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Hypoglycemia unawareness in type 1 diabetes suppresses brain responses to hypoglycemia

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Harvard

Hwang, JJ, Parikh, L, Lacadie, C, Seo, D, Lam, W, Hamza, M, Schmidt, C, Dai, F, Sejling, A-S, Belfort-DeAguiar, R, Constable, RT, Sinha, R & Sherwin, R 2018, 'Hypoglycemia unawareness in type 1 diabetes suppresses brain responses to hypoglycemia' The Journal of clinical investigation, vol. 128, no. 4, pp. 1485-1495. https://doi.org/10.1172/JCI97696

APA

Hwang, J. J., Parikh, L., Lacadie, C., Seo, D., Lam, W., Hamza, M., ... Sherwin, R. (2018). Hypoglycemia unawareness in type 1 diabetes suppresses brain responses to hypoglycemia. The Journal of clinical investigation, 128(4), 1485-1495. https://doi.org/10.1172/JCI97696

CBE

Hwang JJ, Parikh L, Lacadie C, Seo D, Lam W, Hamza M, Schmidt C, Dai F, Sejling A-S, Belfort-DeAguiar R, Constable RT, Sinha R, Sherwin R. 2018. Hypoglycemia unawareness in type 1 diabetes suppresses brain responses to hypoglycemia. The Journal of clinical investigation. 128(4):1485-1495. https://doi.org/10.1172/JCI97696

MLA

Vancouver

Author

Hwang, Janice Jin ; Parikh, Lisa ; Lacadie, Cheryl ; Seo, Dongju ; Lam, Wai ; Hamza, Muhammad ; Schmidt, Christian ; Dai, Feng ; Sejling, Anne-Sophie ; Belfort-DeAguiar, Renata ; Constable, R Todd ; Sinha, Rajita ; Sherwin, Robert. / Hypoglycemia unawareness in type 1 diabetes suppresses brain responses to hypoglycemia. In: The Journal of clinical investigation. 2018 ; Vol. 128, No. 4. pp. 1485-1495.

Bibtex

@article{2eb08aed4b3740be8bc68ae4f25f0c95,
title = "Hypoglycemia unawareness in type 1 diabetes suppresses brain responses to hypoglycemia",
abstract = "BACKGROUND: Among nondiabetic individuals, mild glucose decrements alter brain activity in regions linked to reward, motivation, and executive control. Whether these effects differ in type 1 diabetes mellitus (T1DM) patients with and without hypoglycemia awareness remains unclear.METHODS: Forty-two individuals (13 healthy control [HC] subjects, 16 T1DM individuals with hypoglycemia awareness [T1DM-Aware], and 13 T1DM individuals with hypoglycemia unawareness [T1DM-Unaware]) underwent blood oxygen level-dependent functional MRI brain imaging during a 2-step hyperinsulinemic euglycemic (90 mg/dl)-hypoglycemic (60 mg/dl) clamp for assessment of neural responses to mild hypoglycemia.RESULTS: Mild hypoglycemia in HC subjects altered activity in the caudate, insula, prefrontal cortex, and angular gyrus, whereas T1DM-Aware subjects showed no caudate and insula changes, but showed altered activation patterns in the prefrontal cortex and angular gyrus. Most strikingly, in direct contrast to HC and T1DM-Aware subjects, T1DM-Unaware subjects failed to show any hypoglycemia-induced changes in brain activity. These findings were also associated with blunted hormonal counterregulatory responses and hypoglycemia symptom scores during mild hypoglycemia.CONCLUSION: In T1DM, and in particular T1DM-Unaware patients, there is a progressive blunting of brain responses in cortico-striatal and fronto-parietal neurocircuits in response to mild-moderate hypoglycemia. These findings have implications for understanding why individuals with impaired hypoglycemia awareness fail to respond appropriately to falling blood glucose levels.FUNDING: This study was supported in part by NIH grants R01DK020495, P30 DK045735, K23DK109284, K08AA023545. The Yale Center for Clinical Investigation is supported by an NIH Clinical Translational Science Award (UL1 RR024139).",
author = "Hwang, {Janice Jin} and Lisa Parikh and Cheryl Lacadie and Dongju Seo and Wai Lam and Muhammad Hamza and Christian Schmidt and Feng Dai and Anne-Sophie Sejling and Renata Belfort-DeAguiar and Constable, {R Todd} and Rajita Sinha and Robert Sherwin",
year = "2018",
doi = "10.1172/JCI97696",
language = "English",
volume = "128",
pages = "1485--1495",
journal = "Journal of Clinical Investigation",
issn = "0021-9738",
publisher = "American Society for Clinical Investigation",
number = "4",

}

RIS

TY - JOUR

T1 - Hypoglycemia unawareness in type 1 diabetes suppresses brain responses to hypoglycemia

AU - Hwang, Janice Jin

AU - Parikh, Lisa

AU - Lacadie, Cheryl

AU - Seo, Dongju

AU - Lam, Wai

AU - Hamza, Muhammad

AU - Schmidt, Christian

AU - Dai, Feng

AU - Sejling, Anne-Sophie

AU - Belfort-DeAguiar, Renata

AU - Constable, R Todd

AU - Sinha, Rajita

AU - Sherwin, Robert

PY - 2018

Y1 - 2018

N2 - BACKGROUND: Among nondiabetic individuals, mild glucose decrements alter brain activity in regions linked to reward, motivation, and executive control. Whether these effects differ in type 1 diabetes mellitus (T1DM) patients with and without hypoglycemia awareness remains unclear.METHODS: Forty-two individuals (13 healthy control [HC] subjects, 16 T1DM individuals with hypoglycemia awareness [T1DM-Aware], and 13 T1DM individuals with hypoglycemia unawareness [T1DM-Unaware]) underwent blood oxygen level-dependent functional MRI brain imaging during a 2-step hyperinsulinemic euglycemic (90 mg/dl)-hypoglycemic (60 mg/dl) clamp for assessment of neural responses to mild hypoglycemia.RESULTS: Mild hypoglycemia in HC subjects altered activity in the caudate, insula, prefrontal cortex, and angular gyrus, whereas T1DM-Aware subjects showed no caudate and insula changes, but showed altered activation patterns in the prefrontal cortex and angular gyrus. Most strikingly, in direct contrast to HC and T1DM-Aware subjects, T1DM-Unaware subjects failed to show any hypoglycemia-induced changes in brain activity. These findings were also associated with blunted hormonal counterregulatory responses and hypoglycemia symptom scores during mild hypoglycemia.CONCLUSION: In T1DM, and in particular T1DM-Unaware patients, there is a progressive blunting of brain responses in cortico-striatal and fronto-parietal neurocircuits in response to mild-moderate hypoglycemia. These findings have implications for understanding why individuals with impaired hypoglycemia awareness fail to respond appropriately to falling blood glucose levels.FUNDING: This study was supported in part by NIH grants R01DK020495, P30 DK045735, K23DK109284, K08AA023545. The Yale Center for Clinical Investigation is supported by an NIH Clinical Translational Science Award (UL1 RR024139).

AB - BACKGROUND: Among nondiabetic individuals, mild glucose decrements alter brain activity in regions linked to reward, motivation, and executive control. Whether these effects differ in type 1 diabetes mellitus (T1DM) patients with and without hypoglycemia awareness remains unclear.METHODS: Forty-two individuals (13 healthy control [HC] subjects, 16 T1DM individuals with hypoglycemia awareness [T1DM-Aware], and 13 T1DM individuals with hypoglycemia unawareness [T1DM-Unaware]) underwent blood oxygen level-dependent functional MRI brain imaging during a 2-step hyperinsulinemic euglycemic (90 mg/dl)-hypoglycemic (60 mg/dl) clamp for assessment of neural responses to mild hypoglycemia.RESULTS: Mild hypoglycemia in HC subjects altered activity in the caudate, insula, prefrontal cortex, and angular gyrus, whereas T1DM-Aware subjects showed no caudate and insula changes, but showed altered activation patterns in the prefrontal cortex and angular gyrus. Most strikingly, in direct contrast to HC and T1DM-Aware subjects, T1DM-Unaware subjects failed to show any hypoglycemia-induced changes in brain activity. These findings were also associated with blunted hormonal counterregulatory responses and hypoglycemia symptom scores during mild hypoglycemia.CONCLUSION: In T1DM, and in particular T1DM-Unaware patients, there is a progressive blunting of brain responses in cortico-striatal and fronto-parietal neurocircuits in response to mild-moderate hypoglycemia. These findings have implications for understanding why individuals with impaired hypoglycemia awareness fail to respond appropriately to falling blood glucose levels.FUNDING: This study was supported in part by NIH grants R01DK020495, P30 DK045735, K23DK109284, K08AA023545. The Yale Center for Clinical Investigation is supported by an NIH Clinical Translational Science Award (UL1 RR024139).

U2 - 10.1172/JCI97696

DO - 10.1172/JCI97696

M3 - Journal article

VL - 128

SP - 1485

EP - 1495

JO - Journal of Clinical Investigation

JF - Journal of Clinical Investigation

SN - 0021-9738

IS - 4

ER -

ID: 54746769