166-OR: Brain Responses to Hypoglycemia following Contrasting Hypoglycemia Awareness Restoration Strategies: A Comparison of the HARPdoc and HypoAware Studies

Abstract

Background: Restoration of symptoms in response to hypogycemia has been seen in people with type 1 diabetes (T1D) and impaired awareness of hypoglycaemia (IAH) using an education and diabetes technology approach (HypoAware Study) and a psycho-educational approach addressing cognitions (HARPdoc Trial) . We investigated regional brain responses to hypoglycemia following restoration of IAH between the interventions. Methods: Twelve people with T1D and IAH from HypoAware and from HARPdoc underwent two-step hyperinsulinemic hypoglycemic clamps before and after their intervention. pCASL fMRI brain blood flow images were acquired. A 2x2 study by timepoint ANOVA interaction design was conducted to compare the effect of each intervention on hypoglycemia-euglycemia difference brain blood flow maps. Within group analysis of the difference maps was conducted using paired t-tests. Results: HARPdoc participants were older, mean±SD age 54.1±12.3 vs. 34.7±9.0 yrs (p<0.001) with similar HbA1c, 7.8±0.9 vs. 7.8±0.7%, Gold score, 6.0±1.0 vs. 6.0±1.0, BMI 24.6±4.6 vs. 24.4±3.6 and diabetes duration 22.2±7.2 vs. 23.6±7.7 yrs (all p>0.05) . Each intervention was associated with enhanced activation in the anterior cingulate cortex (ACC) in within group studies (HARPdoc FWEp=0.048, HypoAware FWEp=0.011) . In the between group analysis, a superior frontal gyrus (SFG) region was more activated at hypoglycemia following HARPdoc than HypoAware (FWEp=0.044) . Conclusion: We have shown different brain responses to hypoglycemia in treated IAH depending on the therapeutic approach. Enhanced ACC responses were expected following recovery of symptoms. However, the cognitive approach of HARPdoc enhances the hypoglycemia response in the SFG, known to be involved in self-awareness and appreciation of symptoms, is unique to HARPdoc and is consistent with its psychological and cognitive nature. This may increase the potential for lasting effect. Disclosure P.Jacob: None. S.A.Amiel: Advisory Panel; Medtronic, Novo Nordisk, Other Relationship; Sanofi. M.Nwokolo: None. P.Choudhary: Advisory Panel; Abbott Diabetes, Lilly Diabetes, Medtronic, Research Support; Novo Nordisk, Speaker's Bureau; Dexcom, Inc., Glooko, Inc., Insulet Corporation, Sanofi. Funding Juvenile Diabetes Research Foundation (3-SRA-2017-484-S-B)