Effect of Automated Insulin Delivery on Glucose Counterregulation in Long-Standing Type 1 Diabetes

Automated insulin delivery (AID) systems are likely of value in individuals with long-standing T1D where recurrent hypoglycemia reduces counterregulatory response. This study assessed the impact of 18M AID on counterregulatory response to insulin-induced hypoglycemia in individuals with long-standing T1D and impaired awareness of hypoglycemia. participants mean±SD age 49±16 years and diabetes duration 34±16 years were initiated on AID systems. CGM outcomes were paired with actigraphy data to assess daytime and sleep hypoglycemia exposure every 3 months. Hyperinsulinemic stepped-hypoglycemic clamp experiments were performed at baseline, 6 and 18 months. Ten and nine participants have been followed-up to 6M and 18M respectively. Severe hypoglycemia events were reduced from median (IQR) 3 (3-10) to 0 (0-1) events/person·year over 18M (p=0.005) with improved hypoglycemia severity (HYPO, Pre:1134 (808-1686) to 18M:26 (0-128) , p<0.01) and awareness scores (Clarke, Pre:5 (5-6) to 18M:4 (1-5) , p<0.01) . Hypoglycemia exposure was rapidly reduced with effects sustained (%Time<54 mg/dl, Pre:4 (3-7) , 3M:1 (0-1) , 18M:0 (0-1) , p<0.01) and most marked over periods of sleep (%Time<70mg/dl, Pre:11 (4-17) , 3M:1 (0-3) , 18M:0 (0-1) , p<0.001) . Glucose variability was reduced (p<0.01) with more time in range and less in marked hyperglycemia (p=0.02) . HbA1c and insulin dose were not different. The autonomic symptom response to hypoglycemia improved (Pre:6±2, 6M:6±2, 18M:10±2, p<0.05) with an increase in pancreatic polypeptide (Pre:62±29, 6M:127±44, 18M:187±64 pmol/l, p<0.01) and epinephrine response (Pre:199±53, 6M:332±91, 18M:386±95 pg/ml, p<0.01) . Glucagon and endogenous glucose production response were unchanged. AID systems lead to a sustained reduction of hypoglycemia exposure and improvement in symptom and epinephrine response however with persistent impairment in glucose counterregulation and so ongoing compromised physiologic defense against hypoglycemia. Disclosure A.Flatt: None. I.Lee: Other Relationship; VitalCore Software. M.R.Rickels: Advisory Panel; Sernova, Corp., Vertex Pharmaceuticals Incorporated, Zealand Pharma A/S, Consultant; L-Nutra Inc. A.J.Peleckis: None. C.V.Dalton-bakes: None. H.T.Nguyen: None. S.Ilany: None. A.M.Matus: None. S.K.Malone: None. S.Jang: None. J.Weimer: Other Relationship; Neuralert Technologies, Vasowatch. Funding Public Health Services research grants: RDK091331, UDK070430, UL1 TR001878, and P30 DK19525