# The role of alpha-aminoadipic acid (2-AAA) in residual CVD risk in T2D

> **NIH NIH R21** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2024 · $131,250

## Abstract

PROJECT SUMMARY / ABSTRACT
Cardiovascular disease (CVD) kills 1 in 3 individuals and affects >2 in 3 individuals diagnosed with type 2
diabetes (T2D). Despite optimization of available therapies, CVD remains the leading cause of mortality in
T2D, highlighting the considerable burden of residual risk. Achieving further reduction in CVD morbidity and
mortality in people with T2D requires advancing promising candidate mediators of residual risk. The metabolite
α-aminoadipic acid (2-AAA) predicts the development of both T2D and atherosclerosis, independent of other
known risk factors. This may represent a novel independent risk mechanism for the development of CVD,
particularly among individuals with T2D. Our overarching hypothesis is that 2-AAA is an independent mediator
of CVD risk among individuals with T2D. In the Action to Control Cardiovascular Risk in Diabetes (ACCORD)
trial, both intensive glucose-lowering therapy, and intensive lipid management failed to attenuate CVD risk in
individuals with T2D, and indeed showed evidence of increased risk. We hypothesize this was, in part, due to
residual risk factors, including 2-AAA. We propose an analysis of 2-AAA in existing plasma samples from
N=1,757 participants of the ACCORD study lipid treatment arms, with the following aims: 1) Define the effects
of lipid- and glucose-lowering therapies on plasma 2-AAA, and address whether plasma 2-AAA changes in
response to lipid-targeted therapy or intensive glycemic management. 2) Address the hypothesis that plasma
2-AAA is a CVD risk mechanism among individuals who experienced events despite optimal therapy.
Successful completion of the aims will determine whether 2-AAA levels are impacted by lipid and glycemic
management in T2D and establish whether elevated 2-AAA associates with CVD risk. This will provide
important information on the utility of 2-AAA as a biomarker of risk and plausibility as a novel therapeutic
target, allowing us to refine specific hypotheses to be probed in future studies. These aims represent novel and
important questions and use existing NHLBI-supported sample and data resources to add considerable
scientific value and address a key knowledge gap.

## Key facts

- **NIH application ID:** 10888269
- **Project number:** 5R21HL169186-02
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** Jane F Ferguson
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $131,250
- **Award type:** 5
- **Project period:** 2023-07-15 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10888269

## Citation

> US National Institutes of Health, RePORTER application 10888269, The role of alpha-aminoadipic acid (2-AAA) in residual CVD risk in T2D (5R21HL169186-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10888269. Licensed CC0.

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