Automated Insulin Delivery for Hypoglycemia Avoidance and Glucose Counterregulation in Long-Standing Type 1 Diabetes with Hypoglycemia Unawareness

Objective: Automated insulin delivery (AID) may benefit individuals with long-standing type 1 diabetes where frequent exposure to hypoglycemia impairs counterregulatory responses. This study assessed the effect of 18 months AID on hypoglycemia avoidance and glucose counterregulatory responses to insulin-induced hypoglycemia in long-standing type 1 diabetes complicated by impaired awareness of hypoglycemia.Methods: Ten participants mean +/- standard deviation age 49 +/- 16 and diabetes duration 34 +/- 16 years were initiated on AID. Continuous glucose monitoring was paired with actigraphy to assess awake- and sleep-associated hypoglycemia exposure every 3 months. Hyperinsulinemic hypoglycemic clamp experiments were performed at baseline, 6, and 18 months postintervention. Hypoglycemia exposure was reduced by 3 months, especially during sleep, with effects sustained through 18 months (P <= 0.001) together with reduced glucose variability (P < 0.01).Results: Hypoglycemia awareness and severity scores improved (P < 0.01) with severe hypoglycemia events reduced from median (interquartile range) 3 (3-10) at baseline to 0 (0-1) events/person center dot year postintervention (P = 0.005). During the hypoglycemic clamp experiments, no change was seen in the endogenous glucose production (EGP) response, however, peripheral glucose utilization during hypoglycemia was reduced following intervention [pre: 4.6 +/- 0.4, 6 months: 3.8 +/- 0.5, 18 months: 3.4 +/- 0.3 mg/(kg center dot min), P < 0.05]. There were increases over time in pancreatic polypeptide (Pre:62 +/- 29, 6 months:127 +/- 44, 18 months:176 +/- 58 pmol/L, P < 0.01), epinephrine (Pre: 199 +/- 53, 6 months: 332 +/- 91, 18 months: 386 +/- 95 pg/mL, P = 0.001), and autonomic symptom (Pre: 6 +/- 2, 6 months: 6 +/- 2, 18 months: 10 +/- 2, P < 0.05) responses.Conclusions: AID led to a sustained reduction of hypoglycemia exposure. EGP in response to insulin-induced hypoglycemia remained defective, however, partial recovery of glucose counterregulation was evidenced by a reduction in peripheral glucose utilization likely mediated by increased epinephrine secretion and, together with improved autonomic symptoms, may contribute to the observed clinical reduction in hypoglycemia.