Day-and-Night Closed-Loop Insulin Delivery in a Broad Population of Pregnant Women With Type 1 Diabetes: A Randomized Controlled Crossover Trial.

Abstract

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. We recruited 16 pregnant women (mean [SD]: age 32.8 [5.0] years, T1D duration 19.4 [10.2] years, HbA_1c 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). 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]; <i>P</i> = 0.47). Mean glucose and time spent hyperglycemic >140 mg/dL also did not differ (131.4 vs. 131.4 mg/dL [<i>P</i> = 0.85] and 36.6 vs. 36.1% [<i>P</i> = 0.86], respectively). During closed-loop, fewer hypoglycemic episodes occurred (median 8 [range 1-17] vs. 12.5 [1-53] over 28 days; <i>P</i> = 0.04) and less time at <63 mg/dL (1.6 vs. 2.7%; <i>P</i> = 0.02). Hypoglycemia <50 mg/dL (0.24 vs. 0.47%; <i>P</i> = 0.03) and low blood glucose index (1.0 vs. 1.4; <i>P</i> = 0.01) were lower. Less nocturnal hypoglycemia (2300-0700 h) during closed-loop therapy (1.1 vs. 2.7%; <i>P</i> = 0.008) and a trend toward higher overnight time in target (67.7 vs. 60.6%; <i>P</i> = 0.06) were found. 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.