***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: BACKGROUND AND AIM Hypertension is one of the main cardiovascular risk factors in the elderly . The aims of this work were to evaluate if a one-year intervention with two Mediterranean diets ( Med-diet ) could decrease blood pressure ( BP ) due to a high polyphenol consumption , and if the decrease in BP was mediated by plasma nitric oxide ( NO ) production . METHODS AND RESULTS An intervention sub study of 200 participants at high cardiovascular risk was carried out within the PREDIMED trial . They were r and omly assigned to a low-fat control diet or to two Med-diets , one supplemented with extra virgin olive oil ( Med-EVOO ) and the other with nuts ( Med-nuts ) .  Anthropometrics and clinical parameters were measured at baseline and after one year of intervention , as well as BP , plasma NO and total polyphenol excretion ( TPE ) in urine sample s. Systolic and diastolic BP decreased significantly after a one-year dietary intervention with Med-EVOO and Med-nuts . These changes were associated with a significant increase in TPE and plasma NO . Additionally , a significant positive correlation was observed between changes in urinary TPE , a biomarker of TP intake , and in plasma NO ( Beta = 4.84 ; 95 % CI : 0.57 - 9.10 ) . CONCLUSIONS TPE in spot urine sample was positively correlated with plasma NO in Med-diets supplemented with either EVOO or nuts . The statistically significant increases in plasma NO were associated with a reduction in systolic and diastolic BP levels , adding to the growing evidence that polyphenols might protect the cardiovascular system by improving the endothelial function and enhancing endothelial synthesis of NO CONTEXT Endothelial dysfunction occurs in diagnosed type 2 diabetes mellitus but may also precede development of diabetes . OBJECTIVE To determine whether elevated plasma levels of biomarkers reflecting endothelial dysfunction ( E-selectin ; intercellular adhesion molecule 1 [ ICAM-1 ] ; and vascular cell adhesion molecule 1 [ VCAM-1 ] ) predict development of type 2 diabetes in initially nondiabetic women . DESIGN AND SETTING Prospect i ve , nested case-control study within the Nurses ' Health Study , an ongoing US study initiated in 1976 . PARTICIPANTS Of 121 700 women initially enrolled , 32 826 provided blood sample s in 1989 - 1990 ; of those free of diabetes , cardiovascular disease , or cancer at baseline , 737 developed incident diabetes by 2000 . Controls ( n = 785 ) were selected according to matched age , fasting status , and race . MAIN OUTCOME MEASURE Risk of confirmed clinical ly diagnosed type 2 diabetes by baseline levels of E-selectin , ICAM-1 , and VCAM-1 . RESULTS Baseline median levels of the biomarkers were significantly higher among cases than among controls ( E-selectin , 61.2 vs 45.4 ng/mL ; ICAM-1 , 264.9 vs 247.0 ng/mL ; VCAM-1 , 545.4 vs 526.0 ng/mL [ all P values < or = .004 ] ) . Elevated E-selectin and ICAM-1 levels predicted incident diabetes in logistic regression models conditioned on matching criteria and adjusted for body mass index ( BMI ) , family history of diabetes , smoking , diet score , alcohol intake , activity index , and postmenopausal hormone use . The adjusted relative risks for incident diabetes in the top quintile vs the bottom quintiles were 5.43 for E-selectin ( 95 % confidence interval [ CI ] , 3.47 - 8.50 ) , 3.56 for ICAM-1 ( 95 % CI , 2.28 - 5.58 ) , and 1.12 for VCAM-1 ( 95 % CI , 0.76 - 1.66 ) . Adjustment for waist circumference instead of BMI or further adjustment for baseline levels of C-reactive protein , fasting insulin , and hemoglobin A(1c ) or exclusion of cases diagnosed during the first 4 years of follow-up did not alter these associations . CONCLUSION Endothelial dysfunction predicts type 2 diabetes in women independent of other known risk factors , including obesity and sub clinical inflammation BACKGROUND Epidemiology associates whole-grain ( WG ) consumption with several health benefits . Mounting evidence suggests that WG wheat polyphenols play a role in mechanisms underlying health benefits . OBJECTIVE The objective was to assess circulating concentration , excretion , and the physiologic role of WG wheat polyphenols in subjects with suboptimal dietary and lifestyle behaviors . DESIGN A placebo-controlled , parallel-group r and omized trial with 80 healthy overweight/obese subjects with low intake of fruit and vegetables and sedentary lifestyle was performed . Participants replaced precise portions of refined wheat ( RW ) with a fixed amount of selected WG wheat or RW products for 8 wk . At baseline and every 4 wk , blood , urine , feces , and anthropometric and body composition measures were collected . Profiles of phenolic acids in biological sample s , plasma markers of metabolic disease and inflammation , and fecal microbiota composition were assessed . RESULTS WG consumption for 4 - 8 wk determined a 4-fold increase in serum dihydroferulic acid ( DHFA ) and a 2-fold increase in fecal ferulic acid ( FA ) compared with RW consumption ( no changes ) . Similarly , urinary FA at 8 wk doubled the baseline concentration only in WG subjects . Concomitant reduction in plasma tumor necrosis factor-α ( TNF-α ) after 8 wk and increased interleukin (IL)-10 only after 4 wk with WG compared with RW ( P = 0.04 ) were observed . No significant change in plasma metabolic disease markers over the study period was observed , but a trend toward lower plasma plasminogen activator inhibitor 1 with higher excretion of FA and DHFA in the WG group was found . Fecal FA was associated with baseline low Bifidobacteriales and Bacteroidetes abundances , whereas after WG consumption , it correlated with increased Bacteroidetes and Firmicutes but reduced Clostridium . TNF-α reduction correlated with increased Bacteroides and Lactobacillus . No effect of dietary interventions on anthropometric measurements and body composition was found . CONCLUSIONS WG wheat consumption significantly increased excreted FA and circulating DHFA . Bacterial communities influenced fecal FA and were modified by WG wheat consumption . This trial was registered at clinical trials.gov as NCT01293175 CONTEXT Inflammation is hypothesized to play a role in development of type 2 diabetes mellitus ( DM ) ; however , clinical data addressing this issue are limited . OBJECTIVE To determine whether elevated levels of the inflammatory markers interleukin 6 ( IL-6 ) and  C-reactive protein ( CRP ) are associated with development of  type 2 DM in healthy middle-aged women . DESIGN Prospect i ve , nested case-control study . SETTING The Women 's Health Study , an ongoing US primary prevention , r and omized clinical trial initiated in 1992 . PARTICIPANTS From a nationwide cohort of 27 628 women free of diagnosed DM , cardiovascular disease , and cancer at baseline , 188 women who developed diagnosed DM over a 4-year follow-up period were defined as cases and matched by age and fasting status with 362 disease-free controls . MAIN OUTCOME MEASURES Incidence of confirmed clinical ly diagnosed type 2 DM by baseline levels of IL-6 and CRP . RESULTS Baseline levels of IL-6 ( P<.001 ) and CRP ( P<.001 ) were significantly higher among cases than among controls . The relative risks of future DM for women in the highest vs lowest quartile of these inflammatory markers were 7.5 for IL-6 ( 95 % confidence interval [ CI ] , 3.7 - 15.4 ) and 15.7 for CRP ( 95 % CI , 6.5 - 37.9 ) . Positive associations persisted after adjustment for body mass index , family history of diabetes , smoking , exercise , use of alcohol , and hormone replacement therapy ; multivariate relative risks for the highest vs lowest quartiles were 2.3 for IL-6 ( 95 % CI , 0.9 - 5.6 ; P for trend = .07 ) and 4.2 for CRP ( 95 % CI , 1.5 - 12.0 ; P for trend = .001 ) . Similar results were observed in analyses limited to women with a baseline hemoglobin A(1c ) of 6.0 % or less and after adjustment for fasting insulin level . CONCLUSIONS Elevated levels of CRP and IL-6 predict the development of type 2 DM . These data support a possible role for inflammation in diabetogenesis BACKGROUND AND AIMS Epidemiologic and biological evidence supports an inverse association between polyphenol consumption and the risk of cardiovascular disease ( CVD ) . However , no previous studies have prospect ively evaluated the relationship between polyphenol intake and the incidence of CVD in such a comprehensive way . The aim was to evaluate the association between intakes of total polyphenol and polyphenol subgroups , and the risk of major cardiovascular events ( myocardial infa rct ion , stroke or death from cardiovascular causes ) in the PREDIMED study . METHODS AND RESULTS The present work is an observational study within the PREDIMED trial . Over an average of 4.3 years of follow-up , there were 273 confirmed cases of CVD among the 7172 participants ( 96.3 % ) who completed a vali date d 137-item food frequency question naire ( FFQ ) at baseline .  Polyphenol consumption  was calculated by matching food consumption data from the FFQ with the Phenol-Explorer data base on polyphenol content of each reported food . After multivariate adjustment , a 46 % reduction in risk of CVD risk was observed comparing Q5 vs. Q1 of total polyphenol intake ( HR = 0.54 ; 95 % confidence interval [ CI ] = 0.33 - 0.91 ; P-trend = 0.04 ) . The polyphenols with the strongest inverse associations were flavanols ( HR = 0.40 ; CI 0.23 - 0.72 ; P-trend = 0.003 ) , lignans ( HR = 0.51 ; CI 0.30 - 0.86 ; P-trend = 0.007 ) , and hydroxybenzoic acids ( HR = 0.47 ; CI 0.26 - 0.86 ; P-trend 0.02 ) . CONCLUSION Greater intake of polyphenols , especially from lignans , flavanols , and hydroxybenzoic acids , was associated with decreased CVD risk . Clinical trials are needed to confirm this effect and establish accurate dietary recommendations BACKGROUND We evaluated markers of inflammation and endothelial dysfunction and their associations with incident cardiovascular disease ( CVD ) , all-cause mortality and progression of coronary artery calcium ( CAC ) in patients with type 2 diabetes ( T2D ) and microalbuminuria but without known coronary artery disease ( CAD ) . METHODS Prospect i ve study including 200 patients receiving multifactorial treatment .  Markers of inflammation ( TNF-ɑ , sICAM-1 , sICAM-3 , hsCRP , SAA , IL-1β , IL-6 , IL-8 ) and endothelial dysfunction ( thrombomodulin , sVCAM-1 , sICAM-1 , sICAM-3 , sE-selectin , sP-selectin ) were measured at baseline . Adjustment included traditional CVD risk factors , and full adjustment additionally NT-proBNP and CAC . The " SQRT method " assessed CAC progression after 5.8years , and cut-point was an annualised difference > 2.5 . RESULTS Occurrence of CVD ( n=40 ) and all-cause mortality ( n=26 ) was traced after 6.1years . In adjusted and fully adjusted Cox models , TNF-ɑ was a determinant of CVD and all-cause mortality ( p≤0.007 ) . Further , in adjusted and fully adjusted logistic regression , TNF-ɑ was related to CAC progression ( p≤0.042 ) . Of the other biomarkers , sICAM-3 and thrombomodulin were also associated with both endpoints ( p≤0.046 ) , IL-1β with CVD endpoints ( p=0.021 ) , and sVCAM-1 and sICAM-1 with all-cause mortality ( p≤0.005 ) . Higher composite z-scores including all markers of inflammation and endothelial dysfunction were associated with CVD and all-cause mortality ( p≤0.008 ) . CONCLUSIONS In patients with T2D and microalbuminuria without known CAD and receiving multifactorial treatment , biomarkers of inflammation and endothelial dysfunction were independently associated with CVD , all-cause mortality and CAC progression . Especially TNF-ɑ was a robust determinant , even after adjusting 
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DISSEMINATION By comparing the outcomes from experimental and observational studies , the review will determine whether the overall conclusions related to the phytochemical subclasses are the same between study types for the identified health conditions .