| 1. |
- Aglago, Elom K., et al.
(författare)
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Dietary intake of total, heme and non-heme iron and the risk of colorectal cancer in a European prospective cohort study
- 2023
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Ingår i: British Journal of Cancer. - : Springer Nature. - 0007-0920 .- 1532-1827. ; 128, s. 1529-1540
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Tidskriftsartikel (refereegranskat)abstract
- Background: Iron is an essential micronutrient with differing intake patterns and metabolism between men and women. Epidemiologic evidence on the association of dietary iron and its heme and non-heme components with colorectal cancer (CRC) development is inconclusive.Methods: We examined baseline dietary questionnaire-assessed intakes of total, heme, and non-heme iron and CRC risk in the EPIC cohort. Sex-specific multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were computed using Cox regression. We modelled substitution of a 1 mg/day of heme iron intake with non-heme iron using the leave one-out method.Results: Of 450,105 participants (318,680 women) followed for 14.2 ± 4.0 years, 6162 (3511 women) developed CRC. In men, total iron intake was not associated with CRC risk (highest vs. lowest quintile, HRQ5vs.Q1:0.88; 95%CI:0.73, 1.06). An inverse association was observed for non-heme iron (HRQ5vs.Q1:0.80, 95%CI:0.67, 0.96) whereas heme iron showed a non-significant association (HRQ5vs.Q1:1.10; 95%CI:0.96, 1.27). In women, CRC risk was not associated with intakes of total (HRQ5vs.Q1:1.11, 95%CI:0.94, 1.31), heme (HRQ5vs.Q1:0.95; 95%CI:0.84, 1.07) or non-heme iron (HRQ5vs.Q1:1.03, 95%CI:0.88, 1.20). Substitution of heme with non-heme iron demonstrated lower CRC risk in men (HR:0.94; 95%CI: 0.89, 0.99).Conclusions: Our findings suggest potential sex-specific CRC risk associations for higher iron consumption that may differ by dietary sources.
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| 2. |
- Birukov, Anna, et al.
(författare)
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Immunoglobulin G N-Glycosylation Signatures in Incident Type 2 Diabetes and Cardiovascular Disease
- 2022
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Ingår i: Diabetes Care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 45:11, s. 2729-2736
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE N-glycosylation is a functional posttranslational modification of immunoglobulins (Igs). We hypothesized that specific IgG N-glycans are associated with incident type 2 diabetes and cardiovascular disease (CVD). RESEARCH DESIGN AND METHODS We performed case-cohort studies within the population-based European Prospective Investigation into Cancer and Nutrition (EPIC)–Potsdam cohort (2,127 in the type 2 diabetes subcohort [741 incident cases]; 2,175 in the CVD subcohort [417 myocardial infarction and stroke cases]). Relative abundances of 24 IgG N-glycan peaks (IgG-GPs) were measured by ultraperformance liquid chromatog-raphy, and eight glycosylation traits were derived based on structural similarity. End point–associated IgG-GPs were preselected with fractional polynomials, and prospective associations were estimated in confounder-adjusted Cox models. Diabetes risk associations were validated in three independent studies. RESULTS After adjustment for confounders and multiple testing correction, IgG-GP7, IgG-GP8, IgG-GP9, IgG-GP11, and IgG-GP19 were associated with type 2 diabetes risk. A score based on these IgG-GPs was associated with a higher diabetes risk in EPIC-Potsdam and independent validation studies (843 total cases, 3,149 total non-cases, pooled estimate per SD increase 1.50 [95% CI 1.37–1.64]). Associations of IgG-GPs with CVD risk differed between men and women. In women, IgG-GP9 was inversely associated with CVD risk (hazard ratio [HR] per SD 0.80 [95% CI 0.65–0.98]). In men, a weighted score based on IgG-GP19 and IgG-GP23 was associated with higher CVD risk (HR per SD 1.47 [95% CI 1.20–1.80]). In addition, several derived traits were associated with cardiometabolic disease incidence. CONCLUSIONS Selected IgG N-glycans are associated with cardiometabolic risk beyond classic risk factors, including clinical biomarkers.
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| 3. |
- Frkatović-Hodžić, Azra, et al.
(författare)
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Mapping of the gene network that regulates glycan clock of ageing
- 2023
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Ingår i: Aging. - 1945-4589. ; 15:24, s. 14509-14552
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Tidskriftsartikel (refereegranskat)abstract
- Glycans are an essential structural component of immunoglobulin G (IgG) that modulate its structure and function. However, regulatory mechanisms behind this complex posttranslational modification are not well known. Previous genome-wide association studies (GWAS) identified 29 genomic regions involved in regulation of IgG glycosylation, but only a few were functionally validated. One of the key functional features of IgG glycosylation is the addition of galactose (galactosylation), a trait which was shown to be associated with ageing. We performed GWAS of IgG galactosylation (N=13,705) and identified 16 significantly associated loci, indicating that IgG galactosylation is regulated by a complex network of genes that extends beyond the galactosyltransferase enzyme that adds galactose to IgG glycans. Gene prioritization identified 37 candidate genes. Using a recently developed CRISPR/dCas9 system we manipulated gene expression of candidate genes in the in vitro IgG expression system. Upregulation of three genes, EEF1A1, MANBA and TNFRSF13B, changed the IgG glycome composition, which confirmed that these three genes are involved in IgG galactosylation in this in vitro expression system.
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| 4. |
- Hu, Yang, et al.
(författare)
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Low-Carbohydrate Diet Scores and Mortality Among Adults With Incident Type 2 Diabetes
- 2023
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Ingår i: Diabetes care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 46:4, s. 874-884
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The current study aims to prospectively examine the association between postdiagnosis low-carbohydrate diet (LCD) patterns and mortality among individuals with type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS: Among participants with incident diabetes identified in the Nurses' Health Study and Health Professionals Follow-up Study, an overall total LCD score (TLCDS) was calculated based on the percentage of energy as total carbohydrates. In addition, vegetable (VLCDS), animal (ALCDS), healthy (HLCDS), and unhealthy (ULCDS) LCDS were further derived that emphasized different sources and quality of macronutrients. Multivariable-adjusted Cox models were used to assess the association between the LCDS and mortality. RESULTS: Among 10,101 incident T2D cases contributing 139,407 person-years during follow-up, we documented 4,595 deaths of which 1,389 cases were attributed to cardiovascular disease (CVD) and 881 to cancer. The pooled multivariable-adjusted hazard ratios (HRs, 95% CIs) of total mortality per 10-point increment of postdiagnosis LCDS were 0.87 (0.82, 0.92) for TLCDS, 0.76 (0.71, 0.82) for VLCDS, and 0.78 (0.73, 0.84) for HLCDS. Both VLCDS and HLCDS were also associated with significantly lower CVD and cancer mortality. Each 10-point increase of TLCDS, VLCDS, and HLCDS from prediagnosis to postdiagnosis period was associated with 12% (7%, 17%), 25% (19%, 30%), and 25% (19%, 30%) lower total mortality, respectively. No significant associations were observed for ALCDS and ULCDS. CONCLUSIONS: Among people with T2D, greater adherence to LCD patterns that emphasize high-quality sources of macronutrients was significantly associated with lower total, cardiovascular, and cancer mortality.
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| 5. |
- Ibsen, Daniel B, et al.
(författare)
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Replacement of Red and Processed Meat With Other Food Sources of Protein and the Risk of Type 2 Diabetes in European Populations : The EPIC-InterAct Study
- 2020
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Ingår i: Diabetes Care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 43:11, s. 2660-2667
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: There is sparse evidence for the association of suitable food substitutions for red and processed meat on the risk of type 2 diabetes. We modeled the association between replacing red and processed meat with other protein sources and the risk of type 2 diabetes and estimated its population impact.RESEARCH DESIGN AND METHODS: The European Prospective Investigation into Cancer (EPIC)-InterAct case cohort included 11,741 individuals with type 2 diabetes and a subcohort of 15,450 participants in eight countries. We modeled the replacement of self-reported red and processed meat with poultry, fish, eggs, legumes, cheese, cereals, yogurt, milk, and nuts. Country-specific hazard ratios (HRs) for incident type 2 diabetes were estimated by Prentice-weighted Cox regression and pooled using random-effects meta-analysis.RESULTS: There was a lower hazard for type 2 diabetes for the modeled replacement of red and processed meat `(50 g/day) with cheese (HR 0.90, 95% CI 0.83-0.97) (30 g/day), yogurt (0.90, 0.86-0.95) (70 g/day), nuts (0.90, 0.84-0.96) (10 g/day), or cereals (0.92, 0.88-0.96) (30 g/day) but not for replacements with poultry, fish, eggs, legumes, or milk. If a causal association is assumed, replacing red and processed meat with cheese, yogurt, or nuts could prevent 8.8%, 8.3%, or 7.5%, respectively, of new cases of type 2 diabetes.CONCLUSIONS: Replacement of red and processed meat with cheese, yogurt, nuts, or cereals was associated with a lower rate of type 2 diabetes. Substituting red and processed meat by other protein sources may contribute to the prevention of incident type 2 diabetes in European populations.
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| 6. |
- Ouni, Meriem, et al.
(författare)
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Epigenetic changes in islets of langerhans preceding the onset of diabetes
- 2020
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 69:11, s. 2503-2517
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Tidskriftsartikel (refereegranskat)abstract
- The identification of individuals with a high risk of developing type 2 diabetes (T2D) is fundamental for pre-vention. Here, we used a translational approach and prediction criteria to identify changes in DNA methylation visible before the development of T2D. Islets of Langerhans were isolated from genetically identical 10-week-old female New Zealand Obese mice, which differ in their degree of hyperglycemia and in liver fat content. The application of a semiexplorative approach identified 497 differentially expressed and methylated genes (P = 6.42e-09, hypergeometric test) enriched in pathways linked to insulin secretion and extracellular matrix-receptor interaction. The comparison of mouse data with DNA methylation levels of incident T2D cases from the prospective European Prospective Investigation of Cancer (EPIC)-Potsdam cohort, revealed 105 genes with altered DNA methylation at 605 cytosine-phosphate-guanine (CpG) sites, which were associated with future T2D. AKAP13, TENM2, CTDSPL, PTPRN2, and PTPRS showed the strongest predictive potential (area under the receiver operating characteristic curve values 0.62–0.73). Among the new candidates identified in blood cells, 655 CpG sites, located in 99 genes, were differentially methylated in islets of humans with T2D. Using correction for multiple testing detected 236 genes with an altered DNA methylation in blood cells and 201 genes in diabetic islets. Thus, the introduced translational approach identified novel putative biomarkers for early pancreatic islet aberrations preceding T2D.
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| 7. |
- Prada, Marcela, et al.
(författare)
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Plasma Lipidomic n-6 Polyunsaturated Fatty Acids and Type 2 Diabetes Risk in the EPIC-Potsdam Prospective Cohort Study
- 2023
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Ingår i: Diabetes care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 46:4, s. 836-844
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Evidence on plasma n-6 polyunsaturated fatty acids (PUFAs) and type 2 diabetes risk is inconsistent. We examined the associations of lipid class-specific PUFA concentrations with type 2 diabetes risk. RESEARCH DESIGN AND METHODS: In the prospective European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam cohort (nested case-cohort study: subcohort 1,084 participants, 536 participants with type 2 diabetes, median follow-up 6.5 years), we measured plasma 18:2, 20:3, and 20:4 concentrations in 12 lipid (sub)classes, likely reflecting the plasma concentrations of linoleic acid (18:2n-6), dihomo-γ-linolenic acid (20:3n-6), and arachidonic acid (20:4n-6). The Δ-5 desaturase (D5D) activity was estimated as the 20:4/20:3 ratio. Associations with diabetes were estimated with Cox proportional hazards models. RESULTS: Higher concentrations of 18:2 were inversely associated with type 2 diabetes risk, particularly in lysophosphatidylcholines (hazard ratio [HR] per 1 SD 0.53; 95% CI 0.23-1.26) and monoacylglycerols (HR 0.59; 0.38-0.92). Higher concentrations of 20:3 in phospholipid classes phosphatidylcholines (HR 1.63; 1.23-2.14), phosphatidylethanolamines (HR 1.87; 1.32-2.65), and phosphatidylinositol (HR 1.40; 1.05-1.87); free fatty acids (HR 1.44; 1.10-1.90); and cholesteryl esters (HR 1.47; 1.09-1.98) were linked to higher type 2 diabetes incidence, and these associations remained statistically significant after correction for multiple testing. Higher 20:4 concentrations were not associated with risk. The estimated D5D activity in phospholipids and cholesteryl esters was associated with lower type 2 diabetes risk. Single nucleotide polymorphisms in the D5D-encoding FADS genes explained relatively high proportions of variation of estimated D5D activity in those lipid classes. CONCLUSIONS: Plasma n-6 PUFAs were associated differently with type 2 diabetes, depending on fatty acid and the lipid class.
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| 8. |
- Razquin, Cristina, et al.
(författare)
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Circulating Amino Acids and Risk of Peripheral Artery Disease in the PREDIMED Trial
- 2023
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Ingår i: International Journal of Molecular Sciences. - : MDPI AG. - 1661-6596 .- 1422-0067. ; 24:1
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Tidskriftsartikel (refereegranskat)abstract
- Effective prevention and risk prediction are important for peripheral artery disease (PAD) due to its poor prognosis and the huge disease burden it produces. Circulating amino acids (AA) and their metabolites may serve as biomarkers of PAD risk, but they have been scarcely investigated. The objective was to prospectively analyze the associations of baseline levels of plasma AA (and their pathways) with subsequent risk of PAD and the potential effect modification by a nutritional intervention with the Mediterranean diet (MedDiet). A matched case-control study was nested in the PREDIMED trial, in which participants were randomized to three arms: MedDiet with tree nut supplementation group, MedDiet with extra-virgin olive oil (EVOO) supplementation group or control group (low-fat diet). One hundred and sixty-seven PAD cases were matched with 250 controls. Plasma AA was measured with liquid chromatography/mass spectrometry at the Broad Institute. Baseline tryptophan, serine and threonine were inversely associated with PAD (ORfor 1 SD increase = 0.78 (0.61–0.99); 0.67 (0.51–0.86) and 0.75 (0.59–0.95), respectively) in a multivariable-adjusted conditional logistic regression model. The kynurenine/tryptophan ratio was directly associated with PAD (ORfor 1 SD increase = 1.50 (1.14–1.98)). The nutritional intervention with the MedDiet+nuts modified the association between threonine and PAD (p-value interaction = 0.018) compared with the control group. However, subjects allocated to the MedDiet+EVOO group were protected against PAD independently of baseline threonine. Plasma tryptophan, kynurenine/tryptophan ratio, serine and threonine might serve as early biomarkers of future PAD in subjects at a high risk of cardiovascular disease. The MedDiet supplemented with EVOO exerted a protective effect, regardless of baseline levels of threonine.
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| 9. |
- Schiborn, Catarina, et al.
(författare)
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Retinol and Retinol Binding Protein 4 Levels and Cardiometabolic Disease Risk
- 2022
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Ingår i: Circulation Research. - 1524-4571 .- 0009-7330. ; 131:7, s. 637-649
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Tidskriftsartikel (refereegranskat)abstract
- Background: Despite mechanistic studies linking retinol and RBP4 (retinol binding protein 4) to the pathogenesis of cardiovascular diseases (CVD) and type 2 diabetes (T2D), epidemiological evidence is still conflicting. We investigated whether conflicting results of previous studies may be explained by differences in the association of retinol and RBP4 with cardiometabolic risk across subgroups with distinct sex, hypertension state, liver, or kidney function. Methods: We used case-cohorts nested in the EPIC (European Prospective Investigation Into Cancer and Nutrition)-Potsdam cohort (N=27 548) comprising a random sample of participants (n=2500) and all physician-verified cases of incident CVD (n=508, median follow-up time 8.2 years) and T2D (n=820, median follow-up time 6.3 years). We estimated nonlinear and linear multivariable-adjusted associations between the biomarkers and cardiometabolic diseases by restricted cubic splines and Cox regression, respectively, testing potential interactions with hypertension, liver, and kidney function. Additionally, we performed 2-sample Mendelian Randomization analyses in publicly available data. Results: The association of retinol with cardiometabolic risk was modified by hypertension state (P interaction CVDP interaction T2D<0.001). Retinol was associated with lower cardiometabolic risk in participants with treated hypertension (hazard ratio(per SD) [95% CI]: CVD, 0.71 [0.56-0.90]; T2D, 0.81 [0.70-0.94]) but with higher cardiometabolic risk in normotensive participants (CVD, 1.32 [1.06-1.64]; T2D, 1.15 [0.98-1.36]). Our analyses also indicated a significant interaction between RBP4 and hypertension on CVD risk (P interaction=0.04). Regarding T2D risk, we observed a u-shaped association with RBP4 in women (P nonlinearity=0.01, P effect=0.02) and no statistically significant association in men. The biomarkers' interactions with liver or kidney function were not statistically significant. Hypertension state-specific associations for retinol concentrations with cardiovascular mortality risk were replicated in National Health and Nutrition Examination Survey III. Conclusions: Our findings suggest a hypertension-dependent relationship between plasma retinol and cardiometabolic risk and complex interactions of RBP4 with sex and hypertension on cardiometabolic risk.
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| 10. |
- Sellem, Laury, et al.
(författare)
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Replacement of dietary saturated with unsaturated fatty acids is associated with beneficial effects on lipidome metabolites: a secondary analysis of a randomized trial
- 2023
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Ingår i: American Journal of Clinical Nutrition. - 0002-9165 .- 1938-3207. ; 117:6, s. 1248-1261
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Tidskriftsartikel (refereegranskat)abstract
- Background: The effects of replacing dietary saturated fatty acids (SFAs) with monounsaturated fatty acids (MUFAs) and/or polyunsaturated fatty acids (PUFAs) on the plasma lipidome in relation to the cardiometabolic disease (CMD) risk is poorly understood. Objectives: We aimed to assess the impact of substituting dietary SFAs with unsaturated fatty acids (UFAs) on the plasma lipidome and examine the relationship between lipid metabolites modulated by diet and CMD risk. Methods: Plasma fatty acid (FA) concentrations among 16 lipid classes (within-class FAs) were measured in a subgroup from the Dietary Intervention and VAScular function (DIVAS) parallel randomized controlled trial (n = 113/195), which consisted of three 16-wk diets enriched in SFAs (target SFA:MUFA:n-6PUFA ratio = 17:11:4% total energy [TE]), MUFAs (9:19:4% TE), or a MUFA/PUFA mixture (9:13:10% TE). Similar lipidomics analyses were conducted in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam study (specific case/cohorts: n = 775/1886 for type 2 diabetes [T2D], n = 551/1671 for cardiovascular disease [CVD]). Multiple linear regression and multivariable Cox models identified within-class FAs sensitive to replacement of dietary SFA with UFA in DIVAS and their association with CMD risk in EPIC-Potsdam. Elastic-net regression models identified within-class FAs associated with changes in CMD risk markers post–DIVAS interventions. Results: DIVAS high-UFA interventions reduced plasma within-class FAs associated with a higher CVD risk in EPIC-Potsdam, especially SFA-containing glycerolipids and sphingolipids (e.g., diacylglycerol (20:0) z-score = −1.08; SE = 0.17; P value < 10−8), whereas they increased those inversely associated with CVD risk. The results on T2D were less clear. Specific sphingolipids and phospholipids were associated with changes in markers of endothelial function and ambulatory blood pressure, whereas higher low-density lipoprotein cholesterol concentrations were characterized by higher plasma glycerolipids containing lauric and stearic acids. Conclusions: These results suggest a mediating role of plasma lipid metabolites in the association between dietary fat and CMD risk. Future research combining interventional and observational findings will further our understanding of the role of dietary fat in CMD etiology. This trial was registered in ClinicalTrials.gov as NCT01478958.
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