TY - JOUR
T1 - Automated Insulin Delivery for Hypoglycemia Avoidance and Glucose Counterregulation in Long-Standing Type 1 Diabetes with Hypoglycemia Unawareness
AU - Flatt, Anneliese J.
AU - Peleckis, Amy J.
AU - Dalton-Bakes, Cornelia
AU - Nguyen, Huong Lan
AU - Ilany, Sarah
AU - Matus, Austin
AU - Malone, Susan K.
AU - Goel, Namni
AU - Jang, Sooyong
AU - Weimer, James
AU - Lee, Insup
AU - Rickels, Michael R.
N1 - Publisher Copyright:
Copyright © 2023 Mary Ann Liebert, Inc.
PY - 2023/5/1
Y1 - 2023/5/1
N2 - 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.
AB - 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.
KW - Automated insulin delivery
KW - Glucose counterregulation
KW - Hypoglycemia-associated autonomic failure
KW - Impaired awareness of hypoglycemia
KW - Type 1 diabetes
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U2 - 10.1089/dia.2022.0506
DO - 10.1089/dia.2022.0506
M3 - Article
C2 - 36763336
AN - SCOPUS:85154562746
SN - 1520-9156
VL - 25
SP - 302
EP - 314
JO - Diabetes Technology and Therapeutics
JF - Diabetes Technology and Therapeutics
IS - 5
ER -