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. 2025 May;48(5):1257-1268.
doi: 10.1007/s40618-025-02536-1. Epub 2025 Jan 23.

Fasting plasma methylglyoxal concentrations are associated with higher numbers of circulating intermediate and non-classical monocytes but with lower activation of intermediate monocytes: the Maastricht Study

Xiaodi Zhang  1   2 , Marleen M J van Greevenbroek  1   2 , Jean L J M Scheijen  1   2 , Simone J P M Eussen  2   3   4 , Jaycey Kelly  1   2 , Coen D A Stehouwer  1   2 , Casper G Schalkwijk  5   6 , Kristiaan Wouters  7   8
Affiliations

Fasting plasma methylglyoxal concentrations are associated with higher numbers of circulating intermediate and non-classical monocytes but with lower activation of intermediate monocytes: the Maastricht Study

Xiaodi Zhang et al. J Endocrinol Invest. 2025 May.

Abstract

Purpose: Elevated methylglyoxal (MGO) levels and altered immune cell responses are observed in diabetes. MGO is thought to modulate immune cell activation. The current study investigated whether fasting or post-glucose-load plasma MGO concentrations are associated with circulating immune cell counts and activation in a large cohort study.

Methods: 696 participants of The Maastricht Study (age 60.3 ± 8.4 years, 51.9% women) underwent an oral glucose tolerance test (OGTT). Fasting and post-OGTT plasma MGO concentrations were measured using mass spectrometry. Numbers and activation of circulating immune cells at fasting state were quantified using flow cytometry. Activation scores were calculated by averaging individual marker z-scores for neutrophils (CD11b, CD11c, CD16) and classical, intermediate, and non-classical monocytes (CD11b, CD11c, CX3XR1, HLA-DR). Associations were analysed using multiple linear regression adjusted for potential confounders. Stratified analyses were performed for glucose metabolism status for associations between plasma MGO levels and immune cell counts.

Results: Higher fasting plasma MGO concentrations were significantly associated with higher numbers of intermediate (β = 0.09 [95%CI 0.02; 0.17]) and non-classical monocytes (0.08 [0.002; 0.15]), but with lower activation scores for the intermediate monocytes (-0.14 [-0.22; -0.06]). Stratified analyses showed that positive associations between fasting plasma MGO levels and numbers of intermediate and non-classical monocytes appear only in participants with type 2 diabetes. Post-OGTT plasma MGO concentrations were not consistently associated with immune cells counts or activation.

Conclusion: Higher fasting plasma MGO concentrations are associated with higher intermediate and non-classical monocyte counts but with lower activation of intermediate monocytes.

Keywords: Cardiovascular disease; Circulating monocytes; Methylglyoxal; Neutrophils; Population-based cohort study; Type 2 diabetes.

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Conflict of interest statement

Declarations. Conflict of interest: The authors declare that they have no conflict of interest. Sources of funding: XZ was supported by the China Scholarship Council. The Maastricht Study was supported by the European Regional Development Fund via OP-Zuid, the Province of Limburg, the Dutch Ministry of Economic Affairs (grant 31O.041), Stichting De Weijerhorst (Maastricht, the Netherlands), the Pearl String Initiative Diabetes (Amsterdam, the Netherlands), the Cardiovascular Center (CVC, Maastricht, the Netherlands), School for Mental Health and Neuroscience (MHeNS, Maastricht, The Netherlands), Cardiovascular Research Institute Maastricht (CARIM, Maastricht, the Netherlands), School for Public Health and Primary Care (CAPHRI, Maastricht, the Netherlands), School for Nutrition, Toxicology and Metabolism (NUTRIM, Maastricht, the Netherlands), Stichting Annadal (Maastricht, the Netherlands), Health Foundation Limburg (Maastricht, the Netherlands) and by unrestricted grants from Janssen-Cilag B.V. (Tilburg, the Netherlands), Novo Nordisk Farma B.V. (Alphen aan den Rijn, the Netherlands) and Sanofi-Aventis Netherlands B.V. (Gouda, the Netherlands). Research involving human participants and/or animals: The study has been approved by the institutional medical ethics committee (NL31329.068.10) and the Dutch Ministry of Health, Welfare, and Sports of the Netherlands (permit 131088-105234-PG). Informed consent: All participants gave written informed consent.

Figures

Fig. 1
Fig. 1
Flowchart of the study population selection process
See this image and copyright information in PMC

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