The insulin-like growth factor (IGF)-axis may be implicated in glucose homeostasis, but its longitudinal profile across gestation in relation to the development of gestational diabetes (GDM) is largely unknown. We prospectively investigated IGF-axis biomarkers in early-to-mid pregnancy in relation to subsequent GDM risk in a case-control study of 107 GDM cases and 214 non-GDM controls, with blood samples collection at gestational weeks (GW) 10-14, 15-26, 23-31, and 33-39. Conditional logistic regression was used, adjusting for major risk factors including pre-pregnancy body mass index. Plasma IGF-I and IGF-binding protein (BP)-3 concentrations and IGF-I/IGFBP-3 molar ratio increased whereas IGFBP-2 decreased throughout pregnancy. At GW 10-14, both IGF-I and IGF-I/IGFBP-3 were positively associated with GDM risk; adjusted odds ratio comparing the highest vs. lowest quartile (ORQ4-Q1) was 2.93 (95% confidence interval 1.18-7.30) for IGF-I and 3.31 (1.10-9.98) for IGF-I/IGFBP-3. In contrast, higher IGFBP-2 levels were related to a substantially lower risk of GDM (ORQ4-Q1 0.04, 0.01-0.06). Similar results were observed at GW 15-26. In sum, the IGF-axis, IGFBP-2 in particular, may be implicated in the pathogenesis of GDM with significant associations and incremental predictive value detected as early as GW 10-14, approximately 10-18 weeks earlier before GDM is typically screened for.
- Received April 21, 2016.
- Accepted July 19, 2016.
- © 2016 by the American Diabetes Association.