Mediating Effect of Insulin-Like Growth Factor-I Underlying the Link Between Vitamin D and Gestational Diabetes Mellitus

Vitamin D was well-known to be associated with gestational diabetes mellitus (GDM). Insulin-like growth factor-I (IGF-I) has been linked to vitamin D and GDM, respectively. We hypothesize that changes in IGF-I metabolism induced by 25(OH)D₃ might contribute to GDM. Therefore, we investigated the independent and combined relationships of serum 25(OH)D₃ and IGF-I concentrations with GDM risk, and the mediation effect of IGF-I on 25(OH)D₃. A total of 278 pregnant women (including 125 cases and 153 controls) were recruited in our current study. Maternal serum 25(OH)D₃ and IGF-I were measured in the second trimester. Logistic regression models were used to estimate the associations of 25(OH)D₃ and IGF-I concentrations with the risk of GDM. Mediation analyses were used to explore the mediation effect of IGF-I on the association between 25(OH)D₃ and the risk of GDM. After adjusted for the confounded factors, both the third and fourth quartile of 25(OH)D₃ decreased the risk of GDM (OR = 0.226; 95% CI, 0.103–0.494; OR = 0.109; 95% CI, 0.045–0.265, respectively) compared to the first quartile of 25(OH)D₃. However, the third and fourth quartile of serum IGF-I (OR = 5.174; 95% CI, 2.287–11.705; OR = 12.784; 95% CI, 5.292–30.879, respectively) increased the risk of GDM compared to the first quartile of serum IGF-I. Mediation analyses suggested that 19.62% of the associations between 25(OH)D₃ and GDM might be mediated by IGF-I. The lower concentration of serum 25(OH)D₃ or higher IGF-I in the second trimester was associated with an increased risk of GDM. The serum IGF-I level might be a potential mediator between 25(OH)D₃ and GDM.