Sulfated Progesterone Metabolites That Enhance Insulin Secretion via TRPM3 Are Reduced in Serum From Women With Gestational Diabetes Mellitus

Fan, Hei Man; Mitchell, Alice; Bellafante, Elena; McIlvride, Saraid; Primicheru, Laura I.; Giorgi, Mirko; Eberini, Ivano; Syngelaki, Argyro; Lövgren‐Sandblom, Anita; Jones, Peter M.; McCance, David R.; Sukumar, Nithya; Periyathambi, Nishanthi; Ghebremichael‐Weldeselassie, Yonas; Hunt, Katharine F.; Nicolaides, Kypros H.; Andersson, David A.; Bevan, Stuart; Seed, Paul; Bewick, Gavin; Bowe, James; Fraternali, Franca; Saravanan, Ponnusamy; Marschall, Hanns‐Ulrich; Williamson, Catherine

doi:10.2337/db21-0702

Cited by 4 publications

(3 citation statements)

References 43 publications

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“…Furthermore, GDM leads to a significant financial burden on society and healthcare resources ( 7 , 8 ). Currently, the onset and progression of GDM are uncertain and complex and pathogenesis remains uncertain ( 9 ). Consequently, revealing new diagnostic and therapeutic molecular biomarkers for GDM patients for individualized and effective treatment is crucial.…”

Section: Introductionmentioning

confidence: 99%

The integrated bioinformatic analysis identifies immune microenvironment-related potential biomarkers for patients with gestational diabetes mellitus

Chen,

Dai,

Kan

et al. 2024

Front. Immunol.

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BackgroundGestational diabetes mellitus (GDM), a transient disease, may lead to short- or long-term adverse influences on maternal and fetal health. Therefore, its potential functions, mechanisms and related molecular biomarkers must be comprehended for the control, diagnosis and treatment of GDM.MethodsThe differentially expressed genes (DEGs) were identified using GSE49524 and GSE87295 associated with GDM from the Gene Expression Omnibus database, followed by function enrichment analysis, protein-protein interactions network construction, hub DEGs mining, diagnostic value evaluation and immune infiltration analysis. Finally, hub DEGs, the strongest related to immune infiltration, were screened as immune-related biomarkers.ResultsA hundred and seven DEGs were identified between patients with GDM and healthy individuals. Six hub genes with high diagnostic values, including ALDH1A1, BMP4, EFNB2, MME, PLAUR and SLIT2, were identified. Among these, two immune-related genes (PLAUR and SLIT2) with the highest absolute correlation coefficient were considered immune-related biomarkers in GDM.ConclusionOur study provides a comprehensive analysis of GDM, which would provide a foundation for the development of diagnosis and treatment of GDM.

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Section: Introductionmentioning

confidence: 99%

The integrated bioinformatic analysis identifies immune microenvironment-related potential biomarkers for patients with gestational diabetes mellitus

Chen,

Dai,

Kan

et al. 2024

Front. Immunol.

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“…GDM poses a serious threat to global public health. In China, the incidence of GDM is about 14.8% ( 3 , 4 ). GDM causes a variety of adverse pregnancy outcomes, including premature birth, macrosomia, neonatal respiratory distress syndrome, neonatal hypoglycemia, and neonatal hyperbilirubinemia.…”

Section: Introductionmentioning

confidence: 99%

Serum afamin levels in predicting gestational diabetes mellitus and preeclampsia: A systematic review and meta-analysis

Fan

Liang

et al. 2023

Front. Endocrinol.

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ObjectivesThe association between biomarkers and the risk of gestational diabetes mellitus (GDM) or preeclampsia (PE) has been extensively studied. However, there is still a lack of convenient, specific, and sensitive indicators for early identification of GMD and PE. Therefore, we conducted a meta-analysis of published articles to investigate the value of afamin circulating levels in the early diagnosis of GDM and PE.MethodsWe searched the PubMed, Embase, Cochrane Library, and Web of Science databases for English studies published before November 16, 2022, that examined the association between afamin and GDM or PE. In addition, we searched Clinicaltrials.gov for the relevant completed and ongoing clinical trials. Pooled standard mean differences (SMDs) and weighted mean differences (WMDs) with 95% confidence intervals (CIs) were used to compare the levels of afamin in different groups.ResultsEleven studies were included in our analysis (N = 3047 participants: 1195 GDM, 1407 non-GDM, 195 PE, and 250 non-PE). Subgroup analysis based on different blood collection periods found that the plasma afamin levels in pregnant women with GDM in the first trimester were significantly higher than those in healthy pregnant women (SMD = 0.481, 95% CI: 0.280-0.682), but the analysis showed the opposite results in the second and late stages (SMD = 0.292, 95% CI: -0.092-0.676). The plasma afamin levels of pregnant women with PE in the first trimester (SMD = 0.808, 95% CI: 0.558-1.059) and second/third trimesters (SMD = 0.904, 95% CI: 0.570-1.239) were significantly higher than those in healthy pregnant women.ConclusionThe plasma afamin levels in pregnant women with GDM in the first trimester were significantly higher than those in healthy pregnant women, but the analysis showed the opposite results in the second and third trimesters. The plasma afamin levels in pregnant women with PE in the first, second, and third trimesters were significantly higher than those in healthy pregnant women. Additional large-scale prospective studies are desired to verify these findings, and it is recommended that afamin should be included as a routine diagnostic test for women with GDM and PE.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=339171, identifier CRD42022339171.

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“…Insulin resistance is an important physiological process essential during pregnancy to ensure sufficient fetal nutrition, and the physiological changes in insulin are excessive in women with GDM, usually as a result of β -cell impairment [ 2 ]. GDM complicates approximately 1∼14% of all pregnancies worldwide with higher rates in Asia [ 3 ]. In mainland China, the incidence of GDM is 14.8%, which is similar to the reported incidence of GDM in Hong Kong (14.4%) [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

Clinical Significance of Neuregulin 4, Afamin, and SERPINB1 in Gestational Diabetes Mellitus and Their Relationship with Insulin Resistance

Jin

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Objective. This study aims to explore the serum levels of neuregulin 4 (NRG4), afamin (AFM), and serpin family B member 1 (SERPINB1) in gestational diabetes mellitus (GDM) patients and their relationship with insulin resistance. Method. Serum levels of AFM, SERPINB1, and NRG4 were measured in GDM (n = 58), and non-GDM women (n = 60) using enzyme-linked immunosorbent assay (ELISA) kits. Besides, the serum insulin and glucose levels were also measured followed by calculating the homeostatic model assessment of insulin resistance (HOMA-IR). The correlation was performed using the Pearson analysis. Results. The increased serum levels of AFM and SERPINB1 were revealed in GDM patients as compared with non-GDM women, accompanied by the lower NRG4 serum level. ROCs for AFM concentrations showed an AUC of 0.629 (95% CI: 0.527∼0.731), 0.832 (95% CI: 0.754∼0.909) for the SERPINB1 serum level, and 0.626 (95% CI: 0.524∼0.728) for the NRG4 serum level. The threshold was 108.05 mg/L, 8.75 ng/mL, and 96.25 ng/mL of AFM, SERPINB1, and NRG4. Moreover, the combined ROC of AFM, SERPINB1, and NRG4 serum levels showed higher sensitivity (72.41%) and specificity (85.00%) for the diagnosis of GDM (AUC = 0.839; 95% CI: 0.764∼0.913). In GDM patients, the Pearson analysis revealed a significant correlation between AFM and SERPINB1 (r = 0.776), AFM and NRG4 (r = −0.799), as well as SERPINB1 and NRG4 (r = −0.783). Moreover, AFM and SERPINB1 serum concentrations in GDM patients were positively related to insulin levels, fasting glucose levels, and HOMA-IR values. However, the SERPINB1 serum level was negatively correlated with serum insulin and glucose levels and HOMA-IR. Conclusion. Abnormal serum levels of NRG4, AFM, and SERPINB1, as highly sensitive diagnostic tools, are closely related to insulin resistance in GDM patients.

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Sulfated Progesterone Metabolites That Enhance Insulin Secretion via TRPM3 Are Reduced in Serum From Women With Gestational Diabetes Mellitus

Cited by 4 publications

References 43 publications

The integrated bioinformatic analysis identifies immune microenvironment-related potential biomarkers for patients with gestational diabetes mellitus

The integrated bioinformatic analysis identifies immune microenvironment-related potential biomarkers for patients with gestational diabetes mellitus

Serum afamin levels in predicting gestational diabetes mellitus and preeclampsia: A systematic review and meta-analysis

Clinical Significance of Neuregulin 4, Afamin, and SERPINB1 in Gestational Diabetes Mellitus and Their Relationship with Insulin Resistance

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