Association of plasma biomarkers of fruit and vegetable intake with incident type 2 diabetes: EPIC-InterAct case-cohort study in eight European countries

Abstract: Objective: To investigate the association of plasma vitamin C and carotenoids, as indicators of fruit and vegetable intake, with the risk of type 2 diabetes. Design: Prospective case-cohort study. Setting: Populations from eight European countries. Participants: 9754 participants with incident type 2 diabetes, and a subcohort of 13 662 individuals from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort of 340 234 participants: EPIC-InterAct case-cohort study. Main outcome measure: Incident type 2 diabetes. Results: In a multivariable adjusted model, higher plasma vitamin C was associated with a lower risk of developing type 2 diabetes (hazard ratio per standard deviation 0.82, 95% confidence interval 0.76 to 0.89). A similar inverse association was shown for total carotenoids (hazard ratio per standard deviation 0.75, 0.68 to 0.82). A composite biomarker score (split into five equal groups), comprising vitamin C and individual carotenoids, was inversely associated with type 2 diabetes with hazard ratios 0.77, 0.66, 0.59, and 0.50 for groups 2-5 compared with group 1 (the lowest group). Self-reported median fruit and vegetable intake was 274 g/day, 396 g/day, and 508 g/day for participants in categories defined by groups 1, 3, and 5 of the composite biomarker score, respectively. One standard deviation difference in the composite biomarker score, equivalent to a 66 (95% confidence interval 61 to 71) g/day difference in total fruit and vegetable intake, was associated with a hazard ratio of 0.75 (0.67 to 0.83). This would be equivalent to an absolute risk reduction of 0.95 per 1000 person years of follow up if achieved across an entire population with the characteristics of the eight European countries included in this analysis. Conclusions: These findings indicate an inverse association between plasma vitamin C, carotenoids, and their composite biomarker score, and incident type 2 diabetes in different European countries. These biomarkers are objective indicators of fruit and vegetable consumption, and suggest that diets rich in even modestly higher fruit and vegetable consumption could help to prevent development of type 2 diabetes

The association between circulating 25-hydroxyvitamin D metabolites and type 2 diabetes in European populations: A meta-analysis and Mendelian randomisation analysis

Funder: NIHR Biomedical Research Centre Cambridge: Nutrition, Diet, and Lifestyle Research Theme; Grant(s): IS-BRC-1215-20014Background: Prior research suggested a differential association of 25-hydroxyvitamin D (25(OH)D) metabolites with type 2 diabetes (T2D), with total 25(OH)D and 25(OH)D3 inversely associated with T2D, but the epimeric form (C3-epi-25(OH)D3) positively associated with T2D. Whether or not these observational associations are causal remains uncertain. We aimed to examine the potential causality of these associations using Mendelian randomisation (MR) analysis. Methods and findings: We performed a meta-analysis of genome-wide association studies for total 25(OH)D (N = 120,618), 25(OH)D3 (N = 40,562), and C3-epi-25(OH)D3 (N = 40,562) in participants of European descent (European Prospective Investigation into Cancer and Nutrition [EPIC]–InterAct study, EPIC-Norfolk study, EPIC-CVD study, Ely study, and the SUNLIGHT consortium). We identified genetic variants for MR analysis to investigate the causal association of the 25(OH)D metabolites with T2D (including 80,983 T2D cases and 842,909 non-cases). We also estimated the observational association of 25(OH)D metabolites with T2D by performing random effects meta-analysis of results from previous studies and results from the EPIC-InterAct study. We identified 10 genetic loci associated with total 25(OH)D, 7 loci associated with 25(OH)D3 and 3 loci associated with C3-epi-25(OH)D3. Based on the meta-analysis of observational studies, each 1–standard deviation (SD) higher level of 25(OH)D was associated with a 20% lower risk of T2D (relative risk [RR]: 0.80; 95% CI 0.77, 0.84; p < 0.001), but a genetically predicted 1-SD increase in 25(OH)D was not significantly associated with T2D (odds ratio [OR]: 0.96; 95% CI 0.89, 1.03; p = 0.23); this result was consistent across sensitivity analyses. In EPIC-InterAct, 25(OH)D3 (per 1-SD) was associated with a lower risk of T2D (RR: 0.81; 95% CI 0.77, 0.86; p < 0.001), while C3-epi-25(OH)D3 (above versus below lower limit of quantification) was positively associated with T2D (RR: 1.12; 95% CI 1.03, 1.22; p = 0.006), but neither 25(OH)D3 (OR: 0.97; 95% CI 0.93, 1.01; p = 0.14) nor C3-epi-25(OH)D3 (OR: 0.98; 95% CI 0.93, 1.04; p = 0.53) was causally associated with T2D risk in the MR analysis. Main limitations include the lack of a non-linear MR analysis and of the generalisability of the current findings from European populations to other populations of different ethnicities. Conclusions: Our study found discordant associations of biochemically measured and genetically predicted differences in blood 25(OH)D with T2D risk. The findings based on MR analysis in a large sample of European ancestry do not support a causal association of total 25(OH)D or 25(OH)D metabolites with T2D and argue against the use of vitamin D supplementation for the prevention of T2D

Type 2 diabetes and its characteristics are associated with poor oral health: findings from 60,590 senior women from the E3N study

International audienceBACKGROUND: Type 2 diabetes (T2D) has been identified as a risk factor for poor oral health, however, a limited number of oral health and T2D characteristics have been studied so far. We sought to assess T2D status, age at diagnosis, duration since diagnosis and treatment in relation to a variety of oral diseases. METHODS: Cross-sectional data were analyzed from the E3N (Etude Epidémiologique auprès de femmes de l’Education Nationale) cohort study which enrolled 60,590 women. Participants self-reported oral health status, and T2D cases were identified using diabetes-specific questionnaires and drug reimbursement insurance databases. Multivariable-adjusted ORs and 95% CIs were estimated using logistic regression models. RESULTS: The mean age (SD) of the women was 70 years (7.2), and 4.7% (n = 2857) had T2D. Compared to women without T2D, women with T2D were more likely to report a poor perceived oral health (OR 1.37 [95% CI 1.18, 1.60]), wearing dental prostheses (1.26 [1.14, 1.39]) and having problems of biting and chewing food (1.19 [1.07, 1.33]). In addition, for women with T2D the age at diagnosis (inversely) and the duration (positively) were associated with the likelihood to report poor oral health. CONCLUSIONS: For women with T2D, duration and age at diagnosis are associated with wearing prostheses, problems of biting and chewing, periodontitis and gingivitis

Dietary Copper/Zinc Ratio and Type 2 Diabetes Risk in Women: The E3N Cohort Study

The serum copper (Cu) to zinc (Zn) ratio could be an important determinant of Type 2 diabetes (T2D) risk, but prospective epidemiological data are scarce. We aimed to investigate the association between T2D incidence and the dietary Cu/Zn ratio. A total of 70,991 women from the E3N cohort study were followed for 20 years. The intakes of copper and zinc were estimated at baseline using a validated food frequency questionnaire. We identified and validated 3292 incident T2D cases. Spline analysis showed that a Cu/Zn ratio \u3c 0.55 was associated with a lower risk of T2D. Subgroup analyses comparing women in the highest versus the lowest quintile of Cu/Zn ratio showed the same pattern of association for obese women and those with zinc intake ≥8 mg/day. However, for women with zinc intake \u3c8 mg/day, higher Cu/Zn ratio appeared to be associated with higher T2D risk. Our findings suggest that a lower dietary Cu/Zn ratio is associated with a lower T2D risk, especially among obese women and women with zinc intake \u3e8 mg/day. Further studies are warranted to validate our results

Profiles of Polyphenol Intake and Type 2 Diabetes Risk in 60,586 Women Followed for 20 Years: Results from the E3N Cohort Study

Most studies on dietary polyphenol intake and type 2 diabetes (T2D) risk have focused on total or specific subclasses of polyphenols. Since polyphenols are often consumed simultaneously, the joint effect of an intake of multiple subclasses should be explored. We aimed to identify profiles of the dietary polyphenol subclasses intake associated with T2D. A total of 60,586 women from the Etude Epid&eacute;miologique aupr&egrave;s de femmes de l&rsquo;Education Nationale (E3N) cohort study were followed for 20 years between 1993 and 2014. T2D cases were identified and validated. The individual energy-adjusted daily intakes of 15 subclasses of polyphenols were estimated at baseline using a food frequency questionnaire and the PhenolExplorer database. We used Bayesian profile regression to perform the clustering of the covariates by identifying exposure profiles of polyphenol intakes and, simultaneously, link these to T2D risk by using multivariable Cox regression models. We validated 2740 incident T2D cases during follow-up, and identified 15 distinct clusters with different intake profiles and T2D risk. When compared to the largest cluster (n = 6298 women), higher risks of T2D were observed in three of those clusters, which were composed of women with low or medium intakes of anthocyanins, dihydroflavonols, catechins, flavonols, hydroxybenzoic acids, lignans, and stilbenes. One cluster (n = 4243), characterized by higher intakes of these polyphenol subclasses, exhibited lower T2D risk when compared to the reference cluster. These results highlight the importance of a varied diet of polyphenol-rich foods such as nuts, fruits, and vegetables to prevent T2D risk

Associations Between Device-Measured Physical Activity and Glycemic Control and Variability Indices Under Free-Living Conditions

International audienceBackground: Disturbances of glycemic control and large glycemic variability have been associated with increased risk of type 2 diabetes in the general population as well as complications in people with diabetes. Long-term health benefits of physical activity are well documented but less is known about the timing of potential short-term effects on glycemic control and variability in free-living conditions. Materials and Methods: We analyzed data from 85 participants without diabetes from the Food & You digital cohort. During a 2-week follow-up, device-based daily step count was studied in relationship to glycemic control and variability indices using generalized estimating equations. Glycemic indices, evaluated using flash glucose monitoring devices (FreeStyle Libre), included minimum, maximum, mean, standard deviation, and coefficient of variation of daily glucose values, the glucose management indicator, and the approximate area under the sensor glucose curve. Results: We observed that every 1000 steps/day increase in daily step count was associated with a 0.3588 mg/dL (95% confidence interval [CI]: -0.6931 to -0.0245), a 0.0917 mg/dL (95% CI: -0.1793 to -0.0042), and a 0.0022% (95% CI: -0.0043 to -0.0001) decrease in the maximum glucose values, mean glucose, and in the glucose management indicator of the following day, respectively. We did not find any association between daily step count and glycemic indices from the same day. Conclusions: Increasing physical activity level was linked to blunted glycemic excursions during the next day. Because health-related benefits of physical activity can be long to observe, such short-term physiological benefits could serve as personalized feedback to motivate individuals to engage in healthy behaviors

An International Study on the Determinants of Poor Sleep Amongst 15,000 Users of Connected Devices

International audienceBackground: Sleep is a modifiable lifestyle factor that can be a target for efficient intervention studies to improve the quality of life and decrease the risk or burden of some chronic conditions. Knowing the profiles of individuals with poor sleep patterns is therefore a prerequisite. Wearable devices have recently opened new areas in medical research as potential efficient tools to measure lifestyle factors such as sleep quantity and quality.Objectives: The goal of our research is to identify the determinants of poor sleep based on data from a large population of users of connected devices.Methods: We analyzed data from 15,839 individuals (13,658 males and 2181 females) considered highly connected customers having purchased and used at least 3 connected devices from the consumer electronics company Withings (now Nokia). Total and deep sleep durations as well as the ratio of deep/total sleep as a proxy of sleep quality were analyzed in association with available data on age, sex, weight, heart rate, steps, and diastolic and systolic blood pressures.Results: With respect to the deep/total sleep duration ratio used as a proxy of sleep quality, we have observed that those at risk of having a poor ratio (≤0.40) were more frequently males (odds ratio [OR]female vs male=0.45, 95% CI 0.38-0.54), younger individuals (OR>60 years vs 18-30 years=0.47, 95% CI 0.35-0.63), and those with elevated heart rate (OR>78 bpm vs ≤61 bpm=1.18, 95% CI 1.04-1.34) and high systolic blood pressure (OR>133 mm Hg vs ≤116 mm Hg=1.22, 95% CI 1.04-1.43). A direct association with weight was observed for total sleep duration exclusively.Conclusions: Wearables can provide useful information to target individuals at risk of poor sleep. Future alert or mobile phone notification systems based on poor sleep determinants measured with wearables could be tested in intervention studies to evaluate the benefits

The associations of the Palaeolithic diet alone and in combination with lifestyle factors with type 2 diabetes and hypertension risks in women in the E3N prospective cohort

International audiencePurpose: Patterns of change from the traditional Palaeolithic lifestyle to the modern lifestyle may partly explain the epidemic proportions of non-communicable diseases (NCDs). We investigated to what extent adherence to the Palaeolithic diet (PD) and the Palaeolithic-like lifestyle was associated with type 2 diabetes (T2D) and hypertension risks. Methods: A study of 70,991 women from the E3N (Etude Epidémiologique auprès de femmes de la Mutuelle Générale de l'Education Nationale) cohort, followed up for nearly 20 years. There were 3,292 incident T2D and 12,504 incident hypertension cases that were validated. Dietary data were collected at baseline in 1993 via a food frequency questionnaire. The PD score and the Palaeolithic-like lifestyle score (PD, physical activity, smoking status and body mass index [BMI]) were derived and considered in quintiles. Multivariable Cox regression models were employed to estimate hazard ratios (HR) and 95% confidence intervals (CI) for incident T2D and hypertension. Results: In the fully adjusted models, a 1-SD increase of the PD score was associated with 4% and 3% lower risks of T2D and hypertension, respectively. Those in the highest versus the lowest quintile of the score had HR (95% CI) of 0.88 (0.79, 0.98) and 0.91 (0.86, 0.96) for T2D and hypertension, respectively (P-trend <0.0001). Associations were stronger for the Palaeolithic-like lifestyle score; in the fully adjusted model a 1-SD increase of the score was associated with 19% and 6% lower risks of T2D and hypertension, respectively. Risks lowered successively with each increase in quintile; those in the highest versus the lowest quintile had HR (95% CI) of 0.58 (0.52, 0.65) and 0.85 (0.80, 0.90) for T2D and hypertension, respectively (P-trend < 0.0001).Conclusions: Our data suggest that adhering to a PD based on fruits, vegetables, lean meats, fish, and nuts, and incorporating a Palaeolithic-like lifestyle could be promising options to prevent T2D and hypertension

Validity and reproducibility of a short food frequency questionnaire among patients with chronic kidney disease

International audienceBackgroundA balanced diet is essential to slowing the progression of chronic kidney disease (CKD) and managing the symptoms. Currently, no tool is available to easily and quickly assess energy and macronutrient intake in patients with non end-stage CKD.We aimed to develop and evaluate the validity and reproducibility of a new short 49-item food frequency questionnaire (SFFQ) adapted to patients with CKD.MethodsThe CKD-REIN study is a prospective cohort that enrolled 3033 patients with moderate or advanced CKD from a national sample of nephrology clinics. A sub-sample of 201 patients completed the SFFQ twice, at a one-year interval and were included in the reproducibility study. During this interval, 127 patients also completed six 24-h recalls and were included in the validity study. Main nutrient and dietary intakes were computed. Validity was evaluated by calculating crude, energy-adjusted and de-attenuated correlation coefficients (CC) between FFQ and the mean of the 24-h recall results. Bland-Altman plots were performed and cross-classification into quintiles of consumption of each nutrient and food group was computed. Reproducibility between the two SFFQs was evaluated by intraclass CC (ICC).ResultsRegarding validity, CC ranged from 0.05 to 0.79 (unadjusted CC, median: 0.40) and 0.10 to 0.59 (de-attenuated CC, median: 0.35) for food group and nutrient intakes, respectively. Five of the most important nutrients of interest in CKD, i.e. protein, calcium, phosphorus, potassium, and sodium had de-attenuated CC of 0.46, 0.43, 0.39, 0.32, and 0.12, respectively. The median of classification into the same or adjacent quintiles was 68% and 65% for food and nutrient intakes, respectively, and ranged from 63% to 69% for the five nutrients mentioned before. Bland-Altman plots showed good agreement across the range of intakes. ICC ranged from 0.18 to 0.66 (median: 0.46).ConclusionsThe CKD-REIN SFFQ showed acceptable validity and reproducibility in a sample of patients with CKD, notably for CKD nutrients of importance. It can now be used in large-scale epidemiological studies to easily assess the relations between diet and CKD outcomes as well as in clinical routine. It may also serve as a basis for the development of FFQs in international CKD cohort networks

Validity and reproducibility of a short food frequency questionnaire among patients with chronic kidney disease

Abstract Background A balanced diet is essential to slowing the progression of chronic kidney disease (CKD) and managing the symptoms. Currently, no tool is available to easily and quickly assess energy and macronutrient intake in patients with non end-stage CKD. We aimed to develop and evaluate the validity and reproducibility of a new short 49-item food frequency questionnaire (SFFQ) adapted to patients with CKD. Methods The CKD-REIN study is a prospective cohort that enrolled 3033 patients with moderate or advanced CKD from a national sample of nephrology clinics. A sub-sample of 201 patients completed the SFFQ twice, at a one-year interval and were included in the reproducibility study. During this interval, 127 patients also completed six 24-h recalls and were included in the validity study. Main nutrient and dietary intakes were computed. Validity was evaluated by calculating crude, energy-adjusted and de-attenuated correlation coefficients (CC) between FFQ and the mean of the 24-h recall results. Bland-Altman plots were performed and cross-classification into quintiles of consumption of each nutrient and food group was computed. Reproducibility between the two SFFQs was evaluated by intraclass CC (ICC). Results Regarding validity, CC ranged from 0.05 to 0.79 (unadjusted CC, median: 0.40) and 0.10 to 0.59 (de-attenuated CC, median: 0.35) for food group and nutrient intakes, respectively. Five of the most important nutrients of interest in CKD, i.e. protein, calcium, phosphorus, potassium, and sodium had de-attenuated CC of 0.46, 0.43, 0.39, 0.32, and 0.12, respectively. The median of classification into the same or adjacent quintiles was 68% and 65% for food and nutrient intakes, respectively, and ranged from 63% to 69% for the five nutrients mentioned before. Bland-Altman plots showed good agreement across the range of intakes. ICC ranged from 0.18 to 0.66 (median: 0.46). Conclusions The CKD-REIN SFFQ showed acceptable validity and reproducibility in a sample of patients with CKD, notably for CKD nutrients of importance. It can now be used in large-scale epidemiological studies to easily assess the relations between diet and CKD outcomes as well as in clinical routine. It may also serve as a basis for the development of FFQs in international CKD cohort networks