| 1. |
- Carroll, Harriet A., et al.
(författare)
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The association between water intake and future cardiometabolic disease outcomes in the Malmö Diet and Cancer cardiovascular cohort
- 2024
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Ingår i: PLoS ONE. - 1932-6203. ; 19:1, s. 0296778-0296778
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to explore the longitudinal association between reported baseline water intake and incidence of coronary artery disease (CAD) and type 2 diabetes in the Malmö Diet and Cancer Cohort (n = 25,369). Using cox proportional hazards models, we separately modelled the effect of plain and total (all water, including from food) water on CAD and type 2 diabetes risk, whilst adjusting for age, sex, diet collection method, season, smoking status, alcohol intake, physical activity, education level, energy intake, energy misreporting, body mass index, hypertension, lipid lowering medication, apolipoprotein A, apolipoprotein B, and dietary variables. Sensitivity analyses were run to assess validity. After adjustment, no association was found between tertiles of plain or total water intake and type 2 diabetes risk. For CAD, no association was found comparing moderate to low intake tertiles from plain or total water, however, risk of CAD increased by 12% (95% CI 1.03, 1.21) when comparing high to low intake tertiles of plain water, and by 17% (95% CI 1.07, 1.27) for high versus low tertiles of total water. Sensitivity analyses were largely in agreement. Overall, baseline water intake was not associated with future type 2 diabetes risk, whilst CAD risk was higher with higher water intakes. Our findings are discordant with prevailing literature suggesting higher water intakes should reduce cardiometabolic risk. These findings may be an artefact of limitations within the study, but future research is needed to understand if there is a causal underpinning.
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| 2. |
- Dekkers, Koen, et al.
(författare)
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An online atlas of human plasma metabolite signatures of gut microbiome composition.
- 2022
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Human gut microbiota produce a variety of molecules, some of which enter the bloodstream and impact health. Conversely, dietary or pharmacological compounds may affect the microbiota before entering the circulation. Characterization of these interactions is an important step towards understanding the effects of the gut microbiota on health. In this cross-sectional study, we used deep metagenomic sequencing and ultra-high-performance liquid chromatography linked to mass spectrometry for a detailed characterization of the gut microbiota and plasma metabolome, respectively, of 8583 participants invited at age 50 to 64 from the population-based Swedish CArdioPulmonary bioImage Study. Here, we find that the gut microbiota explain up to 58% of the variance of individual plasma metabolites and we present 997 associations between alpha diversity and plasma metabolites and 546,819 associations between specific gut metagenomic species and plasma metabolites in an online atlas ( https://gutsyatlas.serve.scilifelab.se/ ). We exemplify the potential of this resource by presenting novel associations between dietary factors and oral medication with the gut microbiome, and microbial species strongly associated with the uremic toxin p-cresol sulfate. This resource can be used as the basis for targeted studies of perturbation of specific metabolites and for identification of candidate plasma biomarkers of gut microbiota composition.
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| 3. |
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| 4. |
- Fernandez, Céline, et al.
(författare)
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Plasma Lipidome and Prediction of Type 2 Diabetes in the Population-Based Malmö Diet and Cancer Cohort
- 2020
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Ingår i: Diabetes Care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 43:2, s. 366-373
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Type 2 diabetes mellitus (T2DM) is associated with dyslipidemia, but the detailed alterations in lipid species preceding the disease are largely unknown. We aimed to identify plasma lipids associated with development of T2DM and investigate their associations with lifestyle. RESEARCH DESIGN AND METHODS: At baseline, 178 lipids were measured by mass spectrometry in 3,668 participants without diabetes from the Malmö Diet and Cancer Study. The population was randomly split into discovery (n = 1,868, including 257 incident cases) and replication (n = 1,800, including 249 incident cases) sets. We used orthogonal projections to latent structures discriminant analyses, extracted a predictive component for T2DM incidence (lipid-PCDM), and assessed its association with T2DM incidence using Cox regression and lifestyle factors using general linear models. RESULTS: A T2DM-predictive lipid-PCDM derived from the discovery set was independently associated with T2DM incidence in the replication set, with hazard ratio (HR) among subjects in the fifth versus first quintile of lipid-PCDM of 3.7 (95% CI 2.2-6.5). In comparison, the HR of T2DM among obese versus normal weight subjects was 1.8 (95% CI 1.2-2.6). Clinical lipids did not improve T2DM risk prediction, but adding the lipid-PCDM to all conventional T2DM risk factors increased the area under the receiver operating characteristics curve by 3%. The lipid-PCDM was also associated with a dietary risk score for T2DM incidence and lower level of physical activity. CONCLUSIONS: A lifestyle-related lipidomic profile strongly predicts T2DM development beyond current risk factors. Further studies are warranted to test if lifestyle interventions modifying this lipidomic profile can prevent T2DM.
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| 5. |
- Gallo, Widet, et al.
(författare)
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Replication study reveals miR-483-5p as an important target in prevention of cardiometabolic disease
- 2021
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Ingår i: BMC Cardiovascular Disorders. - : Springer Science and Business Media LLC. - 1471-2261. ; 21
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundAlterations in levels of circulating micro-RNAs might reflect within organ signaling or subclinical tissue injury that is linked to risk of diabetes and cardiovascular risk. We previously found that serum levels of miR-483-5p is correlated with cardiometabolic risk factors and incidence of cardiometabolic disease in a case–control sample from the populations-based Malmö Diet and Cancer Study Cardiovascular Cohort (MDC-CC). We here aimed at replicating these findings and to test for association with carotid atherosclerosis.MethodsWe measured miR-483-5p in fasting serum of 1223 healthy subjects from the baseline examination of the population-based, prospective cohort study Malmö Offspring Study (MOS) and correlated miR-483-5p to cardiometabolic risk factors and to incidence of diabetes mellitus and coronary artery disease (CAD) during 3.7 (± 1.3) years of follow-up using logistic regression. In both MOS and MDC-CC we related mir-483-5p to carotid atherosclerosis measured with ultrasound.ResultsIn cross-sectional analysis miR-483-5p was correlated with BMI, waist circumference, HDL, and sex. After adjustment for age and sex, the association remained significant for all risk factors except for HDL. Logistic regression analysis showed significant associations between miR-483-5p and new-onset diabetes (OR = 1.94, 95% CI 1.06–3.56, p = 0.032) and cardiovascular disease (OR = 1.99, 95% CI 1.06–3.75, p = 0.033) during 3.7 (± 1.3) years of follow-up. Furthermore, miR-483-5p was significantly related with maximum intima-media thickness of the carotid bulb in MDC-CC (p = 0.001), but not in MOS, whereas it was associated with increasing number of plaques in MOS (p = 0.007).ConclusionmiR-483-5p is related to an unfavorable cardiometabolic risk factor profile and predicts diabetes and CAD, possibly through an effect on atherosclerosis. Our results encourage further studies of possible underlying mechanisms and means of modifying miR-483-5p as a possible interventional target in prevention of cardiometabolic disease.
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| 6. |
- Hellstrand, Sophie, et al.
(författare)
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Dietary Data in the Malmö Offspring Study : Reproducibility, Method Comparison and Validation against Objective Biomarkers
- 2021
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Ingår i: Nutrients. - : MDPI AG. - 2072-6643. ; 13:5
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Tidskriftsartikel (refereegranskat)abstract
- Irregular dietary intakes impairs estimations from food records. Biomarkers and method combinations can be used to improve estimates. Our aim was to examine reproducibility from two assessment methods, compare them, and validate intakes against objective biomarkers. We used the Malmö Offspring Study (55% women, 18-71 y) with data from a 4-day food record (4DFR) and a short food frequency questionnaire (SFFQ) to compare (1) repeated intakes (n = 180), (2) intakes from 4DFR and SFFQ (n = 1601), and (3) intakes of fatty fish, fruits and vegetables, and citrus with plasma biomarkers (n = 1433) (3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid [CMPF], β-carotene and proline betaine). We also combined 4DFR and SFFQ estimates using principal component analysis (PCA). Moderate correlations were seen between repeated intakes (4DFR median ρ = 0.41, SFFQ median ρ = 0.59) although lower for specific 4DFR-items, especially fatty/lean fish (ρ ≤ 0.08). Between-method correlations (median ρ = 0.33) were higher for intakes of overall food groups compared to specific foods. PCA scores for citrus (proline betaine ρ = 0.53) and fruits and vegetables (β-carotene: ρ = 0.39) showed the highest biomarker correlations, whereas fatty fish intake from the SFFQ per se showed the highest correlation with CMPF (ρ = 0.46). To conclude, the reproducibility of SFFQ data was superior to 4DFR data regarding irregularly consumed foods. Method combination could slightly improve fruit and vegetable estimates, whereas SFFQ data gave most valid fatty fish intake.
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| 7. |
- Johansson, Madeleine, et al.
(författare)
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PLASMA METABOLOMIC PROFILING PREDICTS AORTIC STIFFNESS AND RISK OF INCIDENT CARDIOVASCULAR DISEASE AND MORTALITY AFTER 16 YEARS OF FOLLOW-UP IN THE GENERAL POPULATION
- 2023
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Ingår i: Journal of Hypertension. - 1473-5598. ; 41:Suppl 3, s. 60-60
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Konferensbidrag (refereegranskat)abstract
- Objective: The mechanisms and metabolomic profile underlying early vascular ageing have not been explored in the general population. We aimed to investigate the plasma metabolomic profile in aortic stiffness (vascular ageing) and associated risk of incident cardiovascular disease and mortality in the general population.Design and method: We analysed 108 metabolites in plasma of 5172 individuals from two prospective population-based cohorts with over 16 years of follow-up. Aortic stiffness was assessed by carotid-femoral pulse wave velocity (PWV). Metabolite-predicted PWV was calculated in the older population based on the LASSO regression model by randomly assigning a training set (80%) and validation set (20%) in the younger cohort. Correlations between metabolite-predicted PWV and traditional cardiovascular risk factors were assessed by Spearman. Cox regression was used to calculate risk of incident cardiovascular disease and mortality, and all-cause mortality. All models were adjusted for age, sex and traditional cardiovascular risk factors.Results: Study characteristics are displayed in Table 1. Aortic stiffness was positively associated with following metabolites: long-chain acyl carnitines (C16:0, C16:1 and C13:0), dimethylguanidino valeric acid (DMGV), glutamate and cysteine, while serine was negatively associated with aortic stiffness (Figure 1A). The plasma metabolome predicted aortic stiffness in the validation cohort with good accuracy (R2 0.25, Figure 1B). Metabolite-predicted aortic stiffness was significantly correlated with age (r = 0.68), SBP (r = 0.49), BMI (r = 0.43), and sex (r = 0.20) in both cohorts cross-sectionally. During an average follow-up of 16 years, aortic stiffness predicted by baseline metabolites was associated with increased risk of incident coronary artery disease, incident stroke, cardiovascular mortality, and all-cause mortality in the older population (Figure 1C).Conclusions: For the first time, we show that aortic stiffness (vascular ageing) is predicted by altered metabolism of glutamate, acylcarnitine, cysteine, serine, and DMGV in the general population. These metabolic disturbances precede aortic stiffness by several years and are also associated with increased cardiovascular risk factor burden, and future risk of coronary artery disease, stroke, cardiovascular mortality, and all-cause mortality. Our results highlight the relevance of investigating the molecular pathways related to aortic stiffness. Further metabolomics studies are warranted to verify these findings in independent populations.
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| 8. |
- Korduner, Johan, et al.
(författare)
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Proteomic and Metabolomic Characterization of Metabolically Healthy Obesity: : A Descriptive Study from a Swedish Cohort
- 2021
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Ingår i: Journal of Obesity. - : Hindawi Limited. - 2090-0708 .- 2090-0716. ; 2021
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Tidskriftsartikel (refereegranskat)abstract
- Background/Aims. Obesity is a well-established risk factor for the development of numerous chronic diseases. However, there is a small proportion of obese individuals that seem to escape these aforementioned conditions—Metabolically Healthy Obesity (MHO). Our aim was to do a metabolic and biomarker profiling of MHO individuals. Method. Associations between different biomarkers (proteomics, lipidomics, and metabolomics) coupled to either MHO or metabolically unhealthy obese (MUO) individuals were analyzed through principal component analysis (PCA). Subjects were identified from a subsample of 416 obese individuals, selected from the Malmö Diet and Cancer study—Cardiovascular arm (MDCS-CV, n = 3,443). They were further divided into MHO (n = 143) and MUO (n = 273) defined by a history of hospitalization, or not, at baseline inclusion, and nonobese subjects (NOC, n = 3,027). Two distinctive principle components (PL2, PP5) were discovered with a significant difference and thus further investigated through their main loadings. Results. MHO individuals had a more metabolically favorable lipid and glucose profile than MUO subjects, that is, lower levels of traditional blood glucose and triglycerides, as well as a trend of lower metabolically unfavorable lipid biomarkers. PL2 (lipidomics, ) showed stronger associations of triacylglycerides with MUO, whereas phospholipids correlated with MHO. PP5 (proteomics, ) included interleukin-1 receptor antagonist (IL-1ra) and leptin with positive relations to MUO and galanin that correlated positively to MHO. The group differences in metabolite profiles were to a large extent explained by factors included in the metabolic syndrome. Conclusion. Compared to MUO individuals, corresponding MHO individuals present with a more favorable lipid metabolic profile, accompanied by a downregulation of potentially harmful proteomic biomarkers. This unique and extensive biomarker profiling presents novel data on potentially differentiating traits between these two obese phenotypes.
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| 9. |
- Lauber, Chris, et al.
(författare)
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Lipidomic risk scores are independent of polygenic risk scores and can predict incidence of diabetes and cardiovascular disease in a large population cohort
- 2022
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Ingår i: PLoS Biology. - : Public Library of Science (PLoS). - 1544-9173 .- 1545-7885. ; 20:3
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Tidskriftsartikel (refereegranskat)abstract
- Type 2 diabetes (T2D) and cardiovascular disease (CVD) represent significant disease burdens for most societies and susceptibility to these diseases is strongly influenced by diet and lifestyle. Physiological changes associated with T2D or CVD, such has high blood pressure and cholesterol and glucose levels in the blood, are often apparent prior to disease incidence. Here we integrated genetics, lipidomics, and standard clinical diagnostics to assess future T2D and CVD risk for 4,067 participants from a large prospective population-based cohort, the Malmö Diet and Cancer-Cardiovascular Cohort. By training Ridge regression-based machine learning models on the measurements obtained at baseline when the individuals were healthy, we computed several risk scores for T2D and CVD incidence during up to 23 years of follow-up. We used these scores to stratify the participants into risk groups and found that a lipidomics risk score based on the quantification of 184 plasma lipid concentrations resulted in a 168% and 84% increase of the incidence rate in the highest risk group and a 77% and 53% decrease of the incidence rate in lowest risk group for T2D and CVD, respectively, compared to the average case rates of 13.8% and 22.0%. Notably, lipidomic risk correlated only marginally with polygenic risk, indicating that the lipidome and genetic variants may constitute largely independent risk factors for T2D and CVD. Risk stratification was further improved by adding standard clinical variables to the model, resulting in a case rate of 51.0% and 53.3% in the highest risk group for T2D and CVD, respectively. The participants in the highest risk group showed significantly altered lipidome compositions affecting 167 and 157 lipid species for T2D and CVD, respectively. Our results demonstrated that a subset of individuals at high risk for developing T2D or CVD can be identified years before disease incidence. The lipidomic risk, which is derived from only one single mass spectrometric measurement that is cheap and fast, is informative and could extend traditional risk assessment based on clinical assays.
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| 10. |
- Melander, Olle, et al.
(författare)
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Comparison of cardiovascular disease and cancer prevalence between Mediterranean and north European middle-aged populations (The Cilento on Ageing Outcomes Study and The Malmö Offspring Study)
- 2021
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Ingår i: Internal and Emergency Medicine. - : Springer Science and Business Media LLC. - 1828-0447 .- 1970-9366. ; 16:6, s. 1567-1572
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Tidskriftsartikel (refereegranskat)abstract
- Mediterranean diet protects from both cardiovascular disease (CVD) and cancer. In the 1960s, Ancel Keys defined the concept of Mediterranean diet in the South Italian region of Cilento and proposed it as a key factor for healthy ageing in the region. The aim of the current study was to compare the prevalence of CVD and cancer between a middle-aged population from Cilento and those of a Northern European population from Malmö, Sweden. We clinically characterized two middle-aged (50–67 years of age) population-based samples from Cilento (n = 809) and Malmö (n = 1025), Sweden, respectively. Logistic regression was used to calculate odds ratios (95% confidence interval) for disease prevalence in Malmö versus Cilento inhabitants adjusted for age and sex (model 1) and adjusted for all cardiometabolic risk factors (model 2). The prevalence of hypertension, current smoking, diabetes mellitus and levels of body mass index and triglycerides were lower, whereas HDL-cholesterol was higher in Malmö than in Cilento. LDL-cholesterol was higher and estimated glomerular filtration rate was lower in Malmö than in Cilento. The odds ratio for cardiovascular disease in Malmö versus Cilento inhabitants was 1.13 (0.69–1.87) (P = 0.62) in model 1, whereas it was significantly elevated in model 2 [2.03 (1.14–3.60) (P = 0.016)]. Moreover, the odds ratio for cancer in Malmö versus Cilento was 2.78 (1.81–4.27) (P < 0.001) in model 1 and 3.11 (1.97–4.92) (P < 0.001) in model 2. The higher odds of CVD and cancer in Malmö versus Cilento, when risk factors were accounted for, suggests the existence of unknown protective factors in Cilento.
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