# Metabolites associated with abnormal glucose metabolism responding to primary care lifestyle intervention

## TL;DR

This study identifies specific metabolites linked to glucose metabolism that change with lifestyle interventions, offering potential targets for preventing type 2 diabetes.

## Contribution

The study introduces a metabolite panel that can distinguish glucose metabolism states and predict lifestyle intervention responses.

## Key findings

- Metabolites like lysophosphatidylcholines with odd-chain fatty acids are associated with improved glucose metabolism.
- Twenty-five metabolites showed baseline differences, responded to lifestyle changes, and correlated with glucose metabolism changes.
- Amino acids, acylcarnitines, and phospholipids were key metabolic signatures affected by lifestyle interventions.

## Abstract

Type 2 diabetes can be prevented by lifestyle intervention. We aimed to identify metabolites that associate with glucose metabolism and respond to lifestyle intervention with evidence-based targets for nutrition and physical activity in individuals at high risk of type 2 diabetes. Standard oral glucose tolerance test (OGTT) was used to categorize 624 participants into those having normal glucose tolerance (NGT), isolated impaired glucose tolerance (IGT), IGT with increased fasting glucose (IGT + IFG), and type 2 diabetes. Plasma LC-MS metabolomics was performed to reveal metabolic signatures. The baseline group differences were analysed with the Kruskal–Wallis test and the effect of intervention with a linear mixed-effects model. Significant differences in the metabolite signature were observed between the baseline groups, particularly in amino acids, acylcarnitines, and phospholipids. Fatty acid amides, phospholipids, amino acids, dimethylguanidinovaleric acid, and 5-aminovaleric acid betaine responded most to the lifestyle intervention. Lysophosphatidylcholines containing odd-chain fatty acids showed associations with improved glucose metabolism. Twenty-five metabolites differed between the baseline groups, responded to the intervention, and were associated with changes in glucose metabolism. The findings suggest a metabolite panel could be used in distinguishing individuals with varying degrees of glucose metabolism and in predicting response to lifestyle interventions.

The online version contains supplementary material available at 10.1038/s41598-025-25749-z.