Activation of ventral striatum by hypoglycemia, with loss of amygdala responses in hypoglycemia unawareness

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Activation of Ventral Striatum by Hypoglycemia, with Loss of Amygdala Responses in Hypoglycemia Unawareness Loss of the ability to recogni Loss of the ability to recognise developing hypoglycemia (hypoglycemia unawareness, HU) increases risk of severe hypoglycemia in insulin-treated diabetes 3-fold. Regional brain responses to acute hypoglycemia were examined using [sup]18[/sup]fluoro-deoxyglucose positron emission tomography (FDG-PET) to measure regional changes in brain glucose kinetics. 13 men with Type 1 diabetes were studied, 6 with good awareness of hypoglycemia (HA, age 35.8[underline]+[/underline]4.6, duration 16.3[underline]+[/underline]3.6yrs, HbA1c 8.9[underline]+[/underline]2.0%) and 7 with HU (36.9[underline]+[/underline]9.1, 16.6[underline]+[/underline]6.1, 7.4[underline]+[/underline]1.6% respectively) were studied. Scans were acquired during controlled euglycemia (5 mmol/l) and hypoglycemia (2.6mmol/l), applied using an insulin clamp procedure, on 2 occasions in random order. The epinephrine responses were much reduced in HU (p[lt]0.0003), who were asymptomatic throughout both studies. Statistical parametric mapping of the FDG uptake data (using SPM2, an upgraded software with enhanced image normalisation) showed a robust increase in FDG uptake in ventral striatum (R+L) in hypoglycemia, to a lesser extent in HU (3.52[underline]+[/underline]1.02 vs 6.1[underline]+[/underline]0.53, p=0.054). Interaction of group and condition was observed in L amygdala, where hypoglycemia increased FDG uptake in HA, but not in HU (-0.40[underline]+[/underline]1.03 vs 3.66[underline]+[/underline]0.42, p=0.007). The response in the ventral striatum to hypoglycemia indicates activation of prefrontal dopaminergic responses, in brain regions involved in control of appetite and motivation. These may be reduced in HU. The failure of the amygdala response in HU suggests habituation to hypoglycemia, consistent with the observation that HU can be induced by prior exposure to hypoglycemia. Mechanisms of habituation may be exploited to devise treatments to reverse HU. JOEL T. DUNN, PAUL K. MARSDEN, IAIN C. CRANSTON, LAURENCE J. REED, STEPHANIE A. AMIEL. 199-OR London, United Kingdom. Complications - Hypoglycemia
Original languageEnglish
Pages (from-to)A47-A47
Publication statusPublished - 2006


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