Recent and long-term glycation markers and asymptomatic cerebral microangiopathy in adults without diabetes: the ILERVAS study

Cerebral microangiopathy encompasses a spectrum of pathological alterations affecting the brain microvasculature. Elevated glycated haemoglobin (HbA1c), a marker of recent glycemic exposure, has been associated with a greater burden of subclinical atherosclerosis in the carotid and femoral territories of non-diabetic individuals. In this study, we aimed to compare the associations of HbA1c and skin autofluorescence (SAF), a marker of long-term advanced glycation end-product accumulation, with asymptomatic cerebral microangiopathy (CM) in adults without diabetes. We performed a cross-sectional analysis of 3,444 participants from the ILERVAS study aged 45–70 years, free of diabetes, cerebrovascular disease, and chronic kidney disease, but presenting at least one cardiovascular risk factor. CM was assessed by transcranial duplex ultrasound and defined as a middle cerebral artery pulsatility index (MCA-PI) > 1.1. Correlations between glycation markers and MCA-PI were examined, and multivariable logistic regression analyses were performed to identify factors independently associated with CM and its severity. CM was detected in 157 participants (4.6%). Both HbA1c and SAF showed weak positive correlations with MCA-PI ( r = 0.067 and r = 0.085, respectively; both p < 0.001). However, neither marker was independently associated with CM overall after adjustment for age, sex, hypertension, dyslipidaemia, and smoking status. In exploratory analyses according to CM severity, HbA1c was independently associated with moderate CM (OR 1.99, 95% CI: 1.45–2.73; p < 0.001), together with age, pulse pressure, and sex, whereas SAF was not associated with either mild or moderate CM. The inclusion of HbA1c improved model fit for moderate CM, but not for mild CM. Both HbA1c and SAF were weakly correlated with MCA-PI, but only HbA1c was independently associated with moderate CM. These findings suggest that recent glycaemic exposure, even in considered non-diabetic range, is already associated with earliest stages of CM.