Association of WISP1/CCN4 with Risk of Overweight and Gestational Diabetes Mellitus in Chinese Pregnant Women

Abstract

Background. Obese women with gestational diabetes mellitus (GDM) have a higher risk of adverse outcomes than women with obesity or GDM alone. Our study is aimed at investigating the discriminatory power of circulatory Wnt1-inducible signaling pathway protein-1 (WISP1), a novel adipocytokine, on the copresence of prepregnancy overweight/obesity and GDM and at clarifying the relationship between the WISP1 level and clinical cardiometabolic parameters. Methods. A total of 313 participants were screened from a multicenter prospective prebirth cohort: Born in Shenyang Cohort Study (BISCS). Subjects were examined with a 2×2 factorial design for body mass index BMI≥24 and GDM. Between 24 and 28 weeks of pregnancy, follow-up individuals underwent an OGTT and blood sampling for cardiometabolic characterization. Results. We observed that the WISP1 levels were elevated in prepregnancy overweight/obesity patients with GDM, compared with nonoverweight subjects with normal blood glucose (3.45±0.89 vs. 2.91±0.75 ng/mL). Multilogistic regression analyses after adjustments for potential confounding factors revealed that WISP1 was a strong and independent risk factor for prepregnancy overweight/obesity with GDM (all ORs>1). In addition, the results of the ROC analysis indicated that WISP1 exhibited the capability to identify individuals with prepregnancy overweight/obesity and GDM (all AUC>0.5). Finally, univariate and multivariate linear regression showed that WISP1 level was positively and independently correlated with fasting blood glucose, systolic blood pressure, and aspartate aminotransferase and was negatively correlated with HDL-C and complement C1q. Conclusions. WISP1 may be critical for the prediction, diagnosis, and therapeutic strategies against obesity and GDM in pregnant women.

Downregulation of miR-451a in plasma may promote prothrombin expression and contribute to high blood coagulation state in gestational diabetes mellitus

“…The role of F2 in hypercoagulation is already known [12]. Other studies have confirmed the importance of F2 in patients with diabetes [14,15]. As was previously reported, prothrombin fragment F2 is a polypeptide fragment produced by the factor Xa complex after hydrolyzing prothrombin during blood coagulation [13].…”

“…Previous studies also indicated metabolic abnormalities in GDM patients. For example, in GDM patients, higher concentrations of HDL were observed in the third trimester of pregnancy, and higher triglyceride levels were found in both the second and third trimesters [14]. Therefore, the hypercoagulable status of GDM patients might be alleviated by targeting miR-451a.…”

Emerging Protein Biomarkers for the Diagnosis or Prediction of Gestational Diabetes—A Scoping Review

“…Wnt1-inducible signaling pathway protein-1 (WISP1) was studied by Liu et al [ 330 ] in 313 pregnant women (GDM n = 61, 2 h 75 g OGTT, IADPSG criteria). The samples were taken at the time of the OGTT.…”

Identification of Diagnostic CpG Signatures in Patients with Gestational Diabetes Mellitus via Epigenome-Wide Association Study Integrated with Machine Learning

“…The prevalence of GDM is quickly rising in the context of the global obesity epidemic [ 48 , 49 ]. GDM is described as carbohydrate intolerance of variable severity with onset or first detection during pregnancy [ 50 ], encompassing abnormal glucose tolerance and diabetes mellitus, which was undiagnosed prior to or began concomitantly during pregnancy [ 51 ]. Besides, epigenetic modification plays a critical role in multiple fundamental cellular processes [ 52 ], in which epigenetic alterations are involved in the early stage of metabolic diseases including GDM [ 53 ].…”