Maternal diet quality during pregnancy and biomarkers of potentially toxic trace element exposure: Data from the ELFE cohort.

The contribution of the diet to potentially toxic trace element exposure in pregnancy has been rarely addressed. The objective of the present study was to determine the association between the maternal diet during pregnancy and biomarkers of exposure for arsenic (As), mercury (Hg) and lead (Pb) at delivery. As was assessed in maternal urine, Hg in maternal hair, and Pb in cord blood, as a proxy for in utero exposure. Based on 2995 women from the ELFE nationwide birth cohort, higher scores for dietary patterns considered healthy were associated with higher concentrations of As and Hg in maternal matrices. Levels of cord blood Pb were inconsistently associated with dietary patterns considered healthy, and lower with a dietary pattern driven by milk and breakfast cereals. Lower levels of Hg were associated with higher Western dietary pattern scores. In conclusion, higher levels of maternal urinary As and hair Hg are associated with diets considered as "Healthy", while cord blood Pb was not strongly correlated with dietary exposure.

Early life exposure to mercury and relationships with telomere length and mitochondrial DNA content in European children.

BACKGROUND: Telomere length (TL) and mitochondrial function expressed as mitochondrial DNA copy number (mtDNAcn) are biomarkers of aging and oxidative stress and inflammation, respectively. Methylmercury (MeHg), a common pollutant in fish, induces oxidative stress. We hypothesized that elevated oxidative stress from exposure to MeHg decreases mtDNAcn and shortens TL. METHODS: Study participants are 6-11-year-old children from the HELIX multi-center birth cohort study, comprising six European countries. Prenatal and postnatal total mercury (THg) concentrations were measured in blood samples, TL and mtDNAcn were determined in child DNA. Covariates and confounders were obtained by questionnaires. Robust regression models were run, considering sociodemographic and lifestyle covariates, as well as fish consumption. Sex, ethnicity, and fish consumption interaction models were also run. RESULTS: We found longer TL with higher pre- and postnatal THg blood concentrations, even at low-level THg exposure according to the RfD proposed by the US EPA. The prenatal association showed a significant linear relationship with a 3.46 % increase in TL for each unit increased THg. The postnatal association followed an inverted U-shaped marginal non-linear relationship with 1.38 % an increase in TL for each unit increased THg until reaching a cut-point at 0.96 µg/L blood THg, from which TL attrition was observed. Higher pre- and postnatal blood THg concentrations were consistently related to longer TL among cohorts and no modification effect of fish consumption nor children's sex was observed. No association between THg exposure and mtDNAcn was found. DISCUSSION: We found evidence that THg is associated with TL but the associations seem to be time- and concentration-dependent. Further studies are needed to clarify the mechanism behind the telomere changes of THg and related health effects.

Maternal pre-pregnancy BMI and offspring hyperactivity-inattention trajectories from 3 to 8 years in the EDEN birth cohort study.

Evidence suggests obesity during pregnancy is associated with offspring attention-deficit hyperactivity disorder. However, studies have been limited to evaluating the association at a single age with inadequate data on important maternal lifestyle confounders and unmeasured familial confounding. The objective of this study was to examine the association between maternal pre-pregnancy body mass index (BMI) and child hyperactivity-inattention symptoms (HIS) at 3, 5 and 8 years. Data came from the EDEN mother-child cohort. Maternal pre-pregnancy BMI status (kg/m2) was calculated using pre-pregnancy weight and height (self-reported by mothers or measured by midwives). HIS were assessed by parental-report on the Strengths and Difficulties Questionnaire at 3, 5 and 8 years of age and used to derive developmental trajectories of HIS (n = 1428). Multivariate models were adjusted for confounders including socioeconomic status, maternal lifestyle behaviours (exercise, diet, smoking, alcohol), childcare and a stimulating home environment. Paternal BMI was used as a negative control. Compared to a normal pre-pregnancy BMI, pre-pregnancy maternal obesity was positively associated with increased odds of a high HIS trajectory between 3 and 8 years old in both unadjusted and adjusted logistic regression (adjusted odds ratio [aOR] 1.87 [95% CI 1.12, 3.12]). Pre-pregnancy overweight was not significantly associated after adjustment for confounders (aOR 1.32 [0.87, 2.01]). Maternal pre-pregnancy obesity, but not overweight, was associated with increased likelihood of a high HIS trajectory in children from 3 to 8 years old. This association persisted despite controlling for many important maternal lifestyle factors and paternal BMI. Further research is warranted to identify possible mediators involved.

Maternal pre-pregnancy obesity and offspring hyperactivity-inattention symptoms at 5 years in preterm and term children: a multi-cohort analysis.

The objective of this study was to determine the relationship between maternal pre-pregnancy body mass index (BMI) and child hyperactivity-inattention symptoms (HIS) at 5 years, including preterm and term-born children, and to determine whether this association varied with gestational age. Maternal pre-pregnancy BMI and offspring HIS were assessed in 10,898 participants born ≥ 33 weeks of gestation from the ELFE cohort and 2646 children born between 23 and 34 weeks from the EPIPAGE 2 cohort. Reported pre-pregnancy weight (kg) and measured height (m) were collected from mothers at inclusion and used to classify BMI (kg/m2). Child HIS were evaluated using the Strengths and Difficulties Questionnaire around 5 years of age. Logistic regression estimated odds ratios (OR) of a high HIS score (≥ 90th percentile) in the ELFE cohort and generalized estimated equations were used in EPIPAGE 2 to account for non-independence of multiple births. As a negative control, paternal BMI was also considered as an exposure of interest in sensitivity analyses. Maternal pre-pregnancy obesity and overweight were associated with child HIS at 5 years in ELFE (adjusted OR [aOR] for obesity 1.27 [1.06, 1.53]; overweight aOR 1.16 [1.00, 1.36]) and pre-pregnancy obesity was associated with high HIS scores in preterm infants of EPIPAGE 2 (aOR 1.48 [1.06, 2.08]). In ELFE, the magnitude of the association increased with decreasing gestational age (interaction p = 0.02). High maternal pre-pregnancy BMI is associated with greater likelihood of high HIS scores in both at-term and preterm children at 5 years of age.

Estimated Substitution of Tea or Coffee for Sugar-Sweetened Beverages Was Associated with Lower Type 2 Diabetes Incidence in Case-Cohort Analysis across 8 European Countries in the EPIC-InterAct Study.

INTRODUCTION: Beverage consumption is a modifiable risk factor for type 2 diabetes (T2D), but there is insufficient evidence to inform the suitability of substituting 1 type of beverage for another. OBJECTIVE: The aim of this study was to estimate the risk of T2D when consumption of sugar-sweetened beverages (SSBs) was replaced with consumption of fruit juice, milk, coffee, or tea. METHODS: In the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct case-cohort study of 8 European countries (n = 27,662, with 12,333 cases of incident T2D, 1992-2007), beverage consumption was estimated at baseline by dietary questionnaires. Using Prentice-weighted Cox regression adjusting for other beverages and potential confounders, we estimated associations of substituting 1 type of beverage for another on incident T2D. RESULTS: Mean ± SD of estimated consumption of SSB was 55 ± 105 g/d. Means ± SDs for the other beverages were as follows: fruit juice, 59 ± 101 g/d; milk, 209 ± 203 g/d; coffee, 381 ± 372 g/d; and tea, 152 ± 282 g/d. Substituting coffee for SSBs by 250 g/d was associated with a 21% lower incidence of T2D (95% CI: 12%, 29%). The rate difference was -12.0 (95% CI: -20.0, -5.0) per 10,000 person-years among adults consuming SSBs ≥250 g/d (absolute rate = 48.3/10,000). Substituting tea for SSBs was estimated to lower T2D incidence by 22% (95% CI: 15%, 28%) or -11.0 (95% CI: -20.0, -2.6) per 10,000 person-years, whereas substituting fruit juice or milk was estimated not to alter T2D risk significantly. CONCLUSIONS: These findings indicate a potential benefit of substituting coffee or tea for SSBs for the primary prevention of T2D and may help formulate public health recommendations on beverage consumption in different populations.

Generalizability of a Diabetes-Associated Country-Specific Exploratory Dietary Pattern Is Feasible Across European Populations.

BACKGROUND: Population-specificity of exploratory dietary patterns limits their generalizability in investigations with type 2 diabetes incidence. OBJECTIVE: The aim of this study was to derive country-specific exploratory dietary patterns, investigate their association with type 2 diabetes incidence, and replicate diabetes-associated dietary patterns in other countries. METHODS: Dietary intake data were used, assessed by country-specific questionnaires at baseline of 11,183 incident diabetes cases and 14,694 subcohort members (mean age 52.9 y) from 8 countries, nested within the European Prospective Investigation into Cancer and Nutrition study (mean follow-up time 6.9 y). Exploratory dietary patterns were derived by principal component analysis. HRs for incident type 2 diabetes were calculated by Prentice-weighted Cox proportional hazard regression models. Diabetes-associated dietary patterns were simplified or replicated to be applicable in other countries. A meta-analysis across all countries evaluated the generalizability of the diabetes-association. RESULTS: Two dietary patterns per country/UK-center, of which overall 3 dietary patterns were diabetes-associated, were identified. A risk-lowering French dietary pattern was not confirmed across other countries: pooled HRFrance per 1 SD: 1.00; 95% CI: 0.90, 1.10. Risk-increasing dietary patterns, derived in Spain and UK-Norfolk, were confirmed, but only the latter statistically significantly: HRSpain: 1.09; 95% CI: 0.97, 1.22 and HRUK-Norfolk: 1.12; 95% CI: 1.04, 1.20. Respectively, this dietary pattern was characterized by relatively high intakes of potatoes, processed meat, vegetable oils, sugar, cake and cookies, and tea. CONCLUSIONS: Only few country/center-specific dietary patterns (3 of 18) were statistically significantly associated with diabetes incidence in this multicountry European study population. One pattern, whose association with diabetes was confirmed across other countries, showed overlaps in the food groups potatoes and processed meat with identified diabetes-associated dietary patterns from other studies. The study demonstrates that replication of associations of exploratory patterns with health outcomes is feasible and a necessary step to overcome population-specificity in associations from such analyses.

Strong adherence to dietary and lifestyle recommendations is associated with decreased type 2 diabetes risk in the AusDiab cohort study.

We aimed to determine whether adherence to the Australian dietary guidelines and an index of healthy behavior was associated with a lower risk of type 2 diabetes (T2D) and to provide estimates of the proportion of preventable cases. Participants of the AusDiab cohort study were followed for 12 years (n = 6242), starting from May 1999, during which T2D cases were identified. The associations between T2D risk and a score of adherence to the dietary guidelines, its components, and a score of adherence to an index of healthy behaviors, (which included smoking, recreational physical activity, waist circumference and adherence to the dietary guidelines), were estimated using Cox proportional hazards ratios (HR) and 95% confidence intervals. The proportion of preventable cases was estimated using the population attributable fraction (PAF). Strong adherence to the dietary guidelines was not associated with T2D risk (HR = 0.64 [95% CI 0.39-1.06]), unless moderate alcohol consumption was considered as beneficial instead of no alcohol consumption (HR = 0.59 [0.36-0.96]). However, strong adherence to the guidelines regarding fruit and dairy intake were both associated with decreased risk of T2D (HR = 0.68 [0.51-0.91]; 0.56 [0.38-0.84], respectively) and could have prevented 23-37% of cases (PAF = 23.3% [7.3-38.2]; 37.1% [14.6-56.0], respectively). Strong adherence to the index of healthy behaviors was associated with decreased risk of T2D (HR = 0.30 [0.17-0.51]) and estimated to prevent almost 60% of T2D (PAF = 59.4% [34.3-76.6]). More than half of T2D cases could be preventable in Australia through modifying health behavior. These results could serve as a basis for prevention programs based on lifestyle modification.

High iodine dietary intake is associated with type 2 diabetes among women of the E3N-EPIC cohort study.

BACKGROUND: Iodine is an essential micronutrient needed for the production of thyroid hormones. Consequently, iodine insufficient and excessive intakes are associated with thyroid disorders. Despite the increase in diabetes prevalence worldwide and the close relationship between thyroid function and the risk of diabetes, the relationship between iodine intake and diabetes has been overlooked. The objective of the present study is to investigate the link between iodine intake and the risk of type 2 diabetes. METHODS: Cox proportional hazards regression models adjusted on potential confounders were used to calculate the hazard ratios and 95% confidence intervals for the associations between dietary iodine intake and type 2 diabetes risk among 71,264 women of the E3N-EPIC cohort. RESULTS: The average iodine intake in the study population was 155.6 µg/day (±47.1 µg/day). After adjusting for the main risk factors for diabetes, for hypo/hyperthyroidism, as well as for phosphorus intakes and consumption of dairy products and seafood, the hazard ratios (95% CI) for type 2 diabetes of women in the 4th (160.7-190.5 µg/day) and 5th (190.6-596.8 µg/day) quintiles groups of iodine intake were 1.27 (1.10-1.47) and 1.28 (1.07-1.53), respectively, compared to women with iodine intake below the 1st quintile (29.3-116.9 µg/day). CONCLUSION: This is the first study to investigate the relationship between dietary iodine intake and the risk of developing type 2 diabetes. More studies are warranted to further investigate the health effects of chronic high iodine intake, and in particular to investigate the biological mechanisms that underlie the association between iodine intake and type 2 diabetes.

Population attributable fractions of the main type 2 diabetes mellitus risk factors in women: Findings from the French E3N cohort.

BACKGROUND: Although many type 2 diabetes mellitus (T2DM) risk factors have been identified, little is known regarding their contributions to the diabetes burden at the population level. METHODS: The study included 72 655 French women from the Etude Epidemiologique de Femmes de la Mutuelle Générale de l'Education Nationale (E3N) prospective cohort followed between 1993 and 2011. Cox multivariable models including the main T2DM risk factors (metabolic, dietary, clinical, socioeconomic and hormonal) and a healthy lifestyle index combining five characteristics (smoking, body mass index [BMI], alcohol consumption, fruit and vegetable consumption, and physical activity) were used to estimate hazard ratios and population attributable fractions (PAFs) for T2DM. RESULTS: In multivariate models, factors with the strongest effect on T2DM risk were, in decreasing order, BMI ≥ 30 kg/m2 (PAF = 43%; 95% confidence interval [CI] 37-47), high adherence to a Western dietary pattern (PAF = 30%; 95% CI 20-40), hypertension (PAF = 26%; 95% CI 20-32), an acidogenic diet (PAF = 24%; 95% CI 16-32), a family history of diabetes (PAF = 20%; 95% CI 17-22), and, with a negative correlation, moderate alcohol consumption (PAF-19%; 95% CI -34, -4). The PAF for an unhealthy lifestyle was 57% (95% CI 50-63). CONCLUSIONS: We have been able to sort out and quantify the effect of various dietary and biological T2DM risk factors simultaneously in a single population, and to highlight the importance of a healthy lifestyle for primary prevention: more than half the T2DM cases could have been prevented through a healthier lifestyle.

Dietary exposure to brominated flame retardants and risk of type 2 diabetes in the French E3N cohort.

INTRODUCTION: The prevalence of type 2 diabetes (T2D) is increasing worldwide. Recent studies have suggested that environmental factors, such as exposure to brominated flame retardants (BFRs), could play a role in the epidemic of T2D. The aim of this study was to analyze the association between the dietary exposure to BFRs (Hexabromocyclododecane (HBCD) and Polybromodiphenylether (PBDE)) and T2D risk in the E3N prospective cohort of French women. RESEARCH DESIGN AND METHODS: Overall, 71,415 women followed for 19 years were included in the study. We performed Cox regression models to analyze the association between dietary exposure to BFRs and T2D risk. RESULTS: Overall 71,415 women were included and 3667 (5.13%) developed a T2D during follow-up. The mean dietary exposure to HBCD and to PBDE was 0.22 ng/kg body weight (BW)/day and 1.21 ng/kg bw/day, respectively. There was a positive linear association between dietary exposure to HBCD and T2D risk starting from the 2nd quintile group (HR: 1.18; 95% CI: 1.06-1.30) to the 5th quintile group (HR: 1.47; 95% CI: 1.29-1.67) when compared to the 1st quintile group. We also found positive although non-linear associations between dietary exposure to PBDE and T2D risk, with an increased HR only for the 2nd and 4th vs. 1st quintile groups (HR: 1.12; 95% CI: 1.02-1.24, and HR: 1.20; 95% CI: 1.08-1.34, respectively). CONCLUSION: The findings suggest an association between dietary exposure to BFRs and T2D risk, highlighting the importance of further investigating this association the long-term health effects of endocrine disruptors in the general population. Additional studies are needed to reproduce these findings in other populations and clarify the underlying biological mechanisms.

Association of Plasma Vitamin D Metabolites With Incident Type 2 Diabetes: EPIC-InterAct Case-Cohort Study.

BACKGROUND: Existing evidence for the prospective association of vitamin D status with type 2 diabetes (T2D) is focused almost exclusively on circulating total 25-hydroxyvitamin D [25(OH)D] without distinction between its subtypes: nonepimeric and epimeric 25(OH)D3 stereoisomers, and 25(OH)D2, the minor component of 25(OH)D. We aimed to investigate the prospective associations of circulating levels of the sum and each of these three metabolites with incident T2D. METHODS: This analysis in the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct case-cohort study for T2D included 9671 incident T2D cases and 13,562 subcohort members. Plasma vitamin D metabolites were quantified by liquid chromatography-mass spectrometry. We used a multivariable Prentice-weighted Cox regression to estimate hazard ratios (HRs) of T2D for each metabolite. Analyses were performed separately within country, and estimates were combined across countries using random-effects meta-analysis. RESULTS: The mean concentrations (SD) of total 25(OH)D, nonepimeric 25(OH)D3, epimeric 25(OH)D3, and 25(OH)D2 were 41.1 (17.2), 40.7 (17.3), 2.13 (1.31), and 8.16 (6.52) nmol/L, respectively. Plasma total 25(OH)D and nonepimeric 25(OH)D3 were inversely associated with incident T2D [multivariable-adjusted HR per 1 SD = 0.81 (95% CI, 0.77, 0.86) for both variables], whereas epimeric 25(OH)D3 was positively associated [per 1 SD HR = 1.16 (1.09, 1.25)]. There was no statistically significant association with T2D for 25(OH)D2 [per 1 SD HR = 0.94 (0.76, 1.18)]. CONCLUSIONS: Plasma nonepimeric 25(OH)D3 was inversely associated with incident T2D, consistent with it being the major metabolite contributing to total 25(OH)D. The positive association of the epimeric form of 25(OH)D3 with incident T2D provides novel information to assess the biological relevance of vitamin D epimerization and vitamin D subtypes in diabetes etiology.

Relative Validity and Reproducibility of a New 44-Item Diet and Food Frequency Questionnaire Among Adults: Online Assessment.

BACKGROUND: Dietary questionnaires currently available which can assess the habitual diet are timely, costly, or not adapted well to the modern diet; thus, there is a need for a shorter food frequency e-Questionnaire (FFeQ) adapted to Western diets, in order to properly estimate energy and macronutrient intakes or rank individuals according to food and nutrient intakes. OBJECTIVE: The aim of this study was to evaluate the relative validity and reproducibility of a 30-minute and 44-item FFeQ in a sample of adults obtained from the general population. METHODS: A sample of French adults was recruited through social media and an advertising campaign. A total of 223 volunteers completed the FFeQ twice at one-year intervals and were included in the reproducibility study. During that interval, 92 participants completed three-to-six 24-hour recalls and were included in the validity study. Nutrient and dietary intakes were computed for all validity and reproducibility participants. The level of agreement between the two methods was evaluated for nutrient and food group intakes using classification into quintiles of daily intake, correlation coefficients and Bland-Altman plots. RESULTS: For relative validity, correlation coefficients ranged from 0.09 to 0.88 (unadjusted correlation coefficients, median: 0.48) and 0.02 to 0.68 (deattenuated and energy adjusted correlation coefficients, median: 0.50) for food group and nutrient intakes, respectively. The median proportion of subjects classified into the same or adjacent quintile was 73% and 66% for food and nutrient intakes, respectively. Bland-Altman plots showed good agreement across the range of intakes. Regarding reproducibility, intraclass correlation coefficients ranged from 0.33 to 0.72 (median: 0.60) and 0.55 to 0.73 (median: 0.64), for food and nutrient intakes, respectively. CONCLUSIONS: The FFeQ showed acceptable validity and reproducibility in a sample of adults based on their food and nutrient intakes. The FFeQ is a promising and low-cost tool that can be used in large-scale online epidemiological studies or clinical routines and could be integrated into evidence-based smartphone apps for assessing diet components.

Nonlinear associations between dietary exposures to perfluorooctanoic acid (PFOA) or perfluorooctane sulfonate (PFOS) and type 2 diabetes risk in women: Findings from the E3N cohort study.

The incidence of type 2 diabetes (T2D) is steadily rising worldwide since the past 30 years. There is increasing interest in understanding the contribution of exposure to endocrine disrupting chemicals (EDCs) to T2D trend. Perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) are stable, persistent, and bioaccumulative synthetic compounds, suspected to act as EDCs and for which the diet is the main route of exposure. We investigated associations between estimated dietary exposure to PFOS and PFOA and the risk of T2D in the large E3N prospective cohort study. Among 71 270 women included in this study, 2680 cases of incident type 2 diabetes were validated during follow-up (1993-2012). Dietary exposure was estimated combining dietary consumption data collected in E3N and food contamination data provided by ANSES in the 2nd French Total Diet Study. The estimated mean dietary exposure to PFOS and PFOA was 0.50 ng/kg body weight/day and 0.86 ng/kg body weight/day respectively. An inverse U-shape association was found when considering PFOA and T2D: women in the 4th, 5th, and 6th decile groups had a HR [95%CI] of 1.21 [1.06-1.46], 1.35 [1.15-1.59], and 1.33 [1.05-1.41], respectively, when compared to women of the 1st decile group, while the other decile groups were not associated to the risk of T2D. The positive association had the strongest effect size for non-obese women (body mass index (BMI) ≤25 kg/m2). No association was found between dietary exposure to PFOS and T2D, except when considering only women with BMI≤25 kg/m2, in which a positive nonlinear association was observed (HR [95%CI] = 1.46 [1.09-1.96], 1.52 [1.09-2.11], and 1.44 [1.01-2.06] for the 6th, 8th, and 9th decile groups respectively). This is the first study to evaluate the association between dietary exposure to PFOA and PFOS and the risk of developing T2D in a large observational study with over 15 years of follow-up. The present study highlights the importance of studying the effects of EDCs in large epidemiological studies including not occupationally exposed populations, as well as the importance of considering exposure to PFOS and PFOA as a relevant risk factor for T2D.

Interplay between genetic predisposition, macronutrient intake and type 2 diabetes incidence: analysis within EPIC-InterAct across eight European countries.

AIMS/HYPOTHESIS: Gene-macronutrient interactions may contribute to the development of type 2 diabetes but research evidence to date is inconclusive. We aimed to increase our understanding of the aetiology of type 2 diabetes by investigating potential interactions between genes and macronutrient intake and their association with the incidence of type 2 diabetes. METHODS: We investigated the influence of interactions between genetic risk scores (GRSs) for type 2 diabetes, insulin resistance and BMI and macronutrient intake on the development of type 2 diabetes in the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct, a prospective case-cohort study across eight European countries (N = 21,900 with 9742 incident type 2 diabetes cases). Macronutrient intake was estimated from diets reported in questionnaires, including proportion of energy derived from total carbohydrate, protein, fat, plant and animal protein, saturated, monounsaturated and polyunsaturated fat and dietary fibre. Using multivariable-adjusted Cox regression, we estimated country-specific interaction results on the multiplicative scale, using random-effects meta-analysis. Secondary analysis used isocaloric macronutrient substitution. RESULTS: No interactions were identified between any of the three GRSs and any macronutrient intake, with low-to-moderate heterogeneity between countries (I2 range 0-51.6%). Results were similar using isocaloric macronutrient substitution analyses and when weighted and unweighted GRSs and individual SNPs were examined. CONCLUSIONS/INTERPRETATION: Genetic susceptibility to type 2 diabetes, insulin resistance and BMI did not modify the association between macronutrient intake and incident type 2 diabetes. This suggests that macronutrient intake recommendations to prevent type 2 diabetes do not need to account for differences in genetic predisposition to these three metabolic conditions.

Circulating Fetuin-A and Risk of Type 2 Diabetes: A Mendelian Randomization Analysis.

Fetuin-A, a hepatic-origin protein, is strongly positively associated with risk of type 2 diabetes in human observational studies, but it is unknown whether this association is causal. We aimed to study the potential causal relation of circulating fetuin-A to risk of type 2 diabetes in a Mendelian randomization study with single nucleotide polymorphisms located in the fetuin-A-encoding AHSG gene. We used data from eight European countries of the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct case-cohort study including 10,020 incident cases. Plasma fetuin-A concentration was measured in a subset of 965 subcohort participants and 654 case subjects. A genetic score of the AHSG single nucleotide polymorphisms was strongly associated with fetuin-A (28% explained variation). Using the genetic score as instrumental variable of fetuin-A, we observed no significant association of a 50 µg/mL higher fetuin-A concentration with diabetes risk (hazard ratio 1.02 [95% CI 0.97, 1.07]). Combining our results with those from the DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) consortium (12,171 case subjects) also did not suggest a clear significant relation of fetuin-A with diabetes risk. In conclusion, although there is mechanistic evidence for an effect of fetuin-A on insulin sensitivity and secretion, this study does not support a strong, relevant relationship between circulating fetuin-A and diabetes risk in the general population.

Micronutrient dietary patterns associated with type 2 diabetes mellitus among women of the E3N-EPIC (Etude Epidémiologique auprès de femmes de l'Education Nationale) cohort study.

BACKGROUND: Micronutrients play a key role in type 2 diabetes mellitus (T2DM), but methodological difficulties arise from their collinearity and interdependencies with foods. The aim of the present study was to identify micronutrient dietary patterns in the E3N-EPIC (Etude Epidémiologique auprès de femmes de l'Education Nationale) cohort and to investigate their association with risk of T2DM. METHODS: Principal component analysis was used to identify micronutrient patterns among 71 270 women from the E3N-EPIC cohort. Associations between micronutrient patterns and risk of T2DM were quantified by hazard ratios (HRs) and 95% confidence intervals (CIs) from Cox proportional hazards regression models, adjusted for potential confounders. RESULTS: Six micronutrient patterns were identified explaining 78% of the total variance in micronutrient intake. A positive association was found between T2DM and a pattern highly correlated with intake of vitamins B2 and B5 (HR 1.34; 95% CI 1.16-1.56). Similarly, a positive association was found with a pattern characterized by high intakes of vitamin B12 and retinol, and a low intake of vitamin C (HR 1.30; 95% CI 1.15-1.48). An inverse association was observed between T2DM and another two patterns: one correlated with magnesium and vitamin B3 (HR 0.75; 95% CI 0.66-0.86), and the other correlated with manganese intake (HR 0.82; 95% CI 0.72-0.94). CONCLUSIONS: The findings of the present study identify micronutrients that have an effect on the risk of T2DM, and enable better understanding of the complexity of the diet when investigating the association between micronutrients and T2DM.

High dietary phosphorus intake is associated with an increased risk of type 2 diabetes in the large prospective E3N cohort study.

Phosphorus is an essential nutrient; the adult recommended daily intake ranges from 550 to 700 mg/day, with a tolerated upper limit of 4000 mg/day. Phosphorus intake has increased in the general population in recent years, and simultaneously an alarming rise of type 2 diabetes incidences has been observed. No study has investigated the relationship between phosphorus intake and the risk of type 2 diabetes. To evaluate the association between phosphorus intake and incidence of type 2 diabetes. Among 71,270 women from the French E3N-EPIC cohort, 1845 cases of incident type 2 diabetes were validated during follow-up (1993-2011). Adjusted Cox proportional hazards regression models were used to calculate hazard ratios and 95% confidence intervals (95% CI) for the associations between phosphorus intake and type 2 diabetes risk, adjusted on potential confounders. The overall mean (±SD) phosphorus intake was 1477 mg/day (±391 mg/day). High phosphorus intake was associated with risk of type 2 diabetes. In multivariate models, compared with women in the 1st quartile of phosphorus intake (<1203 mg/day), those included in the 2nd (1203-1434.0 mg/day), 3rd (1434-1700 mg/day), and 4th (>1700 mg/day) were at a higher risk of type 2 diabetes, with a hazards ratios (95% CI) of 1.18 (1.00-1.38), 1.41 (1.20-1.66) and 1.54 (1.25-1.90), respectively. Our results may have important public health implications for dietary recommendations in the prevention of type 2 diabetes. More studies are warranted to better understand the biological mechanisms underlying this positive association.

Dietary antioxidant capacity and risk of type 2 diabetes in the large prospective E3N-EPIC cohort.

AIMS/HYPOTHESIS: Recent evidence suggests that oxidative stress may contribute to the pathogenesis of type 2 diabetes. The diet, and especially fruit and vegetables, contains a variety of compounds with antioxidant activity, which may have cumulative/synergistic antioxidant effects. The total antioxidant capacity, an index derived from dietary intake, is a single estimate of antioxidant capacity from all dietary antioxidants. The main aim of this study was to investigate the relationship between total antioxidant capacity and risk of type 2 diabetes. METHODS: Among 64,223 women (mean age 52 ± 7 years) from the French E3N-European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, 1751 women had validated type 2 diabetes during 15 years of follow-up. The total antioxidant capacity was estimated with the ferric ion-reducing antioxidant power (FRAP) method. Adjusted Cox proportional hazards regression models were used to calculate HRs and 95% CIs for the associations between total antioxidant capacity and type 2 diabetes risk, adjusted for potential confounders. RESULTS: In multivariable models, higher levels of total antioxidant capacity were associated with a lower risk of type 2 diabetes. Compared with women in the lowest quintile, women in the third, fourth and fifth quintiles for total antioxidant capacity had HRs of 0.74 (95% CI 0.63, 0.86), 0.70 (95% CI 0.59, 0.83) and 0.73 (95% CI 0.60, 0.89), respectively. The inverse association between total antioxidant capacity and risk of type 2 diabetes was linear up to values of 15 mmol/day, after which the effect reached a plateau. CONCLUSIONS/INTERPRETATION: Our findings suggest that the total antioxidant capacity may play an important role in reducing the risk of type 2 diabetes in middle-aged women. More studies are warranted to better understand the biological mechanisms underlying this inverse association.

Diet and risk of diabetic retinopathy: a systematic review.

Diabetic retinopathy is a microvascular complication of diabetes that threatens all individuals with diabetes, leading to vision loss or blindness if left untreated. It is frequently associated with diabetic macular edema, which can occur at any point during the development of diabetic retinopathy. The key factors known to lead to its development include hyperglycemia, hypertension, and the duration of diabetes. Though the diet is important in the development of diabetes, its role in diabetic retinopathy has not been clearly identified. In this systematic review, we aimed to identify, summarize and interpret the literature on the association between the diet and dietary intakes of specific foods, nutrients, and food groups, and the risk of diabetic retinopathy. We searched PubMed and Web of Science for English-language studies evaluating the association between the dietary intake of individual foods, macro or micronutrients, dietary supplements, and dietary patterns and their association with retinopathy or macular edema. After reviewing potentially relevant abstracts and, when necessary, full texts, we identified 27 relevant studies. Identified studies investigated intakes of fruit, vegetables, fish, milk, carbohydrates, fibre, fat, protein, salt, potassium, vitamins C, D, and E, carotenoids, dietary supplements, green tea and alcohol. Studies suggest that adherence to the Mediterranean diet and high fruit, vegetable and fish intake may protect against the development of diabetic retinopathy, although the evidence is limited. Studies concerning other aspects of the diet are not in agreement. The role of the diet in the development of diabetic retinopathy is an area that warrants more attention.