***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 Coffee consumption has been associated with a lower risk of type 2 diabetes  in prospect i ve cohort studies , but the underlying mechanisms remain unclear . The aim of this study was to evaluate the effects of regular and decaffeinated coffee on biological risk factors for type 2 diabetes . Methods R and omized parallel-arm intervention conducted in 45 healthy overweight volunteers who were nonsmokers and regular coffee consumers . Participants were assigned to consumption of 5 cups ( 177 mL each ) per day of instant caffeinated coffee , decaffeinated coffee , or no coffee ( i.e. , water ) for 8 weeks . Results Average age was 40 years and body mass index was 29.5 kg/m2 . Compared with consuming no coffee , consumption of caffeinated coffee  increased adiponectin ( difference in change from baseline 1.4 μg/mL ; 95 % CI : 0.2 , 2.7 ) and interleukin-6 ( difference : 60 % ; 95 % CI : 8 , 138 ) concentrations and consumption of decaffeinated coffee  decreased fetuin-A concentrations ( difference : -20 % ; 95 % CI : -35 , -1 ) . For measures of glucose tolerance , insulin sensitivity , and insulin secretion , no significant differences were found between treatment groups . Conclusions Although no changes in glycemia and /or insulin sensitivity were observed after 8 weeks of coffee consumption , improvements in adipocyte and liver function as indicated by changes in adiponectin and fetuin-A concentrations may contribute to beneficial metabolic effects of long-term coffee consumption . Trial Registration clinical trials.gov BACKGROUND Early studies suggested that  coffee consumption  may increase the risk of chronic disease . OBJECTIVE We investigated prospect ively the association between coffee consumption and the risk of chronic diseases , including type 2 diabetes ( T2D ) , myocardial infa rct ion ( MI ) , stroke , and cancer . DESIGN We used data from 42,659 participants in the European Prospect i ve Investigation into Cancer and Nutrition (EPIC)-Germany study .  Coffee consumption  was assessed by  self-administered food-frequency question naire at baseline , and data on medically verified incident chronic diseases were collected by active and passive follow-up procedures . HRs and 95 % CIs were calculated with multivariate Cox regression models and compared by competing risk analysis . RESULTS During 8.9 y of follow-up , we observed 1432 cases of T2D , 394 of MI , 310 of stroke , and 1801 of cancer as first qualifying events .  Caffeinated  ( HR : 0.94 ; 95 % CI : 0.84 , 1.05 ) or decaffeinated ( HR : 1.05 ; 95 % CI : 0.84 , 1.31 ) coffee consumption ( ≥4 cups/d compared with < 1 cup/d ; 1 cup was defined as 150 mL ) was not associated with the overall risk of chronic disease . A lower risk of T2D was associated with caffeinated ( HR : 0.77 ; 95 % CI : 0.63 , 0.94 ; P-trend 0.009 ) and decaffeinated  ( HR : 0.70 ; 95 % CI : 0.46 , 1.06 ; P-trend : 0.043 ) coffee consumption ( ≥4 cups/d compared with < 1 cup/d ) , but cardiovascular disease and cancer risk were not . The competing risk analysis showed no significant differences between the risk associations of individual diseases . CONCLUSION Our findings suggest that coffee consumption does not increase the risk of chronic disease , but it may be linked to a lower risk of T2D Caffeine increases blood pressure ( BP ) . In men , acute BP elevations after caffeine intake are due to an increase in vascular resistance , with no change in cardiac output . The hemodynamic effects of caffeine have not been studied in women . Accordingly , BP and hemodynamic responses to caffeine were measured in a double-blind trial comparing age-matched men and women at rest and during mental stress .  Caffeine ( 3.3 mg/kg , equivalent to 2 to 3 cups of brewed coffee ) or placebo was given to separate groups of women ( n = 21 and 21 ) and men ( n = 16 and 19 ) ( mean ages 29 and 27 years , respectively ) .  BP , cardiac output , and vascular resistance were observed at rest , during a stressful public-speaking simulation , reading aloud , and recovery . Caffeine caused nearly identical systolic and diastolic BP elevations in women ( 4.5 and 3.3 mm Hg , respectively ) and men ( 4.1 and 3.8 mm Hg , respectively ) . Men given caffeine versus placebo showed the expected elevation in vascular resistance throughout the remainder of the protocol ( p < 0.001 ) , with no difference in cardiac output . In contrast , women responded to caffeine with increases in stroke volume ( p < 0.001 ) and cardiac output ( p < 0.001 ) , with no difference in vascular resistance from women taking placebo .  Men and women have similar BP responses to caffeine , but the BP responses may arise from different hemodynamic mechanisms . Women who consume a dietary dose of caffeine showed an increase in cardiac output , whereas men showed increased vascular resistance Context Previous studies have examined the association between coffee consumption and a variety of specific diseases , such as type 2 diabetes , different types of cancer , and cardiovascular disease . However , the relationship between coffee consumption and all-cause mortality remains unclear . Contribution This study followed 2 large cohorts of men and women who provided data on coffee consumption , other behaviors , and health outcomes every 2 to 4 years over 2 decades . High coffee consumption was not related to increased mortality and may even be associated with lower total and cardiovascular mortality . Caution Misclassification of coffee consumption or confounding by other behavioral factors may account for these observations . The Editors Several epidemiologic studies have examined coffee consumption and risk for coronary heart disease and other chronic diseases , but data on coffee consumption in relation to all-cause and disease-specific mortality are sparse . Some studies found that those who drank coffee were the healthiest cohort members ( 15 ) , an inverse association that has been attributed to a possible confounding effect by morbidity . However , it has recently been suggested that the inverse association between coffee and all-cause mortality is attributable to the beneficial effect of coffee consumption on inflammation ( 6 ) . The Appendix Table lists the previous studies that have examined coffee consumption and the risk for mortality by different causes . Appendix Table . Cohort Studies Addressing the Association between  Coffee Consumption and All-Cause and Disease-Specific Mortality  In support of this hypothesis , we found in a previous study an inverse association between  coffee consumption and several markers of inflammation and endothelial dysfunction ( 7 ) . In addition , in the NHS ( Nurses ' Health Study ) and HPFS ( Health Professionals Follow-up Study ) , consumption of 6 or more cups of coffee per day was associated with a slightly lower risk for fatal coronary heart disease versus nonconsumers in both men and women ( 8) . Moreover , epidemiologic studies have consistently found an association between higher coffee consumption and lower risk for type 2 diabetes ( 9 ) . Finally , several studies have suggested that coffee might decrease the risk for some types of cancer , such as liver , colon , oral , pharyngeal , and esophageal ( 1012 ) . The objective of this study was to assess the association of  coffee consumption with all-cause , cardiovascular disease ( CVD ) , and cancer mortality . The long follow-up and the use of repeated dietary measurements allowed us to assess long-term coffee consumption . In addition , information about incident diseases during the follow-up and up date d measurements of main risk factors for CVD and cancer allowed us to control for potential confounders in detail . Methods Study Population The HPFS was established in 1986 and the NHS in 1976 . Information ( excluding diet ) on the cohort members has been up date d every 2 years . Further details have been published elsewhere ( 13 ) . We used 1980 as baseline for the NHS because this was the first year in which dietary information was collected in this cohort . After excluding participants with CVD or cancer at baseline or those with no information about coffee consumption at baseline ( 1183 persons in the HPFS and 879 in the NHS ) , we included 41736 men and 86214 women who were followed until 2004 . The Harvard School of Public Health and Brigham and Women 's Hospital Human Subjects Committee Review Board approved the study protocol . Assessment of  Coffee Consumption  Dietary question naires were sent to the HPFS participants in 1986 , 1990 , 1994 , and 1998 and to the NHS participants in 1980 , 1984 , 1986 , 1990 , 1994 , and 1998 . In each question naire , participants were asked how often on average during the previous year they had consumed coffee and tea . The participants could choose from 9 responses .  Decaffeinated coffee and different types of caffeinated soft drinks  were first assessed in 1986 in the HPFS and in 1984 in the NHS . We also inquired at baseline about whether the participant 's consumption for each beverage had greatly increased or decreased during the preceding 10 years . Using the U.S. Department of Agriculture food composition sources supplemented with other sources , we estimated that the caffeine content was 137 mg per cup of coffee , 47 mg per cup of tea , 46 mg per can or 12-ounce bottle of a soft drink , and 7 mg per 1-ounce serving of chocolate c and y. We assessed the total intake of caffeine by summing the caffeine content for a unit of each food during the previous year multiplied by a weight proportional to the frequency of its consumption . In our validation study , we obtained high correlations between consumption of coffee and other caffeinated beverages estimated from the food frequency question naire and consumption estimated from repeated 1-week diet records ( coffee , r= 0.78 ; tea , r= 0.93 ; and caffeinated soft drinks , r= 0.85 ) ( 14 ) . Ascertainment of Mortality Deaths were reported by the next of kin or the postal authorities or were ascertained through the National Death Index . We estimated that follow-up for deaths was more than 98 % complete ( 15 ) . For all deaths , we sought death certificates and , when appropriate , requested permission from the next of kin to review medical records . The underlying cause of death was assigned according to the International Classification of Diseases , Eighth Revision ( ICD-8 ) . The primary end point in this analysis was death from any cause . We also conducted analyses according to the main causes of deaths in the cohorts , which were CVD ( ICD-8 codes 390.0 through 458.9 and 795.0 to 795.9 ) and cancer ( ICD-8 codes 140.0 through 207.9 ) , and according to secondary causes of death , such as chronic liver disease and cirrhosis ( ICD-8 code 571.0 ) , chronic obstructive pulmonary disease ( ICD-8 codes 492.0 , 496.0 , and 519.0 ) , diabetes ( ICD-8 codes 250.0 , 250.1 , and 250.9 ) , neurodegenerative diseases ( ICD-8 codes 331.0 and 332.0 ) , and sudden death ( ICD-8 code 798.0 ) . Assessment of Medical History , Anthropometric Data , and Lifestyle Factors In the baseline question naires , we requested information about age ; weight and height ; smoking status ; parental history with respect to myocardial infa rct ion ; menopausal status and use of hormone therapy in women ; and history of hypertension , hypercholesterolemia , and type 2 diabetes mellitus . We up date d this information , with the exception of height and parental history , in the biennial follow-up question naires . We assessed perceived health in 2000 by asking the participants to describe their health as excellent , very good , good , fair , or poor . We calculated body mass index , and we also assessed physical activity biennially . In the HPFS , participants were queried about the average time spent per week during the preceding year in specific activities ( for example , walking outdoors , jogging , and bicycling ) ( 16 ) . The time spent in each activity in hours per week was multiplied by its typical energy expenditure , expressed in metabolic equivalent tasks and then summed over all activities to yield a metabolic equivalent task or hour score . In the NHS , physical activity was reported in hours per week of moderate ( for example , brisk walking ) and vigorous exercise ( for example , strenuous sports and jogging ) ( 17 ) . St and ard portion sizes for alcoholic drinks were specified as a can , bottle , or glass for beer ; 4-oz glass for wine ; and 1 drink or shot for liquor . Detailed information on the validity and reproducibility of the information from the question naires about self-reported weight , physical activity , and alcohol consumption has been reported elsewhere ( 1820 ) . Statistical Analysis We classified participants according to levels of coffee consumption . We calculated person-years of exposure from the date of return of the baseline question naire to the date of death or 1 June 2004 , whichever came first . To reduce within-participant variation and best represent long-term diet , we used the cumulative average of coffee consumption from all available di 
    Output:
    
This observation might reflect the long-term effects of coffee manifested in habitual drinkers who developed tolerance to the acute effects of caffeine .
For example , phenolic compounds in coffee ( chlorogenic acid , ferulic acid , p-coumaric acid ) , magnesium , trigonelline , and quinides have been associated with improved insulin sensitivity ( 4 ) .
Phenolic compounds also have antioxidant activity ( 5 ) .
In addition , diterpenes in coffee ( cafestol and kahweol ) have anticarcinogenic properties ( 6 ) .
Thus , it is plausible that the harmful effects of caffeine could be offset by the beneficial effects of these other components .
The results showed that neither caffeinated nor decaffeinated coffee consumption was associated with an increased risk of total chronic disease , CVD , or cancer ; furthermore , both types of coffee showed an inverse association with the risk of type 2 diabetes .
This indicates that coffee improves adipocyte and liver function , which may decrease the risk of type 2 diabetes .
The work by Floegel et al ( 7 ) adds to the evidence on the null association between habitual coffee consumption  and CVD , cancer , and total mortality , another indicator of the global effect on health ( 11 ) , and suggests that this beverage may produce health benefits .
In short-term studies , nonfiltered coffee has been shown to