Higher direct bilirubin levels during the second trimester of pregnancy is associated with lower risk of gestational diabetes mellitus

Abstract

BackgroundBilirubin concentrations have been recently reported to be negatively associated type 2 diabetes mellitus (T2DM). We examined the association between bilirubin concentrations and gestational diabetes mellitus (GDM).MethodsIn a prospective cohort study (Tongji Maternal and Child Health Cohort, TMCHC), 1739 pregnant women were recruited prior to 16 weeks of gestation and were followed up until delivery. The value of bilirubin was tested and oral glucose tolerance test (OGTT) was conducted to screen GDM. The relationship between serum total bilirubin (TB) concentration and gestational weeks was studied by two‐piecewise linear regression. A subsample of 822 participants with serum bilirubin test during 12 to 22 weeks gestation was conducted to research the association between serum bilirubin levels and risk of GDM by multiple linear regressions and logistic regression.ResultsGDM developed in 9.9% of the participants (172 of 1793). A nonlinear relationship between serum total bilirubin and the gestational week was exhibited through the scatterplot smoothing after adjusted for BMI, age supplements intake, sleep quality, smoking, and alcohol intake. Two‐piecewise linear regression analyses demonstrated threshold effect between serum total bilirubin and the gestational week from 2493 tests of 1739 participants. Serum total bilirubin levels decreased with gestational week up to the turning point 25.6 (β=−0.008, p<0.001). When the gestational weeks exceeded 25.6, TB level was increased slightly (β=0.002, p=0.004).The unadjusted logistic regression analysis indicate that the risk for the development of GDM was lower in the highest tertile of serum direct bilirubin concentrations than that in the lowest tertile (RR, 0.64; 95%CI, 0.44 to 0.95). After adjusting for BMI and age, the RR remains 0.66 ( 95%CI, 0.44 to 0.97). After further adjusting for SBP, DBP, smoking, alcohol intake, sleep quality, and family history of diabetes, hypertension and obesity, the RR was 0.65 ( 95%CI, 0.44 to 0.96). Serum total and indirect bilirubin levels were slightly association with the incidence of GDM. In adjusted logistic regression analysis, highest tertile of serum total bilirubin concentrations has lower risk for the development of GDM than the lowest (RR, 0.87; 95%CI, 0.73 to 1.03). After adjusted for BMI, age and other confounders, the RR was 0.88 (95%CI, 0.70 to 1.12).ConclusionsThe results suggested that higher maternal serum direct bilirubin during second trimester of pregnancy could be a protective factor for the development of GDM later.Support or Funding InformationNational Program on Basic Research Project of China: NO.2013FY114200