BMI in the Associations of Plant-Based Diets with Type 2 Diabetes and Hypertension Risks in Women: The E3N Prospective Cohort Study.

BACKGROUND: Few studies have evaluated the quality of plant-based diets in relation to chronic diseases, and the potential role of BMI is not clearly explored. OBJECTIVES: To study the associations between plant-based diet indices and type 2 diabetes (T2D) and hypertension risks, as well as the extent to which the associations were modified and/or mediated by BMI. METHODS: The study included 74,522 women from the Etude Epidémiologique auprès de femmes de la Mutuelle Générale de l'Education Nationale prospective cohort [mean (SD): age, 52.94 (6.7) years; BMI, 22.970 (3.328) kg/m2]. Dietary data were collected at baseline (1993) via an FFQ. Overall plant-based diet index (PDI), healthful PDI (hPDI), and unhealthful PDI (uPDI) were developed. Multivariable Cox regression models were used to derive HRs and 95% CIs. Effect modification and mediation by BMI were explored. RESULTS: There were 3292 (4.64%) incident cases of T2D and 12,504 (27.14%) incident cases of hypertension over ∼20 years of follow-up. In the multivariable model further adjusted for BMI, higher adherence to PDI and hPDI was associated with lower T2D and hypertension risks, with an HR per 1-SD increase (95% CI) of 0.88 (0.85, 0.91) and 0.96 (0.94, 0.98) for PDI and 0.88 (0.85, 0.92) and 0.94 (0.92, 0.95) for hPDI, respectively. uPDI was not associated with T2D [0.98 (0.94, 1.01)], whereas a positive association was observed with hypertension: 1.04 (1.02, 1.06). There was interaction between PDI and uPDI, as well as BMI, on T2D (P-interaction < 0.001) but not on hypertension (P-interaction > 0.05). In addition, BMI mediated 26-59% and 0.2-59% of diet-T2D and diet-hypertension associations, respectively. CONCLUSIONS: Differential associations between plant-based diets and T2D and hypertension risks were observed among women in this large prospective study. Only healthier plant foods were associated with lower risks, partly through decreasing BMI. The protocol was registered at clinicaltrials.gov as NCT03285230.

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.

PURPOSE: 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 3292 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 fruit, vegetables, lean meats, fish, and nuts, and incorporating a Palaeolithic-like lifestyle could be promising options to prevent T2D and hypertension.

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

BACKGROUND: 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.

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

BACKGROUND: 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.

Dietary inflammatory index and type 2 diabetes risk in a prospective cohort of 70,991 women followed for 20 years: the mediating role of BMI.

AIMS/HYPOTHESIS: Diet is one of the main lifestyle-related factors that can modulate the inflammatory process. Surprisingly the dietary inflammatory index (DII) has been little investigated in relation to type 2 diabetes, and the role of BMI in this relationship is not well established. We studied this association and the role of BMI in the inflammatory process in a large population-based observational study. METHODS: A total of 70,991 women from the E3N (Etude Epidémiologique auprès de femmes de la Mutuelle Générale de l'Education Nationale) cohort study were followed for 20 years. Incident type 2 diabetes cases were identified using diabetes-specific questionnaires and drug reimbursement insurance databases, and 3292 incident cases were validated. The DII was derived from a validated food frequency questionnaire. Multivariable Cox regression models estimated HRs and 95% CIs between DII and incident type 2 diabetes. Interactions were tested between DII and BMI on incident type 2 diabetes and a mediation analysis of BMI was performed. RESULTS: Higher DII scores, corresponding to a higher anti-inflammatory potential of the diet, were associated with a lower risk of type 2 diabetes. Compared with the 1st quintile group, women from the 2nd quintile group (HR 0.85 [95% CI 0.77, 0.94]) up to the 5th quintile group (HR 0.77 [95% CI 0.69, 0.85]) had a lower risk of type 2 diabetes before adjustment for BMI. There was an interaction between DII and BMI on type 2 diabetes risk (pInteraction < 0.0001). The overall association was partly mediated by BMI (58%). CONCLUSIONS/INTERPRETATION: Our findings suggest that a higher anti-inflammatory potential of the diet is associated with a lower risk of type 2 diabetes, and the association may be mediated by BMI. These results may improve our understanding of the mechanisms underlying the role of diet-related anti-inflammation in the pathogenesis of type 2 diabetes in women. Further studies are warranted to validate our results and evaluate whether the results are similar in men.

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.

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

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.

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

BACKGROUND: 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.

Device-based physical activity and late-life depressive symptoms: An analysis of influential factors using share data.

BACKGROUND: Regular physical activity is effective for preventing and managing depression; however, only a few studies have assessed physical activity using device-based measures. We aimed to examine the association between device-based total physical activity and late-life depressive symptoms and explore which factors may explain this relationship. METHODS: Data from 10 European countries who participated in wave 8 of the Survey of Health, Ageing and Retirement in Europe (SHARE) were analyzed. Triaxial accelerometers (Axivity AX3; Axivity, Newcastle UK) were used to assess total physical activity. Depressive symptoms were assessed through the EURO-D scale. Possion regression models and mediation analysis were performed. RESULTS: The final sample included 785 older adults (70 participants had missing data in one or more variables and were excluded from the analysis) [mean (SD): age 68.6 (8.8) years; 59.2 % female]. After adjusting for several confounders, a 10 % increase in the mean acceleration was associated with lower depressive symptoms (B = -0.0228; 95%CI = -0.0395, -0.0061). This association was partly explained by limitations in activities of daily living and quality of life. LIMITATIONS: Cross-sectional design, convenience sample, bi-directionality, lack of cutoff points for classification of the Axivity AX3 placed in the thigh, into intensities. CONCLUSIONS: Higher device-based total physical activity was linked with lower depressive symptoms in older European adults. Future studies employing device-based measures that allow to better capture important physical activity dimensions (i.e., intensity) will better inform about dose-response relationships.

Associations Between Wearable-Specific Indicators of Physical Activity Behaviour and Insulin Sensitivity and Glycated Haemoglobin in the General Population: Results from the ORISCAV-LUX 2 Study.

BACKGROUND: Parameters derived from an acceleration signal, such as the time accumulated in sedentary behaviour or moderate to vigorous physical activity (MVPA), may not be sufficient to describe physical activity (PA) which is a complex behaviour. Incorporating more advanced wearable-specific indicators of PA behaviour (WIPAB) may be useful when characterising PA profiles and investigating associations with health. We investigated the associations of novel objective measures of PA behaviour with glycated haemoglobin (HbA1c) and insulin sensitivity (Quicki index). METHODS: This observational study included 1026 adults (55% women) aged 18-79y who were recruited from the general population in Luxembourg. Participants provided ≥ 4 valid days of triaxial accelerometry data which was used to derive WIPAB variables related to the activity intensity, accumulation pattern and the temporal correlation and regularity of the acceleration time series. RESULTS: Adjusted general linear models showed that more time spent in MVPA and a higher average acceleration were both associated with a higher insulin sensitivity. More time accumulated in sedentary behaviour was associated with lower insulin sensitivity. With regard to WIPAB variables, parameters that were indicative of higher PA intensity, including a shallower intensity gradient and higher average accelerations registered during the most active 8 h and 15 min of the day, were associated with higher insulin sensitivity. Results for the power law exponent alpha, and the proportion of daily time accumulated in sedentary bouts > 60 min, indicated that activity which was characterised by long sedentary bouts was associated with lower insulin sensitivity. A greater proportion of time spent in MVPA bouts > 10 min was associated with higher insulin sensitivity. A higher scaling exponent alpha at small time scales (< 90 min), which shows greater correlation in the acceleration time series over short durations, was associated with higher insulin sensitivity. When measured over the entirety of the time series, metrics that reflected a more complex, irregular and unpredictable activity profile, such as the sample entropy, were associated with lower HbA1c levels and higher insulin sensitivity. CONCLUSION: Our investigation of novel WIPAB variables shows that parameters related to activity intensity, accumulation pattern, temporal correlation and regularity are associated with insulin sensitivity in an adult general population.

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

Background: 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.

Associations of Physical Activity Level and Variability With 6-Month Weight Change Among 26,935 Users of Connected Devices: Observational Real-Life Study.

BACKGROUND: Physical activity (PA) is a modifiable lifestyle factor that can be targeted to increase energy expenditure and promote weight loss. However, the amount of PA required for weight loss remains inconsistent. Wearable activity trackers constitute a valuable opportunity to obtain objective measurements of PA and study large populations in real-life settings. OBJECTIVE: We aim to study the associations of initial device-assessed PA characteristics (average step counts and step count variability) and their evolution with 6-month weight change. METHODS: We analyzed data from 26,935 Withings-connected device users (wearable activity trackers and digital scales). To assess the initial PA characteristics and their 6-month changes, we used data recorded during the first and sixth 30-day periods of activity tracker use. For each of these periods, we used the monthly mean of daily step values as a proxy for PA level and derived the monthly coefficient of variation (CV) of daily step values to estimate PA level variability. Associations between initial PA characteristics and 6-month weight change were assessed using multivariable linear regression analyses controlled for age, sex, blood pressure, heart rate, and the predominant season. Restricted cubic spline regression was performed to better characterize the continuous shape of the associations between PA characteristics and weight change. Secondary analyses were performed by analyzing the 6-month evolution of PA characteristics in relation to weight change. RESULTS: Our results revealed that both a greater PA level and lower PA level variability were associated with weight loss. Compared with individuals who were initially in the sedentary category (<5000 steps/day), individuals who were low active (5000-7499 steps/day), somewhat active (7500-9999 steps/day), and active (≥10,000 steps/day) had a 0.21-kg, a 0.52-kg, and a 1.17-kg greater decrease in weight, respectively (95% CI -0.36 to -0.06, -0.70 to -0.33, and -1.42 to -0.93, respectively). Compared with users whose PA level CV was >63%, users whose PA level CV ranged from 51% to 63%, 40% to 51%, and was ≤40%, had a 0.19-kg, a 0.23-kg, and a 0.33-kg greater decrease in weight, respectively (95% CI -0.38 to -0.01, -0.41 to -0.04, and -0.53 to -0.13, respectively). We also observed that each 1000 steps/day increase in PA level over the 6-month follow-up was associated with a 0.26-kg (95% CI -0.29 to -0.23) decrease in weight. No association was found between the 6-month changes in PA level variability and weight change. CONCLUSIONS: Our results add to the current body of knowledge that health benefits can be observed below the 10,000 steps/day threshold and suggest that not only increased mean PA level but also greater regularity of the PA level may play important roles in short-term weight loss.

Association of Migraine With Incident Hypertension After Menopause: A Longitudinal Cohort Study.

OBJECTIVE: Migraine has been identified as a potential risk factor for hypertension in prospective studies. In women, migraine prevalence decreases after menopause, but no studies have determined whether migraine is associated with hypertension after menopause. This study sought to determine whether history of migraine was associated with an increased risk of hypertension among menopausal women. METHODS: We assessed associations between migraine and hypertension in a longitudinal cohort study of 56,202 menopausal women participating in the French E3N cohort, with follow-up beginning in 1993. We included women who did not have hypertension or cardiovascular disease at the time of menopause. Migraine was classified as ever or never at each questionnaire cycle. Cox proportional hazards models were used to investigate relations between migraine and hypertension, controlling for potential confounding. A secondary analysis with baseline in 2011 considered aura status, grouping participants reporting migraine as migraine with aura, migraine without aura, or unknown migraine type. RESULTS: During 826,419 person-years, 12,501 cases of incident hypertension were identified, including 3,100 among women with migraine and 9,401 among women without migraine. Migraine was associated with an increased risk of hypertension in menopausal women (hazard ratio [HR]migraine 1.29 [95% confidence interval 1.24, 1.35]) and was consistent in post hoc sensitivity analyses, such as when controlling for common migraine medications. Associations between migraine and hypertension were similar whether or not women reported aura (HRmigraine aura 1.54 [1.04, 2.30], HRmigraine no aura 1.32 [0.87, 2.02], p heterogeneity 0.60). Associations were slightly stronger among ever users of menopausal hormone therapy (HRmigraine 1.34 [1.27, 1.41]) than among never users (HRmigraine 1.19 [1.11, 1.28]). CONCLUSIONS: Migraine was associated with an increased risk of hypertension among menopausal women. In secondary analysis, we did not observe a significant difference between migraine with aura and migraine without aura.

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 < 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 <8 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 >8 mg/day. Further studies are warranted to validate our results.

Diabetes, hypertension, body mass index, smoking and COVID-19-related mortality: a systematic review and meta-analysis of observational studies.

OBJECTIVES: We conducted a systematic literature review and meta-analysis of observational studies to investigate the association between diabetes, hypertension, body mass index (BMI) or smoking with the risk of death in patients with COVID-19 and to estimate the proportion of deaths attributable to these conditions. METHODS: Relevant observational studies were identified by searches in the PubMed, Cochrane library and Embase databases through 14 November 2020. Random-effects models were used to estimate summary relative risks (SRRs) and 95% CIs. Certainty of evidence was assessed using the Cochrane methods and the Grading of Recommendations, Assessment, Development and Evaluations framework. RESULTS: A total of 186 studies representing 210 447 deaths among 1 304 587 patients with COVID-19 were included in this analysis. The SRR for death in patients with COVID-19 was 1.54 (95% CI 1.44 to 1.64, I2=92%, n=145, low certainty) for diabetes and 1.42 (95% CI 1.30 to 1.54, I2=90%, n=127, low certainty) for hypertension compared with patients without each of these comorbidities. Regarding obesity, the SSR was 1.45 (95% CI 1.31 to 1.61, I2=91%, n=54, high certainty) for patients with BMI ≥30 kg/m2 compared with those with BMI <30 kg/m2 and 1.12 (95% CI 1.07 to 1.17, I2=68%, n=25) per 5 kg/m2 increase in BMI. There was evidence of a J-shaped non-linear dose-response relationship between BMI and mortality from COVID-19, with the nadir of the curve at a BMI of around 22-24, and a 1.5-2-fold increase in COVID-19 mortality with extreme obesity (BMI of 40-45). The SRR was 1.28 (95% CI 1.17 to 1.40, I2=74%, n=28, low certainty) for ever, 1.29 (95% CI 1.03 to 1.62, I2=84%, n=19) for current and 1.25 (95% CI 1.11 to 1.42, I2=75%, n=14) for former smokers compared with never smokers. The absolute risk of COVID-19 death was increased by 14%, 11%, 12% and 7% for diabetes, hypertension, obesity and smoking, respectively. The proportion of deaths attributable to diabetes, hypertension, obesity and smoking was 8%, 7%, 11% and 2%, respectively. CONCLUSION: Our findings suggest that diabetes, hypertension, obesity and smoking were associated with higher COVID-19 mortality, contributing to nearly 30% of COVID-19 deaths. TRIAL REGISTRATION NUMBER: CRD42020218115.

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 Epidémiologique auprès de femmes de l'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.

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

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.

Mentally tiring work and type 2 diabetes in women: a 22-year follow-up study.

Hypothesis Previous work suggested no or inconsistent associations between components of work-related stress and type 2 diabetes risk, but suggested sex-specific differences should be further investigated, as women potentially had higher risks. Methods We analyzed data from 73 517 women, mostly teachers, from the E3N cohort study followed for 22 years (1992-2014), to study the association between mentally tiring work, used as a proxy of job demands, and type 2 diabetes risk. Univariate and multivariable Cox regression models were used to estimate hazard ratios and 95% confidence intervals. Results A total of 4187 incident cases of type 2 diabetes cases were observed. There was a higher type 2 diabetes risk for women with a 'Very mentally tiring work' when compared to women with 'Little or not mentally tiring work' (HR = 1.21 (1.09-1.35)). This association was independent of unhealthy lifestyle and traditional metabolic factors. An interaction between mentally tiring work and BMI was detected (P < 0.0001), with a stronger association being observed in non-overweight women, HR = 1.26 (1.08-1.47) vs HR = 1.14 (0.98, 1.32), in overweight women. Conclusions We observed an increased risk of type 2 diabetes associated with mentally tiring work, used as a proxy of job demands. These observational results suggest the importance of taking into consideration the potential long-term metabolic impact of work-related stress for women working in a demanding environment. Increased support for such women should be investigated in intervention studies.

Associations Between Migraine and Type 2 Diabetes in Women: Findings From the E3N Cohort Study.

Importance: Little is known about the associations between migraine and type 2 diabetes and the temporality of the association between these 2 diseases. Objective: To evaluate the association between migraine and type 2 diabetes incidence as well as the evolution of the prevalence of active migraine before and after type 2 diabetes diagnosis. Design, Setting, and Participants: We used data from the E3N cohort study, a French prospective population-based study initiated in 1990 on a cohort of women born between 1925 and 1950. The E3N study participants are insured by a health insurance plan that mostly covers teachers. From the eligible women in the E3N study, we included those who completed the 2002 follow-up questionnaire with information available on migraine. We then excluded prevalent cases of type 2 diabetes, leaving a final sample of women who were followed up between 2004 and 2014. All potential occurrences of type 2 diabetes were identified through a drug reimbursement database. Statistical analyses were performed in March 2018. Exposures: Self-reported migraine occurrence. Main Outcomes and Measures: Pharmacologically treated type 2 diabetes. Results: From the 98 995 women in the study, 76 403 women completed the 2002 follow-up survey. Of these, 2156 were excluded because they had type 2 diabetes, leaving 74 247 women. Participants had a mean (SD) age of 61 (6) years at baseline, and all were free of type 2 diabetes. During 10 years of follow-up, 2372 incident type 2 diabetes cases occurred. A lower risk of type 2 diabetes was observed for women with active migraine compared with women with no migraine history (univariate hazard ratio, 0.80 [95% CI, 0.67-0.96], multivariable-adjusted hazard ratio, 0.70 [95% CI, 0.58-0.85]). We also observed a linear decrease in active migraine prevalence from 22% (95% CI, 16%-27%) to 11% (95% CI, 10%-12%) during the 24 years prior to diabetes diagnosis, after adjustment for potential type 2 diabetes risk factors. A plateau of migraine prevalence around 11% was then observed for 22 years after diagnosis. Conclusions and Relevance: We observed a lower risk of developing type 2 diabetes for women with active migraine and a decrease in active migraine prevalence prior to diabetes diagnosis. Further targeted research should focus on understanding the mechanisms involved in explaining these findings.