OBJECTIVE: Loss of ability to recognize hypoglycemia (hypoglycemia unawareness) increases risk of severe hypoglycemia threefold in insulin-treated diabetes. We set out to investigate the cerebral correlates of unawareness in type 1 patients. RESEARCH DESIGN AND METHODS: Regional changes in brain glucose kinetics were measured using [(18)F]-fluorodeoxyglucose (FDG) positron emission tomography (PET), in 13 men with type 1 diabetes--6 with hypoglycemia awareness and 7 with hypoglycemia unawareness--at euglycemia (5 mmol/l) and hypoglycemia (2.6 mmol/l), in random order. RESULTS: Epinephrine responses to hypoglycemia were reduced in hypoglycemia unawareness (P < 0.0003), as were symptoms. Statistical parametric mapping (SPM) of FDG uptake using SPM2 at a statistical threshold of P < 0.005 showed increased FDG uptake in left amygdala in hypoglycemia awareness, but not in hypoglycemia unawareness (region of interest analysis -0.40 +/- 1.03 vs. 3.66 +/- 0.42, respectively; P = 0.007), and robust increase in bilateral ventral striatum during hypoglycemia (region of interest analysis hypoglycemia unawareness 3.52 +/- 1.02 vs. awareness 6.1 +/- 0.53; P = 0.054). Further analysis at the statistical threshold of P < 0.01 showed bilateral attenuated activation of brain stem regions and less deactivation in lateral orbitofrontal cortex in hypoglycemia unawareness. CONCLUSIONS: Ventral striatal, amygdala, brain stem, and orbitofrontal responses to hypoglycemia indicate engagement of appetitive motivational networks, associated with integrated behavioral responses to hypoglycemia. Reduced responses in these networks in hypoglycemia unawareness, particularly failure of amygdala and orbifrontal cortex responses, suggest habituation of higher behavioral responses to hypoglycemia as a basis for unawareness. New approaches may be needed to restore awareness effectively in practice.
OBJECTIVE: Loss of ability to recognize hypoglycemia (hypoglycemia unawareness) increases risk of severe hypoglycemia threefold in insulin-treated diabetes. We set out to investigate the cerebral correlates of unawareness in type 1 patients. RESEARCH DESIGN AND METHODS: Regional changes in brain glucose kinetics were measured using [(18)F]-fluorodeoxyglucose (FDG) positron emission tomography (PET), in 13 men with type 1 diabetes--6 with hypoglycemia awareness and 7 with hypoglycemia unawareness--at euglycemia (5 mmol/l) and hypoglycemia (2.6 mmol/l), in random order. RESULTS:Epinephrine responses to hypoglycemia were reduced in hypoglycemia unawareness (P < 0.0003), as were symptoms. Statistical parametric mapping (SPM) of FDG uptake using SPM2 at a statistical threshold of P < 0.005 showed increased FDG uptake in left amygdala in hypoglycemia awareness, but not in hypoglycemia unawareness (region of interest analysis -0.40 +/- 1.03 vs. 3.66 +/- 0.42, respectively; P = 0.007), and robust increase in bilateral ventral striatum during hypoglycemia (region of interest analysis hypoglycemia unawareness 3.52 +/- 1.02 vs. awareness 6.1 +/- 0.53; P = 0.054). Further analysis at the statistical threshold of P < 0.01 showed bilateral attenuated activation of brain stem regions and less deactivation in lateral orbitofrontal cortex in hypoglycemia unawareness. CONCLUSIONS: Ventral striatal, amygdala, brain stem, and orbitofrontal responses to hypoglycemia indicate engagement of appetitive motivational networks, associated with integrated behavioral responses to hypoglycemia. Reduced responses in these networks in hypoglycemia unawareness, particularly failure of amygdala and orbifrontal cortex responses, suggest habituation of higher behavioral responses to hypoglycemia as a basis for unawareness. New approaches may be needed to restore awareness effectively in practice.
Authors: Elizabeth R Seaquist; Amir Moheet; Anjali Kumar; Dinesh K Deelchand; Melissa Terpstra; Kristine Kubisiak; Lynn E Eberly; Pierre-Gilles Henry; James M Joers; Gülin Öz Journal: J Clin Endocrinol Metab Date: 2017-09-01 Impact factor: 5.958
Authors: Silvia Mangia; Nolawit Tesfaye; Federico De Martino; Anjali F Kumar; Pete Kollasch; Amir A Moheet; Lynn E Eberly; Elizabeth R Seaquist Journal: J Cereb Blood Flow Metab Date: 2012-08-15 Impact factor: 6.200
Authors: Alexander A Shestov; Uzay E Emir; Anjali Kumar; Pierre-Gilles Henry; Elizabeth R Seaquist; Gülin Öz Journal: Am J Physiol Endocrinol Metab Date: 2011-07-26 Impact factor: 4.310
Authors: Charlotte B Smith; Pratik Choudhary; Andrew Pernet; David Hopkins; Stephanie A Amiel Journal: Diabetes Care Date: 2009-04-23 Impact factor: 17.152