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.
- gestational diabetes mellitus
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Correction notice This article has been corrected since it was published. Author name corrected from Hiaming Cao to Haiming Cao.
Contributors ECF analyzed data and wrote the first draft of the manuscript. ML, SNH, YC, JC, JiW contributed to data analysis, statistical approach, and reviewed the manuscript. ECF contributed to study coordination, data interpretation, and manuscript reviewing. ECF, ML, SNH, HC, KK, LR, JoW, and LC contributed to data interpretation and reviewed the manuscript. MYT contributed to laboratory testing and reviewed the manuscript. CZ obtained funding, designed and oversaw the study and revised the manuscript. All authors contributed to the interpretation of the results and revision of the manuscript for important intellectual content and approved the final version of the manuscript. ECF and CZ are the guarantors of this work and, as such, had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
Funding This research was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development intramural funding and included American Recovery and Reinvestment Act funding via contract numbers HHSN275200800013C, HHSN275200800002I, HHSN27500006, HHSN275200800003IC, HHSN275200800014C, HHSN275200800012C, HHSN275200800028C, HHSN275201000009C, and HHSN275201000001Z. YZ was supported by the National Institute of Diabetes and Digestive and Kidney Diseases (grant number K01DK120807). ECF is a participant in the NIH Graduate Partnership Program and a graduate student at Clemson University.
Competing interests None declared.
Patient consent for publication Not required.
Ethics approval This study was carried out following the rules of the Declaration of Helsinki. Institutional review board approval was obtained for all the participating clinical sites (Christiana Care Health System, Columbia University, Fountain Valley, Long Beach Memorial Medical Center, Medical University of South Carolina, New York Hospital Queens, Northwestern University, St. Peter’s University Hospital, Tufts University, University of Alabama at Birmingham, University of California, Irvine, Women and Infants Hospital of Rhode Island), data coordinating centers (Clinical Trials & Surveys Corporation and the Emmes Corporation), and NICHD (approval number: 09-CH-N152). All participants provided written, informed consent.
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement Data are available upon reasonable request. The data, along with a set of guidelines for researchers applying for the data, will be posted to a data-sharing site, the NICHD/DIPHR Biospecimen Repository Access and Data Sharing (https://brads.nichd.nih.gov) (BRADS).
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