A Novel Early Pregnancy Risk Prediction Model for Gestational Diabetes Mellitus

Abstract

Introduction: Accurate early risk prediction for gestational diabetes mellitus (GDM) would target intervention and prevention in women at the highest risk. We evaluated novel biomarker predictors to develop a first-trimester risk prediction model in a large multiethnic cohort. Methods: Maternal clinical, aneuploidy and pre-eclampsia screening markers (PAPP-A, free hCGβ, mean arterial pressure, uterine artery pulsatility index) were measured prospectively at 11–13⁺⁶ weeks’ gestation in 980 women (248 with GDM; 732 controls). Nonfasting glucose, lipids, adiponectin, leptin, lipocalin-2, and plasminogen activator inhibitor-2 were measured on banked serum. The relationship between marker multiples-of-the-median and GDM was examined with multivariate regression. Model predictive performance for early (< 24 weeks’ gestation) and overall GDM diagnosis was evaluated by receiver operating characteristic curves. Results: Glucose, triglycerides, leptin, and lipocalin-2 were higher, while adiponectin was lower, in GDM (p < 0.05). Lipocalin-2 performed best in Caucasians, and triglycerides in South Asians with GDM. Family history of diabetes, previous GDM, South/East Asian ethnicity, parity, BMI, PAPP-A, triglycerides, and lipocalin-2 were significant independent GDM predictors (all p < 0.01), achieving an area under the curve of 0.91 (95% confidence interval [CI] 0.89–0.94) overall, and 0.93 (95% CI 0.89–0.96) for early GDM, in a combined multivariate prediction model. Conclusions: A first-trimester risk prediction model, which incorporates novel maternal lipid markers, accurately identifies women at high risk of GDM, including early GDM.

Pregnancy‐associated plasma protein‐A2 levels are increased in early‐pregnancy gestational diabetes: a novel biomarker for early risk estimation

“…PAPP-A2 might also be able to predict GD development in late pregnancy, although any such association would need to be further investigated in prospective studies. The increased risk of adverse outcomes associated with GD coupled with the frequently late diagnosis of the conditions has given rise to numerous studies focused on identifying early-pregnancy biomarkers for GD [22,24,28,29]. PAPP-A2 levels in early pregnancy may also merit investigation as a potential pre-screening biomarker to identify low-risk women who can be spared from performing the OGTT.…”

Elevated Midtrimester Triglycerides as a Biomarker for Postpartum Hyperglycemia in Gestational Diabetes

“…Further, prospective studies showed that the TG level was an independent risk factor for developing diabetes in middle-aged women [11,12]. In a prospective case-control study, higher TG levels were observed at 11-14 weeks of gestation in women with GDM, and multivariate regression analysis indicated that TG levels were a significant predictor of a subsequent diagnosis of GDM [13]. However, fewer studies have characterized the relationship between TG levels during pregnancy and the risk of postpartum AGM in GDM patients.…”

Glycosylated fibronectin as a first trimester marker for gestational diabetes

“…Adiponectin is another glycoprotein that has been associated with GDM [22]. Adiponectin is a protein hormone that has a role in regulating glucose levels and fatty acid metabolism.…”