Abstract
Background: While hybrid closed-loop therapy shows promise for managing type 1 diabetes during pregnancy, its efficacy is unclear.
Methods: In this multicenter parallel-group controlled trial, we randomized pregnant women with type 1 diabetes and glycated hemoglobin ≥6.5% at nine United Kingdom sites to standard insulin therapy with continuous glucose monitoring (control) or to hybrid closed-loop. The primary outcome was the between-treatment difference in percentage of time with sensor glucose measurements in the pregnancy-specific target range (63-140mg/dL [3.5-7.8mmol/L]) from 16 weeks’ gestation until delivery. Analyses were performed according to intention-to-treat principles. Key secondary outcomes included percentage of time spent hyperglycemic (>140mg/dL [>7.8mmol/L]), overnight time-in-range, glycated hemoglobin, and safety events.
Results: 124 participants aged 31.1 ± 5.3 years (Mean ± SD) and baseline glycated hemoglobin 7.7 ± 1.2% were randomized. The mean (±SD) percentage of time with maternal glucose levels within target range was 68.2% ± 10.5% for closed-loop and 55.6 ± 12.5 for controls (mean adjusted difference, 10.5% percentage points (95% confidence interval [CI], 7.0% to 14.0%; P<0.001). Results were consistent in secondary outcomes, with less time in hyperglycemia; (-10.2% 95% CI -13.8% to – 6.6%); higher overnight time-in-range; (12.3% 95% CI 8.3% to 16.2%), and lower glycated hemoglobin;( -0.31%; 95% CI -0.50% to -0.12%) all favoring closed-loop. Time spent hypoglycemic was low. No unanticipated safety problems associated with using closed-loop during pregnancy occurred (six versus five severe hypoglycemia, one diabetic ketoacidosis per group, seven adverse device events).
Conclusions: Hybrid closed-loop therapy significantly improved maternal glycemia during pregnancy complicated by type 1 diabetes. (Trial registration: ISRCTN56898625.)
One in two babies born to women with type 1 diabetes experience complications, most commonly preterm births, large birthweight, and neonatal care unit admissions.1,2 Maternal antenatal hyperglycemia is the major risk factor for these complications, with highest risk among women entering pregnancy with above-target glycated hemoglobin levels.1 Cohort studies and, more recently, intervention trials have unequivocally demonstrated that pregnancy outcomes improve with improved maternal glucose levels.1-4 However, despite improvements in insulin therapy, continuous glucose monitoring, and high motivation for diabetes self-management, attainment of the pregnancy-specific glucose targets of 63-140mg/dL (3.5-7.8mmol/L) as compared to 70-180mg/dL (3.9-10.0mmol/L) outside of pregnancy, remains elusive for most women.2,5-7
Altered eating patterns, marked gestational variations in insulin sensitivity and stringent pregnancy glucose targets provide formidable challenges for diabetes management.8-10 Striving for lower glucose levels brings increased risk of severe hypoglycemia, a leading cause of maternal morbidity and mortality, while hyperglycemia (>140mg/dL [>7.8mmol/L]) is associated with fetal pancreatic hyperinsulinemia and attendant neonatal complications.4,11,12
Outside of pregnancy, use of hybrid closed-loop therapy is associated with improved glucose control in children and adults,13 but whether the more stringent glucose targets required for optimal pregnancy outcomes can be achieved is unknown. The CamAPS FX is a hybrid closed-loop system that enables automatically adjusted insulin delivery from an insulin pump according to real-time sensor glucose measurements. This system was approved for use during pregnancy in the United Kingdom, based on results from two feasibility studies.14,15 Two key developments subsequently occurred-- First, sensor glucose measurements can now be used to inform user-initiated pre-meal boluses. Second, additional features allow the user to intensify or relax closed-loop insulin delivery and to specify personalized glucose targets that can be adjusted during pregnancy. We tested whether hybrid closed-loop therapy started before 16 weeks’ gestation would improve maternal glucose levels during pregnancy complicated by type 1 diabetes.
Methods: In this multicenter parallel-group controlled trial, we randomized pregnant women with type 1 diabetes and glycated hemoglobin ≥6.5% at nine United Kingdom sites to standard insulin therapy with continuous glucose monitoring (control) or to hybrid closed-loop. The primary outcome was the between-treatment difference in percentage of time with sensor glucose measurements in the pregnancy-specific target range (63-140mg/dL [3.5-7.8mmol/L]) from 16 weeks’ gestation until delivery. Analyses were performed according to intention-to-treat principles. Key secondary outcomes included percentage of time spent hyperglycemic (>140mg/dL [>7.8mmol/L]), overnight time-in-range, glycated hemoglobin, and safety events.
Results: 124 participants aged 31.1 ± 5.3 years (Mean ± SD) and baseline glycated hemoglobin 7.7 ± 1.2% were randomized. The mean (±SD) percentage of time with maternal glucose levels within target range was 68.2% ± 10.5% for closed-loop and 55.6 ± 12.5 for controls (mean adjusted difference, 10.5% percentage points (95% confidence interval [CI], 7.0% to 14.0%; P<0.001). Results were consistent in secondary outcomes, with less time in hyperglycemia; (-10.2% 95% CI -13.8% to – 6.6%); higher overnight time-in-range; (12.3% 95% CI 8.3% to 16.2%), and lower glycated hemoglobin;( -0.31%; 95% CI -0.50% to -0.12%) all favoring closed-loop. Time spent hypoglycemic was low. No unanticipated safety problems associated with using closed-loop during pregnancy occurred (six versus five severe hypoglycemia, one diabetic ketoacidosis per group, seven adverse device events).
Conclusions: Hybrid closed-loop therapy significantly improved maternal glycemia during pregnancy complicated by type 1 diabetes. (Trial registration: ISRCTN56898625.)
One in two babies born to women with type 1 diabetes experience complications, most commonly preterm births, large birthweight, and neonatal care unit admissions.1,2 Maternal antenatal hyperglycemia is the major risk factor for these complications, with highest risk among women entering pregnancy with above-target glycated hemoglobin levels.1 Cohort studies and, more recently, intervention trials have unequivocally demonstrated that pregnancy outcomes improve with improved maternal glucose levels.1-4 However, despite improvements in insulin therapy, continuous glucose monitoring, and high motivation for diabetes self-management, attainment of the pregnancy-specific glucose targets of 63-140mg/dL (3.5-7.8mmol/L) as compared to 70-180mg/dL (3.9-10.0mmol/L) outside of pregnancy, remains elusive for most women.2,5-7
Altered eating patterns, marked gestational variations in insulin sensitivity and stringent pregnancy glucose targets provide formidable challenges for diabetes management.8-10 Striving for lower glucose levels brings increased risk of severe hypoglycemia, a leading cause of maternal morbidity and mortality, while hyperglycemia (>140mg/dL [>7.8mmol/L]) is associated with fetal pancreatic hyperinsulinemia and attendant neonatal complications.4,11,12
Outside of pregnancy, use of hybrid closed-loop therapy is associated with improved glucose control in children and adults,13 but whether the more stringent glucose targets required for optimal pregnancy outcomes can be achieved is unknown. The CamAPS FX is a hybrid closed-loop system that enables automatically adjusted insulin delivery from an insulin pump according to real-time sensor glucose measurements. This system was approved for use during pregnancy in the United Kingdom, based on results from two feasibility studies.14,15 Two key developments subsequently occurred-- First, sensor glucose measurements can now be used to inform user-initiated pre-meal boluses. Second, additional features allow the user to intensify or relax closed-loop insulin delivery and to specify personalized glucose targets that can be adjusted during pregnancy. We tested whether hybrid closed-loop therapy started before 16 weeks’ gestation would improve maternal glucose levels during pregnancy complicated by type 1 diabetes.
| Original language | English |
|---|---|
| Journal | New England Journal of Medicine |
| Volume | 389 |
| Issue number | 17 |
| Early online date | 5 Oct 2023 |
| DOIs | |
| Publication status | Published - 26 Oct 2023 |