egg consumption and diabetes

8/12/2019 Egg Consumption and Diabetes

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Egg Consumption and Risk of Type 2Diabetes in Men and WomenLUCDJOUSSE, MD, DSC1

J. MICHAEL GAZIANO, MD1,2,3JULIEE. BURING, SCD1,2,4,5

I-MINLEE, MBBS, SCD2,5

OBJECTIVE Whereas limited and inconsistent findings have been reported on the relationbetween dietary cholesterol or egg consumption and fasting glucose, no previous study hasexamined the association between egg consumption and type 2 diabetes. This project sought toexamine the relation between egg intake and the risk of type 2 diabetes in two large prospectivecohorts.

RESEARCH DESIGN AND METHODS In this prospective study, we used data fromtwocompleted randomized trials: 20,703 men from the Physicians Health Study I (19822007)and 36,295 women from the Womens Health Study (19922007). Egg consumption wasascertained using questionnaires, and we used the Cox proportional hazard model to estimaterelative risks of type 2 diabetes.

RESULTS During mean follow-up of 20.0 years in men and 11.7 years in women, 1,921men and 2,112 women developed type 2 diabetes. Compared with no egg consumption, mul-tivariable adjusted hazard ratios for type 2 diabetes were 1.09 (95% CI 0.871.37), 1.09 (0.881.34), 1.18 (0.951.45), 1.46 (1.141.86), and 1.58 (1.252.01) for consumption of1, 1,24, 56, and 7 eggs/week, respectively, in men (P for trend 0.0001). Correspondingmultivariable hazard ratios for women were 1.06 (0.921.22), 0.97 (0.831.12), 1.19 (1.031.38), 1.18 (0.881.58), and 1.77 (1.282.43), respectively (Pfor trend 0.0001).

CONCLUSIONS These data suggest that high levels of egg consumption (daily) are as-sociated with an increased risk of type 2 diabetes in men and women. Confirmation of thesefindings in other populations is warranted.

Diabetes Care32:295300, 2009

Type 2 diabetes is highly prevalent

and is associated with high healthcare costs and societal burden (1).

Therefore, it is important to identify mod-ifiable risk factors that may help reducethe risk of type 2 diabetes. Eggs are notonly major sources of dietary cholesterol(200 mg/egg) but also contain other im-portant nutrients such as minerals, vita-m i n s , p r o t e i n s , c a r o t e n o i d s , a n dsaturated (1.5 g/egg), polyunsaturated(0.7 g/egg), and monounsaturated(1.9 g/egg) fatty acids (2,3). Whereas

several of these nutrients have been asso-

ciated with an increased risk of type 2diabetes (i.e., saturated fat and cholesterol[4,5]), other nutrients may confer a lowerrisk of type 2 diabetes (i.e., polyunsatu-rated fat [4]).

Whereas egg consumption was notassociated with coronary heart disease(CHD) or stroke overall, Hu et al. (6) re-ported a twofold increased risk of CHDfor egg consumption of more than one perweek among men with type 2 diabetes inthe Health Professionals Follow-up

Study and a 49% increased risk of CHDamong women in the Nurses Health

Study, compared with intake of less thanone per week. Furthermore, we have re-ported similar findings in U.S. male phy-sicians with type 2 diabetes but not inthose without type 2 diabetes (7), sug-gesting that frequent egg consumptionmay have negative health effects amongindividuals with type 2 diabetes. How-ever, it is not known whether egg con-sumption increases the risk of type 2diabetes itself. In animal experiments, adiet rich in fat has been shown to inducehyperglycemia and hyperinsulinemia (8).In addition, a diet enriched with egg yolkwas associated with elevated plasma glu-cose compared with a control diet in rats(9). Data from the Zutphen Study (10)have indicated a positive association be-tween egg consumption or dietary choles-terol and fasting glucose. However, in arandomized trial of 28 overweight or obesepatients on a carbohydrate-restricted diet,consumption of three eggs per day had noeffectson fastingglucose compared with ab-stentionfromeggs (11). Current data on theeffects of dietary cholesterol on serum cho-lesterol have been inconsistent, ranging

from positive associations (2,12) to lack ofeffect (1214) and may be partly due to alarge variabilityin individual responseto di-etary cholesterol (14,15).

To our knowledge, no previous studyhas examined the association between eggconsumption and the incidence of type 2diabetes in a large prospective cohort ofmen and women. Because eggs can serveas a good source for vitamins, proteins,and other nutrients in the U.S., it is im-portant to determine the net degree ofbenefit and harm of egg consumption onthe risk of type 2 diabetes. The currentstudy examines the associationbetween eggconsumption and incident type 2 diabetesamong men and women who participatedin two large completed randomized controltrials.

RESEARCH DESIGN AND

METHODS We used data from thePhysicians Health Study (PHS) I and the

Womens Health Study (WHS), two com-pleted randomized, double-blind, place-bo-controlled trials designed to study theeffects of aspirin and -carotene (PHS) or

From the 1Division of Aging, Department of Medicine, Brigham and Womens Hospital, Harvard MedicalSchool, Boston, Massachusetts; the 2Division of Preventive Medicine, Department of Medicine, Brighamand Womens Hospital, Harvard Medical School, Boston, Massachusetts; the 3Massachusetts VeteransEpidemiology and Research Information Center (MAVERIC), Boston Veterans Affairs Healthcare System,

Jamaica Plain, Massachusetts; the 4Department of Ambulatory Care and Prevention, Harvard MedicalSchool, Boston, Massachusetts; and the 5Department of Epidemiology, Harvard School of Public Health,Boston, Massachusetts.

Corresponding author: Luc Djousse, [email protected] 9 July 2008 and accepted 8 November 2008.Published ahead of print at http://care.diabetesjournals.org on 18 November 2008. DOI: 10.2337/dc08-

1271. 2009 by the American Diabetes Association. Readers may use this article as long as the work is properly

cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be herebymarked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

E p i d e m i o l o g y / H e a l t h S e r v i c e s R e s e a r c hO R I G I N A L A R T I C L E

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low-dose aspirin and vitamin E (WHS) inthe prevention of cardiovascular diseaseand cancer. Detailed description of thePHS I and WHS has been published pre-viously (1618). Briefly, a total of 22,071U.S. male physicians aged 40 years atentry (1982) were randomized using a22 factorial design to aspirin (325 mg

every other day),-carotene (50 mg everyother day), or their corresponding place-bos. Similarly, 39,876 female health pro-fessionals aged45 years at entry (19921995) were randomized to low-doseaspirin (100 mg on alternate days), vita-min E (600 IU on alternate days), or theircorresponding placebos. Each participantgave written informed consent, and theinstitutional review board at Brigham and

Womens Hospital approved both studyprotocols. For the present analyses, weexcluded 1,368 men because of prevalent

type 2 diabetes (n

641), missing data onegg consumption (n 365), or missingdata on potential confounders: smoking,alcohol intake, BMI, exercise, hyperten-sion, and fruits and vegetables (n 362).

Among women, we excluded 3,581 be-cause of prevalent type 2 diabetes (n 1,171), missing data on egg consumption(n852),or missing data on potential con-founders: BMI, exercise, smoking, energyintake, fruits and vegetables, nutrients, al-cohol consumption, and hypertension (n1,558). Thus, a final sample of 20,703 menand 36,295 women was used in the current

analyses.

Egg consumptionAmong men, information on egg con-sumption was self-reported at baselineusing a simple abbreviated semiquantita-tive food-frequency questionnaire. Partic-ipants were asked to report how often, onaverage, they had eaten one egg duringthe past year. Possible response categoriesincluded rarely/never, 13/month, 1/week, 24/week, 56/week, daily,and 2/day. This information was ob-

tained at baseline and at 24, 48, 72, 96,and 120 months after randomization.Among women, information on eggconsumption was self-reported using a131-item validated food-frequencyquestionnaire (19) at baseline. Womenwere asked to report their average con-sumption of eggs over the past year. Pos-sible response categories were Never or1/month, 13/month, 1/week, 24/week, 56/week, 1/day, 23/day,45/day, and 6/day. Because veryfew subjects consumed one or more eggsper day (7.8% for men and 1.0% for

women), we combined categories of oneper day and beyond for stable estimates.The validity of food-frequency question-naires in similar populations has beenpublished elsewhere (19,20). The corre-lation of egg consumption with dietarycholesterol was 0.61 (P 0.0001) andwith saturated fat among women was

0.26 (P 0.0001).

Ascertainment of incident type 2diabetesType 2 diabetes was ascertained by self-report on annual follow-up question-n a i r e s i n b o t h m e n a n d w o m e n .Follow-up and ascertainment of type 2diabetes cases were completed in March2007. Because all men were physicians,self-report was deemed sufficient. Amongthe female health professionals, self-reports of type 2 diabetes were validated

using American Diabetes Association cri-teria, for which additional informationwas obtained using telephone interviews,supplemental questionnaires,or review ofmedical records from treating physicians(21,22). Overall, the positive predictivevalue for type 2 diabetes validation was91% (21).

Other variablesDemographic data were collected at base-line. In addition, informationon prevalenceof hypertension, hypercholesterolemia,family history of diabetes (WHS only),

smoking, exercise, and alcohol consump-tion was obtained at baseline. Whereas lim-ited data on foods were available in men,detailed dietary information was collectedin the WHS, allowing estimation of energyintake and nutrients.

Statistical analysesWe classified each subject according tothe following categories of egg consump-tion per week: 0, 1, 1, 24, 56, and7. We computed person-time of fol-low-up from baseline until the first occur-

rence of1) type 2 diabetes,2) death, or3)censoring date, the date of receipt of thelast follow-up questionnaire (March2007). Within each egg-consumptiongroup, we calculated the incidence rate oftype 2 diabetes by dividing the number ofcases by the corresponding person-time.

We used Cox proportional hazard modelsto compute multivariable adjusted hazardratios (HRs) with corresponding 95% CIsusing subjects in the lowest category ofegg consumption as the reference group.The initial model adjusted for age,whereas the multivariable model con-

trolled for age (continuous), BMI (25,2529, 30 kg/m2), smoking (never,former, and current smokers), alcoholconsumption (0, 13 drinks/month, 16drinks/week, 1 drinks/day), physicalactivity (vigorous exercise 0,1, 13, 4times per week in men and quintiles ofkilocalories per week expended in lei-

sure-time physical activity in women),and history of hypercholesterolemia andhypertension. Because detailed informa-tion on diet and family history was avail-able for women, the multivariable modelin women also adjusted for family historyof diabetes, energy intake (quintiles), in-take of fruits and vegetables (quintiles),red meat consumption (0.5, 0.50.9,and 1 serving/day), and intake of poly-unsaturated fats (quintiles), saturated fats(quintiles), and trans fats (quintiles). Toexamine whether the relation between egg

and diabetes was mediated by dietary cho-lesterol, we evaluated the risk of diabetesassociated with dietary cholesterol and alsoincluded dietary cholesterol in the multiva-riable model in women. A similar approachwas used for saturated fat. A P value for lin-ear trend was obtained by fitting a continu-ous variable that assigned the median eggconsumption in each egg category in a Coxregression model.

In secondary analyses, we examinedpossible effect modification by prevalenthypercholesterolemia (yes/no) andamount of energy from carbohydrate (low

vs. high), using median energy from car-bohydrate as cut point in women only,where data were available. We tested forstatistical interaction by including themain effects and the product terms be-tween egg consumption and hypercholes-terolemia in a hierarchical Cox regressionmodel (PROC TPHREG in SAS). We alsoconducted sensitivity analyses by exclud-ing subjects with less than 2 years of fol-low-up. We repeated the main analysisusing updated egg consumption at 24,48,72, 96, and 120 months in a time-

dependentCox model in men only, whererepeated measures on egg consumptionwere available. Lastly, we used general-ized linear models and polytomous logis-tic regression to impute missing values forcontinuous and categorical variables, re-spectively. All analyses were completedusing SAS (version 9; SAS Institute, Cary,NC). Significance level was set at 0.05.

RESULTS The mean SD age atrandomization was 53.5 9.4 years(range 39.785.9) in the PHS I and54.5 7.0 years (38.789.9) in the

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WHS. Among egg consumers, the medianegg consumption was approximately oneegg per week in men and women. Table 1presents baseline characteristics of the

study participants. Frequent consump-tion of eggs was associated with higherBMI, higher proportion of current smok-ing, higher prevalence of hypertension,and lower prevalence of hypercholester-olemia. In addition, frequent consump-tion of eggs was associated with older ageand more alcohol consumption in menand higher energy intake, as well as in-takes of saturated and trans fatty acids,and dietary cholesterol in women.

A total of 1,921 new cases of type 2diabetes were documented in men duringa mean follow-up of 20.0 years. Among

women, 2,112 new cases of type 2 diabe-tes occurred during a mean follow-up of11.7 years. From the lowest to the highestcategory of egg consumption, crude inci-

dence rates of diabetes were 35.8, 41.3,42.7, 46.8, 62.4, and 67.0 cases per10,000 person-years in the PHS I. A sim-ilar increase in rates of type 2 diabeteswith egg consumption was observed inwomen, with corresponding crude inci-dence rates of 39.6, 45.8, 43.3, 64.8,76.8, and 112.7 cases per 10,000 person-years, respectively. Whereas consump-tion of up to one egg per week wasgenerally not associated with an increasedrisk of type 2 diabetes in either sex in mul-tivariate analyses, more frequent con-sumption of eggs was associated with an

increased risk of type 2 diabetes (Table2).Compared with subjects who did not re-port egg consumption, intake of seven ormore eggs per week was associated with a

58% increased risk of type 2 diabetes inmen and a 77% increased risk of type 2diabetes in women after adjustment for po-tential confounders (Table 2). Updating eggconsumption using time-dependent Coxregression (PHS I) yielded a stronger rela-tion between egg consumption and inci-dent type 2 diabetes in men with HRs of1.0 (reference), 1.10 (95% CI 0.991.23), 1.31 (1.161.47), 1.40 (1.101.77), 1.77 (1.392.26), and 1.99 (1.233.23), from the lowest to the highestcategory of egg consumption, respec-tively, using a multivariable model as

Table 1Baseline characteristics of 20,703 men and 36,295 women according to egg consumption

Eggs per week

0 1 1 24 56 7

Men

n 1,430 3,025 6,466 6,792 1,378 1,612Age (years) 53.1 9.2 52.8 9.3 53.2 9.3 53.4 9.4 53.8 9.3 56.4 10.0

BMI (kg/m2) 24.1 2.7 24.6 2.6 24.7 2.7 24.9 2.7 25.1 2.9 24.9 3.1Fruits and vegetables per

week

15.2 8.4 14.1 7.4 14.8 7.1 15.3 6.9 15.8 7.4 17.0 8.5

Whole milk 16.7 31.1 37.1 42.8 50.9 54.2

Skim milk 60.8 61.9 67.7 65.9 61.4 53.5Nut intake* 72.2 77.9 80.4 81.8 82.7 77.8

Breakfast cereal 60.7 62.1 74.2 77.7 74.2 58.9Smoking 6.4 8.8 9.8 12.0 14.6 16.8

Never smokers 56.9 51.0 51.1 48.6 46.9 41.6Exercise 84.4 86.2 87.4 87.6 87.4 84.9

Current drinkers of1 perday

21.5 23.3 23.9 25.8 26.4 30.7

Hypertension 22.8 20.3 22.8 22.9 24.7 26.2

High cholesterol 14.6 12.9 12.0 11.1 10.4 10.4Women

n 6,381 10,758 9,222 8,921 647 366

Age (years) 55.2 7.2 54.3 7.0 54.4 6.9 54.5 7.0 54.6 7.0 55.1 7.2BMI (kg/m2) 25.1 4.6 25.7 4.8 25.8 4.8 26.6 5.2 27.4 6.0 26.9 6.0Fruits and vegetables per

week

6.2 3.6 5.7 3.2 6.0 3.1 6.3 3.1 6.4 3.5 6.4 3.8

Red meat (servings/day) 0.45 0.45 0.62 0.46 0.75 0.49 0.93 0.59 1.15 0.76 1.26 0.83

Energy intake (kcal/day) 1,547 506 1,614 498 1,758 503 1,925 530 2,043 585 2,072 605Exercise (kcal/week) 1,078 1,282 931 1,172 911 1,145 882 1,104 833 1,073 800 1,040

Dietary cholesterol (g/day) 0.17 0.06 0.20 0.05 0.22 0.05 0.28 0.05 0.35 0.07 0.44 0.15Transfat (g/day) 1.95 1.11 2.28 1.08 2.35 1.01 2.40 1.00 2.55 1.11 2.41 0.98

Polyunsaturated fat (g/day) 10.6 3.2 11.0 2.9 11.2 2.7 11.4 2.7 11.8 2.8 11.9 3.1Saturated fat (g/day) 17.3 5.2 19.4 4.7 20.0 4.40 20.9 4.4 22.4 4.8 23.1 5.5

Smoking 10.8 12.1 11.8 15.3 19.8 23.5Current drinkers of1 per

day

10.2 9.8 10.8 11.5 10.5 10.4

Hypertension 24.7 23.6 23.4 26.6 29.5 27.1

High cholesterol 38.0 28.9 26.4 25.3 26.1 19.1Family history of diabetes 24.6 24.2 24.1 25.9 27.5 23.5

Data are mean SD or %. *Nut consumption assessed 1 year after randomization. Energy adjusted.

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above (this was not done for women dueto lack of updated information on eggconsumption). Lastly, exclusion of sub-

jects with follow-up time 2 years in ei-ther cohort did not alter the results (P fortrend 0.0001 in men and 0.0001 inwomen).

Dietary cholesterol was positively as-sociated with the risk of diabetes (multi-variable adjusted HR 1.00 [reference],0.94 [95% CI 0.801.11], 1.03 [0.881.21], 1.07 [0.911.25], and 1.28 [1.101.50], from the lowest to the highestquintile of dietary cholesterol, respec-tively (P for trend 0.0001). Additional

adjustment for dietary cholesterol inwomen attenuated the point estimatesin the multivariable model with corre-sponding HRs of 1.00 (reference), 1.05(0.911.21), 0.94 (0.801.10), 1.07(0.901.27), 1.00 (0.731.37), and 1.49(1.062.09), respectively (Pfor trend 0.10). However, saturated fat was not as-

sociated with type 2 diabetes (multivari-able adjusted HR 1.0, 1.03 [0.871.21],1.00 [0.841.19], 1.00 [0.841.20], and1.10 [0.921.33], from the lowest tohighest quintile of energy-adjusted satu-rated fat, respectively). Additional controlfor saturated fat did not alter the results(e.g., HR of 1.78 [1.302.45] withoutand 1.77 [1.282.43] with additionalcontrol for saturated fat, comparing thehighest with the lowest egg consumptioncategories). Imputing missing data didnot change the findings (online appendixTable A1, available at http://dx.doi.org/10.2337/dc08-1271).

In a secondary analysis stratified byprevalent hypercholesterolemia at base-line (Table 3), similar patterns were ob-served in subjects of either sex with andwithout hypercholesterolemia (P for in-teraction 0.37 for men and 0.13 forwomen). Similar relations were observedbetween egg consumption and type 2 di-

abetes when data were stratified by lowenergy from carbohydrate (P for lineartrend 0.0004 for low energy from car-bohydrate and 0.12 for high energy fromcarbohydrate) in women only (data werenot available to estimate carbohydrate in-take in men), and these findings were notaltered when restricted to overweight orobese subjects (online appendix Table A2).

CONCLUSIONS In this large pro-spective study, we have demonstratedthat daily consumption of at least one eggis associated with an increased risk of type2 diabetes in both men and women, inde-

pendently of traditional risk factors fortype 2 diabetes. Furthermore, the ob-served association between egg consump-tion and incident type 2 diabetes was notmodified by prevalent hypercholesterol-emia in either sex.

To the best of our knowledge, this isthe first study to examine prospectively

Table 3Hazard ratios of diabetes according to prevalent hypercholesterolemia and egg consumption

Men Women

Normal cholesterol High or treated cholesterol Normal cholesterol High or treated cholesterolEgg consumption per week

0 1.0 1.0 1.0 1.0

1 1.09 (0.841.42) 1.11 (0.701.74) 1.11 (0.911.37) 1.02 (0.831.25)1 1.03 (0.801.31) 1.28 (0.841.94) 1.00 (0.801.24) 0.98 (0.791.22)

24 1.16 (0.921.48) 1.19 (0.791.81) 1.26 (1.021.55) 1.14 (0.921.42)56 1.34 (1.011.79) 1.78 (1.112.87) 0.88 (0.571.36) 1.68 (1.132.51)

7 1.47 (1.111.94) 1.96 (1.233.12) 1.84 (1.242.75) 1.72 (0.983.02)Pfor trend 0.0001 0.0001 0.0045 0.0028

*Adjusted for age (continuous), BMI (25, 2529.9, and 30 kg/m2), smoking (never, former, and current smokers), alcohol consumption (none, 13 drinks/month, 16 drinks/week, and 1 drink/day), vigorous exercise (0,1, 13, and 4 times per week), and history of hypertension. Adjusted for age (continuous),BMI (25, 2529.9, and 30 kg/m2), smoking (never, former, and current smokers), alcohol consumption (none, 13 drinks/month, 1 6 drinks/week, and 1drink/day), exercise (quintiles of kilocalories per week), red meat intake (0.5, 0.50.9, and 1 serving/day), quintiles of energy intake, fruits and vegetables,saturated fatty acids,transfatty acids, polyunsaturated fatty acids, family history of diabetes, and history of hypertension.

Table 2HR (95% CI) of type 2 diabetes according to egg consumption in men and women

Men Women

n Age adjusted Model 1* n Age adjusted Model 1

Egg intake per week

0 104 1.0 1.0 295 1.0 1.0

1 254 1.16 (0.921.45) 1.09 (0.871.37) 576 1.16 (1.011.34) 1.06 (0.921.22)

1 560 1.19 (0.961.46) 1.09 (0.881.34) 470 1.10 (0.951.27) 0.97 (0.831.12)24 637 1.30 (1.061.61) 1.18 (0.951.45) 669 1.65 (1.441.89) 1.19 (1.031.38)

56 169 1.73 (1.362.21) 1.46 (1.141.86) 56 1.97 (1.482.63) 1.18 (0.881.58)

7 197 1.82 (1.442.31) 1.58 (1.252.01) 46 2.88 (2.113.94) 1.77 (1.282.43)

Pfor trend 0.0001 0.0001 0.0001 0.0001

n cases of type 2 diabetes. *Adjusted for age (continuous), BMI (25, 2529.9, and 30 kg/m2), smoking (never, former, and current smokers), alcoholconsumption (0, 13 drinks/month, 16 drinks/week, and 1 drink/day), vigorous exercise (0, 1, 13, and 4 times per week), and history of hypercholester-olemia and hypertension. Adjusted for age (continuous), BMI (25, 2529.9, and 30 kg/m2), smoking (never, former, and current smokers), alcohol consump-tion (0,13 drinks/month, 16 drinks/week,and1 drink/day), exercise(quintilesof kilocaloriesper week),red meat intake(0.5, 0.50.9, and1 servings/day),quintiles of energy intake, fruits and vegetables, saturated fatty acids, trans fatty acids, polyunsaturated fatty acids, family history of diabetes, and history ofhypercholesterolemia and hypertension.




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the association between egg consumptionand incident type 2 diabetes in a largepopulation of menand women.Before thecurrent study, limited and inconsistentdata (mainly from animal models) havebeen reported in the literature on theeffects of eggs or dietary cholesterol onglucose metabolism. In an animal ex-

periment, a diet rich in fat was shown toinduce hyperglycemia and hyperinsu-linemia (8). Furthermore, Adamopou-los et al. (9) demonstrated that a dietenriched with egg yolk resulted in ele-vated plasma glucose compared with acontrol diet in male Wistar albino rats.Data from the Zutphen Study (10)showed a positive association betweenegg consumption or dietary cholesteroland fasting glucose. These animal studiesand data from the Zutphen Study are con-sistent with our findings. In contrast, in a

randomized trial of 28 overweight orobese subjects on a carbohydrate-restricted diet, consumption of three eggsper day had no effects on fasting glucosecompared with no egg consumption (11).Because the positive associations de-scribed above were observed in studieswithout restricted consumption of carbo-hydrates, it is possible that the hypergly-cemic effect of frequent egg consumptionmight only occur with a diet rich in car-bohydrates. However, our secondary dataanalysis provided no evidence for such ahypothesis in that we observed similar in-

creased risk of type 2 diabetes with con-sumption of one or more eggs per day inwomen with low or high energy intakefrom carbohydrate. Further restriction towomen with BMI 25 kg/m2, to mimicthe above trial of 28 overweight or obesesubjects on restricted carbohydrate diet(11), did not alter these findings. Underthe premise that our observed findingswere driven by dietary cholesterol con-tained in eggs, one possible explanationfor the inconsistency in reported data onthe association between egg consumption

and glucose metabolism could be thelarge variability of individual response todietary cholesterol (14,15,23). Whereasdietary cholesterol has been shown to in-crease plasma cholesterol in hyperre-sponde rs (2,12,24), no e ffe c t wa sdocumented among hyporesponders(1214). Second, the lack of an effect ofegg consumption on fasting glucoseamong obese or overweight subjects inthe only human randomized trial (11)may imply differential physiological ef-fects of eggs in lean versus overweight orobese subjects. However, the lack of re-

peated data on fasting glucose in men andwomen in the present study prevented usfrom further exploring the relation be-tween adiposity, egg consumption, andfasting glucose.

Overall, the observed increased riskof type 2 diabetes with daily consumptionof eggs in the current study raises the pos-

sibility of undesirable health effects withhigh rates of egg consumption and mayhelp explain previously reported in-creased risk of CHD that was restricted toindividuals with type 2 diabetes in theHealth Professional Follow-up Study (6),the Nurses Health Study (6), and in ourearlier publication from the PHS I show-ing an increased risk of mortality (andsuggesting increased risk of CHD andstroke) with frequent egg consumptionby subjects with prevalent type 2 diabe-tes (7). It is possible that frequent egg

consumption may potentiate the risk ofcardiovascular disease by inducing im-paired glucose metabolism and insulinresistance. Future investigations intounderlying physiological mechanismsare warranted.

Besides dietary cholesterol, eggs con-tain other important nutrients that havebeen shown to increase (i.e., saturated fatand cholesterol [4,5,25]) or decrease (i.e.,polyunsaturated fat [4]) the risk of type 2diabetes. It is possible that the individualcontribution from each of these compo-nents as derived not just from eggs but

also from other foods may play a role indetermining the net effect of egg con-sumption. Unfortunately, as noted above,we did not have repeated data on fastingglucose, fasting insulin, and other bi-omarkers of glucose metabolism in eithercohort to comprehensively examine pos-sible physiological mechanisms by whichegg consumption might influence the riskof type 2 diabetes in our cohort. However,in women, where we had data on dietarycholesterol, there was attenuation of theassociation after additional adjustment

for dietary cholesterol. This suggests thatthe observed relation between egg intakeand diabetes may be partially explainedby the cholesterol content of eggs. In con-trast, saturated fat was not associated withtype 2 diabetes, and adjustment for thisdid not attenuate the results.

Additional limitations of the presentstudy include the observational nature ofthe study design in which residual con-founding or unmeasured confoundingcould partly or completely explain our re-sults. In addition, because egg consump-tion was self-reported, we cannot exclude

reporting bias in the present study. How-ever, because information on egg con-sumption was collected before theoccurrence of type 2 diabetes, such re-porting bias is more likely to be nondif-ferential and thus bias the results towardthe null. We did not collect informationon whether participants consumed egg

yolk (rich in cholesterol) to further exam-ine the contribution of dietary cholesterolfrom eggs on type 2 diabetes risk in thisstudy. In addition, we had limited dietarydata for men to further assess the inter-play of eggs and other foods, energy, andnutrients with the risk of type 2 diabetes.The generalizability of our finding is lim-ited as both PHS I and WHS consist ofhomogeneous groups (male physiciansand female health professionals, respec-tively) with the possibility that their be-haviors may differ from those of the

general population. Furthermore, over90% of the study participants were Cau-casian. Given the self-report nature oftype 2 diabetes, we cannot exclude mis-classification of the outcome in thesedata, especially in the WHS where notall participants were physicians, as wasthe case in the PHS. However, in the

WHS, we had a 91% positive predictivevalue in a validation study of self-reportedtype 2 diabetes using American Diabetes

Association criteria, for which data wereattained by telephone interview, supple-mental questionnaire, or review of medi-

cal records from treating physicians (21).Moreover, egg consumption was col-lected before the diagnosis of diabetes;thus, it is likely that any misclassificationof diabetes would be nondifferential andbias the results toward the null. Neverthe-less, the large sample size, the long dura-tion of follow-up, the repeated andstandardized methods for data collectionin both cohorts, and the robustness of thefindings in sensitivity analyses are majorstrengths of this study.

In conclusion, our data are consistent

with possible detrimental effects of dailyconsumption of eggs on the risk of type 2diabetes in both men and women. Be-cause the median egg consumption in thispopulation (one egg per week for menand women) fell within a range not asso-ciated with an increased risk of type 2diabetes, dietary advice to reduce eggconsumption may target individuals whoconsume one or more eggs per day if thesefindings are confirmed in other studies.Given the societal burden of type 2 diabe-tes, confirmation of these findings inother populations and exploration of pos-

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sible underlying biological mechanismsare warranted.

Acknowledgments This study was sup-ported by grants CA-34944, CA-40360, CA-047988, and CA-097193 from the NationalCancer Institute and grants HL-26490, HL-43851, HL-080467, and HL-34595 from the

National Heart, Lung, and Blood Institute, Be-thesda, Maryland.

No potential conflicts of interest relevant tothis article were reported.

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