# Acute effects of hyperglycemia on heart and skeletal muscle microvasculature

> **NIH NIH R01** · UNIVERSITY OF VIRGINIA · 2020 · $652,389

## Abstract

Abstract
This revised application proposes 2 small, single-center, mechanistic clinical trials. Our overarching
hypothesis is that acute hyperglycemia and/or glucose variability (GV) negatively impact microvascular
perfusion in cardiac (CM) and skeletal muscle (SM) and this could in part account for the strongly
negative impact of acute hyperglycemia on clinical outcomes in acute coronary syndromes. While
chronic hyperglycemia provokes functional and anatomic diabetic microvascular disease, and acute
hyperglycemia can raise plasma endothelial cell (EC) stress “biomarkers” concentrations, the functional
microvascular consequences, if any, of acute hyperglycemia and GV are unknown. Microvascular
perfusion is a critical determinant of nutrient and oxygen delivery to SM and CM and is adversely
affected by insulin resistance. Using our considerable experience with contrast enhanced ultrasound
(CEU) measurement of microvascular perfusion in complex metabolic studies we will test in AIM 1 the
effect of acute hyperglycemia on basal and insulin-mediated microvascular perfusion in CM and SM of
healthy humans. In AIM 2 we will quantify microvascular perfusion at baseline, in response to insulin
and in response to meal ingestion in patients with T2DM. We will further test in T2DM whether
decreasing GV and post-prandial hyperglycemic excursions with an SGLT-2 inhibitor (vs placebo) for 12
weeks enhances CM microvascular perfusion, either at baseline, or in response to acute
hyperinsulinemia or to meal ingestion. Aim 3 will identify whether the behavior of the microvasculature
seen in Aims 1 and 2, is matched by the responses of large arteries to either hyperglycemic,
hyperinsulinemic or meal stimuli or drug treatment, measured by flow-mediated dilation (FMD), pulse
wave velocity (PWV), augmentation index (AI), or post-ischemic flow velocity (PIFV). Completion of
these studies will provide unprecedented mechanistic information on the effects of hyperglycemia, GV,
T2DM and T2DM treatment on CM and SM microvascular function.

## Key facts

- **NIH application ID:** 9838280
- **Project number:** 5R01HL142250-02
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** EUGENE Joseph BARRETT
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $652,389
- **Award type:** 5
- **Project period:** 2018-12-15 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9838280

## Citation

> US National Institutes of Health, RePORTER application 9838280, Acute effects of hyperglycemia on heart and skeletal muscle microvasculature (5R01HL142250-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9838280. Licensed CC0.

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