Chronic hyperglycemia is associated with vascular gain impairment in microangiopathic lacunar stroke

Objective. Chronic hyperglycemia is known to contribute to cerebral microangiopathy via an endothelial dysfunction. We hypothesized that gain, as a marker of vascular compliance or stiffness (as its physical inverse), is associated with an increased HbA1c level.Approach. We conducted a retrospective analysis of 94 consecutive patients (27 females, 67 males; median age 72.5 years, IQR 61-80 years) with isolated acute microangiopathic lacunar infarctions. By selecting this specific patient cohort, we minimized the influence of infarct size on dynamic cerebral autoregulation (dCA). dCA parameters-phase and gain- were assessed using transfer function analysis of spontaneous oscillations in blood pressure (BP) and cerebral blood flow velocity in both middle cerebral arteries. HbA1c levels [normal < 5.7% (39 mmol mol^-1), prediabetic 5.7-6.4% (39-46 mmol mol^-1), diabetic ⩾6.5% (>46 mmol mol^-1)], Fazekas grading for small vessel disease was determined on magnet resonance imaging, and other routine diagnostics parameters were recorded.Main results. Neither phase nor gain differed significantly between the Fazekas grading groups. Among the HbA1c categories, phase remained unchanged, whereas gain progressively increased from the normal HbA1c group to the diabetic group significantly in the very low (0.02-0.07 Hz) frequencies (p= .02) and by trend in the low frequency (0.07-0.20 Hz) range (p= .07), while BP and end-tidal carbon dioxide levels were not different across the groups.Significance. In this cohort of patients with microangiopathic lacunar stroke, higher HbA1c levels were associated with increased vascular gain, suggesting a potential link between long-term glucose dysregulation, increased vascular stiffness, and impaired dCA. This finding provides a mechanistic pathway connecting chronic hyperglycaemia to microangiopathic cerebral infarction.