UMMS Affiliation

Senior Scholars Program; School of Medicine, Clinical Translational Research Pathway; Department of Obstetrics and Gynecology; Department of Quantitative Health Sciences; Graduate School of Biomedical Sciences; Program in Molecular Medicine; Department of Pediatrics

Faculty Mentor

Tiffany A. Moore Simas; Silvia Corvera

Publication Date


Document Type



Clinical Epidemiology | Endocrinology, Diabetes, and Metabolism | Female Urogenital Diseases and Pregnancy Complications | Maternal and Child Health | Obstetrics and Gynecology | Women's Health


Background: Gestational diabetes (GDM) is a common pregnancy complication with significant cardiometabolic consequences for mothers and offspring. Previous research from our group suggests that adipose tissue IGFBP-5 and its unique metalloprotease PAPP-A (Pregnancy Associated Plasma Protein-A) may play mechanistic roles in GDM development by regulating functional IGF-1 levels and lipid storage and metabolism.

Aim: To examine the relationship between circulating PAPP-A levels and GDM development. We hypothesized that high first trimester PAPP-A levels would be associated with decreased GDM risk.

Methods: A retrospective cohort of women delivering singleton gestations at UMass Memorial Healthcare (2009, 2010, 2014, 2015) was assembled by abstracting electronic medical records. PAPP-A was measured in first trimester (11-14 weeks), and reported as quartiles of multiples of the mean (MoM) based on gestational age and adjusted for maternal weight and race/ethnicity. GDM diagnosis based on standard 2-step protocol (~24-28 weeks; failed 50g 1hr glucola screen then ≥2 abnormal values per Carpenter-Coustan criteria on 100g 3hr glucose tolerance test). Crude and multivariable-adjusted logistic regression models estimated the association between PAPP-A MoM quartiles and GDM.

Results: Women (N=1,251) were 29.7 (SD:5.7) years old and 12.5 (SD:0.6) weeks gestation at PAPP-A measurement. 7.6% (n=95) developed GDM. Median PAPP-A MoM were 0.7 (inter-quartile range [IQR]=0.5-1.0) among women with GDM and 0.9 (IQR=0.6-1.3) among controls; 39% versus 23% were in the 1st quartile, respectively. After adjusting for pre-pregnancy body mass index, nuchal translucency, crown rump length, smoking status, and parity, women with PAPP-A MoM in 2nd, 3rd, and 4th quartiles had 52% (OR=0.48, 95%CI=0.26-0.88), 45% (OR=0.55, 95%CI=0.30-0.99) and 73% (OR=0.27, 95%CI=0.13-0.53) lower odds of GDM compared to women in the 1st quartile.

Conclusion: Higher PAPP-A MoM levels were associated with lower GDM risk. Future studies will assess whether higher PAPP-A levels are associated with enhanced IGF-1 signaling and improved pregnancy metabolic homeostasis.


Pregnancy Associated Plasma Protein, PAPP-A, Gestional diabetes mellitus, IGFBP-5, IGF-1

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Copyright is held by the author(s), with all rights reserved.

DOI of Published Version


Journal/Book/Conference Title

2016 Senior Scholars Program Poster Presentation Day


Aylin Sert participated in this study as a medical student as part of the Senior Scholars research program at the University of Massachusetts Medical School. This poster was presented on Senior Scholars Program Poster Presentation Day at the University of Massachusetts Medical School, Worcester, MA, on April 27, 2016.

Work funded by the Worcester Foundation for Biomedical Research. Support for Dr. Waring provided by NIH grant KL2TR000160.