. 163-165
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Journal article (peer-reviewed)abstract
- OBJECTIVE. To investigate associations between serum cathepsin S, impaired insulin sensitivity, defective insulin secretion, and diabetes risk in a community-based sample of elderly men without diabetes.RESEARCH DESIGN AND METHODS. Serum cathepsin S, insulin sensitivity (euglycaemic-hyperinsulinaemic clamp), and insulin secretion (early insulin response during an oral glucose tolerance test) were measured in 905 participants of the Uppsala Longitudinal Study of Adult Men (mean age, 71 years). Thirty participants developed diabetes during 6 years of follow-up.RESULTS. After adjustment for age, anthropometric variables, and inflammatory markers, higher cathepsin S was associated with decreased insulin sensitivity (regression coefficient per SD increase -0.09 [95% CI -0.14 to -0.04], P = 0.001), but no association with early insulin response was found. Moreover, higher cathepsin S was associated with a higher risk for developing diabetes (odds ratio per SD increase 1.48 [1.08-2.01], P = 0.01).CONCLUSIONS. Cathepsin S activity appears to be involved in the early dysregulation of glucose and insulin metabolism.
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- Rydell, Andreas, et al.
(author)
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Endothelial dysfunction is associated with impaired lung function in two independent community cohorts
- 2018
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In: Respiratory Medicine. - : Elsevier BV. - 0954-6111 .- 1532-3064. ; 143, s. 123-128
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Journal article (peer-reviewed)abstract
- BackgroundPrior studies investigating the association between endothelial dysfunction and impaired lung function have been small and inconsistent. The primary aim was to investigate the association between endothelial function and lung function in two community-based cohorts.MethodsWe used a discovery/replication approach to study the association between endothelial function and lung function in the Prospective investigation of Obesity, Energy and Metabolism (POEM, discovery cohort, n = 490, mean age 50.3 ± 0.2 years) and the Prospective Study of the Vasculature in Uppsala Seniors (PIVUS, replication cohort, n = 892, mean age 70.2 ± 0.15 years). Spirometry and three different measures of endothelial function were performed including both the invasive forearm technique (endothelium-dependent and endothelium-independent vasodilation [EDV and EIDV, respectively] and noninvasive flow mediated dilation [FMD]).ResultsAn age and sex adjusted association between lower EDV and lower FEV1 was found in POEM and replicated in PIVUS. After merging the two cohorts, 1 standard deviation decrease in EDV was associated with 1.57% lower FEV1 after additional adjustment for smoking status, body mass index, exercise level, and C-reactive protein (95% confidence intervals 0.63–2.51, p = 0.001). The association was slightly lower albeit still statistically significant after excluding participants without cardiovascular disease and chronic respiratory disease and appeared stronger among previous/current smokers vs. non-smokers and in men vs. women (p for interaction = 0.2 and 0.02 respectively).ConclusionsOur findings suggest that even individuals with sub-clinical impairments of lung function in the community have concomitant endothelial dysfunction.
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| 10. |
- Rydell, Andreas, et al.
(author)
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Plasma proteomics and lung function in four community-based cohorts
- 2021
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In: Respiratory Medicine. - : Elsevier. - 0954-6111 .- 1532-3064. ; 176
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Journal article (peer-reviewed)abstract
- BACKGROUND: Underlying mechanism leading to impaired lung function are incompletely understood.OBJECTIVES: To investigate whether protein profiling can provide novel insights into mechanisms leading to impaired lung function.METHODS: We used four community-based studies (n = 2552) to investigate associations between 79 cardiovascular/inflammatory proteins and forced expiratory volume in 1 s percent predicted (FEV1%) assessed by spirometry. We divided the cohorts into discovery and replication samples and used risk factor-adjusted linear regression corrected for multiple comparison (false discovery rate of 5%). We performed Mendelian randomization analyses using genetic and spirometry data from the UK Biobank (n = 421,986) to assess causality.MEASUREMENTS AND MAIN RESULTS: In cross-sectional analysis, 22 proteins were associated with lower FEV1% in both the discovery and replication sample, regardless of stratification by smoking status. The combined proteomic data cumulatively explained 5% of the variation in FEV1%. In longitudinal analyses (n = 681), higher plasma levels of growth differentiation factor 15 (GDF-15) and interleukin 6 (IL-6) predicted a more rapid 5-year decline in lung function (change in FEV1% per standard deviation of protein level -1.4, (95% CI, -2.5 to -0.3) for GDF-15, and -0.8, (95% CI, -1.5 to -0.2) for IL-6. Mendelian randomization analysis in UK-biobank provided support for a causal effect of increased GDF-15 levels and reduced FEV1%.CONCLUSIONS: Our combined approach identified GDF-15 as a potential causal factor in the development of impaired lung function in the general population. These findings encourage additional studies evaluating the role of GDF-15 as a causal factor for impaired lung function.
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