Circulating N-terminal pro B-type natriuretic peptide (NT-proBNP) is a classic diagnostic and prognostic marker for heart failure. However, it is inversely associated with diabetes risk. We aimed to ...investigate relationships of NT-proBNP with risk of diabetes-related complications in initially healthy individuals.
We performed a case-cohort study within the European Prospective Investigation Into Cancer and Nutrition (EPIC)-Potsdam cohort including a random subcohort (
= 1,294) and incident cases of type 2 diabetes (
= 649) and cardiovascular diseases (
= 478). Incident cases of type 2 diabetes (
= 545) were followed up for microvascular (
= 133) and macrovascular (
= 50) complications. Plasma NT-proBNP was measured at baseline in initially healthy participants.
In multivariable models, NT-proBNP was linearly inversely associated with incident type 2 diabetes with a hazard ratio (HR) (95% CI) per doubling in NT-proBNP of 0.91 (0.86, 0.98). The association was only observable in women (0.80 0.72, 0.90) compared with men (0.98 0.91, 1.07). Among people with incident diabetes, NT-proBNP was positively associated with diabetes complications: overall, 1.31 (1.13, 1.53); microvascular complications, 1.20 (1.01, 1.43); and macrovascular complications, 1.37 (1.03, 1.83).
Although higher NT-proBNP levels are associated with lower diabetes risk, NT-proBNP is a biomarker for vascular complications in people who develop diabetes independent of potential confounders. Thus, NT-proBNP might be informative to monitor risk for diabetes-related microvascular and macrovascular complications, which should be further explored in future prospective studies.
Although dietary intake of trans fatty acid (TFA) is a major public health concern because of the associated increase in the risk of cardiovascular events, it remains unclear whether TFAs also ...influence risk of type 2 diabetes (T2D) and whether industrial TFAs (iTFAs) and ruminant TFAs (rTFAs) exert the same effect on health.
To investigate the relationship of 7 rTFAs and iTFAs, including 2 conjugated linoleic acids (CLAs), plasma phospholipid TFAs were measured in a case-cohort study nested within the European Prospective Investigation Into Cancer and Nutrition-Potsdam cohort. The analytical sample was a random subsample (n = 1,248) and incident cases of T2D (n = 801) over a median follow-up of 6.5 years. Using multivariable Cox regression models, we examined associations of TFAs with incident T2D.
The TFA subtypes were intercorrelated with each other, with other fatty acids, and with different food sources. After controlling for other TFAs, the iTFAs (18:1n-6t, 18:1n-9t, 18:2n-6,9t) were not associated with diabetes risk. Some rTFA subtypes were inversely associated with diabetes risk: vaccenic acid (18:1n-7t; hazard ratio HR per SD 0.72; 95% CI 0.58-0.89) and t10c12-CLA (HR per SD 0.81; 95% CI 0.70-0.94), whereas c9t11-CLA was positively associated (HR per SD 1.39; 95% CI 1.19-1.62). Trans-palmitoleic acid (16:1n-7t) was not associated with diabetes risk when adjusting for the other TFAs (HR per SD 1.08; 95% CI 0.88-1.31).
The TFAs' conformation plays an essential role in their relationship to diabetes risk. rTFA subtypes may have opposing relationships to diabetes risk. Previous observations for reduced diabetes risk with higher levels of circulating trans-palmitoleic acid are likely due to confounding.
Recent studies suggest that insulin-like growth factor binding protein 2 (IGFBP-2) may protect against type 2 diabetes, but population-based human studies are scarce. We aimed to investigate the ...prospective association of circulating IGFBP-2 concentrations and of differential methylation in the
gene with type 2 diabetes risk.
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).
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 chromatography, 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.
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.
Selected IgG N-glycans are associated with cardiometabolic risk beyond classic risk factors, including clinical biomarkers.
Background: Habitual red meat consumption was consistently related to a higher risk of type 2 diabetes in observational studies. Potentially underlying mechanisms are unclear. Objective: This study ...aimed to identify blood metabolites that possibly relate red meat consumption to the occurrence of type 2 diabetes. Design: Analyses were conducted in the prospective European Prospective Investigation into Cancer and Nutrition–Potsdam cohort (n = 27,548), applying a nested case-cohort design (n = 2681, including 688 incident diabetes cases). Habitual diet was assessed with validated semiquantitative food-frequency questionnaires. Total red meat consumption was defined as energy-standardized summed intake of unprocessed and processed red meats. Concentrations of 14 amino acids, 17 acylcarnitines, 81 glycerophospholipids, 14 sphingomyelins, and ferritin were determined in serum samples from baseline. These biomarkers were considered potential mediators of the relation between total red meat consumption and diabetes risk in Cox models. The proportion of diabetes risk explainable by biomarker adjustment was estimated in a bootstrapping procedure with 1000 replicates. Results: After adjustment for age, sex, lifestyle, diet, and body mass index, total red meat consumption was directly related to diabetes risk HR for 2 SD (11 g/MJ): 1.26; 95% CI: 1.01, 1.57. Six biomarkers (ferritin, glycine, diacyl phosphatidylcholines 36:4 and 38:4, lysophosphatidylcholine 17:0, and hydroxy-sphingomyelin 14:1) were associated with red meat consumption and diabetes risk. The red meat–associated diabetes risk was significantly (P < 0.001) attenuated after simultaneous adjustment for these biomarkers biomarker-adjusted HR for 2 SD (11 g/MJ): 1.09; 95% CI: 0.86, 1.38. The proportion of diabetes risk explainable by respective biomarkers was 69% (IQR: 49%, 106%). Conclusion: In our study, high ferritin, low glycine, and altered hepatic-derived lipid concentrations in the circulation were associated with total red meat consumption and, independent of red meat, with diabetes risk. The red meat–associated diabetes risk was largely attenuated after adjustment for selected biomarkers, which is consistent with the presumed mediation hypothesis.
To assess the prospective associations of circulating levels of omega 3 polyunsaturated fatty acid (n-3 PUFA) biomarkers (including plant derived α linolenic acid and seafood derived eicosapentaenoic ...acid, docosapentaenoic acid, and docosahexaenoic acid) with incident chronic kidney disease (CKD).
Pooled analysis.
A consortium of 19 studies from 12 countries identified up to May 2020.
Prospective studies with measured n-3 PUFA biomarker data and incident CKD based on estimated glomerular filtration rate.
Each participating cohort conducted de novo analysis with prespecified and consistent exposures, outcomes, covariates, and models. The results were pooled across cohorts using inverse variance weighted meta-analysis.
Primary outcome of incident CKD was defined as new onset estimated glomerular filtration rate <60 mL/min/1.73 m
. In a sensitivity analysis, incident CKD was defined as new onset estimated glomerular filtration rate <60 mL/min/1.73 m
and <75% of baseline rate.
25 570 participants were included in the primary outcome analysis and 4944 (19.3%) developed incident CKD during follow-up (weighted median 11.3 years). In multivariable adjusted models, higher levels of total seafood n-3 PUFAs were associated with a lower incident CKD risk (relative risk per interquintile range 0.92, 95% confidence interval 0.86 to 0.98; P=0.009, I
=9.9%). In categorical analyses, participants with total seafood n-3 PUFA level in the highest fifth had 13% lower risk of incident CKD compared with those in the lowest fifth (0.87, 0.80 to 0.96; P=0.005, I
=0.0%). Plant derived α linolenic acid levels were not associated with incident CKD (1.00, 0.94 to 1.06; P=0.94, I
=5.8%). Similar results were obtained in the sensitivity analysis. The association appeared consistent across subgroups by age (≥60
<60 years), estimated glomerular filtration rate (60-89
≥90 mL/min/1.73 m
), hypertension, diabetes, and coronary heart disease at baseline.
Higher seafood derived n-3 PUFA levels were associated with lower risk of incident CKD, although this association was not found for plant derived n-3 PUFAs. These results support a favourable role for seafood derived n-3 PUFAs in preventing CKD.
Abstract Objective To compare weighting methods for Cox regression and multiple imputation (MI) in a case–cohort study in the context of risk prediction modeling. Study Design and Setting Based on ...the European Prospective Investigation into Cancer and Nutrition Potsdam study, we estimated risk scores to predict incident type-2 diabetes using full cohort data and case–cohort data assuming missing information on waist circumference outside the case–cohort (∼90%). Varying weighting approaches and MI were compared with regard to the calculation of relative risks, absolute risks, and predictive abilities including C -index, the net reclassification improvement, and calibration. Results The full cohort comprised 21,845 participants, and the case–cohort comprised 2,703 participants. Relative risks were similar across all methods and compatible with full cohort estimates. Absolute risk estimates showed stronger disagreement mainly for Prentice and Self & Prentice weighting. Barlow and Langholz & Jiao weighting methods and MI were in good agreement with full cohort analysis. Predictive abilities were closest to full cohort estimates for MI or for Barlow and Langholz & Jiao weighting. Conclusions MI seems to be a valid method for deriving or extending a risk prediction model from case–cohort data and might be superior for absolute risk calculation when compared to weighted approaches.
Background: Habitual red meat consumption was consistently related to a higher risk of type 2 diabetes in observational studies. Potentially underlying mechanisms are unclear.
Objective: This study ...aimed to identify blood metabolites that possibly relate red meat consumption to the occurrence of type 2 diabetes.
Design: Analyses were conducted in the prospective European Prospective Investigation into Cancer and Nutrition–Potsdam cohort (n = 27,548), applying a nested case-cohort design (n = 2681, including 688 incident diabetes cases). Habitual diet was assessed with validated semiquantitative food-frequency questionnaires. Total red meat consumption was defined as energy-standardized summed intake of unprocessed and processed red meats. Concentrations of 14 amino acids, 17 acylcarnitines, 81 glycerophospholipids, 14 sphingomyelins, and ferritin were determined in serum samples from baseline. These biomarkers were considered potential mediators of the relation between total red meat consumption and diabetes risk in Cox models. The proportion of diabetes risk explainable by biomarker adjustment was estimated in a bootstrapping procedure with 1000 replicates.
Results: After adjustment for age, sex, lifestyle, diet, and body mass index, total red meat consumption was directly related to diabetes risk HR for 2 SD (11 g/MJ): 1.26; 95% CI: 1.01, 1.57. Six biomarkers (ferritin, glycine, diacyl phosphatidylcholines 36:4 and 38:4, lysophosphatidylcholine 17:0, and hydroxy-sphingomyelin 14:1) were associated with red meat consumption and diabetes risk. The red meat–associated diabetes risk was significantly (P < 0.001) attenuated after simultaneous adjustment for these biomarkers biomarker-adjusted HR for 2 SD (11 g/MJ): 1.09; 95% CI: 0.86, 1.38. The proportion of diabetes risk explainable by respective biomarkers was 69% (IQR: 49%, 106%).
Conclusion: In our study, high ferritin, low glycine, and altered hepatic-derived lipid concentrations in the circulation were associated with total red meat consumption and, independent of red meat, with diabetes risk. The red meat–associated diabetes risk was largely attenuated after adjustment for selected biomarkers, which is consistent with the presumed mediation hypothesis.
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