Automated insulin delivery for hypoglycemia avoidance and glucose counterregulation in long-standing type 1 diabetes with hypoglycemia unawareness

Abstract: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. Ten participants mean±SD 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 post-intervention. 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). Hypoglycemia awareness and severity scores improved (P<0.01) with severe hypoglycemia events reduced from median(IQR) 3(3-10) at baseline to 0(0-1) events/person·year post-intervention (P=0.005). During the hypoglycemic clamp experiments, no change was seen in the endogenous glucose production response, however, peripheral glucose utilization during hypoglycemia was reduced following intervention (Pre:4.6±0.4, 6M:3.8±0.5, 18M:3.4±0.3 mg·kg-1·min-1, P<0.05). There were increases over time in pancreatic polypeptide (Pre:62±29, 6M:127±44, 18M:176±58 pmol/L, P<0.01), epinephrine (Pre:199±53, 6M:332±91, 18M:386±95 pg/mL, P=0.001), and autonomic symptom (Pre:6±2, 6M:6±2, 18M:10±2, P<0.05) responses. AID led to a sustained reduction of hypoglycemia exposure. Endogenous glucose production 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.