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

Abstract

IntroductionSeveral 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 methodsWithin 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.ResultsThroughout 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).ConclusionsA 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.

The Role of the Adipokines in the Most Common Gestational Complications

“…That effect occurs especially during the pregnancy when the significant increase in chemerin levels is highly pronounced [ 171 , 176 ]. Surprisingly, there was not any correlation between chemerin levels and fasting glucose, C-peptide, and OGTT test results [ 177 , 178 ]. The analyses of relationships between chemerin, fasting insulin, and HOMA-IR (homeostatic model assessment of insulin resistance) values lead to contradictory results.…”

“…The analyses of relationships between chemerin, fasting insulin, and HOMA-IR (homeostatic model assessment of insulin resistance) values lead to contradictory results. Whereas some authors did not observe any significant correlations between those parameters [ 177 ], the others found that chemerin values were positively markedly correlated with HOMA-IR or insulin levels [ 172 , 179 , 180 , 181 ]. Chemerin values were also found to be positively correlated with fatty acid-binding protein 4, interleukin-6, and tumor necrosis factor-α [ 182 ].…”

“…To analyze its utility in the prediction of GDM, it is crucial to evaluate its blood concentrations in patients with GDM and healthy individuals. Some authors found that chemerin concentrations in peripheral blood are significantly increased throughout the pregnancy in patients with GDM [ 172 , 177 , 179 , 182 , 183 , 184 , 185 ]. Whereas some studies reported that chemerin levels are also significantly elevated in the cord blood samples [ 172 , 186 ], the others did not find any differences [ 187 ].…”

“…Nonetheless, it is noteworthy that first and second trimester multiple regression models revealed that chemerin values are positively associated with the elevated risk of GDM, and along with other parameters, chemerin may be treated as an independent risk factor of GDM [ 177 , 182 , 184 , 193 ]. The implementation of the results of chemerin levels measurement improves the predictive values of models used in the prediction of GDM [ 177 , 182 ]. Finally, it is unlikely that its concentration measurement could be used as a single early marker in the prediction of GDM.…”

“… The graphical summary of data concerning chemerin concentration and chemerin mRNA expression levels in GDM patients as compared to control patients. ↑ increase in parameter level as compared to control [ 172 , 177 , 179 , 182 , 183 , 184 , 185 ]; ↓ decrease in parameter level as compared to control [ 191 ]; =: no significant alterations observed as compared to control [ 167 , 176 , 180 , 186 , 187 , 188 , 189 , 190 ] (Created with BioRender.com). …”