Adipokines in early and mid-pregnancy and subsequent risk of gestational diabetes: a longitudinal study in a multiracial cohort

Abstract

Introduction: Several adipokines are implicated in the pathophysiology of gestational diabetes mellitus (GDM), however, longitudinal data in early pregnancy on many adipokines are lacking. We prospectively investigated the association of a panel of adipokines in early and mid-pregnancy with GDM risk.

Research design and methods: Within the National Institute of Child Health and Human Development (NICHD) Fetal Growth Studies-Singletons cohort (n=2802), a panel of 10 adipokines (plasma fatty acid binding protein-4 (FABP4), chemerin, interleukin-6 (IL-6), leptin, soluble leptin receptor (sOB-R), adiponectin, omentin-1, vaspin, and retinol binding protein-4) were measured at gestational weeks (GWs) 10-14, 15-26, 23-31, and 33-39 among 107 GDM cases (ascertained on average at GW 27) and 214 non-GDM controls. Conditional logistic regression was used to estimate ORs of each adipokine and GDM, controlling for known GDM risk factors including pre-pregnancy body mass index.

Results: Throughout pregnancy changes in chemerin, sOB-R, adiponectin, and high-molecular-weight adiponectin (HMW-adiponectin) concentrations from 10-14 to 15-26 GWs were significantly different among GDM cases compared with non-GDM controls. In early and mid-pregnancy, FABP4, chemerin, IL-6 and leptin were positively associated with increased GDM risk. For instance, at 10-14 GWs, the OR comparing the highest versus lowest quartile (ORQ4-Q1) of FABP4 was 3.79 (95% CI 1.63 to 8.85). In contrast, in both early and mid-pregnancy adiponectin (eg, ORQ4-Q1 0.14 (0.05, 0.34) during 10-14 GWs) and sOB-R (ORQ4-Q1 0.23 (0.11, 0.50) during 10-14 GWs) were inversely related to GDM risk. At 10-14 GWs a model that included conventional GDM risk factors and FABP4, chemerin, sOB-R, and HMW-adiponectin improved the estimated prediction (area under the curve) from 0.71 (95% CI 0.66 to 0.77) to 0.77 (95% CI 0.72 to 0.82).

Conclusions: A panel of understudied adipokines including FABP4, chemerin, and sOB-R may be implicated in the pathogenesis of GDM with significant associations detected approximately 10-18 weeks before typical GDM screening.

Keywords: adipokines; cohort; gestational diabetes mellitus; prospective.