TY - JOUR
T1 - Fasting plasma methylglyoxal concentrations are associated with higher numbers of circulating intermediate and non-classical monocytes but with lower activation of intermediate monocytes
T2 - the Maastricht Study
AU - Zhang, Xiaodi
AU - van Greevenbroek, Marleen M. J.
AU - Scheijen, Jean L. J. M.
AU - Eussen, Simone J. P. M.
AU - Kelly, Jaycey
AU - Stehouwer, Coen D. A.
AU - Schalkwijk, Casper G.
AU - Wouters, Kristiaan
PY - 2025/5
Y1 - 2025/5
N2 - 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.
AB - 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.
KW - Methylglyoxal
KW - Circulating monocytes
KW - Neutrophils
KW - Population-based cohort study
KW - Type 2 diabetes
KW - Cardiovascular disease
KW - LEUKOCYTE RECRUITMENT
KW - CELL
KW - INFLAMMATION
KW - INDIVIDUALS
KW - FRACTALKINE
KW - RECEPTOR
KW - RUPTURE
KW - STRESS
KW - TYPE-1
KW - CX3CR1
U2 - 10.1007/s40618-025-02536-1
DO - 10.1007/s40618-025-02536-1
M3 - Article
SN - 1720-8386
VL - 48
SP - 1257
EP - 1268
JO - Journal of Endocrinological Investigation
JF - Journal of Endocrinological Investigation
IS - 5
ER -