# Epigenetic changes and methylglyoxal adducts induced by metabolic regulation in patients with type 1 diabetes that develop complications

> **NIH NIH R21** · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · 2020 · $220,000

## Abstract

Abstract.
The incidence of type 1 diabetes (T1D) has increased as much as 3-4% annually in recent decades. Furthermore,
patients with T1D are vulnerable to developing micro- and macrovascular complications, the leading cause of
death in this population. To reduce mortality in patients with T1D, there is a critical need to identify susceptible
populations prior to the onset of complications so that preventative therapies can be implemented. To do this,
we must identify the specific cellular factors involved in disease etiology. A promising source of these mediatory
cellular factors is poor glycemic control, which is significantly associated with complications. To identify and
characterize these factors, we, along with our Co-Investigator Dr. Rama Natarajan, have accessed samples from
an established, longitudinal clinical study investigating the role of glycemic control on complication progression.
Analysis of samples collected pre-complication development revealed specific metabolites and epigenetic
signatures associated with poor glycemic control; we hypothesize that these may have utility as predictive
biomarkers of complications and will explore this in Aim 1. Analysis of samples collected post-complication
development revealed that these same metabolic and epigenetic markers remained elevated over time, even
after strong glycemic control was established. We hypothesize that these markers are indicative of long-term
poor glycemic control and will explore this in Aim 2. Our goals for Aims 1 and 2 are to build a predictive model
for complications and determine the extent to which metabolic and epigenetic markers are associated with poor
glycemic control. Beyond the utility of metabolic and epigenetic markers for predicting and monitoring disease
progression, we discovered that they influence specific cellular pathways such as glycolysis, lipolysis,
proteolysis, and inflammation. We hypothesize that interrelated components of these pathways play a role in
complication etiology and will explore this in Aim 3. Our goal in Aim 3 is to establish the foundational information
to explore the role of specific pathway components in complication etiology and progression. The work in this
proposal is the first example of combined analysis of metabolic and epigenetic markers in complication etiology.

## Key facts

- **NIH application ID:** 10110519
- **Project number:** 1R21DK127285-01
- **Recipient organization:** BECKMAN RESEARCH INSTITUTE/CITY OF HOPE
- **Principal Investigator:** Sarah C. Shuck
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $220,000
- **Award type:** 1
- **Project period:** 2020-09-15 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10110519

## Citation

> US National Institutes of Health, RePORTER application 10110519, Epigenetic changes and methylglyoxal adducts induced by metabolic regulation in patients with type 1 diabetes that develop complications (1R21DK127285-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10110519. Licensed CC0.

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