PAPP-A | eGDMD

By admin , 18 September 2025

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Literature evidence

Literature link	GPT Summary	Evidence category	Disease type




28323969	This study examined the relationship between first-trimester pregnancy-associated plasma protein A (PAPP-A) concentrations and the subsequent risk of gestational diabetes mellitus (GDM), gestational hypertension, and associated metabolic parameters in the Cambridge Baby Growth Study cohort. Higher PAPP-A levels at week 15 were associated with a lower risk of GDM (odds ratio 0.623, P = 0.0035) and lower mean arterial blood pressures (P = 0.0017 to 0.0069). Additionally, increased PAPP-A was negatively correlated with fasting and 60-minute glucose levels during the week 28 oral glucose tolerance test (P < 0.001) and with insulin resistance (HOMA-IR: P = 1.7 × 10?13). Higher PAPP-A was also linked to improved insulin secretion relative to insulin sensitivity (insulin disposition index: P = 6.5 × 10??). These findings suggest that the relationship between early pregnancy PAPP-A levels and later glucose regulation and blood pressure may be mediated by changes in insulin sensitivity and secretion, offering insight into the potential metabolic role of PAPP-A in pregnancy.	Risk factor	GDM
36837599	Gestational diabetes mellitus (GDM) is a prevalent pregnancy complication and a leading cause of adverse maternal and fetal outcomes. Early diagnosis is crucial, yet current clinical guidelines recommend universal screening with a 75 g oral glucose tolerance test at 24–28 weeks of gestation, often leading to delayed detection and intervention. GDM is closely linked to insulin resistance and endothelial dysfunction, processes that are significantly influenced by placental-derived factors. Recent studies highlight the roles of placental growth factor (PlGF) and pregnancy-associated plasma protein-A (PAPP-A) in modulating insulin sensitivity and vascular function. PlGF is essential for placental vascularization, while PAPP-A facilitates the cleavage of insulin-like growth factor binding protein-4, impacting glucose metabolism. These biomarkers are already utilized for early detection of pregnancy complications such as preeclampsia and fetal aneuploidies, and emerging evidence suggests their potential utility in predicting GDM. However, inconsistencies across studies necessitate further research to validate their clinical applicability for early GDM screening.	Mechanism	Insulin resistance
39175575	This study investigated the associations between first-trimester biomarkers and maternal characteristics in predicting gestational diabetes mellitus (GDM) in a cohort of 1452 Chinese pregnant women, of whom 96 developed GDM. The levels of pregnancy-associated plasma protein A (PAPP-A) and placental growth factor (PLGF) were significantly lower in the GDM group compared to the non-GDM group (PAPP-A: 5.01 vs. 5.73 IU/L, P < 0.001; PLGF: 39.88 vs. 41.81 pg/mL, P = 0.044). A predictive model incorporating maternal characteristics and biomarkers demonstrated good discriminatory ability, with an area under the ROC curve of 0.73 (95% CI: 0.68–0.79, P < 0.001). Logistic regression revealed that higher pregestational BMI, previous GDM history, family history of diabetes, higher mean arterial pressure, and lower PAPP-A levels were independently associated with GDM. The Hosmer-Lemeshow test confirmed excellent model fit (P = 0.929). The study concludes that combining first-trimester biomarkers with maternal characteristics could enhance early risk prediction and aid in identifying women at high risk of developing GDM.	Risk factor	GDM
26362726	This study investigated whether first-trimester biochemical markers of placentation, including pregnancy-associated plasma protein-A (PAPP-A) and placental growth factor (PLGF), are altered in women who develop gestational diabetes mellitus (GDM) and their potential role in improving GDM screening. Among 31,225 singleton pregnancies, including 787 GDM cases, PAPP-A levels were slightly reduced (median 0.949 MoM, p=0.0009), and PLGF levels were slightly increased (median 1.053 MoM, p=0.004) in the GDM group compared to unaffected pregnancies. However, adding PAPP-A and PLGF levels to maternal factors did not improve the performance of GDM screening based on receiver operating characteristic (ROC) curves. The study concludes that first-trimester PAPP-A and PLGF are not useful markers for GDM screening.	Risk factor	GDM
27155776	Initially identified as a placental protein highly abundant in the circulation of pregnant women, pregnancy-associated plasma protein-A (PAPP-A) is now recognized as a widely expressed metalloproteinase with a crucial role in insulin-like growth factor (IGF) regulation. PAPP-A specifically cleaves IGF binding proteins (IGFBPs) -2, -4, and -5, thereby modulating IGF bioavailability at the cellular level. Anchored to glycosaminoglycans on cell surfaces, PAPP-A functions as a growth-promoting enzyme, facilitating localized IGF activation. Its activity is tightly regulated by inhibitors such as pro-MBP and stanniocalcin-2 (STC2), which form covalent complexes with PAPP-A to suppress its proteolytic function. Among its substrates, IGFBP-4 is considered the principal mediator of IGF bioavailability. PAPP-A regulation involves multiple layers, including gene transcription, competitive IGF sequestration by other IGFBPs, and direct proteolytic inhibition. Given its role in IGF signaling, PAPP-A presents a promising therapeutic target for conditions driven by dysregulated IGF activity, with highly specific inhibition strategies offering potential for precision medicine applications.	Mechanism	Insulin resistance
37033400	This study examined the relationship and predictive value of first-trimester pregnancy-associated plasma protein A (PAPP-A), maternal factors, and biochemical markers in predicting gestational diabetes mellitus (GDM) among 4872 pregnant women in southern China. GDM was diagnosed in 15.39% of participants (750 women). Low PAPP-A levels were identified as an independent risk factor for GDM, along with age, pre-gestational BMI, gestational weight gain, previous GDM history, family history of diabetes, fasting plasma glucose (FPG), triglycerides (TG), low-density lipoproteins (LDL), and total cholesterol (TC). However, the predictive ability of PAPP-A alone was limited (AUC = 0.56, 95% CI: 0.53-0.58). When combined with maternal factors and biochemical markers, the model's predictive value improved significantly (AUC = 0.70, 95% CI: 0.68-0.72, P < 0.001). The study concludes that while low PAPP-A levels are an independent risk factor for GDM, their predictive value is enhanced when combined with other clinical and biochemical factors.	Risk factor	GDM