| 1. |
- Burger, Koert N. J., et al.
(författare)
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Dietary Fiber, Carbohydrate Quality and Quantity, and Mortality Risk of Individuals with Diabetes Mellitus
- 2012
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Ingår i: PLoS ONE. - San Fransisco : Public Library of Science (PLoS). - 1932-6203. ; 7:8
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Tidskriftsartikel (refereegranskat)abstract
- Background: Dietary fiber, carbohydrate quality and quantity are associated with mortality risk in the general population. Whether this is also the case among diabetes patients is unknown. Objective: To assess the associations of dietary fiber, glycemic load, glycemic index, carbohydrate, sugar, and starch intake with mortality risk in individuals with diabetes. Methods: This study was a prospective cohort study among 6,192 individuals with confirmed diabetes mellitus (mean age of 57.4 years, and median diabetes duration of 4.4 years at baseline) from the European Prospective Investigation into Cancer and Nutrition (EPIC). Dietary intake was assessed at baseline (1992-2000) with validated dietary questionnaires. Cox proportional hazards analysis was performed to estimate hazard ratios (HRs) for all-cause and cardiovascular mortality, while adjusting for CVD-related, diabetes-related, and nutritional factors. Results: During a median follow-up of 9.2 y, 791 deaths were recorded, 306 due to CVD. Dietary fiber was inversely associated with all-cause mortality risk (adjusted HR per SD increase, 0.83 [95% CI, 0.75-0.91]) and CVD mortality risk (0.76[0.64-0.89]). No significant associations were observed for glycemic load, glycemic index, carbohydrate, sugar, or starch. Glycemic load (1.42[1.07-1.88]), carbohydrate (1.67[1.18-2.37]) and sugar intake (1.53[1.12-2.09]) were associated with an increased total mortality risk among normal weight individuals (BMI <= 25 kg/m(2); 22% of study population) but not among overweight individuals (P interaction <= 0.04). These associations became stronger after exclusion of energy misreporters. Conclusions: High fiber intake was associated with a decreased mortality risk. High glycemic load, carbohydrate and sugar intake were associated with an increased mortality risk in normal weight individuals with diabetes.
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| 2. |
- Chasman, Daniel I., et al.
(författare)
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Integration of genome-wide association studies with biological knowledge identifies six novel genes related to kidney function
- 2012
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 21:24, s. 5329-5343
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Tidskriftsartikel (refereegranskat)abstract
- In conducting genome-wide association studies (GWAS), analytical approaches leveraging biological information may further understanding of the pathophysiology of clinical traits. To discover novel associations with estimated glomerular filtration rate (eGFR), a measure of kidney function, we developed a strategy for integrating prior biological knowledge into the existing GWAS data for eGFR from the CKDGen Consortium. Our strategy focuses on single nucleotide polymorphism (SNPs) in genes that are connected by functional evidence, determined by literature mining and gene ontology (GO) hierarchies, to genes near previously validated eGFR associations. It then requires association thresholds consistent with multiple testing, and finally evaluates novel candidates by independent replication. Among the samples of European ancestry, we identified a genome-wide significant SNP in FBXL20 (P 5.6 10(9)) in meta-analysis of all available data, and additional SNPs at the INHBC, LRP2, PLEKHA1, SLC3A2 and SLC7A6 genes meeting multiple-testing corrected significance for replication and overall P-values of 4.5 10(4)2.2 10(7). Neither the novel PLEKHA1 nor FBXL20 associations, both further supported by association with eGFR among African Americans and with transcript abundance, would have been implicated by eGFR candidate gene approaches. LRP2, encoding the megalin receptor, was identified through connection with the previously known eGFR gene DAB2 and extends understanding of the megalin system in kidney function. These findings highlight integration of existing genome-wide association data with independent biological knowledge to uncover novel candidate eGFR associations, including candidates lacking known connections to kidney-specific pathways. The strategy may also be applicable to other clinical phenotypes, although more testing will be needed to assess its potential for discovery in general.
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| 3. |
- Noethlings, Ute, et al.
(författare)
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Intake of vegetables, legumes, and fruit, and risk for all-cause, cardiovascular, and cancer mortality in a European diabetic population
- 2008
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Ingår i: Journal of Nutrition. - 1541-6100. ; 138:4, s. 775-781
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Tidskriftsartikel (refereegranskat)abstract
- We examined the associations of intake of vegetables, legumes and fruit with all-cause and cause-specific mortality in a population with prevalent diabetes in Europe. A cohort of 10,449 participants with self-reported diabetes within the European Prospective Investigation into Cancer and Nutrition study was followed for a mean of 9 y. Intakes of vegetables, legumes, and fruit were assessed at baseline between 1992 and 2000 using validated country-specific questionnaires. A total of 1346 deaths occurred. Multivariate relative risks (RR) for all-cause mortality were estimated in Cox regression models and FIR for cause-specific mortality were derived in a competing risk model. An increment in intake of total vegetables, legumes, and fruit of 80 g/d was associated with a RR of death from all causes of 0.94 [95% CI 0.90-0.98]. Analyzed separately, vegetables and legumes were associated with a significantly reduced risk, whereas nonsignificant inverse associations for fruit intake were observed. Cardiovascular disease (CVD) mortality and mortality due to non-CVD/non-cancer causes were significantly inversely associated with intake of total vegetables, legumes, and fruit (RR 0.88 [95% CI 0.81-0.95] and 0.90 [0.82-0.99], respectively) but not cancer mortality 0.08 [0.99-1.17]). Intake of vegetables, legumes, and fruit was associated with reduced risks of all-cause and CVD mortality in a diabetic population. The findings support the current state of evidence from general population studies that the protective potential of vegetable and fruit intake is larger for CVD than for cancer and suggest that diabetes patients may benefit from a diet high in vegetables and fruits.
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| 4. |
- Parsa, Afshin, et al.
(författare)
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Common Variants in Mendelian Kidney Disease Genes and Their Association with Renal Function
- 2013
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Ingår i: Journal of the American Society of Nephrology. - 1046-6673 .- 1533-3450. ; 24:12, s. 2105-2117
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Tidskriftsartikel (refereegranskat)abstract
- Many common genetic variants identified by genome-wide association studies for complex traits map to genes previously linked to rare inherited Mendelian disorders. A systematic analysis of common single-nucleotide polymorphisms (SNPs) in genes responsible for Mendelian diseases with kidney phenotypes has not been performed. We thus developed a comprehensive database of genes for Mendelian kidney conditions and evaluated the association between common genetic variants within these genes and kidney function in the general population. Using the Online Mendelian Inheritance in Man database, we identified 731 unique disease entries related to specific renal search terms and confirmed a kidney phenotype in 218 of these entries, corresponding to mutations in 258 genes. We interrogated common SNPs (minor allele frequency >5%) within these genes for association with the estimated GFR in 74,354 European-ancestry participants from the CKDGen Consortium. However, the top four candidate SNPs (rs6433115 at LRP2, rs1050700 at TSC1, rs249942 at PALB2, and rs9827843 at ROBO2) did not achieve significance in a stage 2 meta-analysis performed in 56,246 additional independent individuals, indicating that these common SNPs are not associated with estimated GFR. The effect of less common or rare variants in these genes on kidney function in the general population and disease-specific cohorts requires further research.
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| 5. |
- Pattaro, Cristian, et al.
(författare)
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A meta-analysis of genome-wide data from five European isolates reveals an association of COL22A1, SYT1, and GABRR2 with serum creatinine level
- 2010
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Ingår i: BMC Medical Genetics. - : Springer Science and Business Media LLC. - 1471-2350. ; 11, s. 41-
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Tidskriftsartikel (refereegranskat)abstract
- Background Serum creatinine (SCR) is the most important biomarker for a quick and non-invasive assessment of kidney function in population-based surveys. A substantial proportion of the inter-individual variability in SCR level is explicable by genetic factors. Methods We performed a meta-analysis of genome-wide association studies of SCR undertaken in five population isolates ('discovery cohorts'), all of which are part of the European Special Population Network (EUROSPAN) project. Genes showing the strongest evidence for an association with SCR (candidate loci) were replicated in two additional population-based samples ('replication cohorts'). Results After the discovery meta-analysis, 29 loci were selected for replication. Association between SCR level and polymorphisms in the collagen type XXII alpha 1 (COL22A1) gene, on chromosome 8, and in the synaptotagmin-1 (SYT1) gene, on chromosome 12, were successfully replicated in the replication cohorts (p value = 1.0 × 10-6 and 1.7 × 10-4, respectively). Evidence of association was also found for polymorphisms in a locus including the gamma-aminobutyric acid receptor rho-2 (GABRR2) gene and the ubiquitin-conjugating enzyme E2-J1 (UBE2J1) gene (replication p value = 3.6 × 10-3). Previously reported findings, associating glomerular filtration rate with SNPs in the uromodulin (UMOD) gene and in the schroom family member 3 (SCHROOM3) gene were also replicated. Conclusions While confirming earlier results, our study provides new insights in the understanding of the genetic basis of serum creatinine regulatory processes. In particular, the association with the genes SYT1 and GABRR2 corroborate previous findings that highlighted a possible role of the neurotransmitters GABAA receptors in the regulation of the glomerular basement membrane and a possible interaction between GABAAreceptors and synaptotagmin-I at the podocyte level.
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| 6. |
- Saadatian-Elahi, Mitra, et al.
(författare)
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Plasma phospholipid fatty acid profiles and their association with food intakes: results from a cross-sectional study within the European Prospective Investigation into Cancer and Nutrition
- 2009
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Ingår i: American Journal of Clinical Nutrition. - : Elsevier BV. - 1938-3207 .- 0002-9165. ; 89:1, s. 331-346
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Tidskriftsartikel (refereegranskat)abstract
- Background: Plasma phospholipid fatty acids have been correlated with food intakes in populations with homogeneous dietary patterns. However, few data are available on populations with heterogeneous dietary patterns. Objective: The objective was to investigate whether plasma phospholipid fatty acids are suitable biomarkers of dietary intakes across populations involved in a large European multicenter study. Design: A cross-sectional study design nested to the European Prospective Investigation into Cancer and Nutrition (EPIC) was conducted to determine plasma fatty acid profiles in > 3000 subjects from 16 centers, who had also completed 24-h dietary recalls and dietary questionnaires. Plasma fatty acids were assessed by capillary gas chromatography. Ecological and individual correlations were calculated between fatty acids and select food groups. Results: The most important determinant of plasma fatty acids was region, which suggests that the variations across regions are largely due to different food intakes. Strong ecological correlations were observed between fish intake and long-chain n-3 polyunsaturated fatty acids (r = 0.78, P < 0.01), olive oil and oleic acid (r = 0.73, P < 0.01), and margarine and elaidic acid (r = 0.76, P < 0.01). Individual correlations varied across the regions, particularly between olive oil and oleic acid and between alcohol and the saturation index, as an indicator of stearoyl CoA desaturase activity. Conclusions: These findings indicate that specific plasma phospholipid fatty acids are suitable biomarkers of some food intakes in the EPIC Study. Moreover, these findings suggest complex interactions between alcohol intake and fatty acid metabolism, which warrants further attention in epidemiologic studies relating dietary fatty acids to alcohol-related cancers and other chronic diseases. Am J Clin Nutr 2009; 89: 331-46.
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| 7. |
- Siegert, Sabine, et al.
(författare)
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Genome-wide investigation of gene-environment interactions in colorectal cancer
- 2013
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Ingår i: Human Genetics. - : Springer Science and Business Media LLC. - 1432-1203 .- 0340-6717. ; 132:2, s. 219-231
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Tidskriftsartikel (refereegranskat)abstract
- Colorectal cancer (CRC), one of the most frequent neoplasias worldwide, has both genetic and environmental causes. As yet, however, gene-environment (G x E) interactions in CRC have been studied mostly for a small number of candidate genes only. Therefore, we investigated the possible interaction, in CRC etiology, between single-nucleotide polymorphisms (SNPs) on the one hand, and overweight, smoking and alcohol consumption on the other, at a genome-wide level. To this end, we adopted a two-tiered approach comprising a case-only screening stage I (314 cases) and a case-control validation stage II (259 cases, 1,002 controls). Interactions with the smallest p value in stage I were verified in stage II using multiple logistic regression analysis adjusted for sex and age. In addition, we specifically studied known CRC-associated SNPs for possible G x E interactions. Upon adjustment for sex and age, and after allowing for multiple testing, however, only a single SNP (rs1944511) was found to be involved in a statistically significant interaction, namely with overweight (multiplicity-corrected p = 0.042 in stage II). Several other G x E interactions were nominally significant but failed correction for multiple testing, including a previously reported interaction between rs9929218 and alcohol consumption that also emerged in our candidate SNP study (nominal p = 0.008). Notably, none of the interactions identified in our genome-wide analysis was with a previously reported CRC-associated SNP. Our study therefore highlights the potential of an "agnostic" genome-wide approach to G x E analysis.
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| 8. |
- Sluik, Diewertje, et al.
(författare)
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Associations Between General and Abdominal Adiposity and Mortality in Individuals With Diabetes Mellitus
- 2011
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Ingår i: American Journal of Epidemiology. - Cary : Oxford University Press (OUP). - 0002-9262 .- 1476-6256. ; 174:1, s. 22-34
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Tidskriftsartikel (refereegranskat)abstract
- Individuals with diabetes mellitus are advised to achieve a healthy weight to prevent complications. However, fat mass distribution has hardly been investigated as a risk factor for diabetes complications. The authors studied associations between body mass index, waist circumference, waist/hip ratio, and waist/height ratio and mortality among individuals with diabetes mellitus. Within the European Prospective Investigation into Cancer and Nutrition, a subcohort was defined as 5,435 individuals with a confirmed self-report of diabetes mellitus at baseline in 1992-2000. Participants were aged 57.3 (standard deviation, 6.3) years, 54% were men, the median diabetes duration was 4.6 (interquartile range, 2.0-9.8) years, and 22% of the participants used insulin. Body mass index, as indicator of general obesity, was not associated with higher mortality, whereas all measurements of abdominal obesity showed a positive association. Associations generally were slightly weaker in women. The strongest association was observed for waist/height ratio: In the fifth quintile, the hazard rate ratio was 1.88 (95% confidence interval: 1.33, 2.65) for men and 2.46 (95% confidence interval: 1.46, 4.14) for women. Measurements of abdominal, but not general, adiposity were associated with higher mortality in diabetic individuals. The waist/height ratio showed the strongest association. Respective indicators might be investigated in risk prediction models.
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| 9. |
- Sluik, Diewertje, et al.
(författare)
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HbA(1c) Measured in Stored Erythrocytes Is Positively Linearly Associated with Mortality in Individuals with Diabetes Mellitus
- 2012
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7:6, s. e38877-
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Observational studies have shown that glycated haemoglobin (HbA(1c)) is related to mortality, but the shape of the association is less clear. Furthermore, disease duration and medication may modify this association. This observational study explored the association between HbA(1c) measured in stored erythrocytes and mortality. Secondly, it was assessed whether disease duration and medication use influenced the estimates or were independently associated with mortality. Methods: Within the European Prospective Investigation into Cancer and Nutrition a cohort was analysed of 4,345 individuals with a confirmed diagnosis of diabetes at enrolment. HbA(1c) was measured in blood samples stored up to 19 years. Multivariable Cox proportional hazard regression models for all-cause mortality investigated HbA(1c) in quartiles as well as per 1% increment, diabetes medication in seven categories of insulin and oral hypoglycaemic agents, and disease duration in quartiles. Results: After a median follow-up of 9.3 years, 460 participants died. Higher HbA(1c) was associated with higher mortality: Hazard Ratio for 1%-increase was 1.11 (95% CI 1.06, 1.17). This association was linear (P-nonlinearity = 0.15) and persistent across categories of medication use, disease duration, and co-morbidities. Compared with metformin, other medication types were not associated with mortality. Longer disease duration was associated with mortality, but not after adjustment for HbA(1c) and medication. Conclusion: This prospective study showed that persons with lower HbA(1c) had better survival than those with higher HbA(1c). The association was linear and independent of disease duration, type of medication use, and presence of co-morbidities. Any improvement of HbA(1c) appears to be associated with reduced mortality risk.
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| 10. |
- Sluik, Diewertje, et al.
(författare)
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Lifestyle factors and mortality risk in individuals with diabetes mellitus: are the associations different from those in individuals without diabetes?
- 2014
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 1432-0428 .- 0012-186X. ; 57:1, s. 63-72
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Tidskriftsartikel (refereegranskat)abstract
- Aims/hypothesis Thus far, it is unclear whether lifestyle recommendations for people with diabetes should be different from those for the general public. We investigated whether the associations between lifestyle factors and mortality risk differ between individuals with and without diabetes. Methods Within the European Prospective Investigation into Cancer and Nutrition (EPIC), a cohort was formed of 6,384 persons with diabetes and 258,911 EPIC participants without known diabetes. Joint Cox proportional hazard regression models of people with and without diabetes were built for the following lifestyle factors in relation to overall mortality risk: BMI, waist/height ratio, 26 food groups, alcohol consumption, leisure-time physical activity, smoking. Likelihood ratio tests for heterogeneity assessed statistical differences in regression coefficients. Results Multivariable adjusted mortality risk among individuals with diabetes compared with those without was increased, with an HR of 1.62 (95% CI 1.51, 1.75). Intake of fruit, legumes, nuts, seeds, pasta, poultry and vegetable oil was related to a lower mortality risk, and intake of butter and margarine was related to an increased mortality risk. These associations were significantly different in magnitude from those in diabetes-free individuals, but directions were similar. No differences between people with and without diabetes were detected for the other lifestyle factors. Conclusions/interpretation Diabetes status did not substantially influence the associations between lifestyle and mortality risk. People with diabetes may benefit more from a healthy diet, but the directions of association were similar. Thus, our study suggests that lifestyle advice with respect to mortality for patients with diabetes should not differ from recommendations for the general population.
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