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- Nowak, Christoph, et al.
(författare)
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Metabolite profiles during an oral glucose tolerance test reveal new associations with clamp-measured insulin sensitivity
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Impaired insulin sensitivity (IS) is a major risk factor for cardiovascular disease and type 2 diabetes. Metabolomic profiling during an oral glucose tolerance test (OGTT) can reveal early pathogenic alterations in healthy individuals. Our aim was to identify IS biomarkers and gain new pathophysiologic insights by applying untargeted metabolomics to repeated OGTT plasma samples in association with a hyperinsulinemic-euglycemic clamp assessment. We studied 192 metabolites identified by non-targeted liquid chromatography/mass spectrometry in plasma samples taken at 0, 30, and 120 min during an OGTT in 470 non-diabetic 71-yr-old men. Insulin sensitivity was associated with 35 metabolites at one or more time points in multivariable-adjusted linear regression. The trajectories of nine metabolites during the OGTT were related to IS, six of which (oleic and palmitoleic acid, decanoyl- and dodecanoylcarnitine, deoxycholate-glycine and hexose) showed no associations with IS in the baseline fasting state. The strongest effects were detected for medium-chain acylcarnitines, which increased between 30-120 min in insulin-resistant individuals compared to those with normal IS. In this large community sample, we identified novel associations between clamp-measured IS and metabolite profiles that became apparent only after an oral glucose challenge. Associations of differential medium-chain acylcarnitine and monounsaturated fatty acid trajectories with IS provide new insights into the pathogenesis of insulin resistance.
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- Yi-Ting, Lin, 1981-, et al.
(författare)
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Association of the gut microbiome composition with 24-hour blood pressure measurements in 4,459 participants from the SCAPIS cohort
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- BackgroundHypertension is a multifactorial condition affected by genetic and environmental factors. Previous studies have indicated a link between gut microbiome characteristics and blood pressure regulation but studies were limited by small sample size, restriction to office measurements, and/or using amplicon sequencing techniques, limiting taxonomic resolution and functional profiling. This study aims to examine the relationship between the gut microbiome composition measured with deep shotgun metagenomics and blood pressure measured over 24 hours.MethodsWe analyzed data from 4,459 participants without antihypertensive medication from two sites of the Swedish CArdioPulmonary BioImage Study (SCAPIS). In the first step, we assessed the association of each metagenomic species with mean 24-hour systolic and diastolic blood pressure in regression models adjusting for age, sex, country of birth, plate effect and microbiota richness, in 3,480 participants from Uppsala. Species identified in the first step were assessed for replication in the 879 participants from Malmö/Lund. As a second step, we applied models additionally adjusted for smoking, renal function, and diabetes mellitus.ResultsWe found Dorea longicatena to be positively associated with both systolic and diastolic blood pressure in fully adjusted models and Alistipes sp. 6CPBBH3, to be negatively associated. Dorea longicatena and Alistipes family have previously both been linked to metabolic outcomes. Moreover, we found Roseburia faecis and Collinsella aerofaciens to be positively associated with mean systolic blood pressure, and Fusicatenibacter saccharivorans, Coprococcus comes, and Clostridium sp. TM06-18 positively with mean diastolic blood pressure in the fully adjusted analysis. ConclusionsIn the large, well characterized population-based study SCAPIS, we found specific bacterial species associated with blood pressure. Further studies are needed to understand the causal mechanisms.
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- Iggman, David, 1981-, et al.
(författare)
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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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Annan publikation (övrigt vetenskapligt/konstnärligt)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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