Moderately high levels of plasma methylglyoxal are associated with lacunar infarcts – The Maastricht Study

Methylglyoxal (MGO), a by-product of glycolysis and major precursor in the formation of advanced glycation endproducts (AGEs), is increased during ageing and in diabetes and plays a role in peripheral microvascular dysfunction. Whether MGO affects the brain microvasculature is unknown. The aim of this study is to investigate whether higher plasma MGO concentrations are cross-sectionally associated with markers for cerebral small vessel disease (CSVD) and with cognitive impairment. In participants of the Maastricht Study, a population-based cohort study oversampled with type 2 diabetes (age=59.7+/-8.2, 49.9%=male, 26% type 2 diabetes [by design]), MGO concentrations were measured with UPLC-MS/MS in plasma collected after overnight fasting. Participants underwent magnetic resonance imaging (MRI) (n=1789) and cognitive testing (n=2515). Markers for CSVD (white matter hyper intensities [WMH], lacunar infarction, and cerebral microbleeds) were obtained from MRI data. Logistic and linear regressions were performed to assess the association of plasma MGO with CSVD markers and with cognitive function, respectively. Associations were adjusted for confounding factors, including age, sex, cognitive function, lifestyle factors, and health status. No linear associations were found in any of the outcomes. We found that, when dividing the population into tertiles (low, moderately high, high) based on plasma MGO concentration, moderately high compared to low levels of plasma MGO were associated with increased odds of having a lacunar infarct (odds ratio:2.3, 95%CI:1.3-4.0). This was not observed for high plasma MGO (odds ratio:1.6, 95%CI:0.8-2.9). In summary, in this study, moderately high plasma MGO is associated with higher odds of having had a lacunar infarct.