Urinary and Serum Angiogenic Markers in Women With Preexisting Diabetes During Pregnancy and Their Role in Preeclampsia Prediction

Zen, Monica; Padmanabhan, Suja; Zhang, Kewei; Kirby, Adrienne; Cheung, N. Wah; Lee, Vincent; Alahakoon, Thushari I.

doi:10.2337/dc19-0967

Cited by 17 publications

(7 citation statements)

References 27 publications

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“…No major advances have been made in this field since White’s classification ( White, 1949 ) and generalizing findings from studies of existing PE prediction models, such as the Fetal Medicine Foundation (FMF) algorithm, is problematic due to the small number of women with T1DM in the study population ( Rolnik et al, 2017b ). This is despite previous reports of PE biomarkers performing differently in pregnancies complicated by pregestational diabetes ( Zen et al, 2019 ). Moreover, large clinical trials investigating PE biomarkers and risk prediction models often pool data from type 1 and type 2 diabetes mellitus groups together or exclude them completely ( Agrawal et al, 2017 ; Guy et al, 2020 ; Serra et al, 2020 ).…”

Section: Introductioncontrasting

confidence: 77%

“…Similarly, placental angiogenic markers were some of the poorest PE predictors discussed in this review ( Wotherspoon et al, 2016a ; Kelly et al, 2019 ). Despite the initial optimism surrounding angiogenic factor discovery ( Levine et al, 2004 ), their accuracy has been called into question in the general population ( Kleinrouweler et al, 2012 ), and a recent study of pregnant women with diabetes found that the sFlt-1/PlGF ratio was driven by PlGF in these pregnancies with little difference in sFlt-1 between the PE and normotensive groups ( Zen et al, 2019 ). Therefore, only PlGF might hold a benefit for PE prediction in a system with T1DM.…”

Section: Discussionmentioning

confidence: 99%

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Pre-Eclampsia Biomarkers for Women With Type 1 Diabetes Mellitus: A Comprehensive Review of Recent Literature

Freimane

Kerrigan

Eastwood

et al. 2022

Front. Bioeng. Biotechnol.

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Background: Pre-eclampsia is a serious consideration for women with type 1 diabetes mellitus (T1DM) planning pregnancy. Risk stratification strategies, such as biomarkers measured in the first trimester of pregnancy, could help identify high-risk women. The literature on T1DM-specific pre-eclampsia biomarkers is expanding. We aimed to provide a narrative review of recently published evidence to identify the most promising biomarker candidates that could be targeted for clinical implementation in existing PE models.Methods: A search using MeSH terms was carried out of Medline, EMBASE, Maternity and Infant Care, Web of Science, and Scopus for relevant papers published since 2015 inclusive and in English. The time limit was applied from the publication of the preceding systematic review in this field. Included studies had pre-eclampsia as a primary outcome, measured one or more serum, plasma or urine biomarkers at any time during pregnancy, and had a distinct group of women with T1DM who developed pre-eclampsia. Studies with pre-eclampsia as a composite outcome were not considered. No restrictions on study types were applied. A narrative synthesis approach was adopted for analysis.Results: A total of 510 records were screened yielding 18 eligible studies relating to 32 different biomarkers. Higher first-trimester levels of HbA1c and urinary albumin were associated with an increased risk of pre-eclampsia development in women with T1DM. Urinary neutrophil gelatinase-associated lipocalin and adipokines were novel biomarkers showing moderate predictive ability before 15 gestational weeks. Two T1DM-specific pre-eclampsia prediction models were proposed, measuring adipokines or urinary neutrophil gelatinase-associated lipocalin together with easily attainable maternal clinical characteristics. Contradicting previous literature, pre-eclampsia risk in women with T1DM was correlated with vitamin D levels and atherogenic lipid profile in the context of haptoglobin phenotype 2-2. Pregnancy-associated plasma protein-A and soluble endoglin did not predict pre-eclampsia in women with T1DM, and soluble Fms-like tyrosine kinase 1 only predicted pre-eclampsia from the third trimester.Conclusion: Maternally derived biomarkers reflecting glycemic control, insulin resistance and renal dysfunction performed better as PE predictors among women with T1DM than those derived from the placenta. These biomarkers could be trialed in current PE prediction algorithms to tailor them for women with T1DM.

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Section: Introductioncontrasting

confidence: 77%

Section: Discussionmentioning

confidence: 99%

Pre-Eclampsia Biomarkers for Women With Type 1 Diabetes Mellitus: A Comprehensive Review of Recent Literature

Freimane

Kerrigan

Eastwood

et al. 2022

Front. Bioeng. Biotechnol.

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show abstract

“…Yu and colleagues demonstrated that women with type 1 diabetes (DM1) and PE had increased sFlt1, decreased PlGF and increased sFlt1/PlGF ratio compared with controls 39 . Three others cohort studies investigating a preeclamptic population with preexisting diabetes, reported increased sFlt1, decreased PlGF and increased sFlt1/PlGF ratio before PE onset relative to non PE women [47][48][49] .…”

Section: Discussionmentioning

confidence: 98%

Placental and maternal sFlt1/PlGF expression in gestational diabetes mellitus

Nuzzo

Giuffrida

Moretti

et al. 2021

Sci Rep

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Gestational diabetes mellitus (GDM) and preeclampsia (PE) are both characterized by endothelial dysfunction and GDM women have higher incidence of PE. The placenta plays a key role in PE pathogenesis but its contribution to PE during GDM remains unclear. Herein, we compared placental and maternal blood anti-angiogenic soluble fms-like tyrosine kinase-1 (sFlt1) and pro-angiogenic Placental Growth Factor (PlGF) expressions in GDM and GDM-PE pregnancies compared to controls (CTRL) and PE cases. Electrochemiluminescence immunoassays showed a significantly higher maternal blood sFlt1/PlGF values in GDM-PE relative to CTRL and GDM pregnancies. We reported that placental PlGF gene expression was significantly decreased in GDM, PE and GDM-PE relative to CTRL. However, PlGF protein levels were significantly increased in GDM and GDM-PE relative to CTRL and PE placentae. Finally, sFlt1 gene expression was significantly increased in PE relative to CTRL, GDM and GDM-PE placentae. In contrast, sFlt1 protein expression was significantly decreased in GDM-PE relative to CTRL, GDM and PE placentae. Finally, higher sFlt1/PlGF ratio in GDM-PE maternal blood suggest that sFlt1 overproduction is related to PE onset also in GDM pregnancies even though characterized by a less severe endothelial dysfunction in terms of angiogenic biomarkers.

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“…The role of the sFlt-1/PIGF ratio has been documented previously in several studies conducted on type 1 and type 2 diabetes mellitus [ 53 , 54 ]; recently, Nuzzo et al [ 37 ] have also identified an increased placental and maternal sFlt1/PlGF ratio in women with GDM who develop preeclampsia.…”

Section: Discussionmentioning

confidence: 73%

Angiogenic Imbalance and Inflammatory Biomarkers in the Prediction of Hypertension as Well as Obstetric and Perinatal Complications in Women with Gestational Diabetes Mellitus

Lara-Barea

Sánchez-Lechuga

Campos‐Caro

et al. 2022

JCM

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Gestational diabetes mellitus (GDM) increases the risk of hypertensive disorders of pregnancy (HDP). We aimed to analyze the altered inflammatory markers and angiogenic factors among women with GDM to identify pregnant women at higher risk of developing HDP. Methods: This was a prospective study of 149 women without hypertension diagnosed in the third trimester with GDM. Inflammatory markers and angiogenic factors were measured at 28–32 weeks of pregnancy. Obstetric and perinatal outcomes were evaluated. Results: More than eight percent of the women developed HDP. Higher levels of the soluble fms-like tyrosine kinase-1/placental growth factor (sFlt-1/PIGF) ratio (4.9 ± 2.6 versus 2.3 ± 1.3, respectively; p < 0.001) and leptin (10.9 ± 0.8 versus 10.08 ± 1.1, respectively; p = 0.038), as well as lower levels of adiponectin (10.5 ± 1.3 versus 12.9 ± 2.7, respectively; p = 0.031), were seen in women who developed HDP versus normotensive women with GDM. A multivariable logistic regression analysis showed that adiponectin had a protective effect with 0.45-fold odds (0.23–0.83; p = 0.012), and that the sFlt-1/PIGF ratio was associated with 2.70-fold odds of developing HDP (CI 95%: 1.24–5.86; p = 0.012). Conclusion: An increase in angiogenic imbalance in the sFlt-1/PIGF ratio in women with GDM was detected and may be an indicator of developing HDP in addition to any subsequent obstetric and perinatal complications.

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Urinary and Serum Angiogenic Markers in Women With Preexisting Diabetes During Pregnancy and Their Role in Preeclampsia Prediction

Cited by 17 publications

References 27 publications

Pre-Eclampsia Biomarkers for Women With Type 1 Diabetes Mellitus: A Comprehensive Review of Recent Literature

Pre-Eclampsia Biomarkers for Women With Type 1 Diabetes Mellitus: A Comprehensive Review of Recent Literature

Placental and maternal sFlt1/PlGF expression in gestational diabetes mellitus

Angiogenic Imbalance and Inflammatory Biomarkers in the Prediction of Hypertension as Well as Obstetric and Perinatal Complications in Women with Gestational Diabetes Mellitus

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