# Medical optimization & management of pregnancies with overt type 2 diabetes (MOMPOD) - Admin Supplement 3: Effect of Overt Type 2 Diabetes and Metformin Treatment on Placental Transport Proteins

> **NIH NIH R01** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2020 · $165,167

## Abstract

PROJECT SUMMARY/ABSTRACT
Over 100,000 pregnant women with overt type 2 diabetes (T2DM) give birth in the United States every year
and this number is expected to double by 2030. Medical treatment of T2DM in pregnancy is generally restricted
to insulin because data on the safety and efficacy of oral hypoglycemic agents (e.g., metformin) for T2DM are
limited. However, over one-third of infants born to women with T2DM experience an adverse outcome, such as
premature delivery, large-for-gestational age (LGA), hypoglycemia, hyperbilirubinemia, or birth trauma,
suggesting that current treatment regimens fall short of optimizing outcomes. The lack of clinical trials enrolling
pregnant women limits our knowledge about the critical role of the placenta in pregnancy outcomes. The
placenta is a temporary organ in pregnancy that supplies the fetus with nutrition, protects the fetus from toxins,
and eliminates waste from the fetus. This barrier function is maintained by placental drug transport proteins
(e.g., MultiDrug Resistance protein, MDR1; Breast Cancer Resistance Protein, BCRP; Organic Anion
Transporting Polypeptide, OATP2A1 and OATP2B1; Organic Cation Transporter, OCT3). In addition, glucose
transporters (GLUT) are responsible for the transplacental movement of glucose, which is essential in T2DM
pregnant women. These placental transport proteins are not well-characterized in pregnant women with T2DM
treated with insulin alone or with insulin plus metformin. The long-term goal in the parent award is to optimize
maternal and infant outcomes in T2DM complicating pregnancy with metformin treatment. The goal in this
administrative supplement is to measure T2DM- and metformin-mediated effects on placental transport
proteins. The central hypothesis is that key placental drug and GLUT transport proteins are upregulated in
women with T2DM treated with insulin alone compared to healthy women, which could lead to increased
exposure of the fetus to medications and a higher supply of glucose to the fetus. Importantly, we hypothesize
that metformin treatment of pregnant women with T2DM will result in downregulation of key placental drug and
GLUT transport proteins to normal levels. We will test these hypotheses by quantitative targeted proteomic
analyses of some of the placental tissue collected for the parent study. We propose the following specific aims:
1) Quantify protein levels of key placental transporters in pregnant women with and without T2DM, and 2)
Determine the effect of metformin on protein levels of key placental transporters. Completion of these studies
will provide critical information on the role of placental transport proteins in drug safety and efficacy in pregnant
women.

## Key facts

- **NIH application ID:** 10176988
- **Project number:** 3R01HD086139-04S1
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** DIANE C BERRY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $165,167
- **Award type:** 3
- **Project period:** 2016-09-23 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10176988

## Citation

> US National Institutes of Health, RePORTER application 10176988, Medical optimization & management of pregnancies with overt type 2 diabetes (MOMPOD) - Admin Supplement 3: Effect of Overt Type 2 Diabetes and Metformin Treatment on Placental Transport Proteins (3R01HD086139-04S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10176988. Licensed CC0.

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