# Determinants of alpha-aminoadipic acid (2-AAA) and relationship to diabetes

> **NIH NIH R01** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2021 · $465,580

## Abstract

Diabetes is a major global health concern, associated with significantly increased mortality and high incidence
of co-morbidities. The lysine-derived metabolite α-aminoadipic acid (2-AAA) was identified as a novel predictor
of diabetes development in Framingham Heart Study (FHS) participants and validation samples (N~2,000). In
these subjects, increased plasma 2-AAA in healthy individuals was associated with increased future risk of
diabetes (12-year follow-up), identifying at-risk individuals even after adjustment for known risk factors. Several
subsequent studies have confirmed the association between 2-AAA and diabetes, but the mechanisms remain
unknown. Preliminary data support a role for 2-AAA in insulin secretion and diabetes pathophysiology, and
suggest genetic determinants of 2-AAA relate to diabetes and diabetic complications. However it is not yet
clear whether 2-AAA is itself causal in diabetes development, or is a biomarker for altered metabolic
processes. Many questions remain as to mechanisms of action. In this proposal, we will examine the
determinants of 2-AAA, by studying lysine-2-AAA metabolism in subjects with extreme levels of 2-AAA before
and after dietary intervention (Aim 1); identify the genetic predictors of 2-AAA (Aim 2); and examine the genetic
architecture of 2-AAA and disease (Aim 3). These aims will advance our long-term research objective, to
understand determinants of 2-AAA, and establish utility of 2-AAA and related pathways as a novel therapeutic
target in diabetes.

## Key facts

- **NIH application ID:** 10164763
- **Project number:** 5R01DK117144-04
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** Jane F Ferguson
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $465,580
- **Award type:** 5
- **Project period:** 2018-08-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10164763

## Citation

> US National Institutes of Health, RePORTER application 10164763, Determinants of alpha-aminoadipic acid (2-AAA) and relationship to diabetes (5R01DK117144-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10164763. Licensed CC0.

---

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