TY - JOUR
T1 - Cerebral glycogen in humans following acute and recurrent hypoglycemia
T2 - Implications on a role in hypoglycemia unawareness
AU - Oz, Gulin
AU - DiNuzzo, Mauro
AU - Kumar, Anjali
AU - Moheet, Amir
AU - Khowaja, Ameer
AU - Kubisiak, Kristine
AU - Eberly, Lynn E
AU - Seaquist, Elizabeth R
N1 - Publisher Copyright:
© 2016, © The Author(s) 2016.
PY - 2017/8/1
Y1 - 2017/8/1
N2 - Supercompensated brain glycogen levels may contribute to the development of hypoglycemia-associated autonomic failure (HAAF) following recurrent hypoglycemia (RH) by providing energy for the brain during subsequent periods of hypoglycemia. To assess the role of glycogen supercompensation in the generation of HAAF, we estimated the level of brain glycogen following RH and acute hypoglycemia (AH). After undergoing 3 hyperinsulinemic, euglycemic and 3 hyperinsulinemic, hypoglycemic clamps (RH) on separate occasions at least 1 month apart, five healthy volunteers received [1-13C]glucose intravenously over 80+ h while maintaining euglycemia. 13C-glycogen levels in the occipital lobe were measured by 13C magnetic resonance spectroscopy at ∼8, 20, 32, 44, 56, 68 and 80 h at 4 T and glycogen levels estimated by fitting the data with a biophysical model that takes into account the tiered glycogen structure. Similarly, prior 13C-glycogen data obtained following a single hypoglycemic episode (AH) were fitted with the same model. Glycogen levels did not significantly increase after RH relative to after euglycemia, while they increased by ∼16% after AH relative to after euglycemia. These data suggest that glycogen supercompensation may be blunted with repeated hypoglycemic episodes. A causal relationship between glycogen supercompensation and generation of HAAF remains to be established.
AB - Supercompensated brain glycogen levels may contribute to the development of hypoglycemia-associated autonomic failure (HAAF) following recurrent hypoglycemia (RH) by providing energy for the brain during subsequent periods of hypoglycemia. To assess the role of glycogen supercompensation in the generation of HAAF, we estimated the level of brain glycogen following RH and acute hypoglycemia (AH). After undergoing 3 hyperinsulinemic, euglycemic and 3 hyperinsulinemic, hypoglycemic clamps (RH) on separate occasions at least 1 month apart, five healthy volunteers received [1-13C]glucose intravenously over 80+ h while maintaining euglycemia. 13C-glycogen levels in the occipital lobe were measured by 13C magnetic resonance spectroscopy at ∼8, 20, 32, 44, 56, 68 and 80 h at 4 T and glycogen levels estimated by fitting the data with a biophysical model that takes into account the tiered glycogen structure. Similarly, prior 13C-glycogen data obtained following a single hypoglycemic episode (AH) were fitted with the same model. Glycogen levels did not significantly increase after RH relative to after euglycemia, while they increased by ∼16% after AH relative to after euglycemia. These data suggest that glycogen supercompensation may be blunted with repeated hypoglycemic episodes. A causal relationship between glycogen supercompensation and generation of HAAF remains to be established.
KW - C magnetic resonance spectroscopy
KW - biophysical modeling
KW - glycogen
KW - hypoglycemia-associated autonomic failure
KW - supercompensation
UR - http://www.scopus.com/inward/record.url?scp=85026430388&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85026430388&partnerID=8YFLogxK
U2 - 10.1177/0271678X16678240
DO - 10.1177/0271678X16678240
M3 - Article
C2 - 27834283
AN - SCOPUS:85026430388
SN - 0271-678X
VL - 37
SP - 2883
EP - 2893
JO - Journal of Cerebral Blood Flow and Metabolism
JF - Journal of Cerebral Blood Flow and Metabolism
IS - 8
ER -