Summary
Activation of
CD
4
+
T cells helps to establish and maintain immune responses. During infection with lymphocytic choriomeningitis virus (
LCMV
) clone 13, the
CD
4
+
T‐cell responses are ...lost. In this study, we were interested in the nature of the
CD
4
+
T‐cell responses following infection with
LCMV
clone 13. To pursue this question, we infected
C
57
BL
/6 mice with
LCMV
clone 13. We used a
GP
66‐80
MHC C
lass
II
tetramer to determine whether the
CD
4
+
T cells were present following infection with
LCMV
clone 13. We determined that the cells were present and antigen specific, but not functional. We attributed their dysfunction to the presence of
CD
4
+
T‐cell inhibitory ligands. We further stained for the presence of
CD
4
+
T‐cell inhibitory ligands. We found that the during chronic infection the number of
CD
4
+
T cells expressing programmed death‐1 and
CD
160 were greater over the time–course study than the other
CD
4
+
T‐cell inhibitory ligands. These data show that using
CD
4
+
T
‐cell inhibitory ligands as a reagent for characterization can help in understanding the complex immune responses associated with persistent infections.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
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 (
I
2
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.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The influence of artificial sweeteners on metabolic diseases is controversial. Artificially sweetened beverages have been associated with an increased risk of type 2 diabetes (T2D) but biases and ...reverse causation have been suspected to have influenced the observed association. In addition, it has been suggested that investigation into the relationship between the frequency and duration of the consumption of packet or tablet artificial sweeteners and T2D risk is necessary.
We used data from 61,440 women in the prospective E3N-European Prospective Investigation into Cancer and Nutrition study, conducted between 1993 and 2011. We estimated hazards ratios (HRs) and 95% CIs of T2D risk associated with both the frequency and the duration of use of artificial sweeteners consumed in packets or tablets.
Compared to "never or rare" consumers of artificial sweeteners, those using them "always or almost always" had an increased risk of T2D (HR = 1.83 95% CI 1.66-2.02 in the multivariate model MM, HR = 1.33 95% CI 1.20-1.47 when further adjusted for body mass index, BMI). Women consuming artificial sweeteners in packets or tablets for more than 10 years also had an increased risk of T2D compared to never or rare users (HR = 2.10 95% CI 1.83-2.40 in the MM and HR = 1.15 95% CI 1.00-1.33 when adjusted for BMI, respectively).
Our data suggest that both a higher frequency and a longer consumption of artificial sweeteners in packets or tablets was associated with T2D risk, independently of major T2D risk factors, but partially mediated by adiposity. A precautionary principle should be applied to the promotion of these products that are still largely recommended as healthy sugar substitutes.
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BFBNIB, NMLJ, NUK, PNG, UL, UM, UPUK
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.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
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.
摘要
背景
虽然目前已经确定了2型糖尿病(T2DM)的多个危险因素，但是有关它们在人群水平对糖尿病负担所造成的影响却知之甚少。
方法
研究纳入了72655名法国女性患者，患者来自于法国国家教育互助会的一项流行病学前瞩性队列研究(Etude Epidemiologique de Femmes de la Mutuelle Générale de l'Education Nationale，E3N)，随访时间为1993至2011年。使用包括T2DM主要危险因素(代谢、饮食、临床、社会经济以及激素方面因素)以及结合5个方面特征(吸烟、体重指数BMI、酒精消耗量、水果与蔬菜消耗量、以及体力活动)的健康生活方式指数的Cox多变量模型来评估T2DM的危险比以及人群归因分数(population attributable fractions，PAFs)。
结果
在多变量模型中，对T2DM风险影响最强的因素按照降序分别是BMI ≥ 30 kg/m2(PAF = 43%；95%置信区间CI为37‐47)、长期坚持西方饮食模式(PAF=30%；95% CI为20‐40)、高血压(PAF = 26%；95% CI为20‐32)、产酸饮食(PAF = 24%；95% CI为16‐32)、糖尿病家族史(PAF = 20%；95% CI为17‐22)以及呈负相关的适量饮酒(PAF = ‐19%；95% CI为‐34, ‐4)。不健康生活方式的PAF为57%(95% CI为50‐63)。
结论
我们已经能够在单一人群中同时对T2DM的各种饮食与生物危险因素的影响进行分类与量化，并且强调了健康生活方式对一级预防的重要性:超过一半的T2DM是可以通过更健康的生活方式来预防发生的。
Highlights
If all the women from the E3N study had followed a healthy lifestyle, 57% of cases of type 2 diabetes mellitus (T2DM) cases could have been prevented.
This study helps sort out and quantify the effects of various dietary and biological T2DM risk factors, and highlights the importance of a healthy lifestyle for primary prevention.
Clinicians could use these results to explain to their patients how lifestyle changes can directly affect their risks of developing T2DM.
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FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
Meat intake has been consistently shown to be positively associated with incident type 2 diabetes. Part of that association may be mediated by body iron status, which is influenced by genetic ...factors. We aimed to test for interactions of genetic and dietary factors influencing body iron status in relation to the risk of incident type 2 diabetes.
The case-cohort comprised 9,347 case subjects and 12,301 subcohort participants from eight European countries. Single nucleotide polymorphisms (SNPs) were selected from genome-wide association studies on iron status biomarkers and candidate gene studies. A ferritin-related gene score was constructed. Multiplicative and additive interactions of heme iron and SNPs as well as the gene score were evaluated using Cox proportional hazards regression.
Higher heme iron intake (per 1 SD) was associated with higher ferritin levels (β = 0.113 95% CI 0.082; 0.144), but not with transferrin (-0.019 -0.043; 0.006) or transferrin saturation (0.016 -0.006; 0.037). Five SNPs located in four genes (rs1799945
H63D, rs1800562
C282Y, rs236918
, rs744653
, and rs855791
V736A) were associated with ferritin. We did not detect an interaction of heme iron and the gene score on the risk of diabetes in the overall study population (
= 0.16,
= 0.21) but did detect a trend toward a negative interaction in men (
= 0.04,
= 0.03).
We found no convincing evidence that the interplay of dietary and genetic factors related to body iron status associates with type 2 diabetes risk above the level expected from the sum or product of the two individual exposures.
Population-specificity of exploratory dietary patterns limits their generalizability in investigations with type 2 diabetes incidence.
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.
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.
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.
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.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Summary Non-human primate (NHP) models of tuberculosis (TB) immunity and pathogenesis, especially rhesus and cynomolgus macaques, are particularly attractive because of the high similarity of the ...human and macaque immune systems. However, little is known about the MHC class II epitopes recognized in macaques, thus hindering the establishment of immune correlates of immunopathology and protective vaccination. We characterized immune responses in rhesus macaques vaccinated against and/or infected with Mycobacterium tuberculosis (Mtb), to a panel of antigens currently in human vaccine trials. We defined 54 new immunodominant CD4+ T cell epitopes, and noted that antigens immunodominant in humans are also immunodominant in rhesus macaques, including Rv3875 (ESAT-6) and Rv3874 (CFP10). Pedigree and inferred restriction analysis demonstrated that this phenomenon was not due to common ancestry or inbreeding, but rather presentation by common alleles, as well as, promiscuous binding. Experiments using a second cohort of rhesus macaques demonstrated that a pool of epitopes defined in the previous experiments can be used to detect T cell responses in over 75% of individual monkeys. Additionally, 100% of cynomolgus macaques, irrespective of their latent or active TB status, responded to rhesus and human defined epitope pools. Thus, these findings reveal an unexpected general repertoire overlap between MHC class II epitopes recognized in both species of macaques and in humans, showing that epitope pools defined in humans can also be used to characterize macaque responses, despite differences in species and antigen exposure. The results have general implications for the evaluation of new vaccines and diagnostics in NHPs, and immediate applicability in the setting of macaque models of TB.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Summary
Activation of CD4+ T cells helps to establish and maintain immune responses. During infection with lymphocytic choriomeningitis virus (LCMV) clone 13, the CD4+ T‐cell responses are lost. In ...this study, we were interested in the nature of the CD4+ T‐cell responses following infection with LCMV clone 13. To pursue this question, we infected C57BL/6 mice with LCMV clone 13. We used a GP66‐80 MHC Class II tetramer to determine whether the CD4+ T cells were present following infection with LCMV clone 13. We determined that the cells were present and antigen specific, but not functional. We attributed their dysfunction to the presence of CD4+ T‐cell inhibitory ligands. We further stained for the presence of CD4+ T‐cell inhibitory ligands. We found that the during chronic infection the number of CD4+ T cells expressing programmed death‐1 and CD160 were greater over the time–course study than the other CD4+ T‐cell inhibitory ligands. These data show that using CD4+ T‐cell inhibitory ligands as a reagent for characterization can help in understanding the complex immune responses associated with persistent infections.
Full text
Available for:
BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
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.
摘要
背景
微量营养物质对于2型糖尿病(T2DM)具有重要的影响, 但是对其的研究却很困难, 因为它们与食物之间具有共线性以及相互依赖性。当前这项研究的目的是在国家妇女教育改革计划(Etude Epidémiologique auprès de femmes de l’Education Nationale, E3N‐EPIC)队列研究中鉴定出相关的微量营养物质膳食模式, 并且调查它们与T2DM风险之间的关系。
方法
使用主成分分析法明确了71270名来自E3N‐EPIC队列研究的妇女的微量营养物质膳食模式。使用Cox比例风险回归模型, 校正潜在混杂因素后, 根据危险比(HRs)以及95%置信区间(CIs)进行量化, 评估微量营养物质膳食模式与T2DM风险之间的关系。
结果
明确了6种微量营养物质膳食模式, 在摄入的微量营养物质总方差中占比为78%。发现T2DM与摄入维生素B2以及B5的膳食模式呈高度正相关(HR 1.34;95% CI 1.16‐1.56)。同样, 还发现T2DM与大量摄入B12以及视黄醇, 并且较少摄入维生素C的膳食模式呈正相关(HR 1.30;95% CI 1.15‐1.48)。观察到T2DM与另外两种膳食模式呈负相关:一种与镁以及维生素B3的摄入量有关(HR 0.75;95% CI 0.66‐0.86), 另一种与锰的摄入量有关(HR 0.82;95% CI 0.72‐0.94)。
结论
当前这项研究结果表明微量营养物质可以影响T2DM的风险, 有助于我们在进一步研究微量营养物质与T2DM之间关系时能够更好地理解饮食的复杂性。
Highlights
This study shows how the use of micronutrient patterns enables investigation of the association between diet and type 2 diabetes mellitus (T2DM), explaining the complexity of the diet.
The results suggest a protective effect of vitamins C and B3, magnesium, and manganese against T2DM.
A positive association was found between the intake of vitamins B2, B12, and retinol and the risk of T2DM.
Full text
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FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
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