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

Anneliese J. Flatt, Amy J. Peleckis, Cornelia Dalton-Bakes, Huong Lan Nguyen, Sarah Ilany, Austin Matus, Susan K. Malone, Namni Goel, Sooyong Jang, James Weimer, Insup Lee, Michael R. Rickels

Research output: Contribution to journalArticlepeer-review


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·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·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.

Original languageEnglish (US)
Pages (from-to)302-314
Number of pages13
JournalDiabetes Technology and Therapeutics
Issue number5
StatePublished - May 1 2023


  • Automated insulin delivery
  • Glucose counterregulation
  • Hypoglycemia-associated autonomic failure
  • Impaired awareness of hypoglycemia
  • Type 1 diabetes

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology
  • Medical Laboratory Technology


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