Early maternal circulating alkaline phosphatase with subsequent gestational diabetes mellitus and glucose regulation: a prospective cohort study in China

Purpose: 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.

Methods: 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.

Results: 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).

Conclusions: 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.