Hypoglycemia unawareness in type 1 diabetes suppresses brain responses to hypoglycemia

Janice Jin Hwang, Lisa Parikh, Cheryl Lacadie, Dongju Seo, Wai Lam, Muhammad Hamza, Christian Schmidt, Feng Dai, Anne Sophie Sejling, Renata Belfort-Deaguiar, R. Todd Constable, Rajita Sinha, Robert Sherwin

Research output: Contribution to journalArticlepeer-review

32 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1485-1495
Number of pages11
JournalJournal of Clinical Investigation
Volume128
Issue number4
DOIs
StatePublished - Apr 2 2018
Externally publishedYes

ASJC Scopus subject areas

  • General Medicine

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