Recurrent hypoglycaemia in type 1 diabetes (T1D) may culminate in impaired awareness of hypoglycaemia (IAH). While neuroimaging studies identified affected brain regions, more complex perspectives integrating vascular dynamics with endocrine profile are missing. 26 healthy adults, 30 T1D patients with normal hypoglycaemia awareness (NAH), and 25 T1D patients with IAH underwent a hyperinsulinaemic stepped clamp (euglycaemia → hypoglycaemia 50 mg.dL -1 ) combined with pseudo-continuous arterial spin-labelling MRI. Cerebral blood flow (CBF) and sympathetic vasomotor-range (0.02-0.05 Hz) CBF oscillations were modelled against serially sampled plasma cortisol, epinephrine, norepinephrine and glucagon. In healthy controls, hypoglycaemia evoked robust thalamo-striatal and salience–interoceptive CBF increases (mean Cohen’s d across significant clusters=0.93) and suppression of vasomotor oscillations ( d =0.71). T1D retained CBF response but failed to attenuate oscillations ( dT1D>controls =0.43). IAH further blunted hypoglycaemia-associated CBF increase, especially in thalamus, striatum and insula ( dNAH>IAH =0.51). Hormone-CBF coupling differed quantitatively: cortisol/epinephrine–CBF correlations were positive in controls (r=0.37/0.26), negative in NAH (-0.16/-0.40) and strongly positive in IAH (0.42/0.46). Thus, our findings indicate that T1D disrupts dynamic, sympathetic modulation of CBF, whereas IAH additionally impairs perfusion reserve and shows maladaptive catecholamine-dependent CBF regulation, suggesting a qualitatively distinct neurovascular phenotype.
Filip et al. (Thu,) studied this question.