# Diabetes Induced Disc Degeneration and Prevention

> **NIH NIH R01** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2020 · $538,879

## Abstract

PROJECT SUMMARY
Low back pain is a global health epidemic commonly associated with painful intervertebral disc (IVD)
degeneration (IDD) and its increasing incidence involves economic costs over $100 billion. Research into
mechanisms and novel treatments for IDD is a major research priority. Important recent studies provide
evidence that type 2 diabetes mellitus (T2DM) and diet can increase painful IDD and spine surgery
complications. Establishing a mechanistic relationship between T2DM and IDD may result in novel therapies
for T2DM patients and all IDD patients. Our broad goal is to characterize and improve understanding of
mechanisms for T2DM- and diet-induced IDD and to develop safe and effective treatments to maintain a
healthy spine and to slow the progression of painful IDD. Little research investigates relationships between
diet, T2DM, and IDD and our preliminary data provide among the first causal relationships. Our data suggest
that DM-induced IDD involves ectopic calcifications and that reducing the accumulation of advanced glycation
endproducts (AGEs) and pro-inflammatory cytokines may help mitigate some of the observed IDD.
The proposed studies test our overall hypothesis that dietary ingestion of AGEs and T2DM induces
pathological and age-accelerated IDD due to AGE accumulation systemically and also in spinal tissues leading
to increased pro-inflammatory cytokines, crosslinking, and ectopic calcifications of IVDs and endplates (EPs).
We believe these ectopic calcifications and AGE associated crosslinks create stress concentrations and brittle
material behaviors that are partially responsible for the microfractures, fissures, and fibrotic healing attempts
commonly observed in painful human IDD in both DM and non-DM patients.
Aim 1 will test this hypothetical model using T2DM, high-AGE ingestion, and Receptor for AGE (RAGE)
knockout mice to investigate the roles of AGEs and pro-inflammatory cytokines in contributing to IDD and
ectopic calcifications. Aim 2 investigates AGE and hyperglycemia effects on IVD organs in order to distinguish
between systemic and spine tissue level effects while identifying pathways for IDD and ectopic calcification.
Aim 3 will test for direct relationships between AGEs, IDD and ectopic calcifications in human IVDs and cells
from autopsy.
This project is significant because of the tremendous health burden of IDD, the new insights that will be gained
regarding causes and treatment of IDD, and the complementary mouse and human studies. The approach is
innovative because there are remarkably few studies relating T2DM and IDD, and our novel hypothetical model
provides a framework that may impact IDD treatments for both T2DM and non-T2DM patients. Successful
completion of this project will provide new insights into the relationships between systemic health and IDD in
mice and humans with investigations that may result in novel treatments relevant to all IDD patients.

## Key facts

- **NIH application ID:** 9936369
- **Project number:** 5R01AR069315-05
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** James C. Iatridis
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $538,879
- **Award type:** 5
- **Project period:** 2016-06-10 → 2021-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9936369

## Citation

> US National Institutes of Health, RePORTER application 9936369, Diabetes Induced Disc Degeneration and Prevention (5R01AR069315-05). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9936369. Licensed CC0.

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