155-OR: ADA Presidents’ Select Abstract: Symptom Responses to Hypoglycemia Are Related to Connectivity Change between the Thalamus and Frontal Lobes

Abstract

Neuroimaging studies highlight the importance of thalamic activation in response to hypoglycemia in people with and without type 1 diabetes (T1D). This activation is characteristically attenuated in impaired awareness of hypoglycaemia (IAH), a major risk factor for severe hypoglycemia. We investigated changes in connectivity of the thalamus with other brain regions during hypoglycemia. Methods: Fourteen people without diabetes (no diabetes, ND), 15 with T1D and normal awareness of hypoglycemia (NAH) and 22 with IAH, all right-handed, age, sex and gender matched, underwent a hyperinsulinemic glucose clamp during which we acquired blood oxygen level dependent fMRI at euglycemia (90mg/dL) and at onset of hypoglycemia (48mg/dL). Connectivity was studied using the CONN toolbox in SPM12. A thalamic seed was used in a seed-to-voxel analysis with and without the increase in symptoms at hypoglycemia as an explanatory regressor variable. Results: Symptom scores in response to hypoglycemia rose earliest and to the greatest levels in NAH (11.0 to 18.3, p= 0.029). The rise in symptom scores in ND was not significant at this timepoint (9.2 to 13.8, p= 0.057), whilst IAH showed no symptom change (10.5 to 9.8, p= 0.7). In ND, hypoglycemia increased thalamic connectivity with the right frontal pole (pFDR = 0.018). This did not occur in diabetes, either in NAH or IAH. The NAH group demonstrated a positive relationship between change in symptoms with change in connectivity of the thalamus and a left frontal pole region (pFDR = 0.035), whereas an overlapping area had a negative correlation in ND (pFDR = 0.001). There was no correlation in IAH. Conclusion: During hypoglycemia, those with T1D display aberrantly enhanced thalamic connectivity with brain regions responsible for complex behavior. Disruption of this network occurs in IAH and may be the mechanism for failure of perception of the onset of hypoglycemia and reduced hypoglycemia avoidance behaviors, increasing severe hypoglycemia risk. Disclosure P. Jacob: None. M. Nwokolo: Other Relationship; Self; Sanofi. O. ODaly: None. F.O. Zelaya: None. S.A. Amiel: Advisory Panel; Self; Medtronic, Novo Nordisk A/S, Roche Pharma. Other Relationship; Self; Diabetes UK. P. Choudhary: Advisory Panel; Self; Abbott, Eli Lilly and Company, Insulet Corporation, Medtronic. Research Support; Self; European Union, JDRF. Speaker’s Bureau; Self; Dexcom, Inc., Novartis AG, Novo Nordisk A/S, Sanofi-Aventis. Funding JDRF (3-SRA-2017-484-S-B)