Camille E. Powe, MD, a physician investigator in the Division of Endocrinology, Department of Medicine and Department of Obstetrics and Gynecology at Massachusetts General Hospital and an associate professor at Harvard Medical School, and a team of investigators in both Medicine and Obstetrics and Gynecology at MGH published the results of a new study in Nature Medicine, Placental IGFBP1 Levels During Early Pregnancy and the Risk of Insulin Resistance and Gestational Diabetes.

What Question Did You Set Out to Answer?

Insulin resistance is a hallmark of normal physiology in late pregnancy and also underlies gestational diabetes mellitus (GDM).

In this study, we set to answer the question: What are the proteins secreted by the placenta that impact maternal insulin resistance during pregnancy?

What Approach Did You Use?

We performed whole-transcriptome RNA-Seq analysis on 434 human placental samples collected from a pregnancy cohort that performed oral glucose tolerance tests at 24-32 weeks of gestation.

We looked for the strongest associations between placental gene expression and maternal insulin resistance.

We then measured our top hit in plasma samples from three pregnancy cohorts (including two based at MGH).

What Did You Find?

We identified IGFBP1 as the placental transcript with the strongest association with insulin resistance. Low placental and circulating IGFBP1 levels were strongly associated with maternal insulin resistance. Early pregnancy circulating levels of IGFBP1 predicted later diagnosis of gestational diabetes.

A GDM subtype characterized by high insulin resistance and increased risk of adverse outcomes had low IGFBP1 levels throughout pregnancy.

What Are the Clinical Implications?

Our work sets the stage for novel approaches to modulate insulin resistance in pregnancy and prevent or treat GDM. Given that IGFBP1 deficiency was strongly associated with a particular high-risk GDM subtype, it may be a precision biomarker that will set the stage for future GDM precision therapeutics.

What Are the Next Steps?

We are planning to study other proteins that are related to IGFBP1 including insulin-like growth factor 2 and placental growth hormone in human pregnancy and gestational diabetes.

Paper Cited:

Hivert, M. F., White, F., Allard, C., James, K., Majid, S., Aguet, F., Ardlie, K. G., Florez, J. C., Edlow, A. G., Bouchard, L., Jacques, P. É., Karumanchi, S. A., & Powe, C. E. (2024). Placental IGFBP1 levels during early pregnancy and the risk of insulin resistance and gestational diabetes. Nature medicine, 10.1038/s41591-024-02936-5. Advance online publication.

About the Massachusetts General Hospital

Massachusetts General Hospital, founded in 1811, is the original and largest teaching hospital of Harvard Medical School. The Mass General Research Institute conducts the largest hospital-based research program in the nation, with annual research operations of more than $1 billion and comprises more than 9,500 researchers working across more than 30 institutes, centers and departments. MGH is a founding member of the Mass General Brigham healthcare system.