# Adipokines as Biomarkers of Cachexia and High-Risk Rheumatoid Arthritis

> **NIH VA I01** · PHILADELPHIA VA MEDICAL CENTER · 2021 · —

## Abstract

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease associated with arthritis and significant
disability. The disease is also associated with a greater risk of early death. Active RA is also associated with
greater use of energy, which results in unhealthy weight loss and muscle loss, and likely contributes to the
substantial risk of disability and death. This study focuses on markers that can be measured in the blood that
may identify these processes more clearly and identify those at greatest risk of these adverse outcomes.
Adipokines, or fat-secreted cytokines, are important regulators of energy usage in the body. For example,
adiponectin, aptly named the “starvation signal”, is thought to boost appetite and alter energy usage in an effort
to maintain adequate energy availability in lean times. Therefore, high adiponectin levels are likely to be
observed in patients who have experienced low energy availability as a result of their disease. High levels of
adiponectin may help identify individuals at high risk. High adiponectin levels have been associated with
greater mortality in chronic inflammatory conditions such as congestive heart failure and renal disease, and
correlated with evidence of muscle loss. While similar studies have not been performed in RA, high adiponectin
levels are associated with other adverse outcomes including joint damage progression. While observations in
RA have led to speculation that adiponectin may play a causal role in the disease, we instead hypothesize that
high serum adiponectin levels are in fact a marker of low energy availability in RA and therefore predictive of
adverse outcomes. We previously demonstrated that weight loss in RA is associated with a higher risk of
death. Accessible measures that are able to identify at-risk individuals would improve identification of high-risk
disease to help focus therapy. This is an issue of precision medicine in the VA, since therapies for RA are
expensive and likely over-utilized. Results of this study will affect how researchers consider adipokines and
their role in the disease process. Aim 1 will leverage the VA Rheumatoid Arthritis (VARA) registry and National
Data Bank (NDB). Each include an extensive DNA and serum repository among patients with RA and linkages
to reliable and extensive clinical data. Aim 2 leverages a landmark clinical trial to evaluate prediction of
outcomes in two common treatment strategies. Aim 3 is mechanistic and ancillary to Dr. Baker's existing VA-
funded cohort with comprehensive longitudinal assessments of muscle and fat mass. Dr. Baker's cohort will be
augmented through collaboration with two RA investigators to compile the largest-ever longitudinal RA cohort
with muscle and fat assessments. The overall goal is to gain insight into the relationship between adiponectin
and the disease, weight, obesity, muscle loss, disability and risk of early death. Aim 1 will determine if
circulating adiponectin and variants in the adipon...

## Key facts

- **NIH application ID:** 9825378
- **Project number:** 5I01CX001703-02
- **Recipient organization:** PHILADELPHIA VA MEDICAL CENTER
- **Principal Investigator:** JOSHUA F. BAKER
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2021
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2019-01-01 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9825378

## Citation

> US National Institutes of Health, RePORTER application 9825378, Adipokines as Biomarkers of Cachexia and High-Risk Rheumatoid Arthritis (5I01CX001703-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9825378. Licensed CC0.

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