# Metabolomics of obstructive sleep apnea

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2021 · $1,119,884

## Abstract

ABSTRACT
Obstructive sleep apnea (OSA) is a common disorder that is increasing in prevalence. OSA is known to have
heterogeneous pathophysiology, with different subtypes, clinical consequence, and treatment
responses among individual patients. A recent publication from the Sleep Research Society and National
Heart, Lung and Blood Institute highlighted the potential clinical utility of quantitative OSA biomarkers identified
using unbiased “omics” approaches.There are currently no established quantitative biomarkers that can be
used to understand heterogeneity or inform clinical practice. Thus, the present study proposes to utilize
metabolomic methods which reflect dynamic responses to hypoxia to identify metabolite signatures in OSA. The
overarching hypothesis motivating this proposal is that blood-borne metabolite signatures that result
from metabolic insults caused by the cyclical intermittent hypoxia, recurrent arousals and lack of deep
sleep characteristic of OSA will provide a quantitative biomarker to better understand disease
heterogeneity and inform clinical care. In Aim 1, we will differentiate OSA from non-OSA leveraging well-
phenotyped samples carefully chosen from a large pool of patients from existing research projects (Aim 1A).
Our preliminary suggest clear metabolite differences between patients with OSA and controls. Furthermore, we
will leverage these existing samples to determine if established OSA symptom subtypes of disturbed sleep (e.g.,
insomnia), excessive sleepiness, and minimally symptomatic have distinct metabolomic profiles (Aim 1B) which
will provide insights into identified differences in cardiovascular risk and support a precision medicine approach.
These analyses utilizing banked samples are supported by a carefully designed prospective study of OSA
patients before and after positive airway pressure (PAP) treatment in Aim 2. The study is designed to control for
bias related to site-specific variance in sampling and data collection using state-of-the-art causal modeling
techniques. As part of the prospective study, we will perform complementary analyses supporting metabolomic
signatures (Aim 2A), determine a metabolomic signature that correlates with hours and days of PAP usage (Aim
2B) and evaluate whether the metabolomic changes with PAP treatment differ by obesity (Aim 2C) or symptom
subtype (Aim 2D). In support of this Aim, preliminary data suggest metabolomic changes with PAP treatment..
Finally, in Aim 3 we will leverage existing samples of obese OSA subjects that were previously randomized to
one of three treatments – weight-loss alone, PAP alone, or combined weight-loss and PAP. Differences in
metabolomic changes among these three randomized groups will provide insights into the relative roles of
obesity and cyclical intermittent hypoxia on metabolic responses and pathways. Ultimately, results from this
proposal will provide comprehensive information on metabolomic signatures that can be utilized as
quantitat...

## Key facts

- **NIH application ID:** 10204094
- **Project number:** 5R01HL142981-02
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Aalim M Weljie
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $1,119,884
- **Award type:** 5
- **Project period:** 2020-07-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10204094

## Citation

> US National Institutes of Health, RePORTER application 10204094, Metabolomics of obstructive sleep apnea (5R01HL142981-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10204094. Licensed CC0.

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