# Islet Autoimmunity Reversion as a Model of T1D Resiliency

> **NIH NIH R21** · UNIVERSITY OF COLORADO DENVER · 2020 · $155,500

## Abstract

Project Summary
Type 1 diabetes (T1D) is a substantial public health burden because affected individuals require lifelong insulin
treatment and are at high risk for secondary comorbidities. While the etiology of T1D is not fully understood, it
is generally accepted that both the development of islet autoimmunity and progression from islet autoimmunity
to clinical T1D involves a complex interplay of genetic and environmental factors. Epigenetic modifications,
including DNA methylation, may be markers of the effects of environmental exposures on gene expression and
are likely to be crucial mechanisms involved in gene regulation. The development of preventive public health
interventions is dependent on our ability to understand these mechanisms. The Diabetes Autoimmunity Study
in the Young (DAISY) is a cohort of 2,547 children at high risk for T1D who have been followed for the
appearance of autoimmunity and progression to T1D. We propose to study epigenetic and gene expression
biomarkers in DAISY, in order to elucidate why some individuals with islet autoimmunity develop T1D
(progressors), others continue to produce antibodies but do not develop T1D (maintainers), and more
importantly, why some individuals revert to being autoantibody negative and do not progress to T1D
(reverters). We believe the reverters represent a resilient group that may hold key information about the
epigenetic and gene expression mechanisms that minimize risk of progression to T1D. We propose to follow
211 individuals who developed islet autoimmunity during DAISY follow-up, and 1) identify DNA methylation
patterns before and after the onset of islet autoimmunity among reverters (n=52), progressors (n=87), and
maintainers (n=72); and 2) identify gene expression changes after the onset of islet autoimmunity among
reverters, maintainers, and progressors. Pathway analyses will then allow us to integrate methylation and
expression patterns identified in the two aims and will inform our understanding of the relevant biology.
Together, these aims will close gaps in our understanding of the islet autoimmune disease process through the
identification of epigenetic and gene expression patterns that lead to islet autoantibody reversion. This
research foundation will facilitate future studies aimed at identifying the upstream environmental influences on
reversion. Using islet autoantibody reversion as a model of disease resolution, the proposed study has
important implications for the development of public health interventions that will manipulate these
environmental exposures and prevent progression from islet autoimmunity to clinical T1D.

## Key facts

- **NIH application ID:** 9881244
- **Project number:** 5R21AI142483-02
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** JILL M NORRIS
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $155,500
- **Award type:** 5
- **Project period:** 2019-03-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9881244

## Citation

> US National Institutes of Health, RePORTER application 9881244, Islet Autoimmunity Reversion as a Model of T1D Resiliency (5R21AI142483-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9881244. Licensed CC0.

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