To the best of our knowledge, no previous study has examined the association between egg consumption and the incidence of gestational diabetes. Given available experimental and epidemiologic evidence (1–8), we hypothesized that higher preconceptional and early-pregnancy egg consumption may be associated with increased risk of gestational diabetes. We investigated this hypothesis and evaluated the association between dietary cholesterol and gestational diabetes risk in a cohort study of 3,158 pregnant women and in an independent case-control study (185 cases, 411 controls).

To the best of our knowledge, no previous study has examined possible associations of egg consumption preconception and during early pregnancy with gestational diabetes risk. Findings from the present studies of a positive association of egg consumption with gestational diabetes risk are in line with results from some (4–6), though not all (20–21), previous studies concerning egg consumption and type 2 diabetes risk among men and nonpregnant women. For instance, Djoussé et al. (4) reported that high levels of egg consumption were associated with increased risks of incident type 2 diabetes in both men (hazard ratio = 1.58, 95% CI: 1.25, 2.01) and women (hazard ratio = 1.77, 95% CI: 1.28, 2.43). Data from animal studies also support positive associations of egg and/or dietary cholesterol intake with glucose metabolism (8). A diet enriched with cholesterol significantly increased fasting plasma cholesterol (P < 0.01), total lipid (P < 0.01), and glucose (P < 0.05) concentrations in study animals (8). However, our findings are not in agreement with results from a randomized trial of 28 overweight men who were placed on a carbohydrate-restricted low-fat diet (20). In that study, participants randomized to a regimen of 3 eggs/day had no differences in fasting glucose concentrations when compared with participants randomized to a no-egg-intake regimen. The null findings in this randomized trial may be attributable to the characteristics of the study population and to the insulin-resistance-lowering effect of the special carbohydrate-restriction and low-fat diet common to all study participants (22). Larger observational and intervention studies conducted in diverse study populations including reproductive-age and pregnant women will be needed to properly disentangle and quantify the independent effects of the nutritive constituents of eggs (e.g., cholesterol, ω-3 polyunsaturated fatty acids, and lutein (23)) on glucose homeostasis.

We are aware of only 1 prior study that examined possible associations between total cholesterol intake during pregnancy and gestational diabetes risk. González-Clemente et al. (7) evaluated 335 pregnant women who were screened for gestational diabetes and who reported information on dietary intake (including cholesterol) for the previous year. The authors noted that 41 women with gestational diabetes reported a higher mean cholesterol intake than 294 women without gestational diabetes (145.3 mg/1,000 kcal (standard error, 4.5) vs. 134.5 mg/1,000 kcal (standard error, 1.6); P = 0.03). The odds of gestational diabetes were 1.88 for each 50-mg/1,000 kcal increment of cholesterol intake (95% CI: 1.09, 3.23). Results from our studies are consistent with those from other studies that have documented associations of cholesterol intake with incident type 2 diabetes in men and nonpregnant women (6, 24, 25). Feskens et al. (6) reported a positive association of dietary cholesterol with incident type 2 diabetes. This association was also confirmed in the Nurses’ Health Study (24) and the Iowa Women's Health Study (25).

By analyzing data from both a cohort study and a case-control study, we were able to replicate study findings across 2 independent study populations. We were also able to capitalize on the strengths of each study while minimizing the impact of limitations inherent in each study design. The prospective design of the Omega Study and the exclusion of women with diagnosed pregestational diabetes reduced the potential for bias from recall differences or dietary changes secondary to the disorder. Collection of dietary intake information in early pregnancy, before gestational diabetes was diagnosed, enhanced causal inference given our increased ability to infer the temporal relation of egg and cholesterol intakes with subsequent gestational diabetes risk. Additionally, the high follow-up rate of enrolled Omega Study participants (>95%) minimized possible selection bias. The Alpha Study afforded increased statistical power to examine relations of interest. The low participation rates, particularly among controls, suggest the possibility that our case and control groups may not have been representative of the underlying populations from which they were sampled. However, characteristics of participating control subjects were similar to those of all women delivering at the study hospitals (11). Case and control participants may have also differed in their ability and willingness to report dietary habits. Additionally, because of the cross-sectional design and the fact that Alpha Study participants’ dietary reporting period included late pregnancy, we cannot exclude the possibility of reverse causality. The directions and magnitudes of point estimates, however, differed little across the 2 studies. This consistency suggests that potential for bias from participation and recall differences or dietary changes secondary to the disorder are unlikely explanations for the Alpha Study findings.

Several limitations should be considered when interpreting our study results. First, because maternal egg consumption was self-reported, we cannot exclude the possibility of reporting error. However, because dietary intake information was collected prior to gestational diabetes testing and diagnosis in the Omega Study, reporting errors are likely to have resulted in attenuation of observed associations. Second, we did not collect information on whether participants consumed egg yolks or egg whites only. Consequently, we were not able to assess gestational diabetes risk in relation to different patterns of egg consumption. Third, universal glucose tolerance testing in early pregnancy is not part of standard obstetric care; hence, we cannot exclude the possibility that some subjects in our study had undiagnosed pregestational diabetes. However, 95% of Omega Study subjects reported having undergone regular medical examinations within the 24-month period before the index pregnancy, and the cumulative incidence of gestational diabetes in our study cohort was consistent with observations in other settings (14). These observations serve to allay concerns. Fourth, as with all observational studies, although we adjusted for known and suspected confounders, we cannot exclude the possibility of residual confounding from unmeasured covariates such as dietary glycemic index. Finally, the generalizability of our findings is limited to largely white, well-educated obstetric populations of women who register for prenatal care early in pregnancy and participate in regular annual medical examinations. Their dietary behaviors, including egg consumption, are likely to differ from those of women from other socioeconomic, racial, and ethnic backgrounds.

The mechanisms by which high egg and cholesterol consumption might influence glucose homeostasis and diabetes risks are largely unknown. Investigators have speculated that observed associations may be attributable to the hyperglycemic and hyperinsulinemic influence of diets high in cholesterol and animal fat (13). Others have speculated that oxysterols, a family of 27-carbon cholesterol oxidation derivatives, are potentially involved in the initiation and progression of cardiometabolic disorders, including diabetes (26). Malle et al. (27) found that increased monocyte-derived myeloperoxidase (a heme enzyme secreted by activated phagocytes that generates an array of oxidants proposed to play critical roles in host defense and tissue damage) activity contributes to chronic systemic inflammatory conditions in cholesterol-fed rabbits. Björkbacka et al. (28) also linked elevated serum cholesterol concentrations to activated proinflammatory signaling cascades in animal models. Further, Lewis et al. (29) noted that increased cholesterol intake increases serum levels of amyloid A, a marker of inflammation. Taken together, these observations support the thesis that chronic systematic inflammation may be involved in the pathogenesis of gestational diabetes (30). Adiposity, particularly central adiposity, is an important component in the pathophysiologic milieu of insulin resistance syndrome, hyperglycemia, and hyperinsulinemia. Future studies designed to comprehensively assess genetic and nongenetic factors that account for the large variability in individual responses to dietary cholesterol are warranted (31).