# Epidemiology A Metabolite Score Explains Relationships of Unintentional Weight Loss with Mortality and Mobility Limitation

## TL;DR

A metabolite score helps explain how unintentional weight loss in older adults is linked to higher risks of death and mobility issues.

## Contribution

A novel metabolite score is developed to better understand the health risks of unintentional weight loss in older adults.

## Key findings

- A one-SD higher metabolite score was linked to 44% higher mortality risk in older adults.
- The score explained 39% of the mortality risk from unintentional weight loss, more than traditional risk factors.
- The score also explained 27% of the mobility limitation risk from unintentional weight loss.

## Abstract

Unintentional weight loss (UWL) is related to mortality and functional decline. Using 77 metabolites associated with UWL risk in the Health, Aging and Body Composition participants, we investigated whether a composite metabolite score explained the relationship of UWL with mortality and mobility limitation. First, we selected 27 metabolites associated with incident UWL (>3% annual loss vs weight stable) using penalized logistic regression. Next, we created an UWL metabolite score, sum of 27 standardized metabolites weighted by their association with incident UWL, with a higher score indicating a greater potential risk for UWL. Among 2,286 participants (mean age 75, 37% Black, 51% women), those with UWL had 60% higher mortality and 25% higher hazard of mobility limitation risk after weight loss compared with weight-stable individuals, adjusting for age, race, sex, and study site. Older adults with one-SD higher UWL metabolite score had significantly higher mortality (HR = 1.44 [1.23, 1.52]) and mobility limitation risk (HR = 1.23 [1.15, 1.32]). The UWL metabolite score attenuated 39% of the relationship UWL and mortality, greater than 11% attenuated by traditional risk factors (i.e. demographics, lifestyle, and health conditions) and 16% by clinical biomarkers (cholesterol, glucose, kidney function, and inflammation biomarkers). Similarly, the UWL metabolite score attenuated 27% of the relationship between UWL and mobility limitation risk, contributing an additional 22% beyond traditional risk factors. This targeted metabolic characterization of UWL captures a substantial portion of the mortality and mobility limitation risks not explained by commonly measured health indicators, highlighting its potential value in risk assessment among older adults.

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Source: https://tomesphere.com/paper/PMC12761111