In this large prospective study, we have demonstrated that daily consumption of at least one egg is associated with an increased risk of type 2 diabetes in both men and women, independently of traditional risk factors for type 2 diabetes. Furthermore, the observed association between egg consumption and incident type 2 diabetes was not modified by prevalent hypercholesterolemia in either sex.
To the best of our knowledge, this is the first study to examine prospectively the association between egg consumption and incident type 2 diabetes in a large population of men and women. Before the current study, limited and inconsistent data (mainly from animal models) have been reported in the literature on the effects of eggs or dietary cholesterol on glucose metabolism. In an animal experiment, a diet rich in fat was shown to induce hyperglycemia and hyperinsulinemia (8
). Furthermore, Adamopoulos et al. (9
) demonstrated that a diet enriched with egg yolk resulted in elevated plasma glucose compared with a control diet in male Wistar albino rats. Data from the Zutphen Study (10
) showed a positive association between egg consumption or dietary cholesterol and fasting glucose. These animal studies and data from the Zutphen Study are consistent with our findings. In contrast, in a randomized trial of 28 overweight or obese subjects on a carbohydrate-restricted diet, consumption of three eggs per day had no effects on fasting glucose compared with no egg consumption (11
). Because the positive associations described above were observed in studies without restricted consumption of carbohydrates, it is possible that the hyperglycemic effect of frequent egg consumption might only occur with a diet rich in carbohydrates. However, our secondary data analysis provided no evidence for such a hypothesis in that we observed similar increased risk of type 2 diabetes with consumption of one or more eggs per day in women with low or high energy intake from carbohydrate. Further restriction to women with BMI ≥25 kg/m2
, to mimic the above trial of 28 overweight or obese subjects on restricted carbohydrate diet (11
), did not alter these findings. Under the premise that our observed findings were driven by dietary cholesterol contained in eggs, one possible explanation for the inconsistency in reported data on the association between egg consumption and glucose metabolism could be the large variability of individual response to dietary cholesterol (14
). Whereas dietary cholesterol has been shown to increase plasma cholesterol in hyperresponders (2
), no effect was documented among hyporesponders (12
). Second, the lack of an effect of egg consumption on fasting glucose among obese or overweight subjects in the only human randomized trial (11
) may imply differential physiological effects of eggs in lean versus overweight or obese subjects. However, the lack of repeated data on fasting glucose in men and women in the present study prevented us from further exploring the relation between adiposity, egg consumption, and fasting glucose.
Overall, the observed increased risk of type 2 diabetes with daily consumption of eggs in the current study raises the possibility of undesirable health effects with high rates of egg consumption and may help explain previously reported increased risk of CHD that was restricted to individuals with type 2 diabetes in the Health Professional Follow-up Study (6
), the Nurses’ Health Study (6
), and in our earlier publication from the PHS I showing an increased risk of mortality (and suggesting increased risk of CHD and stroke) with frequent egg consumption by subjects with prevalent type 2 diabetes (7
). It is possible that frequent egg consumption may potentiate the risk of cardiovascular disease by inducing impaired glucose metabolism and insulin resistance. Future investigations into underlying physiological mechanisms are warranted.
Besides dietary cholesterol, eggs contain other important nutrients that have been shown to increase (i.e., saturated fat and cholesterol [4
]) or decrease (i.e., polyunsaturated fat [4
]) the risk of type 2 diabetes. It is possible that the individual contribution from each of these components as derived not just from eggs but also from other foods may play a role in determining the net effect of egg consumption. Unfortunately, as noted above, we did not have repeated data on fasting glucose, fasting insulin, and other biomarkers of glucose metabolism in either cohort to comprehensively examine possible physiological mechanisms by which egg consumption might influence the risk of type 2 diabetes in our cohort. However, in women, where we had data on dietary cholesterol, there was attenuation of the association after additional adjustment for dietary cholesterol. This suggests that the observed relation between egg intake and diabetes may be partially explained by the cholesterol content of eggs. In contrast, saturated fat was not associated with type 2 diabetes, and adjustment for this did not attenuate the results.
Additional limitations of the present study include the observational nature of the study design in which residual confounding or unmeasured confounding could partly or completely explain our results. In addition, because egg consumption was self-reported, we cannot exclude reporting bias in the present study. However, because information on egg consumption was collected before the occurrence of type 2 diabetes, such reporting bias is more likely to be nondifferential and thus bias the results toward the null. We did not collect information on whether participants consumed egg yolk (rich in cholesterol) to further examine the contribution of dietary cholesterol from eggs on type 2 diabetes risk in this study. In addition, we had limited dietary data for men to further assess the interplay of eggs and other foods, energy, and nutrients with the risk of type 2 diabetes. The generalizability of our finding is limited as both PHS I and WHS consist of homogeneous groups (male physicians and female health professionals, respectively) with the possibility that their behaviors may differ from those of the general population. Furthermore, over 90% of the study participants were Caucasian. Given the self-report nature of type 2 diabetes, we cannot exclude misclassification of the outcome in these data, especially in the WHS where not all participants were physicians, as was the case in the PHS. However, in the WHS, we had a 91% positive predictive value in a validation study of self-reported type 2 diabetes using American Diabetes Association criteria, for which data were attained by telephone interview, supplemental questionnaire, or review of medical records from treating physicians (21
). Moreover, egg consumption was collected before the diagnosis of diabetes; thus, it is likely that any misclassification of diabetes would be nondifferential and bias the results toward the null. Nevertheless, the large sample size, the long duration of follow-up, the repeated and standardized methods for data collection in both cohorts, and the robustness of the findings in sensitivity analyses are major strengths of this study.
In conclusion, our data are consistent with possible detrimental effects of daily consumption of eggs on the risk of type 2 diabetes in both men and women. Because the median egg consumption in this population (one egg per week for men and women) fell within a range not associated with an increased risk of type 2 diabetes, dietary advice to reduce egg consumption may target individuals who consume one or more eggs per day if these findings are confirmed in other studies. Given the societal burden of type 2 diabetes, confirmation of these findings in other populations and exploration of possible underlying biological mechanisms are warranted.