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. 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.

Impaired Awareness of Hypoglycemia Disrupts Blood Flow to Brain Regions Involved in Arousal and Decision Making in Type 1 Diabetes

“…The depth of hypoglycemia in the PET study may explain why there was a more extensive cortical response and why the thalamus was activated in both HA and IAH. Together, Dunn et al (11), the current study, and Hwang et al (12) have demonstrated regional CBF changes at various stages of hypoglycemia. Reduced activity was seen in the right lateral OFC in IAH compared with HA during hypoglycemia.…”

“…*P , 0.05, **P , 0.005 for euglycemia vs. hypoglycemia; #P , 0.05, ##P , 0.005 for HA vs. IAH. participants was more extensive than that seen by Hwang et al (12), who described decreased activity in the OFC with no change in the DLPFC. This may reflect our stronger hypoglycemic stimulus of 47 mg/dL (2.6 mmol/L) versus 60 mg/dL (3.3 mmol/L) in the Hwang et al study.…”

“…Significant changes have been described in smaller, similar studies (9). As Hwang et al (12) suggested, previous calculations of sample size have not been based on complex and relatively uncommon conditions, such as IAH in type 1 diabetes. Finally, we should comment on our participant selection.…”

“…Whether this is due to adaptations in brain regions involved in behavior and decision making is unknown. Positron emission tomography (PET) and functional MRI (fMRI) have been used to investigate brain responses to hypoglycemia in individuals without diabetes and with type 1 diabetes; however, the described impacts of hypoglycemia awareness status are not conclusive (9)(10)(11)(12). Data on global blood flow, an important possible mediator for differences in response, have been discrepant between studies (10,13).…”

Impaired hypoglycemia awareness in diabetes: epidemiology, mechanisms and therapeutic approaches

“…У больных СД1 с сохранным распознаванием гипогликемии нарушается активация префронтальной коры и angular gyrus, а у больных с НРГ активность мозга во время гипогликемии не меняется. Выраженность реакции головного мозга ассоциирована с гормональным ответом на гипогликемию и выраженностью ее симптомов [33].…”