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 - Funding Information:
This work was supported by Public Health Service research grants R01 DK091331 (to M.R.R.), UL1 TR001878 (University of Pennsylvania Center for Human Phenomic Science), P30 DK19525 (University of Pennsylvania Diabetes Research Center), K99NR017416 (to S.K.M.), and R01 DK11788 (to N.G.); National Aeronautics and Space Administration (NASA) grants NNX14AN49G and 80NSSC20K0243 (to N.G.); Pennsylvania Department of Health grant SAP 4100079750 (to I.L.); the Charles B. Humpton, Jr. Endowed Fellowship in Diabetes Research (to A.J.F.); and the Human Metabolism Resource of the University of Pennsylvania Institute for Diabetes, Obesity & Metabolism. Medtronic supplied discounted 670G insulin pumps and glucose monitoring devices for the study through investigator-initiated grant NERP16-015 (to M.R.R.).
Funding Information:
This work was supported by Public Health Service research grants R01 DK091331 (to M.R.R.), UL1 TR001878 (University of Pennsylvania Center for Human Phenomic Science), P30 DK19525 (University of Pennsylvania Diabetes Research Center), K99NR017416 (to S.K.M.), and R01 DK11788 (to N.G.); National Aeronautics and Space Administration (NASA) grants NNX14AN49G and 80NSSC 20K0243 (to N.G.); Pennsylvania Department of Health grant SAP 4100079750 (to I.L.); the Charles B. Humpton, Jr. Endowed Fellowship in Diabetes Research (to A.J.F.); and the Human Metabolism Resource of the University of Pennsylvania Institute for Diabetes, Obesity & Metabolism. Medtronic supplied discounted 670G insulin pumps and glucose monitoring devices for the study through investigatorinitiated grant NERP16-015 (to M.R.R.).
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
UR - http://www.scopus.com/inward/record.url?scp=85154562746&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85154562746&partnerID=8YFLogxK
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 -