# Estrogen-Mediated Impairments of Vascular Health in Diabetes

> **NIH NIH R01** · AUGUSTA UNIVERSITY · 2022 · $644,470

## Abstract

Diabetes has recently been referred to as “the epidemic of the 21st century” and contributes to a substantial
economic burden on the United States public health. Cardiovascular disease (CVD) accounts for 80% of
morbidity and mortality in diabetes, however, women with type 1 diabetes have a substantially greater risk for
CVD compared to men with diabetes. A critical barrier to understanding this sexual dimorphism in CVD risk is
the lack of knowledge regarding the role of estrogen (E2) on vascular health in diabetic women. Oxidative
stress is a common phenotype in patients with diabetes and is routinley associated with hyperglycemia and
diabetic complications. In addition, sirtuin1 (Sirt1) has been proposed to play a fundemental role in regulating
nitric oxide (NO) bioavailability, and is lower in patients with diabetes. Accordingly, our central hypothesis is
that an elevated concentration of E2 in women with type 1 diabetes contributes to a reduction in NO-
bioavailability and vascular health through two separate pathways; an increase in oxidative stress and a
decrease in circulating Sirt1. In support, compelling preliminary data indicate that the natural increase in
vascular health from menses to the late follicular phase of the menstrual cycle is lost in the presence of type 1
diabetes. In addition, this loss is associated with increased oxidative stress and lower Sirt1. To investigate the
impact of E2 on vascular health in women with diabetes, we propose to utilize the menstrual cycle as a natural
and novel method to investigate changes in sex-steroid hormones. We will perform a comprehensive
assessment of vascular health in men and at two different times during the menstrual cycle in premenopausal
women with and without type 1 diabetes: 1) during the menses (low estrogen/low progesterone) and 2) late
follicular (elevated estrogen/low progesterone) phases. In addition, we will employ two novel treatments that
may mitigate future CVD risk in patients with diabetes. Findings will not only contribute to understanding the
molecular mechanisms associated with sex disparities of CVD risk in diabetes, they may identify novel
therapeutic approaches to decrease estrogen-mediated vascular dysfunction in women with diabetes. This
proposal demonstrates the true model of translational research and represents a major shift in the approach
to understanding the sexual dimorphism of CVD risk in patients with type 1 diabetes.

## Key facts

- **NIH application ID:** 10324568
- **Project number:** 5R01HL137087-05
- **Recipient organization:** AUGUSTA UNIVERSITY
- **Principal Investigator:** Ryan A Harris
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $644,470
- **Award type:** 5
- **Project period:** 2018-02-01 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10324568

## Citation

> US National Institutes of Health, RePORTER application 10324568, Estrogen-Mediated Impairments of Vascular Health in Diabetes (5R01HL137087-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10324568. Licensed CC0.

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