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.

Effects of route of administration on oxytocin-induced changes in regional cerebral blood flow in humans

“…We conducted whole-brain cluster-level inference for all analyses, reporting clusters significant at α = 0.05 using familywise error (FWE) correction and a cluster-forming threshold of P = 0.005 (uncorrected). Our statistical thresholds were determined a priori based on our own previous work investigating the effects of intranasal spray OT on rCBF in humans 16 and are standardly applied in pharmacological ASL studies measuring rCBF [91][92][93][94][95][96] . For the paired t-tests, in recognition of the increased risk of false positives given the large number of paired t-tests (3 × 8 = 24), we mark clusters that do not survive correction for multiple testing following adjustment of the Pvalue using conservative Bonferroni correction for the 24 paired-t-tests performed with an asterisk (*) (P adjusted = 0.05/24 = 0.002) (see Tables 2-4).…”

Impaired Awareness of Hypoglycemia Disrupts Blood Flow to Brain Regions Involved in Arousal and Decision Making in Type 1 Diabetes

“…As previously reported (15), consenting, eligible volunteers avoided alcohol, caffeine, and strenuous activity for 48 h before study. Participants were admitted to the King's College Hospital Clinical Research Facility the evening before scanning, after their evening meal.…”

“Less is more”: a dose-response account of intranasal oxytocin pharmacodynamics in the human brain

“…We used cluster-level inference at α = 0.05 using family-wise error (FWE) correction for multiple comparisons and a cluster-forming threshold of p=0.005 (uncorrected). These statistical thresholds were determined a priori based on our own work investigating the effects of intranasal oxytocin on rCBF in humans 21,37 and are standardly applied in ASL studies measuring rCBF [99][100][101][102][103][104] . participants from each brain region and treatment level (group-based covariance statistics) [54][55][56][57][58] .…”