Hypoglycemic thalamic activation in type 1 diabetes is associated with preserved symptoms despite reduced epinephrine

Abstract

Brain responses to low plasma glucose may be key to understanding the behaviors that prevent severe hypoglycemia in type 1 diabetes. This study investigated the impact of long duration, hypoglycemia aware type 1 diabetes on cerebral blood flow responses to hypoglycemia. Three-dimensional pseudo-continuous arterial spin labeling magnetic resonance imaging was performed in 15 individuals with type 1 diabetes and 15 non-diabetic controls during a two-step hyperinsulinemic glucose clamp. Symptom, hormone, global cerebral blood flow and regional cerebral blood flow responses to hypoglycemia were measured. Epinephrine release during hypoglycemia was attenuated in type 1 diabetes, but symptom score rose comparably in both groups. A rise in global cerebral blood flow did not differ between groups. Regional cerebral blood flow increased in the thalamus and fell in the hippocampus and temporal cortex in both groups. Type 1 diabetes demonstrated lesser anterior cingulate cortex activation; however, this difference did not survive correction for multiple comparisons. Thalamic cerebral blood flow change correlated with autonomic symptoms, and anterior cingulate cortex cerebral blood flow change correlated with epinephrine response across groups. The thalamus may thus be involved in symptom responses to hypoglycemia, independent of epinephrine action, while anterior cingulate cortex activation may be linked to counterregulation. Activation of these regions may have a role in hypoglycemia awareness and avoidance of problematic hypoglycemia.