Objective
<p>Impaired
awareness of hypoglycemia (IAH) in type 1 diabetes (T1D) is a major risk factor
for severe hypoglycemia (SH), and is associated with atypical responses to hypoglycemia
in brain regions involved in arousal, decision-making and memory. Whether restoration of hypoglycemia awareness
alters these responses is unknown. We sought to investigate the impact of awareness
restoration on brain responses to hypoglycemia.</p>
<p> </p>
<p>Research
Design and Methods</p>
<p>Twelve T1D
IAH adults underwent pseudo-continuous arterial spin labelling functional MRI
during a hypoglycemic clamp (5mmol/L-2.6mmol/L), before and after a hypoglycemia
avoidance program of structured education (Dose Adjustment for Normal Eating,
DAFNE), specialist support and sensor-augmented pump therapy (Medtronic
Minimed™ 640G). Hypoglycemic cerebral blood flow (CBF) responses were compared
pre- and post-intervention using predefined region of interest analysis of the
thalamus, anterior cingulate cortex (ACC), orbitofrontal cortex (OFC) and
hippocampus.</p>
<p> </p>
<p>Results</p>
<p>Post-intervention,
Gold and Clarke scores fell (6.0±1.0 to 4.0±1.6, p=0.0002; 5.7±1.7 to 3.4±1.8,
p=0.0008), SH rates reduced (1.5±2 to 0.3±0.5 episodes per year, p=0.03), hypoglycemic
symptom scores increased (18.8±6.3 to 27.3±12.7, p=0.02), epinephrine
responses did not change (p=0.2). Post-intervention, hypoglycemia induced
greater increases in ACC CBF (p=0.01, peak voxel coordinates [6,40,-2]),
while thalamic and OFC activity did not change.</p>
<p> </p>
<p>Conclusions</p>
<p>Increased blood
flow is seen within brain pathways involved in internal self-awareness and decision-making
(ACC) after restoration of hypoglycemia awareness, suggesting partial recovery
of brain responses lost in IAH. Resistance of frontothalamic networks, involved
in arousal and emotion processing, may explain why not all IAH individuals
achieve awareness restoration with education and technology alone. </p>
Decision-Making Involvement and Prediction of Adherence in Youth With Type 1 Diabetes: A Cohort Sequential Study