Gender-Related Differences in Cerebrovascular Reactivity to L-Arginine in Middle-Aged Type 1 Diabetes Patients

Type 1 diabetes (T1D) increases the risk for cerebral microangiopathy. However, the association between gender and cerebral microcirculatory dysfunction in T1D remains undetermined. Therefore, we have conducted a comparative analysis of cerebral endothelial-mediated microcirculatory parameters between middle-aged Caucasian females and males with type 1 diabetes. The present study examined the nitric oxide-induced vasomotor reactivity of middle cerebral arteries (MCA using transcranial Doppler and L-arginine infusion (L-arg VMR)). The study compared L-arg VMR between 23 males and 26 females with type 1 diabetes without a history of overt cerebrovascular disease. Mean L-arg VMR and baseline MCA flow velocity (V rest) were higher in females than in males (20.1 ± 5.4 vs. 14.6 ± 7.1% p < 0.01 and 73, 54-106 vs. 60.7-77 cm/s p < 0.01, respectively). Males were older than females (39.7 [range: 31.3-55.7] vs. 36.5 [range: 25.0-45.5] years, p = 0.02) and were characterized by later T1D onset and higher insulin/24 h, triglyceride levels and body mass index (BMI). Higher L-arg VMR in females persisted when co-variated with patients' age, age of onset, BMI, triglyceride level and V rest. Cerebral vasomotor reactivity to L-arginine showed greater efficacy in middle-aged females than in males with T1D, independent of age and disease course. The protective effect of the female gender on cerebral endothelium function has been demonstrated in type 1 diabetes.