Zoe A Stewart1,2, Malgorzata E Wilinska1, Sara Hartnell2, Leanne K O'Neil3, Gerry Rayman4, Eleanor M Scott5, Katharine Barnard6, Conor Farrington7, Roman Hovorka1, Helen R Murphy8,2,3,9. 1. Wellcome Trust-Medical Research Council Institute of Metabolic Science, University of Cambridge, Cambridge, U.K. 2. Wolfson Diabetes and Endocrine Clinic, Cambridge University Hospitals NHS Foundation Trust, Cambridge, U.K. 3. Elsie-Bertram Diabetes Centre, Norfolk and Norwich University Hospitals NHS Foundation Trust, Norwich, U.K. 4. Ipswich Diabetes Centre, Ipswich Hospital NHS Trust, Ipswich, U.K. 5. Division of Epidemiology and Biostatistics, Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, U.K. 6. Faculty of Health and Social Science, Bournemouth University, Bournemouth, U.K. 7. Cambridge Centre for Health Services Research, University of Cambridge, Cambridge, U.K. 8. Wellcome Trust-Medical Research Council Institute of Metabolic Science, University of Cambridge, Cambridge, U.K. hm386@medschl.cam.ac.uk. 9. Norwich Medical School, University of East Anglia, Norwich, U.K.
Abstract
OBJECTIVE: Despite advances in technology, optimal glucose control remains elusive and neonatal complications remain ubiquitous in type 1 diabetes (T1D) pregnancy. Our aim was to examine the safety, efficacy, and longer-term feasibility of day-and-night closed-loop insulin delivery. RESEARCH DESIGN AND METHODS: We recruited 16 pregnant women (mean [SD]: age 32.8 [5.0] years, T1D duration 19.4 [10.2] years, HbA1c 8.0% [1.1], and BMI 26.6 [4.4] kg/m2) to an open-label, randomized, crossover trial. Participants completed 28 days of closed-loop and sensor-augmented pump (SAP) insulin delivery separated by a washout period. Afterward, participants could continue to use the closed-loop system up to 6 weeks postpartum. The primary end point was the proportion of time with glucose levels within the target range (63-140 mg/dL). RESULTS: The proportion of time with glucose levels within target was comparable during closed-loop and SAP insulin delivery (62.3 vs. 60.1% [95% CI -4.1 to 8.3]; P = 0.47). Mean glucose and time spent hyperglycemic >140 mg/dL also did not differ (131.4 vs. 131.4 mg/dL [P = 0.85] and 36.6 vs. 36.1% [P = 0.86], respectively). During closed-loop, fewer hypoglycemic episodes occurred (median 8 [range 1-17] vs. 12.5 [1-53] over 28 days; P = 0.04) and less time at <63 mg/dL (1.6 vs. 2.7%; P = 0.02). Hypoglycemia <50 mg/dL (0.24 vs. 0.47%; P = 0.03) and low blood glucose index (1.0 vs. 1.4; P = 0.01) were lower. Less nocturnal hypoglycemia (2300-0700 h) during closed-loop therapy (1.1 vs. 2.7%; P = 0.008) and a trend toward higher overnight time in target (67.7 vs. 60.6%; P = 0.06) were found. CONCLUSIONS: Closed-loop insulin delivery was associated with comparable glucose control and significantly less hypoglycemia than SAP therapy. Larger, longer-duration multicenter trials are now indicated to determine clinical efficacy of closed-loop insulin delivery in T1D pregnancy and the impact on neonatal outcomes.
RCT Entities:
OBJECTIVE: Despite advances in technology, optimal glucose control remains elusive and neonatal complications remain ubiquitous in type 1 diabetes (T1D) pregnancy. Our aim was to examine the safety, efficacy, and longer-term feasibility of day-and-night closed-loop insulin delivery. RESEARCH DESIGN AND METHODS: We recruited 16 pregnant women (mean [SD]: age 32.8 [5.0] years, T1D duration 19.4 [10.2] years, HbA1c 8.0% [1.1], and BMI 26.6 [4.4] kg/m2) to an open-label, randomized, crossover trial. Participants completed 28 days of closed-loop and sensor-augmented pump (SAP) insulin delivery separated by a washout period. Afterward, participants could continue to use the closed-loop system up to 6 weeks postpartum. The primary end point was the proportion of time with glucose levels within the target range (63-140 mg/dL). RESULTS: The proportion of time with glucose levels within target was comparable during closed-loop and SAP insulin delivery (62.3 vs. 60.1% [95% CI -4.1 to 8.3]; P = 0.47). Mean glucose and time spent hyperglycemic >140 mg/dL also did not differ (131.4 vs. 131.4 mg/dL [P = 0.85] and 36.6 vs. 36.1% [P = 0.86], respectively). During closed-loop, fewer hypoglycemic episodes occurred (median 8 [range 1-17] vs. 12.5 [1-53] over 28 days; P = 0.04) and less time at <63 mg/dL (1.6 vs. 2.7%; P = 0.02). Hypoglycemia <50 mg/dL (0.24 vs. 0.47%; P = 0.03) and low blood glucose index (1.0 vs. 1.4; P = 0.01) were lower. Less nocturnal hypoglycemia (2300-0700 h) during closed-loop therapy (1.1 vs. 2.7%; P = 0.008) and a trend toward higher overnight time in target (67.7 vs. 60.6%; P = 0.06) were found. CONCLUSIONS: Closed-loop insulin delivery was associated with comparable glucose control and significantly less hypoglycemia than SAP therapy. Larger, longer-duration multicenter trials are now indicated to determine clinical efficacy of closed-loop insulin delivery in T1D pregnancy and the impact on neonatal outcomes.
Authors: Carol J Levy; Nicole C Foster; Stephanie N DuBose; Shivani Agarwal; Sarah K Lyons; Anne L Peters; Gabriel I Uwaifo; Linda A DiMeglio; Jennifer L Sherr; Sarit Polsky Journal: J Diabetes Sci Technol Date: 2020-11-20