# Preventing hypoglycemia-mediated arrhythmias and cardiac damage in type 1 diabetes

> **NIH NIH R56** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2022 · $370,563

## Abstract

Project Summary/Abstract
Hypoglycemia as a complication in the treatment of diabetes is associated with up to 10% of all
deaths in type 1 diabetes. Altered autonomic function in diabetes and recurrent hypoglycemia can
increase cardiovascular mortality. Hypoglycemia induced mortality is hypothesized to occur
through two separate mechanisms: 1) acute hypoglycemia mediated cardiac arrhythmias and 2)
recurrent hypoglycemia induced changes in autonomic function that increase risk of major
cardiovascular events such as myocardial infarction (MI). Preliminary results revealed that 1) rats
with type 1 diabetes have increased mortality associated with increased parasympathetic tone,
and 2) recurrent hypoglycemia increases damage from an MI. Aim 1 will utilize in vivo studies in
rats and transgenic mice to test blockade of the parasympathetic nervous system and target
downstream pathways through the cardiac ryanodine receptor to reduce hypoglycemia-induced
cardiac arrhythmias. Additionally, ex vivo heart perfusions will be used to test the involvement of
parasympathetic nervous system mediated arrhythmias via the ryanodine receptor. Aim 2 will
address the mechanisms of how recurrent hypoglycemia predisposes to worse outcome from a
subsequent MI by utilizing in vivo rats and transgenic mice. Rodents will undergo an
experimentally induced myocardial infarction after 3 days of recurrent hypoglycemia. The role of
the parasympathetic nervous system and ryanodine receptors will be tested by pharmacological
blockade and genetic disruption (transgenic mice), respectively. Overall, it is expected that the
increased parasympathetic tone in type 1 diabetes mediates fatal cardiac arrhythmias during
acute severe hypoglycemia, and recurrent hypoglycemia increases parasympathetic tone leading
to increased damage from a subsequent MI. Additionally, mechanistic studies will reveal that
ryanodine receptors are the downstream mediators of both arrhythmias and damage from an MI.
Results from both studies have clinical implications for improving targeting strategies to prevent
cardiovascular mortality associated with hypoglycemia in people with diabetes.

## Key facts

- **NIH application ID:** 10687405
- **Project number:** 1R56HL160835-01
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** Candace M Reno
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $370,563
- **Award type:** 1
- **Project period:** 2022-09-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10687405

## Citation

> US National Institutes of Health, RePORTER application 10687405, Preventing hypoglycemia-mediated arrhythmias and cardiac damage in type 1 diabetes (1R56HL160835-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10687405. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*