caffeinated and decaffeinated coffee consumption and risk of … · health implications. an inverse...

Caffeinated and DecaffeinatedCoffee Consumption and Riskof Type 2 Diabetes: A SystematicReview and a Dose-ResponseMeta-analysis

OBJECTIVE

Previous meta-analyses identified an inverse association of coffee consumptionwith the risk of type 2 diabetes. However, an updated meta-analysis is neededbecause new studies comparing the trends of association for caffeinated anddecaffeinated coffee have since been published.

RESEARCH DESIGN AND METHODS

PubMed and Embase were searched for cohort or nested case-control studiesthat assessed the relationship of coffee consumption and risk of type 2 diabetesfrom1966 to February 2013. A restricted cubic spline random-effectsmodelwasused.

RESULTS

Twenty-eight prospective studies were included in the analysis, with 1,109,272study participants and 45,335 cases of type 2 diabetes. The follow-up durationranged from 10 months to 20 years. Compared with no or rare coffee consump-tion, the relative risk (RR; 95% CI) for diabetes was 0.92 (0.90–0.94), 0.85 (0.82–0.88), 0.79 (0.75–0.83), 0.75 (0.71–0.80), 0.71 (0.65–0.76), and 0.67 (0.61–0.74) for1–6 cups/day, respectively. The RR of diabetes for a 1 cup/day increase was 0.91(0.89–0.94) for caffeinated coffee consumption and 0.94 (0.91–0.98) for decaf-feinated coffee consumption (P for difference = 0.17).

CONCLUSIONS

Coffee consumption was inversely associated with the risk of type 2 diabetes in adose-responsemanner. Both caffeinated and decaffeinated coffeewas associatedwith reduced diabetes risk.Diabetes Care 2014;37:569–586 | DOI: 10.2337/dc13-1203

Type 2 diabetes is a chronic disease with high rates of morbidity and mortality. Theworldwide prevalence of type 2 diabetes is increasing, and the global number ofpeople with diabetes is estimated to reach 366 million by the year 2030 (1). The riskof blindness, renal disease, and amputation among those with type 2 diabetes is 20to 40 times higher than that of people without diabetes. Furthermore, those withtype 2 diabetes have a two to five times higher risk of myocardial infarction and twoto three times higher risk of stroke (2). Given its significant burden, identifyingmodifiable lifestyle factors is imperative for the prevention of diabetes.

1Department of Nutrition, Harvard School ofPublic Health, Boston, MA2Saw Swee Hock School of Public Health andDepartment of Medicine, Yong Loo Lin School ofMedicine, National University of Singapore andNational University Health System, Singapore3Department of Epidemiology, Harvard School ofPublic Health, Boston, MA4Channing Division of Network Medicine,Brigham and Women’s Hospital and HarvardMedical School, Boston, MA

Corresponding author: Frank B. Hu, [email protected].

Received 22 May 2013 and accepted 27September 2013.

This article contains Supplementary Data onlineat http://care.diabetesjournals.org/lookup/suppl/doi:10.2337/dc13-1203/-/DC1.

© 2014 by the American Diabetes Association.See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.

Ming Ding,1 Shilpa N. Bhupathiraju,1

Mu Chen,1 Rob M. van Dam,1,2

and Frank B. Hu1,3,4

Diabetes Care Volume 37, February 2014 569

META

-ANALYSIS

mailto:[email protected]

mailto:[email protected]

http://care.diabetesjournals.org/lookup/suppl/doi:10.2337/dc13-1203/-/DC1


http://creativecommons.org/licenses/by-nc-nd/3.0/

http://creativecommons.org/licenses/by-nc-nd/3.0/

Coffee is one of the most widelyconsumed beverages around the world;thus, investigating its association withvarious diseases has important publichealth implications. An inverseassociation between coffee consumptionand risk of type 2 diabetes was firstreported in a Dutch population (3). Insubsequent years, this finding has beenconfirmed in most (4–10) but not all (11–13) studies. Two previous meta-analysesof coffee consumption and risk of type 2diabetes have been published. van Damand Hu (14) included nine cohort studiesand reported a lower risk of type 2diabetes for high coffee consumptioncompared with no coffee consumptionwith little between-study heterogeneity.Huxley et al. (15) included 18 prospectivestudies and found an inversemonotonousassociation between the number of cupsof coffee consumed and diabetes risk, butthey double-counted data from the samecohort (16,17). Since the publication ofthese meta-analyses, 10 additionalprospective studies on the associationbetween coffee consumption anddiabetes have been published(6,8,10,12,18–23).

A key issue that remains to be resolved iswhether consumption of caffeinated anddecaffeinated coffee is similarlyassociatedwith the risk of type 2 diabetes.Such results would provide insight intothe role of caffeine in the putativerelationship between coffee consumptionand diabetes risk. The meta-analysis byHuxley et al. (15) included only six studieson decaffeinated coffee, and estimateswere less precise than for caffeinatedcoffee because of lower consumptionlevels. Eight subsequent prospectivestudies evaluated the association withdecaffeinated coffee, approximatelydoubling the amount of data ondecaffeinated coffee and diabetes risk(8,10,12,18–21,24). We thereforeperformed an updated systematic reviewand a dose-response meta-analysis of allavailable data on the association of bothcaffeinated and decaffeinated coffeeconsumption with the risk of type 2diabetes.

RESEARCH DESIGN AND METHODS

Search Strategy and Selection CriteriaWe searched the PubMed and Embasedatabases for prospective cohort

studies or nested case-control studiesthat evaluated the association betweencoffee consumption and risk of type 2diabetes between January 1966 andFebruary 2013. The computer-basedsearches included the key words coffeeand diabetes. No Medical SubjectHeadings terms were used because ofthe clear definitions of coffee anddiabetes. Reference lists of retrievedarticles were manually scanned for allrelevant additional studies and reviewarticles. We restricted the search tostudies on humans and written in English.

Study SelectionStudies included in this meta-analysismet the following criteria: 1) the studydesign was prospective cohort or nestedcase-control; 2) the articles werepublished in English; 3) the exposurewas categorized coffee consumption,including total coffee, caffeinatedcoffee, or decaffeinated coffee; and 4)the outcome was risk of type 2 diabetes.Studies were excluded if they werecross-sectional in design and ifinformation on dose-response modelingwas inadequate, including the numberof participants and cases, relative risk(RR) and SE for the estimate, and dose ofcoffee consumption in each exposurecategory.

Data Extraction and QualityAssessmentOne author (M.D.) assessed studyeligibility and extracted the data, andanother (M.C.) independently double-checked the available data. Thefollowing data were extracted fromeach study: first author’s name, year ofpublication, geographical location,follow-up time, sex, age, number of type2 diabetes events, number ofparticipants, categories of coffeeconsumption, type of assessment oftype 2 diabetes, covariates adjusted forin themultivariable analysis, and RRs forall categories of coffee consumption. Ifstudies based on the same cohort werepublished several times, only the mostrecent article was selected. If a studyonly reported caffeinated coffeeconsumption instead of total coffeeconsumption, caffeinated coffeeconsumption was also included in thetotal coffee consumption analysis. TheNewcastle-Ottawa quality assessment

scale (NOS) was used to evaluate thestudy quality of the included articles.The scale ranges from 0 to 9 points, withhigher points indicating higher studyquality. Specifically, loss to follow-upwas assessed as an item in the NOS forindividual studies. In the present meta-analysis, we assumed that loss to follow-up was random.

To perform a dose-response meta-analysis, we assigned the median ormean coffee consumption in eachcategory of consumption to thecorresponding RR for each study. If themean or median consumption percategory was not reported, themidpoint of the upper and lowerboundaries in each category wasassigned as the mean consumption. Ifthe upper boundary for the highestcategory was not provided, the assignedmean value was 25% higher than thelower boundary of that category. If thelower boundary for the lowest categorywas not provided, the assigned meanvalue was one-half of the upperboundary of that category.

Data Synthesis and AnalysisTo analyze the trend of coffeeconsumption and risk of type 2 diabetes,we used both semiparametric andparametric methods. For thesemiparametric method, four coffeeconsumption groups were generated,namely lowest, third highest, secondhighest, and highest. For each includedstudy, the lowest and the highest coffeeconsumption categories correspondedto the lowest and highest groups,respectively. For studies with fourexposure categories, the second andthird categories corresponded to thesecond and third highest groups,respectively. For studies with threeexposure categories, the middlecategory corresponded to either thesecond or the third highest group,whichever median coffee consumptionamount was most similar. If the studyhad more than four exposurecategories, two consumption groups,other than the lowest and highest, werechosen on the basis of their similarity ofthe amount of coffee consumption inthat category to the second and thirdhighest groups. For each group, arandom-effects model was used to poolthe RR of type 2 diabetes (25). Statistical

570 Coffee and Risk of Type 2 Diabetes Diabetes Care Volume 37, February 2014

heterogeneity in each group wasassessed by Cochrane Q test, with P ,0.1 indicating significant between-studyheterogeneity.

For the parametric method, a random-effects dose-response meta-analysiswas performed (26). The number ofcases and participants in each coffeeconsumption category was extracted toestimate the covariance of the RR ineach study. Together with the observedadjusted variance of the RR, weestimated the variance/covariancematrix of the data. The weight of eachstudy was calculated as the inverse ofthe variance/covariance matrix. Weused generalized least squares modelswith maximum likelihood method toestimate the coefficients for eachstudy, and we fit a random-effectsgeneralized linear model. Additionally,we tested for potential nonlinearityin the association between coffeeconsumption and type 2 diabetes by arandom-effects restricted cubic splinemodel with three knots. Statacommands GLST for model fitting andLINCOME for estimating effect wereused for the fitted model.

Stratified analyses were performed forstudy location, sex, diabetes assessment

method, and type of coffee (i.e.,caffeinated, decaffeinated), and thesubgroup difference was tested in theassociation of coffee consumption withrisk of type 2 diabetes. We assessed thepotential for publication bias through aformal Egger regression symmetry test.All analyses were conducted with Stata10 (StataCorp, College Station, TX)statistical software.

RESULTS

Characteristics of StudiesThe initial search identified 800potentially relevant citations. Afterscreening titles and abstracts, weidentified 39 studies for furtherevaluation (Fig. 1). We excluded sixstudies with a cross-sectional studydesign, three that were abstracts ofconference posters, and two that wererepeated in the same cohort. The resultsof the remaining 28 studies, comprising1,109,272 study participants and 45,335cases of type 2 diabetes, were includedin the meta-analysis (3–13,17–24,27–35). Characteristics of all 28 studieswere shown in Table 1. The duration offollow-up for incident type 2 diabetesranged from 10 months to 20 years,with a median follow-up of 11 years.

Thirteen studies were conducted in theU.S., 11 in Europe, and 4 in Asia. In ninestudies, type 2 diabetes was self-reported; the outcome of six studieswasassessed by means of a glucosetolerance test, and the outcome of theother studies was confirmed by eithermedical records or national registries.One study was a nested case-controldesign, and the remaining 27 wereprospective cohort studies. Ten studiesassessed both caffeinated anddecaffeinated coffee, and only one eachassessed caffeinated coffee anddecaffeinated coffee. Fifteen studies didnot distinguish caffeinated coffee anddecaffeinated coffee, and sevenassessed caffeine consumption. Themean NOS score was 7 (of a possible 9points), suggesting a high quality of thestudies included in the meta-analysis.The points were mainly lost in exposureassessment and adequacy of follow-upof cohorts: Six studies assessed coffeeconsumption by structured interview,and five addressed the percentage ofloss to follow-up.

Total Coffee Consumption and Risk ofType 2 DiabetesFigure 2 shows the results of differentlevels of total coffee consumption

Figure 1—Study selection process of the identified articles.

care.diabetesjournals.org Ding and Associates 571

http://care.diabetesjournals.org

Table

1—Basicch

aracteristicsoftheincludedstudies

Authors

Country

Sex

Age

at

baseline

(year)

Follo

w-up(year)

Nn

Type2

diabetes

assessmen

t

Coffee

exposure

(cups/day)

RR

(95%

CI)

Confoundingadjustmen

ts

NOS

(0–9points)

vanDam

andFesken

s20

02(3)

Europe

Both

30–60

1–13

17,111

306

Self-rep

orted

Totalcoffee

Educationallevel,leisure

timephysicalactivity,

occup

ationalp

hysical

activity,alcoho

l

consum

ption,cigarette

smoking,history

of

cardiovascular

disease,

know

nhypertension

,

andknow

n

hypercholesterolemia

6

#2

1.00(1.00–

1.00

)

3–4

0.79(0.57–

1.10

)

5–6

0.73(0.53–

1.01

)

$7

0.50(0.35–

0.72

)

Reu

nan

enet

al.20

03(11)

Europe

Both

20–98

304,227

a19

,518

855

Confirm

edcases

Totalcoffee

Age,sex,BMI,sm

oking,

andleisure

time

physicalactivity

8

#2

1.00(1.00–

1.00

)

3–4

1.01(0.81–

1.27

)

5–6

0.98(0.79–

1.21

)

$7

0.92(0.73–

1.16

)

Carlssonet

al.20

04(7)

Europe

Both

30–60

2010

,652

408

Confirm

edcases

Totalcoffee

Age,sex,BMI,ed

ucation,

leisure

timephysical

activity,alcohol

consumption,and

smoking

6

#2

1.00(1.00–

1.00

)

3–4

0.70(0.48–

1.01

)

5–6

0.71(0.50–

1.01

)

$7

0.65(0.44–

0.96

)

Rosengren

etal.20

04(27)

Europe

F39

–65

181,36

174

Confirm

edcases

Totalcoffee

Age,sm

oking,low

physicalactivity,

education,B

MI,and

serum

cholesteroland

triglycerides

8

#2

1.00(1.00–

1.00

)

3–4

0.56(0.32–

0.98

)

5–6

0.45(0.23–

0.90

)

.6

0.57(0.26–

1.29

)

Salazar-Martinez

etal.20

04(4)

U.S.

Both

M40

–75

M12

41,934

1,33

3Confirm

edCaffeine(m

en)b

Age;totalcaloricintake;

family

history

of

diabetes;alcohol

consumption;sm

oking

status;men

opausal

statusand

postmen

opausal

horm

oneuse;intakes

ofglycem

icload

,trans

fat,polyunsaturated

fattyacid,cerealfi

ber,

andmagnesium;BMI;

andphysicalactivity

6

F30

–55

F18

self-rep

ort

131.00(1.00–

1.00

)

741.06(0.89–

1.26

)

172

1.01

(0.85–1.20)

323

0.94(0.78–

1.12

)

566

0.80(0.66–

0.97

)

M84

,276

Caffeine(w

omen

)b

F4,08

569

1.00(1.00–

1.00

)

193

1.02(0.93–

1.11

)

328

0.90(0.82–

0.99

)

432

0.85(0.77–

0.94

)

708

0.70(0.63–

0.79

)

Con

tinu

edon

p.57

3


Table

1—Continued

Authors

Country

Sex

Age

at

baseline

(year)

Follo

w-up(year)

Nn

Type2

diabetes

assessmen

t

Coffee

exposure

(cups/day)

RR

(95%

CI)


ts

NOS

(0–9points)

vanDam

etal.20

04(28)

Europe

Both

50–74

6.4

1,31

212

8OGTT

Totalcoffee

Age;sex;B

MI;waist-hip

ratio;p

hysicalactivity;

alcoholconsumption;

cigarettesm

oking;

history

of

cardiovascular

disease;

useof

antihypertensive

medication;

andintake

offiber,totalenergy,

saturatedfat,and

polyunsaturated

fat

8

#2

1.00

(1.00–1.00

)

3–4

0.94

(0.56–1.55

)

5–6

0.92

(0.53–1.61

)

$7

0.69

(0.31–1.51

)

Greenberget

al.20

05(35)

U.S.

Both

32–88

8.4

7,00

617

0Self-rep

orted

Caffeinated

coffee

Percapitaincome,

educationallevel,race,

sex,physicalactivity,

smokingstatus,

alcoholconsumption,

BMI,age,

andtypeof

diet;variablesfor

consumptionof

caffeineandallthree

beverages

werein

the

regressionmodel

simultaneo

usly

6

01.00

(1.00–1.00

)

,2

0.82

(0.55–1.23

)

240.75

(0.50–1.13

)

$4

0.37

(0.22–0.64

)

Decaf.coffee

01.00

(1.00–1.00

)

,2

0.62

(0.34–1.11

)

2–4

0.43

(0.20–0.93

)

Caffeineb

751.00

(1.00–1.00

)

225

0.69

(0.42–1.11

)

375

0.73

(0.38–1.41

)

525

0.65

(0.30–1.42

)

750

0.65

(0.24–1.77

)

Isoet

al.20

06(9)

Asia

Both

40–65

517

,413

444

Self-rep

orted

Totalcoffee

Family

history

ofdiabetes,

smokingstatus,

alcoholintake,

magnesium

intake,

hoursofw

alking,hours

ofexercise,and

consumptionofother

beverages

6

,2

0.82

(0.55–1.23

)

2–4

0.75

(0.50–1.13

)

$4

0.37

(0.22–0.64

)

$3

0.58

(0.37–0.90

)

Caffeineb

571.00

(1.00–1.00

)

137

1.00

(0.73–1.37

)

199

0.98

(0.73–1.33

)

273

1.00

(0.74–1.37

)

416

0.67

(0.47–0.95

)

Con

tinu

edon

p.57

4



Table

1—Continued

Authors

Country

Sex

Age

at

baseline

(year)

Follo

w-up(year)

Nn

Type2

diabetes

assessmen

t

Coffee

exposure

(cups/day)

RR

(95%

CI)


ts

NOS

(0–9points)

Paynteret

al.20

06(29)

U.S.

Both

45–64

912

,204

1,43

7Self-rep

orted

Totalcoffee

(men

)Age,race,ed

ucation,

family

history

of

diabetes,BMI,waist-

hip

ratio,totalcaloric

intake,d

ietary

fiber,

smoking,alcohol

consumption,leisure

activity,and

hypertension

8

01.00

(1.00–1.00)

,1

1.02

(0.76–1.38)

11.01

(0.76–1.34)

2–3

0.93

(0.70–1.22)

$4

0.69

(0.50–0.96)

Totalcoffee

(women

)

01.00

(1.00–1.00)

,1

1.23

(0.93–1.62)

11.06

(0.83–1.36)

2–3

0.89

(0.68–1.16)

$4

0.66

(0.45–0.96)

Pereiraet

al.20

06(13)

U.S.

FMean61

1128

,812

1,41

8Self-rep

orted

Totalcoffee

Age,ed

ucation,baseline

hypertension,alcohol,

smokingstatus,

cigarettepack-years,

BMI,waist-hip

ratio,

physicalactivity,

energy

intake,totalfat,

Keys

score,cereal

fiber,tea

consumption,and

sodaconsumption

6

01.00

(1.00–1.00)

,1

0.95

(0.77–1.18)

1–3

1.01

(0.85–1.19)

4–5

0.85

(0.69–1.04)

$6

0.79

(0.61–1.02)

Caffeinated

coffee

01.00

(1.00–1.00)

,1

0.92

(0.76–1.11)

1–3

0.88

(0.70–1.12)

4–5

0.89

(0.64–1.23)

$6

1.00

(0.84–1.19)

Decaf.coffee

01.00

(1.00–1.00)

,1

0.98

(0.83–1.16)

1–3

1.01

(0.84–1.21)

4–5

0.59

(0.44–0.80)

$6

0.68

(0.43–1.09)

Con

tinu

edon

p.57

5


Table

1—Continued

Authors

Country

Sex

Age

at

baseline

(year)

Follo

w-up(year)

Nn

Type2

diabetes

assessmen

t

Coffee

exposure

(cups/day)

RR

(95%

CI)


ts

NOS

(0–9points)

vanDam

etal.20

06(5)

U.S.

F26

–46

2088

,259

1,263

Self-rep

orted

Totalcoffee

Age;sm

okingstatus;BMI;

physicalactivity;

alcoholconsumption;

use

ofhorm

one

replacementtherapy;

oralcontracep

tive

use;

family

history

oftype2

diabetes;history

of

hypertension

;historyof

hypercholesterolemia;

consumptionofsugar-

sweetened

softdrinks;

consumptionofpun

ch;

andquintilesof

processedmeat

consumption,the

polyunsaturated-to-

saturatedfatintake

ratio,totalenergy

intake,theglycem

ic

index,andcerealfiber

intake

5

01.00

(1.00–1.00)

,1

0.93

(0.80–1.09)

10.87

(0.73–1.03)

2–3

0.58

(0.49–0.68)

$4

0.53

(0.41–0.68)

Caffeinated

coffee

01.00

(1.00–1.00)

,1

1.00

(0.86–1.17)

10.89

(0.75–1.07)

2–3

0.62

(0.52–0.74)

$4

0.61

(0.46–0.81)

Decaf.coffee

01.00

(1.00–1.00)

,1

0.86

(0.74–0.99)

10.87

(0.68–1.11)

2–3

0.52

(0.36–0.74)

Caffeineb

221.00

(1.00–1.00)

930.88

(0.75–1.04)

180

0.89

(0.75–1.05)

341

0.74

(0.62–0.89)

528

0.55

(0.45–0.67)

Smithet

al.20

06(30)

U.S.

Both

$50

891

084

OGTT

Totalcoffee

Sex,age,

physicalactivity,

BMI,sm

oking,alcohol,

hypertension,and

baselinefastingplasm

a

glucose

7

01.00

(1.00–1.00)

1–2

0.66

(0.38–1.14)

3–4

0.53

(0.26–1.08)

$5

0.60

(0.26–1.40)

Aden

eyet

al.20

07(24)

U.S.

FMean31

10mo

1,744

75OGTT

Caffeinated

coffee

Maternalage,

smoking

duringpregn

ancy,

regularalcoholu

se

before

pregnan

cy,

maternalrace,

prepregn

ancy

BMI,

chronichypertension,

andaveragedaily

caloricintake

6

None

1.00

(1.00–1.00)

Moderate

0.58

(0.33–1.02)

High

0.76

(0.40–1.46)

Con

tinu

edon

p.57

6



Table

1—Continued

Authors

Country

Sex

Age

at

baseline

(year)

Follo

w-up(year)

Nn

Type2

diabetes

assessmen

t

Coffee

exposure

(cups/day)

RR

(95%

CI)


ts

NOS

(0–9points)

Fuhrm

anet

al.20

09(31)

U.S.

M35

–79

2.6

4,68

551

9OGTT

Totalcoffeec

Age,BMI,sm

okingstatus,

family

history

of

diabetes,ed

ucation,

alcoholintake,index

of

physicalactivity,and

milk

andsugarintake

7

1–2

1.00(1.00–

1.00

)

30.79(0.69–

1.00

)

$4

0.75(0.58–

0.97

)

Ham

eret

al.20

08(32)

Europe

Both

35–55

11.7

5,82

338

7OGTT

Totalcoffee

Five-yearagecategories,

sex,ethnicity,

employm

entgrad

e,

plusBMIcatego

ry,

waist-hip

ratio,

smoking,sex-specific

alcoholintake

tertiles,

physicalactivity

category,fam

ily

history

ofdiabetes,

hypertension,

cholesterol,total

energy

intake,d

iet

pattern,andmutual

adjustmen

tforall

beveragetype

8

01.00(1.00–

1.00

)

#1

0.83(0.60–

1.14

)

2–3

0.85(0.60–

1.20

)

.3

0.80(0.54–

1.18

)

Decaf.coffee

01.00(1.00–

1.00

)

#1

1.13(0.87–

1.47

)

;2–

30.87(0.58–

1.30

)

.3

0.65(0.36–

1.16

)

Odegaard

etal.20

08(33)

Asia

Both

45–74

5.7

36,908

1,88

9Confirm

edself-

report

Totalcoffee

Age

atrecruitmen

t,year

ofinterview,sex,

dialect,ed

ucation,

hypertension,smoking

status,alcohol

consumption,BMI,

physicalactivity,

dietary

variables,and

magnesium

9

,1

1.00(1.00–

1.00

)

10.94(0.81–

1.09

)

2–3

0.83(0.68–

1.01

)

$4

0.70(0.53–

0.93

)

Bidel

etal.20

08(17)

Europe

Both

35–74

5–20

21,826

862

Confirm

edcases

Totalcoffee

Age,BMI,alcohol

consumption,

smoking,physical

activity,andglucose

tolerance

test

7

0–2

1.00(1.00–

1.00

)

3–4

0.85(0.70–

1.04

)

5–6

0.78(0.65–

0.95

)

$7

0.64(0.51–

0.80

)

Con

tinu

edon

p.57

7


Table

1—Continued

Authors

Country

Sex

Age

at

baseline

(year)

Follo

w-up(year)

Nn

Type2

diabetes

assessmen

t

Coffee

exposure

(cups/day)

RR

(95%

CI)


ts

NOS

(0–9points)

Kato

etal.20

09(34)

Asia

Both

40–69

1055

,826

2,69

4Confirm

ed

self-rep

ort

Totalcoffee

(men

)

Age,BMI,sm

okingstatus,

alcoholdrinking,family

history

ofdiabetes,

physicalactivity,

history

of

hypertension,

perceived

men

tal

stress,levelsoftypeA

beh

avior,andhoursof

sleep

8

01.00

(1.00–1.00)

1–2d

0.93

(0.80–1.08)

3–4d

0.84

(0.71–1.01)

1–2

0.84

(0.73–0.97)

3–4

0.83

(0.68–1.02)

$5

0.82

(0.60–1.11)

Totalcoffee

(women

)

01.00

(1.00–1.00)

1–2d

0.90

(0.76–1.06)

3–4d

0.95

(0.77–1.17)

1–2

0.81

(0.69–0.96)

3–4

0.62

(0.45–0.84)

$5

0.40

(0.20–0.78)

Obaet

al.20

10(10)

Asia

Both

,70

1013

,540

453

Self-rep

orted

Caffeinated

coffee

(men

)

Age,sm

okingstatus,BMI,

physicalactivity,

lengthofed

ucationin

years,alcohol

consumption,total

energy

intake,fat

intake,andwomen

’s

men

opausalstatusto

exam

inebeverageand

chocolate

snacks

6

01.00

(1.00–1.00)

1/moto

6/wk

0.69

(0.50–0.97)

$1

0.69

(0.49–0.98)

Caffeinated

coffee

(women

)

01.00

(1.00–1.00)

1/moto

6/wk

1.08

(0.74–1.60)

$1

0.70

(0.44–1.12)

Decaf.coffee

(men

)

01.00

(1.00–1.00)

$1e

1.09

(0.73–1.61)

Decaf.coffee

(women

)

01.00

(1.00–1.00)

$1e

0.66

(0.36–1.23)

Caffeine(m

en)b

421.00

(1.00–1.00)

790.81

(0.60–1.10)

218

0.95

(0.69–1.30)

Caffeine(w

omen

)b

601.00

(1.00–1.00)

971.26

(0.88–1.82)

226

0.95

(0.63–1.43)

Con

tinu

edon

p.57

8



Table

1—Continued

Authors

Country

Sex

Age

at

baseline

(year)

Follo

w-up(year)

Nn

Type2

diabetes

assessmen

t

Coffeeexposure

(cups/day)

RR

(95%

CI)


ts

NOS

(0–9points)

Zhan

get

al.20

11(23)

U.S.

Both

45–74

7.6

1,14

118

8OGTT

Totalcoffee

Age,sex,smoking,alcohol

use,family

history

of

diabetes,physical

activity,andBMI

7

01.00(1.00–

1.00

)

1–2

0.93(0.55–

1.57

)

3–4

0.87(0.53–

1.44

)

5–7

0.72(0.43–

1.23

)

8–11

0.78(0.44–

1.37

)

$12

0.33(0.13–

0.81

)

vanDierenet

al.20

09(22)

Europe

Both

49–70

1040

,011

918

Confirm

ed

self-rep

ort

Totalcoffee

Cohort,sex,age,

BMI,

highested

ucation,

physicalactivity,fam

ily

history

ofdiabetes,

smoking,alcohol

intake,e

nergy

intake,

energy-adjusted

saturatedfatintake,

energy-adjusted

fiber

intake,e

nergy-

adjusted

vitamin

C

intake,

hypercholesterolemia,

andhypertension

6

0–1

1.00(1.00–

1.00

)

1–2

0.88(0.69–

1.11

)

2–3

0.94(0.75–

1.17

)

3–4

0.75(0.60–

0.92

)

4–6

0.74(0.61–

0.91

)

.6

0.84(0.65–

1.08

)

Boggset

al.20

10(21)

U.S.

F30

–69

1246

,906

3,67

1Self-rep

orted

Caffeinated

coffee

Age,questionnaire

cycle,

energy

intake,

education,fam

ily

history

ofdiabetes,

vigo

rousactivity,

smoking,glycem

ic

index,cerealfiber,

sugar-sw

eetened

soft

drinks,B

MI,history

of

hypertension,and

history

ofhigh

cholesterol

6

0e1.00(1.00–

1.00

)

1cup/m

oto

,1cup/day

0.94(0.86–

1.04

)

10.90(0.81–

1.01

)

2–3

0.82(0.72–

0.93

)

$4

0.83(0.69–

1.01

)

Decaf.coffee

0e1.00(1.00–

1.00

)

1cup/m

oto

,1cup/day

1.04(0.93–

1.16

)

11.07(0.92–

1.25

)

2–3

1.01(0.83–

1.24

)

$4

1.10(0.81–

1.49

)

Con

tinu

edon

p.57

9


Table

1—Continued

Authors

Country

Sex

Age

at

baseline

(year)

Follo

w-up(year)

Nn

Type2

diabetes

assessmen

t

Coffee

exposure

(cups/day)

RR

(95%

CI)


ts

NOS

(0–9points)

Sartorelliet

al.20

10(20)

Europe

F41

–72

1169

,532

1,41

5Confirm

ed

self-rep

ort

Totalcoffee

Age,h

istory

ofdiabetes

in

ascendants,q

uartiles

ofphysicalactivity

level,quartilesof

alcoholintake,

educationallevel,

hypercholesterolemia,

hypertension,

smoking,en

ergy-

adjusted

fiber

and

saturatedfat,total

energy

without

alcohol,men

opausal

status,horm

one

replacemen

ttherapy

asatime-dep

enden

t

variab

le,use

oforal

contracep

tivesat

baseline,

andtime-

dep

enden

tBMI

7

01.00

(1.00–1.00

)

#1

1.04

(0.87–1.26

)

1.1–

2.9

0.86

(0.73–1.02

)

$3

0.73

(0.61–0.87

)

Caffeinated

coffee

01.00

(1.00–1.00

)

#1

0.85

(0.74–0.97

)

.1

0.67

(0.57–0.78

)

Decaf.coffee

01.00

(1.00–1.00

)

#1

0.69

(0.51–0.93

)

.1

0.67

(0.47–0.95

)

Caffeineb

481.00

(1.00–1.00

)

126

0.84

(0.72–0.96

)

209

0.77

(0.66–0.89

)

397

0.67

(0.58–0.78

)

Goto

etal.20

11(12)

U.S.

FMean60

1071

835

9Confirm

ed

self-rep

ort

Caffeinated

coffee

Age,race,d

urationof

follow-up,timeof

blooddraw,smoking

status,physical

activity,family

history

ofdiabetes,alcohol

use,totalcalories,and

BMI

7

01.00

(1.00–1.00

)

#1

0.92

(0.46–1.84

)

2–3

0.96

(0.48–1.94

)

$4

0.71

(0.31–1.61

)

Decaf.coffee

01.00

(1.00–1.00

)

#1

1.31

(0.84–2.03

)

2–3

0.91

(0.42–2.00

)

$4

0.92

(0.26–3.27

)

Caffeineb

131.00

(1.00–1.00

)

140

1.53

(0.71–3.30

)

366

1.70

(0.79–3.62

)

656

1.32

(0.61–2.82

)

Hjellviket

al.20

11(6)

Europe

Both

40–45

5–20

362,045

9,88

6Confirm

edcases

Totalcoffee

Year

ofbirth

and,where

relevant,sex,BMI,

smoking,ed

ucation,

andphysicalactivity

7

,1

1.00

(1.00–1.00

)

1–4

0.84

(0.79–0.89

)

5–8

0.65

(0.61–0.70

)

.9

0.63

(0.58–0.69

)

Con

tinu

edon

p.58

0



Table

1—Continued

Authors

Country

Sex

Age

at

baseline

(year)

Follo

w-up(year)

Nn

Type2

diabetes

assessmen

t

Coffee

exposure

(cups/day)

RR

(95%

CI)


ts

NOS

(0–9points)

Floegelet

al.20

12(8)

Europe

Both

35–65

8.9

42,659

1,43

2Confirm

ed

self-rep

ort

Caffeinated

coffee

Age,center,sex,sm

oking,

alcoho

lintake,physical

activity,education,

employment,vitamin

andmineralsupplement

useduring

past4wk,

totalenergyintake,tea

intake,decaf.coffee

intake,BMI,waist-hip

ratio,andprevalent

hypertension

7

,1

1.00

(1.00–1.00

)

1–2

0.89

(0.69–1.16

)

2–3

0.92

(0.76–1.13

)

3–4

0.82

(0.65–1.02

)

$4

0.77

(0.63–0.94

)

Decaf.coffee

,1

1.00

(1.00–1.00

)

1–2

0.97

(0.68–1.39

)

2–3

1.11

(0.84–1.48

)

3–4

0.70

(0.41–1.19

)

$4

0.70

(0.46–1.06

)

Bhupathirajuet

al.20

13(19)

U.S.

Both

M40

–75

F30

–55

M22

F24

39,059

2,86

5Confirm

ed

self-rep

ort

Caffeinated

coffee(m

en)

Age;totalcaloricintake;

family

history

of

diabetes;alcohol

consumption;sm

oking

status;men

opausal

status;

postmen

opausal

horm

oneuse;intake

of

glycem

icload

,trans

fat,polyunsaturated

fattyacid,cerealfiber,

andmagnesium;BMI;

andphysicalactivity

6

,1

1.00

(1.00–1.00

)

1–3

0.95

(0.88–1.03

)

4–5

0.92

(0.82–1.05

)

$6

0.65

(0.49–0.85

)

Caffeinated

coffee

(women

)

,1

1.00

(1.00–1.00

)

1–3

0.91

(0.86–0.95

)

4–5

0.78

(0.72–0.85

)

$6

0.65

(0.58–0.73

)

M74

,749

F7,370

Decaf.coffee

(men

)

01.00

(1.00–1.00

)

,1

0.92

(0.84–1.01

)

1–3

0.84

(0.75–0.93

)

$4

0.84

(0.68–1.03

)

Decaf.coffee

(women

)

01.00

(1.00–1.00

)

,1

0.95

(0.89–1.00

)

1–3

0.86

(0.81–0.92

)

$4

0.73

(0.64–0.84

)

Con

tinu

edon

p.58

1


Table

1—Continued

Authors

Country

Sex

Age

at

baseline

(year)

Follo

w-up(year)

Nn

Type2

diabetes

assessmen

t

Coffee

exposure

(cups/day)

RR

(95%

CI)


ts

NOS

(0–9points)

Dooet

al.20

13(18)

U.S.

Both

45–75

1475

,140

8,58

2Confirm

edcases

Totalcoffee

(men

)Age

andadjusted

for

ethnicity,BMI,physical

activity,ed

ucation,

history

of

hypertension,en

ergy,

alcoholintake,

smokingstatus,

sugaredsodas,d

ietary

fiber

per

4,18

4kJ,and

processed

meatper

4,184kJ

9

01.00

(1.00–1.00

)

,1

1.12

(1.01–1.24

)

11.06

(0.97–1.17

)

21.05

(0.95–1.16

)

$3

0.95

(0.84–1.08

)

Totalcoffee(w

omen

)

01.00

(1.00–1.00

)

,1

1.08

(0.98–1.19

)

10.96

(0.87–1.05

)

20.82

(0.74–0.91

)

$3

0.69

(0.59–0.81

)

Caffeinated

coffee

(men

)

01.00

(1.00–1.00

)

,1

1.07

(0.98–1.18

)

11.02

(0.93–1.11

)

20.99

(0.91–1.09

)

$3

0.86

(0.75–0.98

)

Caffeinated

coffee

(women

)

01.00

(1.00–1.00

)

,1

1.02

(0.94–1.12

)

10.93

(0.86–1.01

)

20.75

(0.68–0.83

)

$3

0.65

(0.54–0.78

)

Decaf.coffee

(men

)

01.00

(1.00–1.00

)

,1

1.08

(1.00–1.16

)

11.03

(0.93–1.15

)

$2

1.07

(0.93–1.23

)

Decaf.coffee

(women

)

01.00

(1.00–1.00

)

,1

1.07

(0.99–1.15

)

11.03

(0.92–1.14

)

$2

0.85

(0.72–1.01

)

Decaf.,decaffeinated

;F,female;

M,m

ale;

mo,month;OGGT,oralglucose

tolerance

test;wk,week.

aIn

person-years.bIn

mg/day.c Inservings/day.dIn

cups/week.

eIn

cups/month.



compared with the lowest category.Compared with the lowest category(median consumption 0 cups/day), thepooled RR for incident type 2 diabetesfor individuals in the highest categoryof consumption (5 cups/day) was 0.70(95% CI 0.65–0.75, I2 = 50%, P forheterogeneity = 0.001). Thecorresponding RRs were 0.80 (0.75–0.85, I2 = 71%, P , 0.001) for thesecond highest category (3.5 cups/day)and 0.91 (0.88–0.94, I2 = 19%, P = 0.17)for the third highest category (1 cup/day) of coffee consumption. Thus,there was evidence for substantialbetween-study heterogeneity inresults for the highest two categoriesof coffee consumption.

Dose-Response Analyses of TotalCoffee Consumption and Risk ofDiabetesWe performed a dose-response meta-analysis in 27 studies to test for alinear trend between total coffeeconsumption and risk of type 2 diabetesand to estimate RRs for specific amountsof coffee consumption. One studyincluded coffee consumption of .12

cups/day for the highest category (23);we treated this observation as an outlierand excluded it from the dose-responseanalysis. There was a strong inverseassociation between coffeeconsumption and risk of type 2 diabetes(Fig. 3). A cubic spline model accountedfor more variance in the outcome thandid a linear model (likelihood ratio testP , 0.001), suggesting that theassociation was not fully linear.Compared with participants with nocoffee consumption, the RR estimateddirectly from the cubic spline modelfor 1–6 cups/day was 0.92 (95% CI0.90–0.94), 0.85 (0.82–0.88), 0.79(0.75–0.83), 0.75 (0.71–0.80), 0.71(0.65–0.76), and 0.67 (0.61–0.74),respectively.

To test whether the inverse associationbetween coffee consumption and riskof type 2 diabetes was different forunadjusted and adjusted RRs, weperformed a dose-response meta-analysis of the unadjusted data in 27studies (Supplementary Fig. 1). Thespline curve of the unadjusted datawas similar to that of the

multivariable-adjusted data, indicatingthat adjustment for potentialconfounders minimally affected effectestimates for the association betweencoffee consumption and a lower risk ofdiabetes.

Comparison of Associations forCaffeinated and Decaffeinated CoffeeBoth caffeinated and decaffeinatedcoffee consumption was inverselyassociated with risk of type 2 diabetes(Supplementary Fig. 2). Compared withparticipants with the lowest level ofcaffeinated coffee consumption, the RRfor incident type 2 diabetes was 0.74(95% CI 0.67–0.81, I2 = 56%, P forheterogeneity = 0.005) for the highestcategory (median consumption 5 cups/day), 0.82 (0.75–0.91, I2 = 74%,P , 0.001) for the second highestcategory (3.5 cups/day), and 0.92 (0.89–0.96, I2 = 6.6%, P = 0.38) for the thirdhighest category (1 cup/day). Comparedwith those with the lowest level ofdecaffeinated coffee consumption, thecombined RR for incident type 2diabetes was 0.80 (0.70–0.91, I2 = 62%,P = 0.001) for the highest category

Figure 2—Forest plot of the associations between total coffee consumption and risk of type 2 diabetes. Compared with the lowest category (medianconsumption 0 cups/day), the pooled RR for incident type 2 diabetes was 0.70 (95% CI 0.65–0.75, I2 = 50%, P for heterogeneity = 0.001) for thehighest category of consumption, 0.80 (0.75–0.85, I2 = 71%, P, 0.001) for the second highest, and 0.91 (0.88–0.94, I2 = 19%, P = 0.17) for the thirdhighest category of coffee consumption.




(4 cups/day), 0.95 (0.88–1.02, I2 = 53%,P = 0.02) for the second highest category(2 cups/day), and 0.98 (0.92–1.05, I2 =62%, P = 0.003) for the third highestcategory (0.5 cups/day). Heterogeneitywas shown for five of the six subgroups.Seven of 12 studies adjusted forcaffeinated and decaffeinated coffeeconsumption simultaneously. Theassociation was slightly stronger forcaffeinated coffee consumption than fordecaffeinated coffee consumption (P =0.03 for the second highest group, P =0.07 for the highest group)(Supplementary Table 1).

We conducted a linear dose-responseanalysis for caffeinated anddecaffeinated coffee consumptionseparately (11 studies). For a 1 cup/dayincrease in caffeinated coffeeconsumption, the RR for type 2 diabeteswas 0.91 (95% CI 0.89–0.94), and for a1 cup/day increase in decaffeinatedcoffee consumption, the RR was 0.94(0.91–0.98, P for difference = 0.17). Weperformed a dose-response analysisbetween caffeine consumption and type2 diabetes risk based on seven of theincluded studies (4,9,12,17,21,22,35)and found that for every 140 mg/day(;1 cup/day coffee) higher caffeineconsumption, the RR for type 2 diabeteswas 0.92 (0.90–0.94). Of note, none of

the included studies controlled forcoffee intake when modeling caffeineintake and diabetes.

Stratified AnalysisIn stratified analyses, the inverseassociations between coffee consumptionand risk of diabetes were similar bygeographical region (U.S., Europe, andAsia), sex, and diabetes assessmentmethod (P for interaction. 0.05 for allgroups) (Supplementary Table 1).

Sensitivity AnalysisFor the dose-response analysis of totalcoffee consumption with diabetes, afterwe included the observation withextremely high coffee consumption(23), the results did not change.Significant heterogeneity was found forthe highest and second highest totalcoffee consumption, which might beattributable to the heterogeneousamount of coffee consumption in thesecategories. The dose-response analysisaccounted for the heterogeneousconsumption amount of individualstudies and showed an appropriategoodness of fit (P = 0.14).

Heterogeneity was also found inseparate analyses of caffeinated anddecaffeinated coffee consumption. Inaddition to considering differentconsumption amounts, we stratified

the analyses by whether thestudies included caffeinated anddecaffeinated coffee consumptionsimultaneously in the same model. Inthese analyses, the heterogeneity ateach level of caffeinated anddecaffeinated coffee consumptiondecreased significantly, with evenmore inverse results for bothcaffeinated and decaffeinated coffeeconsumption (Supplementary Fig. 3).

Publication BiasThe Egger test provided no evidence ofpublication bias at any levels of totalcoffee, caffeinated coffee, anddecaffeinated coffee consumption(Supplementary Table 2).

CONCLUSIONS

The findings from this systematic reviewand meta-analysis, based on 1,109,272study participants and 45,335 cases oftype 2 diabetes, demonstrate a robustinverse association between coffeeconsumption and risk of diabetes.Compared with no coffee consumption,consumption of 6 cups/day of coffeewas associated with a 33% lower risk oftype 2 diabetes. Caffeinated coffee anddecaffeinated coffee consumption wereboth associated with a lower risk of type2 diabetes. The association between

Figure 3—Dose-response analysis of the association between coffee consumption and risk of type 2 diabetes. For the overall association betweencoffee consumption and risk of diabetes, P, 0.001; for the goodness of fit of themodel, P = 0.14; and for the likelihood ratio test compared with thenested linear model, P , 0.001.







coffee consumption and diabetes riskwas consistent for men and women andfor European, U.S., and Asianpopulations.

There has been some debate about therole of caffeine in the development ofinsulin resistance and diabetes. Short-term studies in humans have shown thatcaffeine intake results in an acutereduction of insulin sensitivity, whichmay be due to adenosine receptorantagonism and increased epinephrinerelease caused by caffeine (36). Otherstudies have found that whencontrolling for total coffee intake,caffeine intake was no longer associatedwith diabetes risk (5,19). Nonetheless,these results need to be interpretedwith caution because the highcorrelation between coffee and caffeineconsumption makes it more difficult toseparate their effects. The presentmeta-analysis shows that bothcaffeinated and decaffeinated coffeeconsumption is associated with a lowerrisk of diabetes. The results were moreinverse when only including the studiesadjusting for caffeinated anddecaffeinated coffee simultaneously inthe model. Because caffeinated coffeeconsumption is inversely related todecaffeinated coffee consumption,caffeinated coffee is a positiveconfounder for the association ofdecaffeinated coffee with diabetes andvice versa. Thus, the association isstrengthened when both variables areadjusted simultaneously. Moreover,because the consumption of caffeinatedcoffee is much higher than decaffeinatedcoffee, the results appear to be morerobust for caffeinated coffee. However,the difference for continuous analysisbetween caffeinated and decaffeinatedcoffee (1 cup/day increment) was notstatistically significant. These resultssuggest that components of coffee otherthan caffeine are responsible for thisputative beneficial effect. Although thepresent results show that higher caffeineconsumption is inversely associated withthe risk of diabetes, this association islikely to be confounded by othercomponents of coffee because of thecollinearity of caffeine and thosecomponents.

Plausible biological mechanisms thatmay contribute to the inverse

association between coffeeconsumption and diabetes risk havebeen demonstrated in animal modelsand in vitro studies implicating severalcoffee components in reducing insulinresistance and improving glucosemetabolism. Chlorogenic acid, aphenolic compound, is a majorcomponent of coffee and has beenshown to reduce blood glucoseconcentrations in animal experiments(37). Chlorogenic acid may reduceglucose absorption in the intestines bycompetitively inhibiting glucose-6-phosphate translocase and reducingsodium-dependent glucose transport inthe brush border membrane vesicles(38), by reducing oxidative stress as aresult of its antioxidant properties, andby reducing liver glucose output (39).Other components of coffee may alsoimprove glucose metabolism, includinglignans, quinides, and trigonelline(40–42). Coffee is also a good source ofmagnesium, which has been associatedwith a lower risk of type 2 diabetes (43).However, adjustment for magnesiumintake did not substantially attenuatethe inverse association (4,5), suggestingthat other bioactive compounds incoffee may also be responsible. Inaddition, because some of thecompounds, such as lignans andmagnesium, also exist in other foods, itis difficult to attribute the benefits ofcoffee on diabetes to these specificcompounds only.

This meta-analysis has severalsignificant strengths. The mean NOSscore of 7 of 9 ensured the relativelyhigh quality of the included studies. All28 studies used a prospective design;thus, the differential misclassificationof coffee consumption attributable torecall bias was minimized. Given theobservational nature of the studies,residual confounding might be anexplanation for the findings. However,higher coffee consumption wasgenerally associated with a less healthylifestyle, including a high prevalence ofcigarette smoking, less physicalactivity, and a less healthy diet. Thus,the true association between coffeeand diabetes risk might be strongerthan observed. Indeed, the similarityfound in the present adjusted andunadjusted results indicates that the

association is unlikely to besubstantially confounded by knowndiabetes risk factors. Nonetheless, it isdifficult to establish the causalitybetween coffee consumption anddiabetes solely based on observationalevidence.

Because most of the studies coffee wasassessed through self-reported dietaryquestionnaires, misclassification ofcoffee intake is inevitable. However, themisclassification is likely to benondifferential with respect to theoutcome because of the prospectivedesign of the studies, which might haveattenuated the observed association.Only five studies addressed the loss tofollow-up percentage. However, the lossto follow-up is unlikely to be associatedwith coffee consumption and may haveresulted in selection bias. Coffeebrewing methods were not assessed inthe studies. However, most coffee islikely to be filtered coffee, and theresults from studies conducted invarious populations, including U.S.,European, and Asian, were similar,indicating consistency of the resultsdespite potentially differentpreparation and processing methods. Inaddition, none of the studies assessedthe amount of sugar and dairy added tocoffee. However, the amount of sugarand dairy added to coffee is likely to besmall compared with other foodsources. Finally, because of theobservational nature of the studies, acausal relationship cannot beestablished with these data alone.

In conclusion, this meta-analysisprovides strong evidence that higherconsumption of coffee is associatedwith a significantly lower risk ofdiabetes. Both caffeinated coffee anddecaffeinated coffee are associatedwith reduced diabetes risk. Longer-termrandomized controlled trials are neededto establish causality and to elucidatethe underlying mechanisms.

Funding. This research was supported byNational Institutes of Health grant DK-58845.

Duality of Interest. No potential conflicts ofinterest relevant to this article were reported.

Author Contributions. M.D. contributed tothe data research, extraction, and analyses andwrote themanuscript.M.D., S.N.B.,M.C., R.M.v.D.,and F.B.H. contributed substantially to the study


conception and design, data analysis andinterpretation, and drafting and critical revision ofthe manuscript for important intellectual content.S.N.B. contributed to the manuscript organizationand reviewed and edited the manuscript. M.C.double-checked the extracted data and reviewedthemanuscript. R.M.v.D. and F.B.H. contributed tothe introduction and discussion and reviewed andedited the manuscript. F.B.H. is the guarantor ofthis work and, as such, had full access to all thedata in the study and takes responsibility for theintegrity of the data and the accuracy of the dataanalysis.

References1. Wild S, Roglic G, Green A, Sicree R, King H.

Global prevalence of diabetes: estimatesfor the year 2000 and projections for 2030.Diabetes Care 2004;27:1047–1053

2. Nathan DM. Long-term complications ofdiabetes mellitus. N Engl J Med 1993;328:1676–1685

3. van Dam RM, Feskens EJM. Coffeeconsumption and risk of type 2 diabetesmellitus. Lancet 2002;360:1477–1478

4. Salazar-Martinez E, Willett WC, Ascherio A,et al. Coffee consumption and risk for type2 diabetes mellitus. Ann Intern Med 2004;140:1–8

5. van DamRM,WillettWC,Manson JE, Hu FB.Coffee, caffeine, and risk of type 2diabetes: a prospective cohort study inyounger and middle-aged U.S. women.Diabetes Care 2006;29:398–403

6. Hjellvik V, Tverdal A, Strøm H. Boiled coffeeintake and subsequent risk for type 2diabetes. Epidemiology 2011;22:418–421

7. Carlsson S, Hammar N, Grill V, Kaprio J.Coffee consumption and risk of type 2diabetes in Finnish twins. Int J Epidemiol2004;33:616–617

8. Floegel A, Pischon T, Bergmann MM,Teucher B, Kaaks R, Boeing H. Coffeeconsumption and risk of chronic diseasein the European Prospective Investigationinto Cancer and Nutrition (EPIC)-Germany study. Am J Clin Nutr 2012;95:901–908

9. Iso H, Date C, Wakai K, Fukui M, TamakoshiA; JACC Study Group. The relationshipbetween green tea and total caffeine intakeand risk for self-reported type 2 diabetesamong Japanese adults. Ann Intern Med2006;144:554–562

10. Oba S, Nagata C, Nakamura K, et al.Consumption of coffee, green tea, oolongtea, black tea, chocolate snacks and thecaffeine content in relation to risk ofdiabetes in Japanese men and women. Br JNutr 2010;103:453–459

11. Reunanen A, Heliovaara M, Aho K. Coffeeconsumption and risk of type 2 diabetesmellitus. Lancet 2003;361:702–703; authorreply 703

12. Goto A, Song Y, Chen BH,Manson JE, BuringJE, Liu S. Coffee and caffeine consumption

in relation to sex hormone-binding globulinand risk of type 2 diabetes inpostmenopausal women. Diabetes 2011;60:269–275

13. Pereira MA, Parker ED, Folsom AR. Coffeeconsumption and risk of type 2 diabetesmellitus: an 11-year prospective study of 28812 postmenopausal women. Arch InternMed 2006;166:1311–1316

14. van Dam RM, Hu FB. Coffee consumptionand risk of type 2 diabetes: a systematicreview. JAMA 2005;294:97–104

15. Huxley R, Lee CM, Barzi F, et al. Coffee,decaffeinated coffee, and tea consumptionin relation to incident type 2 diabetesmellitus: a systematic review with meta-analysis. Arch Intern Med 2009;169:2053–2063

16. Hu G, Jousilahti P, Peltonen M, Bidel S,Tuomilehto J. Joint association of coffeeconsumption and other factors to the riskof type 2 diabetes: a prospective study inFinland. Int J Obes (Lond) 2006;30:1742–1749

17. Bidel S, Silventoinen K, Hu G, Lee DH, KaprioJ, Tuomilehto J. Coffee consumption, serumgamma-glutamyltransferase and risk oftype II diabetes. Eur J Clin Nutr 2008;62:178–185

18. Doo T, Morimoto Y, Steinbrecher A,Kolonel LN, Maskarinec G. Coffee intakeand risk of type 2 diabetes: theMultiethnic Cohort. Public Health Nutr. 27February 2013 [Epub ahead of print]

19. Bhupathiraju SN, Pan A, Malik VS, et al.Caffeinated and caffeine-free beveragesand risk of type 2 diabetes. Am J Clin Nutr2013;97:155–166

20. Sartorelli DS, Fagherazzi G, Balkau B, et al.Differential effects of coffee on the risk oftype 2 diabetes according to mealconsumption in a French cohort of women:the E3N/EPIC cohort study. Am J Clin Nutr2010;91:1002–1012

21. Boggs DA, Rosenberg L, Ruiz-Narvaez EA,Palmer JR. Coffee, tea, and alcohol intake inrelation to risk of type 2 diabetes in AfricanAmerican women. Am J Clin Nutr 2010;92:960–966

22. van Dieren S, Uiterwaal CS, van der SchouwYT, et al. Coffee and tea consumption andrisk of type 2 diabetes. Diabetologia 2009;52:2561–2569

23. Zhang Y, Lee ET, Cowan LD, Fabsitz RR,Howard BV. Coffee consumption and theincidence of type 2 diabetes in men andwomen with normal glucose tolerance: theStrong Heart Study. Nutr Metab CardiovascDis 2011;21:418–423

24. Adeney KL, Williams MA, Schiff MA, Qiu C,Sorensen TK. Coffee consumption and therisk of gestational diabetes mellitus. ActaObstet Gynecol Scand 2007;86:161–166

25. Higgins JP, Thompson SG, Deeks JJ,Altman DG. Measuring inconsistency

in meta-analyses. BMJ 2003;327:557–560

26. Greenland S, Longnecker MP. Methodsfor trend estimation from summarizeddose-response data, with applications tometa-analysis. Am J Epidemiol 1992;135:1301–1309

27. Rosengren A, Dotevall A, Wilhelmsen L,Thelle D, Johansson S. Coffee and incidenceof diabetes in Swedish women:a prospective 18-year follow-up study.J Intern Med 2004;255:89–95

28. van Dam RM, Dekker JM, Nijpels G,Stehouwer CD, Bouter LM, Heine RJ;Hoorn study. Coffee consumption andincidence of impaired fasting glucose,impaired glucose tolerance, and type 2diabetes: the Hoorn Study. Diabetologia2004;47:2152–2159

29. Paynter NP, Yeh HC, Voutilainen S, et al.Coffee and sweetened beverageconsumption and the risk of type 2 diabetesmellitus: the atherosclerosis risk incommunities study. Am J Epidemiol 2006;164:1075–1084

30. Smith B, Wingard DL, Smith TC, Kritz-Silverstein D, Barrett-Connor E. Does coffeeconsumption reduce the risk of type 2diabetes in individuals with impairedglucose? Diabetes Care 2006;29:2385–2390

31. Fuhrman BJ, Smit E, Crespo CJ, Garcia-Palmieri MR. Coffee intake and risk ofincident diabetes in Puerto Rican men:results from the Puerto Rico Heart HealthProgram. Public Health Nutr 2009;12:842–848

32. Hamer M, Witte DR, Mosdøl A, MarmotMG, Brunner EJ. Prospective study of coffeeand tea consumption in relation to risk oftype 2 diabetes mellitus among men andwomen: the Whitehall II study. Br J Nutr2008;100:1046–1053

33. Odegaard AO, Pereira MA, Koh WP,Arakawa K, Lee HP, Yu MC. Coffee, tea, andincident type 2 diabetes: the SingaporeChinese Health Study. Am J Clin Nutr 2008;88:979–985

34. Kato M, Noda M, Inoue M, Kadowaki T,Tsugane S; JPHC Study Group. Psychologicalfactors, coffee and risk of diabetes mellitusamong middle-aged Japanese:a population-based prospective study inthe JPHC study cohort. Endocr J 2009;56:459–468

35. Greenberg JA, Axen KV, Schnoll R, BoozerCN. Coffee, tea and diabetes: the role ofweight loss and caffeine. Int J Obes (Lond)2005;29:1121–1129

36. Thong FS, Graham TE. Caffeine-inducedimpairment of glucose tolerance isabolished by beta-adrenergic receptorblockade in humans. J Appl Physiol (1985)2002;92:2347–2352

37. van Dam RM. Coffee consumption and riskof type 2 diabetes, cardiovascular diseases,



and cancer. Appl Physiol Nutr Metab 2008;33:1269–1283

38. Arion WJ, Canfield WK, Ramos FC, et al.Chlorogenic acid andhydroxynitrobenzaldehyde: new inhibitorsof hepatic glucose 6-phosphatase. ArchBiochem Biophys 1997;339:315–322

39. Svilaas A, Sakhi AK, Andersen LF, et al. Intakesof antioxidants in coffee,wine, and vegetables

are correlated with plasma carotenoids inhumans. J Nutr 2004;134:562–567

40. van Dam RM. Coffee and type 2 diabetes:from beans to beta-cells. Nutr MetabCardiovasc Dis 2006;16:69–77

41. van Dijk AE, Olthof MR, Meeuse JC, SeebusE, Heine RJ, van Dam RM. Acute effects ofdecaffeinated coffee and the major coffeecomponents chlorogenic acid and

trigonelline on glucose tolerance. DiabetesCare 2009;32:1023–1025

42. Greenberg JA, Boozer CN, Geliebter A.Coffee, diabetes, and weight control. Am JClin Nutr 2006;84:682–693

43. Lopez-Ridaura R, Willett WC, Rimm EB,et al. Magnesium intake and risk of type 2diabetes in men and women. Diabetes Care2004;27:134–140


caffeinated and decaffeinated coffee consumption and risk of … · health implications. an inverse...

Documents