| Objective: To evaluate maternal dietary cholesterol intake drung pregnancy and investigate the association of dietary cholesterol intake and different sources of cholesterol intake with gestational diabetes mellitus(GDM)risk and blood glucose levels of oral glucose tolerance test(OGTT)in a Chinese prospective cohort study.Furthermore,the association between serum cholesterol absorption and synthesis marker levels and GDM were evaluated in a prospective nested case-control study.Methods: A number of 2124 pregnant women in The Tongji Maternal and Child Health Cohort(TMCHC)study were included in the prospective cohort study.A validated semiquantitative food frequency questionnaire(FFQ)was used to assess dietary cholesterol prior to GDM diagnosis.GDM was diagnosed according to the 75-g 2-h OGTT at 24-28 gestational weeks.Logistic regression analyses were used to evaluate the association between maternal cholesterol intake during pregnancy and GDM risk and the results were presented as odds ratios(ORs)with 95% confidence interval(CIs).Generalized linear models were conducted to examine the association of cholesterol intake with maternal fasting blood glucose(FBG),1-h post-load blood glucose(1-h PBG)and 2-h PBG of OGTT.Stratified analyses by potential GDM factors and estimated P values for interaction terms to explore the potential effects modification.Furthermore,Logistic regression analyses were used to evaluate the association between different sources of cholesterol intake or cholesterol-rich food consumption during pregnancy and GDM risk.Generalized linear models were conducted to examine the association of different sources of cholesterol intake or cholesterol-rich food consumption during pregnancy with FBG,(1-h PBG)and 2-h PBG of OGTT.Stratified analyses by potential GDM factors and estimated P values for interaction terms to explore the potential effects modification.A nested case-control study was conducted to evaluate the association between serum cholesterol absorption and synthesis marker levels and GDM in this cohort.The levels of serum cholesterol absorption and synthesis markers at baseline were quantified by using gas chromatography-mass spectrometer.Serum concentration of total cholesterol(TG),triglyceride(TG),high density lipoproteins cholesterol(HDL-C,)and low density lipoproteins cholesterol(LDL-C),were analyzed using enzymatic-spectrophotometric methods.Serum insulin was quantified by a solid phase two-site enzyme immunoassay.Correlation between cholesterol metabolic markers was measured by using Pearson correlation coefficient.Conditional logistic regression models were used to examine the association between each cholesterol metabolic marker and its ratio to TC and GDM risk.Results:(1)The association between dietary cholesterol intake during pregnancy with GDM risk and blood glucose levelsA total of 207 GDM case were identified among 2124 pregnant women in our study,the corresponding incidence rate was 9.7%.The average of dietary cholesterol intake during was 379.1 mg/d.Moreover,71.0% of them had more than 300 mg/d cholesterol intake.The incidence rates of GDM in each quintile of energy-adjusted total cholesterol intake were 6.8%,8.7%,9.4%,10.8%,12.9%,respectively(P = 0.037).In Logistic regression models,after adjusted for maternal age,prepregnancy BMI,education;average personal income;primiparity,family history of diabetes,smoking before pregnancy,drinking before pregnancy,leisure-time physical activity,gestational weight gain from pregnancy to OGTT(GWGO),total energy intake,intake of vitamin C,vitamin E,total fiber,saturated fatty acid,monounsaturated fatty acids,and polyunsaturated fatty acids,the Odds ratios(ORs)for GDM were 1.32(95% confidence interval(CI): 0.78,2.23),1.30(95% CI: 0.77,2.21),1.75(95% CI: 1.03,3.00),2.10(95% CI: 1.24,3.58)for successive quintiles of dietary cholesterol intake,respectively(P for trend = 0.003),comparing with lowest quintile.A 100-mg per day increase in dietary cholesterol intake was associated with an 18% increase GDM risk(OR: 1.18,95% CI: 1.07,1.30).Generalized linear models demonstrated that a 100-mg per day increase in dietary cholesterol intake was associated with increase of 0.01 mmol/L FBG(95% CI: 0.00,0.02,P = 0.012),0.07mmol/L 1 h PBG(95% CI: 0.02,0.11,P = 0.003)rather than 2 h PBG(β = 0.03,95% CI:-0.00,0.07,P = 0.075)in fully models.In stratified analyses,the association between dietary cholesterol intake and GDM risk were not significantly modified by maternal age,prepregnancy BMI,GWGO,parity,leisure-time physical activity,and family history of diabetes(all P for interactions were > 0.05)(2)The association between different sources of cholesterol intake or cholesterol-rich food consumption during pregnancy with GDM risk and blood glucose levels.Eggs are one of the largest sources of cholesterol in our study,accounting for 64.2% of total dietary cholesterol,followed by fish and shellfish(including fish,shrimp,crab,shellfish,etc.),red meats,milks and dairies,other foods(including poultry,animal organs,and animal fat,etc).In the fully models,the ORs for GDM were 1.07(95% CI: 0.61,1.86),1.55(95% CI: 0.92,2.61),1.90(95% CI: 1.13,3.17),1.83(95% CI: 1.08,3.07)for successive quintiles of cholesterol from eggs consumption,respectively(P for trend = 0.005),comparing with lowest quintile.A 100-mg per day increase in cholesterol from eggs consumption was associated with a 16% increase GDM risk(OR 1.16,95% CI: 1.04,1.29).In addition,we did not observe the significant association between other sources of cholesterol(red meats,fish and shellfish,milk and dairies,and other foods)and GDM risk.Generalized linear models demonstrated that a 100-mg per day increase in dietary cholesterol from egg consumption was associated with increase of 0.01 mmol/L FBG(95% CI: 0.00,0.03,P = 0.016)in fully models.In Logistic regression models,after adjusted for covariates,the risk of GDM in pregnant women with eggs consumption of 7 or more than 7 egg per week was 1.99 times(OR: 1.99,95% CI: 1.15,3.46)and 2.51 times(OR: 2.51,95% CI: 1.38,4.56)that of pregnant women with eggs consumption of less than 3 egg per week,respectively.A 1-egg per week increase in eggs consumption was associated with a 7% increase GDM risk(OR: 1.07,95% CI: 1.02,1.11).Compared with pregnant women whose eggs consumption was less than 7 egg per week,the risk of GDM increased by 48%(OR: 1.48,95% CI: 1.09,2.00)for pregnant women whose eggs consumption was more than 7 egg per week.In stratified analyses,the association between dietary cholesterol from eggs consumption and GDM risk were not significantly modified by maternal age,prepregnancy BMI,GWGO,parity,leisure-time physical activity,and family history of diabetes(all P for interactions were > 0.05)(3)The association between serum cholesterol absorption and synthesis marker levels and GDM risk.The nested case-control study included 156 pregnant women,included 52 GDM cases and 104 controls,matched for age,prepregnancy BMI,parity and gestational age of serum sampling.Pearson correlation coefficient showed that there was a positive correlation between cholesterol absorption markers,as well as the association between cholesterol synthesis markers,and a negative correlation between cholesterol absorption markers and synthesis markers.In conditional logistic regression models,after adjusted for potential confounders,per 1 Standard Deviation(SD)increased in ratio of lathosterol to TC(log-transformed),reflecting the choleseterol synthesis,the risk of GDM increased by 70%(OR: 1.70,95% CI: 1.04,2.76).Per 1 SD increased in ratio of cholestanol,campesterol,and β-Sitosterol to TC(log-transformed),reflecting the choleseterol absorption efficiency,the risk of GDM decreased by 42%,42% and 38%,respectively.Furthermore,for 1 SD increase in the ratio of cholesterol synthesis markers(lathosterol)to synthetic markers(β-Sitosterol,campesterol,cholestanol,and stigmasterol)(logtransformed),the ORs for GDM were 2.02(95% CI: 1.18,3.45),2.16(95% CI: 1.24,3.75),2.07(95% CI: 1.22,3.51),and 1.85(95% CI: 1.12,3.07),respectively.Conclusions:(1)Dietary cholesterol intake in pregnant women was relative high in urban areas in China.Higher dietary cholesterol intake during pregnancy was associated with greater risk of GDM.Moreover,dietary cholesterol intake was significantly positively associated with FBG and 1-h PBG.(2)Eggs are one of the largest sources of cholesterol in our study.Higher dietary cholesterol intake from eggs or eggs consumption(≥ 7 egg per week)during pregnancy was associated with greater risk of GDM.(3)Lower levels of serum cholesterol absorption markers and higher levels of synthetic markers were significantly associated the increased risk of GDM.The higher ratios of synthetic markers to absorption markers were significantly associated the increased risk of GDM.The higher cholesterol synthesis and lower cholesterol absorption in early pregnancy may be a risk factor for GDM in pregnant women. |