# Myeloperoxidase (MPO) Enzymatic Activity, but Not Its Protein Concentration, Is Associated with the Risk of Type 2 Diabetes in Females, Regardless of Obesity Status

## TL;DR

This study shows that MPO enzymatic activity, not protein levels, is linked to type 2 diabetes in females, regardless of obesity.

## Contribution

The study is the first to show that MPO enzymatic activity is independently associated with T2DM in females.

## Key findings

- Females with T2DM had three-fold higher serum MPO activity than controls.
- MPO-specific activity remained significantly associated with T2DM after adjusting for age and fat mass.
- MPO protein concentration was not different between T2DM and control groups.

## Abstract

To date, neutrophil-derived myeloperoxidase (MPO), a key mediator of inflammation and oxidative stress, has predominantly been assessed in peripheral fluids by protein concentration rather than enzymatic activity, mainly due to methodological limitations. However, MPO activity directly reflects the enzyme’s cytotoxic potential and pathogenic role in inflammatory diseases. To address this gap, we employed an optimized immunocapture assay to evaluate MPO activity, specific activity, and protein concentration in females with type 2 diabetes mellitus (T2DM), a condition tightly linked to chronic low-grade inflammation and obesity. Our findings revealed that females with T2DM exhibited nearly three-fold higher serum MPO activity and more than two-fold greater specific activity compared to controls with no differences in MPO protein concentration. Notably, MPO-specific activity remained significantly associated with T2DM (p < 0.01 to p < 0.001 across multivariate models), even after adjusting for age and dual-energy X-ray absorptiometry-derived measures of total and regional fat mass. Only android/gynoid fat distribution retained marginal significance in these models. This study is the first demonstration that MPO enzymatic activity, rather than protein concentration, is independently linked to T2DM in females. These findings underscore the importance of assessing functional MPO activity in the context of metabolic disease and support its potential role as a pathophysiological marker.