Maternal circulating adipokine profile and insulin resistance in women at high risk of developing gestational diabetes mellitus

Guelfi, Kym J.; Ong, Ming Jing; Li, Shaofu; Wallman, Karen; Doherty, Dorota A.; Fournier, Paul A.; Newnham, John P.; Keelan, Jeffrey A.

doi:10.1016/j.metabol.2017.08.003

Cited by 35 publications

(32 citation statements)

References 29 publications

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“… 8 However, in a study among 123 Australian women who were mostly (84%) Caucasian, and had a prior GDM pregnancy, there were no differences in FABP4 levels at approximately 14 GWs or 28 GWs between women with and without recurrent GDM. 25 Our findings add to the limited prospective data by demonstrating that FABP4 is associated with GDM risk among a diverse sample of pregnant women, and that higher concentrations of FABP4 among women with GDM persisted throughout pregnancy.…”

Section: Discussionsupporting

confidence: 58%

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

Francis

Hinkle

et al. 2020

BMJ Open Diab Res Care

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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.

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Section: Discussionsupporting

confidence: 58%

“… 15 Most previously reviewed studies 5 reported that higher leptin was associated with increased GDM risk, although three studies reported no associations. 25 43 44 …”

Section: Discussionmentioning

confidence: 99%

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

Francis

Hinkle

et al. 2020

BMJ Open Diab Res Care

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“…Among the 806 articles retrieved, 31 were eligible; 14 were FABP4 studies [ 8 , 17 – 19 , 26 – 36 ], seven were nesfatin-1 studies [ 10 , 12 , 20 , 37 – 40 ], seven were OC studies [ 14 , 21 , 41 – 45 ], and three articles covered both FABP4 and nesfatin-1 [ 11 , 46 , 47 ]. The 31 studies involved 4590 participants; 2059 were GDM patients and 2531 were healthy pregnant women [ 8 , 10 – 12 , 14 , 17 – 21 , 26 – 47 ] (Fig. 1 ).…”

Section: Resultsmentioning

confidence: 99%

“…Although the potential roles of circulating FABP4, nesfatin-1, and OC in GDM have been the focus of research in recent decades, the results have been controversial due to different ethnicities, assay methods, and diagnostic/definition of GDM [ 17 – 21 ]. Therefore, the primary goal of this research was to obtain more comprehensive results to elucidate the association between circulating concentrations of these adipokines and women with GDM.…”

Section: Introductionmentioning

confidence: 99%

Circulating FABP4, nesfatin-1, and osteocalcin concentrations in women with gestational diabetes mellitus: a meta-analysis

Sun

Zhang

et al. 2020

Lipids Health Dis

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Objective: Recent studies have investigated the circulating adipocyte fatty acid binding protein (FABP4), nesfatin-1, and osteocalcin (OC) concentrations in women diagnosed with gestational diabetes mellitus (GDM), but the findings prove to be conflicting. The objective of this research was to systematically assess the relationship of circulating levels of above adipokines with GDM. Methods: Pubmed, Embase, Web of Science, Cochrane library, OVID, and Scopus were performed to locate articles published up to January 31, 2020. Pooled standard mean differences (SMDs) with 95% confidence intervals (CIs), and 95% predictive intervals (PIs) were calculated by random-effects models to compare levels of adipokines between GDM cases and control groups. Cumulative and single-arm meta-analyses were also performed. Results: Thirty-one studies comprising 4590 participants were included. No significant differences were found between GDM women and healthy controls in circulating nesfatin-1 levels (4.56 vs. 5.02 ng/mL; SMD = − 0.11, 95% CI-0.61-0.38, 95% PI-1.63-1.41). Nevertheless, circulating FABP4 and OC levels observed in GDM women outnumbered normal controls (FABP4, 23.68 vs. 16.04 ng/mL; SMD = 2.99, 95% CI 2.28-3.69, 95% PI 0.28-5.71; OC, 52.34 vs. 51.04 ng/mL; SMD = 0.68, 95% CI 0.31-1.05, 95% PI-0.48-1.84). The cumulative meta-analysis showed that the SMDs of circulating FABP4 and OC levels had stabilized between the two groups. Conclusions: Elevated circulating FABP4 and OC levels were observed in GDM women, but nesfatin-1 levels did not change, the PI of OC crossed the no-effect threshold. The results suggested that FABP4 is more suitable as a biomarker of GDM compared to OC in a future study, which is useful in identifying pregnant women who are likely to develop GDM and providing prompt management strategies.

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“…In support of our lack of differences in several adipokines, a recent study evaluating a FABP4, leptin, chemerin, adiponectin, and resistin at 14 and 28 weeks of pregnancy in a high-risk GDM population (ie, all with previous GDM) detected only lower levels of adiponectin. 40 However, other studies have shown elevated levels of FABP4 in GDM, 41,42 and in a systematic review, they reported elevated levels of leptin in GDM and inconclusive result for resistin 26 between GDM and non-GDM.…”

Section: Discussionmentioning

confidence: 96%

Adipokines and macrophage markers during pregnancy—Possible role for sCD163 in prediction and progression of gestational diabetes mellitus

Ueland

Michelsen

Aukrust

et al. 2019

Diabetes Metabolism Res

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Aims The risk of gestational diabetes mellitus (GDM) is increased in overweight and obese women potentially involving secreted mediators from adipose tissue. Our main aim was to evaluate if circulating adipokines and monocyte/macrophage markers were dysregulated in GDM and the influence body mass and indices of glucose metabolism had on this association. We further explored if early detection of these markers improved prediction of GDM and if they remained modified during long‐term follow‐up. Materials and methods Population‐based prospective cohort study in 273 pregnant women with markers measured four times during pregnancy and at 5‐year follow‐up. Results sCD163 was higher (25% at 14‐16 weeks, P < 0.001) and adiponectin lower (−17% at 14‐16 weeks, P < 0.01) early in pregnancy and at 5‐year follow‐up in GDM women, independent of BMI, and other GDM risk factors. Leptin, adiponectin, and chemerin were robustly associated with glucose metabolism throughout pregnancy while sCD163 was inversely associated with β‐cell function early in pregnancy in women with increased BMI. Finally, the markers at 14 to 16 weeks displayed modest discriminatory properties with regard to prediction of GDM (AUC < 0.7). Using a combination of fasting glucose and sCD163, 53% of GDM could be identified when 25% of the population scored positive suggesting some merit in a multimarker approach. Conclusions sCD163 and adiponectin were dysregulated in GDM, independent of body mass. None of the adipokines or monocyte/macrophage activation markers displayed clinically useful properties alone for early detection of GDM. Activation of monocytes/macrophages may be an important event in the early development of GDM.

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Maternal circulating adipokine profile and insulin resistance in women at high risk of developing gestational diabetes mellitus

Abstract: Maternal glucose and adipokine profile is altered early in pregnancy in women with a history of GDM who subsequently develop recurrent disease.

Cited by 35 publications

References 29 publications

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

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

Circulating FABP4, nesfatin-1, and osteocalcin concentrations in women with gestational diabetes mellitus: a meta-analysis

Adipokines and macrophage markers during pregnancy—Possible role for sCD163 in prediction and progression of gestational diabetes mellitus

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