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Brain responses to hypoglycemia raise questions regarding recovery
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SAN FRANCISCO — Patients with type 1 diabetes with impaired awareness of hypoglycemia show different brain activation patterns than patients with greater awareness, according to research presented at the American Diabetes Association’s 74th Scientific Sessions.
Shifts in emotional and cognitive responses experienced by patients with impaired awareness of hypoglycemia (IAH) could contribute to challenges in avoiding the state and regaining awareness and may be a target for therapy.
“In patients with impaired awareness compared with in-tact awareness, acute hypoglycemia is associated with deactivation or lack of appropriate activation in brain regions involved in the stress response, autonomic activation and the emotional salience of these stressful stimuli,” Pratik Choudhary MD, MRCP, of King’s College London, said during his presentation.
Choudhary and colleagues looked at 17 men with type 1 diabetes; 9 men (mean age, 37.1±9.3; mean HbA1c, 7.8±1.3%; mean diabetes duration, 13.8±14.2 years) were hypoglycemia-aware (HA) with Clarke scores ≤3 and no recent severe hypoglycemia (SH), and 8 men (mean age, 35.3±7.5 years; mean HbA1c, 7.4±0.8%; mean diabetes duration, 23.2±14.7) had impaired awareness of hypoglycemia with Clarke score ≥4 and previous SH. Non-diabetic controls were slightly younger but evenly matched for age and glycemic control.
The scientists used 15 O-water positron emission tomography to evaluate brain perfusion through the successive stages of euglycemia (90mg/dl), hypoglycemia (46.8mg/dl for 50min) and recovery (90mg/dl), applied by hyperinsulinemic clamping. Statistical parametric mapping with significance thresholds allowed researchers to measure regional differences in changes in perfusion, marking brain activation.
From baseline, men with IAH showed reduced stress hormone (epinephrine) and absent symptom (autonomic scores, neuroglycopenic) responses to hypoglycemia compared with HA.
Brain deactivation in lingual gyri was observed with IAH vs. activation in HA. In early hypoglycemia, IAH showed activation in bilateral orbitofrontal, right insular and left dorsolateral prefrontal cortices. In late hypoglycemia, IAH showed no activation of anterior cingulate cortex and precuneus, which was activated in HA.
During the recovery stage, patients with IAH demonstrated deactivated right insula and amygdala, compared with activated in HA, but did not deactivate medial temporal gyrus; they also showed activation of dorsolateral pre-frontal cortex, which was deactivated in HA,
“We think it’s possible that these emotional and motivational responses to acute hypoglycemia and their sustained responses after recovery from hypoglycemia, including the emotion and memory of these events, may be barriers to restoration to hypoglycemia avoidance,” Choudhary said. “Restoration awareness may be potential therapeutic targets in future studies.”
With funding already solidified for further research, Choudhary is recruiting patients with hyper unawareness for a 6-month trial to investigate how many they can restore and their brain responses.
“A question these studies raise is, are these differences in reward perception the cause of unawareness, or are they the reason why we can’t restore them?” Choudhary said.
The neuroimaging data does appear to match up with qualitative data from interviews conducted with patients with unawareness, who notably don’t perceive it as a problem.
“Part of that might because when they remain hypoglycemic, there get no internal stress reaction, they get no unpleasantness because there’s no deactivation in the reward centers,” Choudary said. “So internally, it’s quite easy to see why there’s no motivation to avoid that situation, whereas it might feel unpleasant with high glucose.”
For More Information: Choudhary P. Abstract 385-OR. Presented at: American Diabetes Association’s 74th Scientific Sessions; June 13-17, 2014; San Francisco.
Disclosures: Choudary reports no relevant disclosures.