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Competing Interests: HRM is a member of the UK and European Medtronic Scientific Advisory Boards and reports receiving speaker honoraria from Dexcom, Abbott Diabetes Care, Novo Nordisk, and Ypsomed. EMS reports receiving speaker honoraria from Abbott Diabetes Care.

Norbert Freinkel emphasized the need for "more aggressive therapy with exogenous insulin" during type 1 diabetes (T1D) pregnancy. Recent advances in diabetes technology, continuous glucose monitoring (CGM), and hybrid closed-loop (HCL) insulin delivery systems allow us to revisit Freinkel's observations from a contemporary perspective. The Continuous Glucose Monitoring in Women With Type 1 Diabetes in Pregnancy Trial (CONCEPTT) led to international recommendations that CGM be offered to all pregnant women with T1D to help them meet their pregnancy glucose targets and improve neonatal outcomes. However, despite CGM use, only 35% of trial participants reached the pregnancy glucose targets by 35 weeks' gestation, which is too late for optimal obstetric and neonatal outcomes. The constant vigilance to CGM data and insulin dose adjustment, with perpetual worry about the impact of hyperglycemia on the developing fetal structures, leave many pregnant women feeling overwhelmed. HCL systems that can adapt to marked gestational changes in insulin sensitivity and pharmacokinetics may help to bridge the gap between the nonpregnant time in range glycemic targets (70-180 mg/dL) and the substantially more stringent pregnancy-specific targets (TIRp) (63-140 mg/dL) required for optimal obstetric and neonatal outcomes. Use of HCL (CamAPS FX system) was associated with a 10.5% higher TIRp, 10.2% less hyperglycemia, and 12.3% higher overnight TIRp. Clinical benefits were accompanied by 3.7 kg (8 lb) less gestational weight gain and consistently achieved across a representative patient population of insulin pump or injection users, across trial sites, and across maternal HbA1c categories. Working collaboratively, women, HCL technology, and health care teams achieved improved glycemia with less worry, less work, and more positive pregnancy experiences., (© 2024 by the American Diabetes Association.)

Introduction: Recent high-profile calls have emphasized that women's experiences should be considered in maternity care provisioning. We explored women's experiences of using closed-loop during type 1 diabetes (T1D) pregnancy to inform decision-making about antenatal rollout and guidance and support given to future users. Methods: We interviewed 23 closed-loop participants in the Automated insulin Delivery Among Pregnant women with T1D (AiDAPT) trial after randomization to closed-loop and ∼20 weeks later. Data were analyzed thematically. Results: Women described how closed-loop lessened the physical and mental demands of diabetes management, enabling them to feel more normal and sleep better. By virtue of spending increased time-in-range, women also worried less about risks to their baby and being judged negatively by health care professionals. Most noted that intensive input and support during early pregnancy had been crucial to adjusting to, and developing confidence in, the technology. Women emphasized that attaining pregnancy glucose targets still required ongoing effort from themselves and the health care team. Women described needing education to help them determine when, and how, to intervene and when to allow the closed-loop to operate without interference. All women reported more enjoyable pregnancy experiences as a result of using closed-loop; some also noted being able to remain longer in paid employment. Conclusions: Study findings endorse closed-loop use in T1D pregnancy by highlighting how the technology can facilitate positive pregnancy experiences. To realize fully the benefits of closed-loop, pregnant women would benefit from initial intensive oversight and support together with closed-loop specific education and training. Clinical Trial Registration number: NCT04938557.

Objective: To describe glucose metrics in a high-risk population of women with type 2 diabetes (T2DM) in pregnancy and to explore the associations with neonatal outcomes. Research Design and Methods: Prospective observational study of 57 women. Continuous glucose monitoring (CGM) trajectories were determined from metrics collected in early and late gestation using the first and last two (mean 16 and 35) weeks of Freestyle Libre data. Logistic regression was used to examine associations of CGM metrics with neonatal hypoglycemia (glucose <2.6 mmol/L requiring intravenous dextrose) and large for gestational age (LGA) (>90th percentile for gestational age and sex). Pregnancy-specific target glucose range was 3.5-7.8 mmol/L (63-140 mg/dL). Results: Forty-one women used CGM for 15 weeks (mean age 33 years, 73% Aboriginal or Torres Strait Islander, 32% living remotely). There was limited change in average metrics from early to late pregnancy. For the subgroup with sensor use >50% ( n  = 29), mean time in range (TIR) increased by 9%, time above range reduced by 12%, average glucose reduced by 1 mmol/L, and time below range increased by 3%. Neonatal hypoglycemia was associated with most CGM metrics, HbA1c and CGM targets, particularly those from late pregnancy. LGA was associated with hyperglycemic metrics from early pregnancy. Each 1% increase TIR was associated with a 4%-5% reduction in risk of neonatal complications. Conclusion: In this high-risk group of women with T2DM, CGM metrics only improved during pregnancy in those with greater sensor use and were associated with LGA in early pregnancy and neonatal hypoglycemia throughout. Culturally appropriate health care strategies are critical for successful use of CGM technology.

Background: Hybrid closed-loop insulin therapy has shown promise for management of type 1 diabetes during pregnancy; however, its efficacy is unclear., Methods: In this multicenter, controlled trial, we randomly assigned pregnant women with type 1 diabetes and a glycated hemoglobin level of at least 6.5% at nine sites in the United Kingdom to receive standard insulin therapy or hybrid closed-loop therapy, with both groups using continuous glucose monitoring. The primary outcome was the percentage of time in the pregnancy-specific target glucose range (63 to 140 mg per deciliter [3.5 to 7.8 mmol per liter]) as measured by continuous glucose monitoring from 16 weeks' gestation until delivery. Analyses were performed according to the intention-to-treat principle. Key secondary outcomes were the percentage of time spent in a hyperglycemic state (glucose level >140 mg per deciliter), overnight time in the target range, the glycated hemoglobin level, and safety events., Results: A total of 124 participants with a mean (±SD) age of 31.1±5.3 years and a mean baseline glycated hemoglobin level of 7.7±1.2% underwent randomization. The mean percentage of time that the maternal glucose level was in the target range was 68.2±10.5% in the closed-loop group and 55.6±12.5% in the standard-care group (mean adjusted difference, 10.5 percentage points; 95% confidence interval [CI], 7.0 to 14.0; P<0.001). Results for the secondary outcomes were consistent with those of the primary outcome; participants in the closed-loop group spent less time in a hyperglycemic state than those in the standard-care group (difference, -10.2 percentage points; 95% CI, -13.8 to -6.6); had more overnight time in the target range (difference, 12.3 percentage points; 95% CI, 8.3 to 16.2), and had lower glycated hemoglobin levels (difference, -0.31 percentage points; 95% CI, -0.50 to -0.12). Little time was spent in a hypoglycemic state. No unanticipated safety problems associated with the use of closed-loop therapy during pregnancy occurred (6 instances of severe hypoglycemia, vs. 5 in the standard-care group; 1 instance of diabetic ketoacidosis in each group; and 12 device-related adverse events in the closed-loop group, 7 related to closed-loop therapy)., Conclusions: Hybrid closed-loop therapy significantly improved maternal glycemic control during pregnancy complicated by type 1 diabetes. (Funded by the Efficacy and Mechanism Evaluation Program; AiDAPT ISRCTN Registry number, ISRCTN56898625.)., (Copyright © 2023 Massachusetts Medical Society.)

This article summarises the Joint British Diabetes Societies for Inpatient Care guidelines on the management of glycaemia in pregnant women with diabetes on obstetric wards and delivery units, Joint British Diabetes Societies (JBDS) for Inpatient Care Group, ABCD (Diabetes Care) Ltd. The updated guideline offers two approaches - the traditional approach with tight glycaemic targets (4.0-7.0 mmol/L) and an updated pragmatic approach (5.0-8.0 mmol/L) to reduce the risk of maternal hypoglycaemia whilst maintaining safe glycaemia. This is particularly relevant for women with type 1 diabetes who are increasingly using Continuous Glucose Monitoring (CGM) and Continuous Subcutaneous Insulin Infusion (CSII) during pregnancy. All women with diabetes should have a documented delivery plan agreed during antenatal clinic appointments. Hyperglycaemia following steroid administration can be managed either by increasing basal and prandial insulin doses, typically by 50% to 80%, or by adding a variable rate of intravenous insulin infusion (VRIII). Glucose levels, either capillary blood glucose or CGM glucose levels, should be measured at least hourly from the onset of established labour, artificial rupture of membranes or admission for elective caesarean section. If intrapartum glucose levels are higher than 7.0 or 8.0 mmol/L on two consecutive occasions, VRIII is recommended. Hourly capillary blood glucose rather than CGM glucose measurements should be used to adjust VRIII. The recommended substrate fluid to be administered alongside a VRIII is 0.9% sodium chloride solution with 5% glucose and 0.15% potassium chloride (KCl) (20 mmol/L) or 0.3% KCl (40 mmol/L) at 50 ml/hr. Both the VRIII and CSII rates should be reduced by at least 50% after delivery., (© 2021 Diabetes UK.)

Background: Diabetes in pregnancy is associated with preterm delivery, birthweight extremes, and increased rates of congenital anomaly, stillbirth, and neonatal death. We aimed to identify and compare modifiable risk factors associated with adverse pregnancy outcomes in women with type 1 diabetes and those with type 2 diabetes and to identify effective maternity clinics., Methods: In this national population-based cohort study, we used data for pregnancies among women with type 1 or type 2 diabetes collected in the first 5 years of the National Pregnancy in Diabetes audit across 172 maternity clinics in England, Wales, and the Isle of Man, UK. Data for obstetric complications (eg, preterm delivery [<37 weeks' gestation], large for gestational age [LGA] birthweight [>90th percentile]) and adverse pregnancy outcomes (congenital anomaly, stillbirth, neonatal death) were obtained for pregnancies completed between Jan 1, 2014, and Dec 31, 2018. We assessed associations between modifiable (eg, HbA 1c , BMI, pre-pregnancy care, maternity clinic) and non-modifiable risk factors (eg, age, ethnicity, deprivation, duration of type 1 diabetes) with pregnancy outcomes in women with type 1 diabetes compared with those with type 2 diabetes. We calculated associations between maternal factors and perinatal deaths using a regression model, including diabetes type and duration, maternal age, BMI, deprivation quintile, first trimester HbA 1c , preconception folic acid, potentially harmful medications, and third trimester HbA 1c ., Findings: Our dataset included 17 375 pregnancy outcomes in 15 290 pregnant women. 8690 (50·0%) of 17 375 pregnancies were in women with type 1 diabetes (median age at delivery 30 years [10-90th percentile 22-37], median duration of diabetes 13 years [3-25]) and 8685 (50·0%) were in women with type 2 diabetes (median age at delivery 34 years [27-41], median duration of diabetes 3 years [0-10]). The rates of preterm delivery (3325 [42·5%] of 7825 pregnancies among women with type 1 diabetes, 1825 [23·4%] of 7815 with type 2 diabetes; p<0·0001), and LGA birthweight (4095 [52·2%] of 7845 with type 1 diabetes, 2065 [26·2%] of 7885 with type 2 diabetes; p<0·0001) were higher in type 1 diabetes. The prevalence of congenital anomaly (among women with type 1 diabetes: 44·8 per 1000 livebirths, terminations, and fetal losses; among women with type 2 diabetes: 40·5 per 1000 livebirths, terminations, and fetal losses; p=0·17) and stillbirth (type 1 diabetes: 10·4 per 1000 livebirths and stillbirths; type 2 diabetes: 13·5 per 1000 livebirths and stillbirths; p=0·072) did not significantly differ between diabetes types, but rates of neonatal death were higher in mothers with type 2 diabetes than in those with type 1 diabetes (type 1 diabetes: 7·4 per 1000 livebirths; type 2 diabetes 11·2 per 1000 livebirths; p=0·013). Across the whole study population, independent risk factors for perinatal death (ie, stillbirth or neonatal death) were third trimester HbA 1c of 6·5% (48 mmol/mol) or higher (odds ratio 3·06 [95% CI 2·16-4·33] vs HbA 1c <6·5%), being in the highest deprivation quintile (2·29 [1·16-4·52] vs the lowest quintile), and having type 2 diabetes (1·65 [1·18-2·31] vs type 1 diabetes). Variations in HbA 1c and LGA birthweight were associated with maternal characteristics (age, diabetes duration, deprivation, BMI) without substantial differences between maternity clinics., Interpretation: Our data highlight persistent adverse pregnancy outcomes in women with type 1 or type 2 diabetes. Maternal glycaemia and BMI are the key modifiable risk factors. No maternity clinics were had appreciably better outcomes than any others, suggesting that health-care system changes are needed across all clinics., Funding: None., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objective: To determine if temporal glucose profiles differed between 1 ) women who were randomized to real-time continuous glucose monitoring (RT-CGM) or self-monitored blood glucose (SMBG), 2 ) women who used insulin pumps or multiple daily insulin injections (MDIs), and 3 ) women whose infants were born large for gestational age (LGA) or not, by assessing CGM data obtained from the Continuous Glucose Monitoring in Women With Type 1 Diabetes in Pregnancy Trial (CONCEPTT)., Research Design and Methods: Standard summary metrics and functional data analysis (FDA) were applied to CGM data from the CONCEPTT trial (RT-CGM, n = 100; SMBG, n = 100) taken at baseline and at 24- and 34-weeks' gestation. Multivariable regression analysis determined if temporal differences in 24-h glucose profiles occurred between comparators in each of the three groups., Results: FDA revealed that women using RT-CGM had significantly lower glucose (0.4-0.8 mmol/L [7-14 mg/dL]) for 7 h/day (0800 h to 1200 h and 1600 h to 1900 h) compared with those with SMBG. Women using pumps had significantly higher glucose (0.4-0.9 mmol/L [7-16 mg/dL]) for 12 h/day (0300 h to 0600 h, 1300 h to 1800 h, and 2030 h to 0030 h) at 24 weeks with no difference at 34 weeks compared with MDI. Women who had an LGA infant ran a significantly higher glucose by 0.4-0.7 mmol/L (7-13 mg/dL) for 4.5 h/day at baseline, by 0.4-0.9 mmol/L (7-16 mg/dL) for 16 h/day at 24 weeks, and by 0.4-0.7 mmol/L (7-13 mg/dL) for 14 h/day at 34 weeks., Conclusions: FDA of temporal glucose profiles gives important information about differences in glucose control and its timing, which are undetectable by standard summary metrics. Women using RT-CGM were able to achieve better daytime glucose control, reducing fetal exposure to maternal glucose., (© 2020 by the American Diabetes Association.)

Background: Pregnant women with diabetes are identified as being more vulnerable to the severe effects of COVID-19 and advised to stringently follow social distancing measures. Here, we review the management of diabetes in pregnancy before and during the lockdown. Methods: Majority of antenatal diabetes and obstetric visits are provided remotely, with pregnant women attending hospital clinics only for essential ultrasound scans and labor and delivery. Online resources for supporting women planning pregnancy and for self-management of pregnant women with type 1 diabetes (T1D) using intermittent or continuous glucose monitoring are provided. Retinal screening procedures, intrapartum care, and the varying impact of lockdown on maternal glycemic control are considered. Alternative screening procedures for diagnosing hyperglycemia during pregnancy and gestational diabetes mellitus (GDM) are discussed. Case histories describe the remote initiation of insulin pump therapy and automated insulin delivery in T1D pregnancy. Results: Initial feedback suggests that video consultations are well received and that the patient experiences for women requiring face-to-face visits are greatly improved. As the pandemic eases, formal evaluation of remote models of diabetes education and technology implementation, including women's views, will be important. Conclusions: Research and audit activities will resume and we will find new ways for supporting pregnant women with diabetes to choose their preferred glucose monitoring and insulin delivery.

Aim: To describe the continuous glucose monitoring (CGM) profiles of type 1 diabetes (T1D) offspring in the early neonatal period and its association with maternal intrapartum glucose control., Methods: A prospective observational study of T1D pregnant women and their neonatal offspring. Women had a CGM sensor inserted 2-3 days before delivery. Infants had a masked CGM sensor inserted as soon as possible after delivery. Maternal glycemic outcomes were time-in-target (70-140 mg/dL [3.9-7.8 mmol/L]), hyperglycemia >140 mg/dL (7.8 mmol/L), and mean CGM glucose during the 24 h preceding delivery. Neonatal outcomes included lowest recorded blood glucose concentration, and CGM measures (glucose <47 mg/dL [2.6 mmol/L], time-in-target (47-144 mg/dL [2.6-8.0 mmol/L]), glucose standard deviation [SD]) during the first 72 h of life., Results: Data were available for 16 mother-infant pairs. Mothers had a mean age (SD) 32.3 (4.3) years, T1D duration 17.6 (6.8) years, first antenatal glycated hemoglobin 7.4 (0.8)% (57 [8.5] mmol/mol). In the 24 h preceding delivery, mothers spent mean (SD) 72 (20)% time-in-target (70-140 mg/dL [3.9-7.8 mmol/L]), 19 (15)% time >140 mg/dL (7.8 mmol/L), and 9 (9)% time <70 mg/dL (3.9 mmol/L) with mean (SD) CGM glucose 113 (9) mg/dL (6.3 [0.7] mmol/L). Fifteen infants (93.8%) had ≥1 blood glucose concentration <47 mg/dL (2.6 mmol/L), and five had ≥1 blood glucose concentration <18 mg/dL (1.0 mmol/L). The mean infant CGM glucose on days 1, 2, and 3 of life was 63 (14), 67 (13), 76 (11) mg/dL (3.5 [0.8], 3.7 [0.7], and 4.2 [0.6] mmol/L). Four infants (25%) spent >50% time with CGM glucose levels <47 mg/dL (2.6 mmol/L) on day 1., Conclusions: CGM detected widespread neonatal hypoglycemia, even among mothers with good intrapartum glucose control.

Studies from Scotland and Canada confirm large increases in the incidence of pregnancies complicated by pregestational type 1 diabetes (T1D). With this increased antenatal workload comes more specialization and staff expertise, which may be important as diabetes technology use increases. While euglycemia remains elusive and obstetrical intervention (earlier delivery, increased operative deliveries) is increasing, there have been some notable successes in the past 5-10 years. These include a decline in the rates of congenital anomaly (Canada) and stillbirths (U.K.) and substantial reductions in both maternal hypoglycemia (both moderate and severe) across many countries. However, pregnant women with T1D still spend ∼30-45% of the time (8-11 h/day) hyperglycemic during the second and third trimesters. The duration of maternal hyperglycemia appears unchanged in routine clinical care over the past decade. This ongoing fetal exposure to maternal hyperglycemia likely explains the persistent rates of large for gestational age (LGA), neonatal hypoglycemia, and neonatal intensive care unit (NICU) admissions in T1D offspring. The Continuous Glucose Monitoring in Women With Type 1 Diabetes in Pregnancy Trial (CONCEPTT) found that pregnant women using real-time continuous glucose monitoring (CGM) spent 5% less time (1.2 h/day) hyperglycemic during the third trimester, with clinically relevant reductions in LGA, neonatal hypoglycemia, and NICU admissions. This article will review the progress in our understanding of the intensive glycemic treatment of T1D pregnancy, focusing in particular on the recent technological advances in CGM and automated insulin delivery. It suggests that even with advanced diabetes technology, optimal maternal dietary intake is needed to minimize the neonatal complications attributed to postprandial hyperglycemia., (© 2018 by the American Diabetes Association.)

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, HbA 1c 8.0% [1.1], and BMI 26.6 [4.4] kg/m 2 ) 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., (© 2018 by the American Diabetes Association.)

Tight glucose control during labor and delivery is recommended for pregnant women with type 1 diabetes. This can be challenging to achieve using the current treatment modalities. The automated nature of closed loop and its ability to adapt to real-time glucose levels make it well suited for use during labor, delivery, and the immediate postpartum period. We report observational data of participants from two randomized crossover trials who chose to continue using closed loop during labor, delivery, and postpartum. Labor was defined as the 24 h before delivery and postpartum as the 48 h after delivery. The glucose target range during pregnancy was 3.5-7.8 mmol/L (63-140 mg/dL) and 3.9-10 mmol/L (70-180 mg/dL) after delivery. Twenty-seven (84.4%) of the potential 32 trial participants used closed loop through labor, delivery, and postpartum. Use of closed loop was associated with 82.0% (interquartile range [IQR] 49.3, 93.0) time-in-target range during labor and delivery and a mean glucose of 6.9 ± 1.4 mmol/L (124 ± 25 mg/dL). Closed loop performed well throughout vaginal, elective, and emergency cesarean section deliveries. Postpartum, women spent 83.3% (IQR 75.2, 94.6) time-in-target range (3.9-10.0 mmol/L [70-180 mg/dL]), with a mean glucose of 7.2 ± 1.4 mmol/L (130 ± 25 mg/dL). There was no difference in maternal glucose concentration between mothers of infants with and without neonatal hypoglycemia (6.9 ± 1.6 mmol/L and 6.8 ± 1.1 mmol/L [124 ± 29 mg/dL and 122 ± 20 mg/dL] respectively; P = 0.84). Automated closed-loop insulin delivery is feasible during hospital admissions for labor, delivery, and postpartum. Larger scale studies are needed to evaluate its efficacy compared with current clinical approaches as well as understand how women and healthcare providers will adopt this technology.

Background: In patients with type 1 diabetes who are not pregnant, closed-loop (automated) insulin delivery can provide better glycemic control than sensor-augmented pump therapy, but data are lacking on the efficacy, safety, and feasibility of closed-loop therapy during pregnancy., Methods: We performed an open-label, randomized, crossover study comparing overnight closed-loop therapy with sensor-augmented pump therapy, followed by a continuation phase in which the closed-loop system was used day and night. Sixteen pregnant women with type 1 diabetes completed 4 weeks of closed-loop pump therapy (intervention) and sensor-augmented pump therapy (control) in random order. During the continuation phase, 14 of the participants used the closed-loop system day and night until delivery. The primary outcome was the percentage of time that overnight glucose levels were within the target range (63 to 140 mg per deciliter [3.5 to 7.8 mmol per liter])., Results: The percentage of time that overnight glucose levels were in the target range was higher during closed-loop therapy than during control therapy (74.7% vs. 59.5%; absolute difference, 15.2 percentage points; 95% confidence interval, 6.1 to 24.2; P=0.002). The overnight mean glucose level was lower during closed-loop therapy than during control therapy (119 vs. 133 mg per deciliter [6.6 vs. 7.4 mmol per liter], P=0.009). There were no significant differences between closed-loop and control therapy in the percentage of time in which glucose levels were below the target range (1.3% and 1.9%, respectively; P=0.28), in insulin doses, or in adverse-event rates. During the continuation phase (up to 14.6 additional weeks, including antenatal hospitalizations, labor, and delivery), glucose levels were in the target range 68.7% of the time; the mean glucose level was 126 mg per deciliter (7.0 mmol per liter). No episodes of severe hypoglycemia requiring third-party assistance occurred during either phase., Conclusions: Overnight closed-loop therapy resulted in better glucose control than sensor-augmented pump therapy in pregnant women with type 1 diabetes. Women receiving day-and-night closed-loop therapy maintained glycemic control during a high proportion of the time in a period that encompassed antenatal hospital admission, labor, and delivery. (Funded by the National Institute for Health Research and others; Current Controlled Trials number, ISRCTN71510001.).

Background: Women with type 1 diabetes strive for optimal glycemic control before and during pregnancy to avoid adverse obstetric and perinatal outcomes. For most women, optimal glycemic control is challenging to achieve and maintain. The aim of this study is to determine whether the use of real-time continuous glucose monitoring (RT-CGM) will improve glycemic control in women with type 1 diabetes who are pregnant or planning pregnancy., Methods/design: A multi-center, open label, randomized, controlled trial of women with type 1 diabetes who are either planning pregnancy with an HbA1c of 7.0 % to ≤10.0 % (53 to ≤ 86 mmol/mol) or are in early pregnancy (<13 weeks 6 days) with an HbA1c of 6.5 % to ≤10.0 % (48 to ≤ 86 mmol/mol). Participants will be randomized to either RT-CGM alongside conventional intermittent home glucose monitoring (HGM), or HGM alone. Eligible women will wear a CGM which does not display the glucose result for 6 days during the run-in phase. To be eligible for randomization, a minimum of 4 HGM measurements per day and a minimum of 96 hours total with 24 hours overnight (11 pm-7 am) of CGM glucose values are required. Those meeting these criteria are randomized to RT- CGM or HGM. A total of 324 women will be recruited (110 planning pregnancy, 214 pregnant). This takes into account 15 and 20 % attrition rates for the planning pregnancy and pregnant cohorts and will detect a clinically relevant 0.5 % difference between groups at 90 % power with 5 % significance. Randomization will stratify for type of insulin treatment (pump or multiple daily injections) and baseline HbA1c. Analyses will be performed according to intention to treat. The primary outcome is the change in glycemic control as measured by HbA1c from baseline to 24 weeks or conception in women planning pregnancy, and from baseline to 34 weeks gestation during pregnancy. Secondary outcomes include maternal hypoglycemia, CGM time in, above and below target (3.5-7.8 mmol/l), glucose variability measures, maternal and neonatal outcomes., Discussion: This will be the first international multicenter randomized controlled trial to evaluate the impact of RT- CGM before and during pregnancy in women with type 1 diabetes., Trial Registration: ClinicalTrials.gov Identifier: NCT01788527 Registration Date: December 19, 2012.

Objective: Continuous glucose monitoring (CGM) is increasingly used to assess glucose control in diabetes. The objective was to examine how analysis of glucose data might improve our understanding of the role temporal glucose variation has on large-for-gestational-age (LGA) infants born to women with diabetes., Research Design and Methods: Functional data analysis (FDA) was applied to 1.68 million glucose measurements from 759 measurement episodes, obtained from two previously published randomized controlled trials of CGM in pregnant women with diabetes. A total of 117 women with type 1 diabetes (n = 89) and type 2 diabetes (n = 28) who used repeated CGM during pregnancy were recruited from secondary care multidisciplinary obstetric clinics for diabetes in the U.K. and Denmark. LGA was defined as birth weight ≥90th percentile adjusted for sex and gestational age., Results: A total of 54 of 117 (46%) women developed LGA. LGA was associated with lower mean glucose (7.0 vs. 7.1 mmol/L; P < 0.01) in trimester 1, with higher mean glucose in trimester 2 (7.0 vs. 6.7 mmol/L; P < 0.001) and trimester 3 (6.5 vs. 6.4 mmol/L; P < 0.01). FDA showed that glucose was significantly lower midmorning (0900-1100 h) and early evening (1900-2130 h) in trimester 1, significantly higher early morning (0330-0630 h) and throughout the afternoon (1130-1700 h) in trimester 2, and significantly higher during the evening (2030-2330 h) in trimester 3 in women whose infants were LGA., Conclusions: FDA of CGM data identified specific times of day that maternal glucose excursions were associated with LGA. It highlights trimester-specific differences, allowing treatment to be targeted to gestational glucose patterns., (© 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.)

Ineffective management of blood glucose levels during preconception and pregnancy has been associated with severe maternal and fetal complications in women with pre-existing diabetes. Studies have demonstrated that preconception counseling and pre-pregnancy care can dramatically reduce these risks. However, pregnancy-related outcomes in women with diabetes continue to be less than ideal. This review highlights and discusses a variety of patient, provider, and organizational factors that can contribute to these suboptimal outcomes. Based on the findings of studies reviewed and authors' clinical and research experiences, recommendations have been proposed focusing on various aspects of care provided, including improved accessibility to effective preconception and pregnancy-related care and better organized clinic consultations that are sensitive to women's diabetes and pregnancy needs.

Background: Performance of continuous glucose monitors (CGMs) may be lower when glucose levels are changing rapidly, such as occurs during physical activity. Our aim was to evaluate accuracy of a current-generation CGM during moderate-intensity exercise in type 1 diabetes (T1D) pregnancy., Subjects and Methods: As part of a study of 24-h closed-loop insulin delivery in 12 women with T1D (disease duration, 17.6 years; glycosylated hemoglobin, 6.4%) during pregnancy (gestation, 21 weeks), we evaluated the Freestyle Navigator(®) sensor (Abbott Diabetes Care, Alameda, CA) during afternoon (15:00-18:00 h) and morning (09:30-12:30 h) exercise (55 min of brisk walking on a treadmill followed by a 2-h recovery), compared with sedentary conditions (18:00-09:00 h). Plasma (reference) glucose, measured at regular 15-30-min intervals with the YSI Ltd. (Fleet, United Kingdom) model YSI 2300 analyzer, was used to assess CGM performance., Results: Sensor accuracy, as indicated by the larger relative absolute difference (RAD) between paired sensor and reference glucose values, was lower during exercise compared with rest (median RAD, 11.8% vs. 18.4%; P<0.001). These differences remained significant when correcting for plasma glucose relative rate of change (P<0.001). Analysis by glucose range showed lower accuracy during hypoglycemia for both sedentary (median RAD, 24.4%) and exercise (median RAD, 32.1%) conditions. Using Clarke error grid analysis, 96% of CGM values were clinically safe under resting conditions compared with only 87% during exercise., Conclusions: Compared with sedentary conditions, accuracy of the Freestyle Navigator CGM was lower during moderate-intensity exercise in pregnant women with T1D. This difference was particularly marked in hypoglycemia and could not be solely explained by the glucose rate of change associated with physical activity.

Objective: To evaluate the safety and efficacy of closed-loop insulin delivery in well-controlled pregnant women with type 1 diabetes treated with continuous subcutaneous insulin infusion (CSII)., Research Design and Methods: A total of 12 women with type 1 diabetes (aged 32.9 years, diabetes duration 17.6 years, BMI 27.1 kg/m(2), and HbA(1c) 6.4%) were randomly allocated to closed-loop or conventional CSII. They performed normal daily activities (standardized meals, snacks, and exercise) for 24 h on two occasions at 19 and 23 weeks' gestation. Plasma glucose time in target (63-140 mg/dL) and time spent hypoglycemic were calculated., Results: Plasma glucose time in target was comparable for closed-loop and conventional CSII (median [interquartile range]: 81 [59-87] vs. 81% [54-90]; P = 0.75). Less time was spent hypoglycemic (<45 mg/dL [0.0 vs. 0.3%]; P = 0.04), with a lower low blood glucose index (2.4 [0.9-3.5] vs. 3.3 [1.9-5.1]; P = 0.03), during closed-loop insulin delivery., Conclusions: Closed-loop insulin delivery was as effective as conventional CSII, with less time spent in extreme hypoglycemia.

Objective: This study evaluated closed-loop insulin delivery with a model predictive control (MPC) algorithm during early (12-16 weeks) and late gestation (28-32 weeks) in pregnant women with type 1 diabetes., Research Design and Methods: Ten women with type 1 diabetes (age 31 years, diabetes duration 19 years, BMI 24.1 kg/m(2), booking A1C 6.9%) were studied over 24 h during early (14.8 weeks) and late pregnancy (28.0 weeks). A nurse adjusted the basal insulin infusion rate from continuous glucose measurements (CGM), fed into the MPC algorithm every 15 min. Mean glucose and time spent in target (63-140 mg/dL), hyperglycemic (>140 to ≥ 180 mg/dL), and hypoglycemic (<63 to ≤ 50 mg/dL) were calculated using plasma and sensor glucose measurements. Linear mixed-effects models were used to compare glucose control during early and late gestation., Results: During closed-loop insulin delivery, median (interquartile range) plasma glucose levels were 117 (100.8-154.8) mg/dL in early and 126 (109.8-140.4) mg/dL in late gestation (P = 0.72). The overnight mean (interquartile range) plasma glucose time in target was 84% (50-100%) in early and 100% (94-100%) in late pregnancy (P = 0.09). Overnight mean (interquartile range) time spent hyperglycemic (>140 mg/dL) was 7% (0-40%) in early and 0% (0-6%) in late pregnancy (P = 0.25) and hypoglycemic (<63 mg/dL) was 0% (0-3%) and 0% (0-0%), respectively (P = 0.18). Postprandial glucose control, glucose variability, insulin infusion rates, and CGM sensor accuracy were no different in early or late pregnancy., Conclusions: MPC algorithm performance was maintained throughout pregnancy, suggesting that overnight closed-loop insulin delivery could be used safely during pregnancy. More work is needed to achieve optimal postprandial glucose control.

A gap currently exists between our expectations of tight blood glucose control and the reality of safely achieving it before and during pregnancy. Technological and pharmaceutical advances will not in isolation prevent poor pregnancy outcomes without recognising the social, cultural and behavioural context of the women living with diabetes. Neither will behavioural and/or educational programmes completely overcome the fundamentally disordered metabolic pathways and physiological challenges of pregnancy. Improved integration of the technological, behavioural and educational aspects of diabetes care will pave the way for truly personalized, interdisciplinary diabetes management and ultimately improved pregnancy outcomes for women with diabetes and their infants.

Objective: To evaluate the effectiveness of continuous glucose monitoring during pregnancy on maternal glycaemic control, infant birth weight, and risk of macrosomia in women with type 1 and type 2 diabetes., Design: Prospective, open label randomised controlled trial., Setting: Two secondary care multidisciplinary obstetric clinics for diabetes in the United Kingdom., Participants: 71 women with type 1 diabetes (n=46) or type 2 diabetes (n=25) allocated to antenatal care plus continuous glucose monitoring (n=38) or to standard antenatal care (n=33)., Intervention: Continuous glucose monitoring was used as an educational tool to inform shared decision making and future therapeutic changes at intervals of 4-6 weeks during pregnancy. All other aspects of antenatal care were equal between the groups., Main Outcome Measures: The primary outcome was maternal glycaemic control during the second and third trimesters from measurements of HbA(1c) levels every four weeks. Secondary outcomes were birth weight and risk of macrosomia using birthweight standard deviation scores and customised birthweight centiles. Statistical analyses were done on an intention to treat basis., Results: Women randomised to continuous glucose monitoring had lower mean HbA(1c) levels from 32 to 36 weeks' gestation compared with women randomised to standard antenatal care: 5.8% (SD 0.6) v 6.4% (SD 0.7). Compared with infants of mothers in the control arm those of mothers in the intervention arm had decreased mean birthweight standard deviation scores (0.9 v 1.6; effect size 0.7 SD, 95% confidence interval 0.0 to 1.3), decreased median customised birthweight centiles (69% v 93%), and a reduced risk of macrosomia (odds ratio 0.36, 95% confidence interval 0.13 to 0.98)., Conclusion: Continuous glucose monitoring during pregnancy is associated with improved glycaemic control in the third trimester, lower birth weight, and reduced risk of macrosomia., Trial Registration: Current Controlled Trials ISRCTN84461581.

Aims/hypothesis: Maternal hyperglycaemia alone does not explain the incidence of large offspring amongst women with type 1 diabetes. The objective of the study was to determine if there is an association between placental function, as measured by angiogenic factors, and offspring birthweight z score in women with type 1 diabetes. Methods: This cohort study included samples from 157 Continuous Glucose Monitoring in Pregnant Women with Type 1 Diabetes (CONCEPTT) trial participants. Correlations were estimated between birthweight z score and placental growth factor (PlGF) and soluble fms-like tyrosine kinase (sFlt-1) levels measured at baseline and at 24 and 34 weeks of gestation. Linear regression was used to assess the relationship between birthweight z score and placental health, as measured by PlGF and sFlt-1/PlGF ratio, stratified by glycaemic status (continuous glucose monitoring and HbA1c measures) and adjusted for potential confounders of maternal BMI, smoking and weight gain. Higher PlGF levels and lower sFlt-1/PlGF ratios represent healthy placentas, while lower PlGF levels and higher sFlt-1/PlGF ratios represent unhealthy placentas. Results: Among CONCEPTT participants, the slopes relating PlGF levels to birthweight z scores differed according to maternal glycaemia at 34 weeks of gestation (p = 0.003). With optimal maternal glycaemia (HbA1c < 48 mmol/mol [6.5%]/ or continuous glucose monitoring time above range ≤ 30%), birthweight z scores were reduced towards zero (normal weight) with increasing PlGF values (representing a healthy placenta), and increased with decreasing PlGF values. With suboptimal glycaemic status (HbA1c ≥ 48 mmol/mol [6.5%] or time above range > 30%), increasing PlGF values were associated with heavier infants. Those with a healthy placenta (PlGF > 100) and suboptimal glycaemic control had a higher mean z score (2.45) than those with an unhealthy placenta (mean z score = 1.86). Similar relationships were seen when using sFlt-1/PlGF ratio as a marker for a healthy vs unhealthy placenta. Conclusions/interpretation: In women with type 1 diabetes, infant birthweight is influenced by both glycaemic status and placental function. In women with suboptimal glycaemia, infant birthweight was heavier when placentas were healthy. Suboptimal placental function should be considered in the setting of suboptimal glycaemia and apparently 'normal' birthweight. [ABSTRACT FROM AUTHOR]