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Emerging clinical evidence has implied that alkaline phosphatase (ALP) may contribute to gestational diabetes mellitus (GDM). However, there were no studies to reveal the independent and prospective associations between ALP and GDM. Our aim was to explore the independent and prospective associations between early maternal ALP level and GDM risk and glucose regulation. In a prospective cohort study with 2073 singleton mothers at four maternity units in China, maternal serum ALP levels were measured before 20 gestational weeks. Using logistic regression, we analyzed the relationship between maternal ALP level and risk of GDM. We further explored the relationships of ALP level to fasting blood glucose (FBG), 1-h and 2-h post-load blood glucose (1-h, 2-h PBG) with multiple linear regression. Finally, we analyzed the association between maternal ALP level and isolated impaired fasting glucose (i-IFG) and isolated impaired glucose tolerance (i-IGT) risk. The maximum value of maternal ALP level was 90 U/L, within the normal range. After adjustment for confounding factors, the odds ratio (ORs) of GDM increased linearly with ALP level (p for overall association = 0.002, p for nonlinear association = 0.799), with the OR comparing the highest versus lowest quartile of 2.47 (95% CI 1.47, 4.15). Moreover, each additional of 10 U/L ALP level was associated with a 2% higher FBG (p = 0.043) and a 12% higher 1-h PBG (p = 0.004). Higher ALP level also increased the risk of i-IFG (OR 3.73, 95% CI 1.17–11.86) and i-IGT (OR 2.03, 95% CI 1.07–3.84). Even within the upper limit of normal, higher early maternal ALP level could increase the risk of GDM. Moreover, both FBG and PBG were increased with early maternal ALP.

Bilirubin concentrations have been recently reported to be negatively associated with type 2 diabetes mellitus. We examined the association between bilirubin concentrations and gestational diabetes mellitus. In a prospective cohort study, 2969 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 was conducted to screen gestational diabetes mellitus. The relationship between serum bilirubin concentration and gestational weeks was studied by two-piecewise linear regression. A subsample of 1135 participants with serum bilirubin test during 16-18 weeks gestation was conducted to research the association between serum bilirubin levels and risk of gestational diabetes mellitus by logistic regression. Gestational diabetes mellitus developed in 8.5 % of the participants (223 of 2969). Two-piecewise linear regression analyses demonstrated that the levels of bilirubin decreased with gestational week up to the turning point 23 and after that point, levels of bilirubin were increased slightly. In multiple logistic regression analysis, the relative risk of developing gestational diabetes mellitus was lower in the highest tertile of direct bilirubin than that in the lowest tertile (RR 0.60; 95 % CI, 0.35-0.89). The results suggested that women with higher serum direct bilirubin levels during the second trimester of pregnancy have lower risk for development of gestational diabetes mellitus.