A Diabetes Pregnancy Technology Roadmap: The 2023 Norbert Freinkel Award Lecture.

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.

Impact of COVID-19 on gestational diabetes pregnancy outcomes in the UK: A multicentre retrospective cohort study.

OBJECTIVE: To determine the impact of implementing emergency care pathway(s) for screening, diagnosing and managing women with gestational diabetes (GDM) during COVID-19. DESIGN: Retrospective multicentre cohort. SETTING: Nine National Health Service (NHS) Hospital Trusts/Health boards in England and Scotland. POPULATION: 4915 women with GDM pre-pandemic (1 April 2018 to 31 March 2020), and 3467 women with GDM during the pandemic (1 May 2020 to 31 March 2021). METHODS: We examined clinical outcomes for women with GDM prior to and during the pandemic following changes in screening methods, diagnostic testing, glucose thresholds and introduction of virtual care for monitoring of antenatal glycaemia. MAIN OUTCOME MEASURES: Intervention at birth, perinatal mortality, large-for-gestational-age infants and neonatal unit admission. RESULTS: The new diagnostic criteria more often identified GDM women who were multiparous, had higher body mass index (BMI) and greater deprivation, and less frequently had previous GDM (all p < 0.05). During COVID, these women had no differences in the key outcome measures. Of the women, 3% were identified with pre-existing diabetes at antenatal booking. Where OGTT continued during COVID, but virtual care was introduced, outcomes were also similar pre- and during the pandemic. CONCLUSIONS: Using HbA1c and fasting glucose identified a higher risk GDM population during the pandemic but this had minimal impact on pregnancy outcomes. The high prevalence of undiagnosed pre-existing diabetes suggests that women with GDM risk factors should be offered HbA1c screening in early pregnancy.

Roadmap to the Effective Use of Continuous Glucose Monitoring in Pregnancy.

The landscape for managing type 1 diabetes during pregnancy has been transformed by increasing use of continuous glucose monitoring (CGM). Women are aiming for pregnancy-specific glucose targets or 70% time in range for pregnancy (TIRp; 63-140 mg/dL) as soon as possible, knowing that every extra 5% TIRp has benefits for reducing the risks of complications in their babies. Ongoing monitoring of maternal A1C (at pregnancy confirmation and at 20, 28, and 36 weeks' gestation) remains useful. Intensification of glycemic management and instruction in using CGM (if not already used) is recommended for individuals with an A1C >6.0% after 20 weeks. A better understanding of CGM-documented glycemic changes throughout pregnancy is needed to inform future management of gestational diabetes and pregnancy in people with type 2 diabetes. Research regarding overcoming barriers to CGM use and optimal TIRp targets for pregnant individuals with type 2 diabetes from diverse racial/ethnic groups is urgently needed.

Continuous Glucose Monitoring Metrics in High-Risk Pregnant Women with Type 2 Diabetes.

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.

A Randomized Trial of Closed-Loop Insulin Delivery Postpartum in Type 1 Diabetes.

OBJECTIVE: This study aimed to evaluate the efficacy of closed-loop insulin delivery postpartum. RESEARCH DESIGN AND METHODS: In this open-label, randomized controlled trial, postpartum individuals with type 1 diabetes were randomized to hybrid closed-loop insulin delivery with the MiniMed 670G/770G system in automode or sensor-augmented pump therapy in the first 12-weeks postpartum followed by a continuation phase with closed-loop insulin delivery for all until 24 weeks postpartum. RESULTS: Eighteen participants (mean ± SD age 32 ± 3.5 years, diabetes duration 22 ± 7.3 years, and early pregnancy HbA1c 52 ± 6.8 mmol/mol [6.9 ± 0.9%]) completed 24 weeks of postpartum follow-up. In the randomized phase, percent time in range 70-180 mg/dL (3.9-10 mmol/L) did not differ between groups (79.2 ± 8.7% vs. 78.2 ± 6.0%; P = 0.41). Participants randomized to closed-loop insulin delivery spent less time <70 mg/dL (3.9 mmol/L) and <54 mg/dL (3.0 mmol/L) (1.7 ± 0.8% vs. 5.5 ± 3.3% [P < 0.001] and 0.3 ± 0.2% vs. 1.1 ± 0.9% [P = 0.008]). Time >180 mg/dL (10 mmol/L) was not different between groups (18.7 ± 8.8% vs. 15.9 ± 7.7%; P = 0.21). In the continuation phase, those initially randomized to sensor-augmented pump therapy had less time <70 mg/dL after initiation of closed-loop insulin delivery (5.5 ± 3.3% vs. 3.3 ± 2.2%; P = 0.039). The closed-loop group maintained similar glycemic metrics in both study phases. There were no episodes of diabetic ketoacidosis or severe hypoglycemia in the randomized or continuation phase in either group. CONCLUSIONS: Women randomized to closed-loop insulin delivery postpartum had less hypoglycemia than those randomized to sensor-augmented pump therapy. There were no safety concerns. These findings are reassuring for use of closed-loop insulin delivery postpartum because of its potential to reduce hypoglycemia.

Listening to Women: Experiences of Using Closed-Loop in Type 1 Diabetes Pregnancy.

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.

Automated Insulin Delivery in Women with Pregnancy Complicated by Type 1 Diabetes.

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.).

MAGIC (maternal glucose in pregnancy) understanding the glycemic profile of pregnancy, intensive CGM glucose profiling and its relationship to fetal growth: an observational study protocol.

BACKGROUND: Continuous glucose monitoring (CGM) provides the most objective method of assessing glucose in daily life. Although there have been small, short-term physiologic studies of glucose metabolism in 'healthy' pregnant women a comprehensive, longitudinal description of changes in glucose over the course of pregnancy and how glucose dysregulation earlier in pregnancy relates to traditional third trimester screening for gestational diabetes, fetal growth and pregnancy outcomes is lacking. This study aims to characterise longitudinal changes in glycemia across gestation using CGM, in order to understand the evolution of dysglycemia and its relationship to fetal growth. METHOD/DESIGN: A multi-centre, prospective, observational, cohort study of 500 healthy pregnant women, recruited in the first trimester of pregnancy. Masked CGM will be performed for a 14-day period on five occasions across pregnancy at ~ 10-12, 18-20, 26-28, 34-36 weeks gestation and postnatally. Routinely collected anthropometric and sociodemographic information will be recorded at each visit including: weight, height, blood pressure, current medication. Age, parity, ethnicity, smoking will be recorded. Blood samples will be taken at each visit for HbA1c and a sample stored. Details on fetal growth from ultrasound scans and the OGTT results will be recorded. Maternal and neonatal outcomes will be collected. CGM glucose profiling is the exposure of interest, and will be performed using standard summary statistics, functional data analysis and glucotyping. The primary maternal outcome is clinical diagnosis of GDM. The primary neonatal outcome is large for gestational age (LGA) (> 90th centile defined by customised birthweight centile). The relationship of glucose to key secondary maternal and neonatal outcomes will be explored. DISCUSSION: This study will ascertain the relationship of maternal dysglycemia to fetal growth and outcomes. It will explore whether CGM glucose profiling can detect GDM before the OGTT; or indeed whether CGM glucose profiling may be more useful than the OGTT at detecting LGA and other perinatal outcomes. TRIAL REGISTRATION: ISRCTN 15,706,303 https://www.isrctn.com/ISRCTN15706303 Registration date: 13th March 2023.

Metabolomic insights into maternal and neonatal complications in pregnancies affected by type 1 diabetes.

AIMS/HYPOTHESIS: Type 1 diabetes in pregnancy is associated with suboptimal pregnancy outcomes, attributed to maternal hyperglycaemia and offspring hyperinsulinism (quantifiable by cord blood C-peptide). We assessed metabolomic patterns associated with risk factors (maternal hyperglycaemia, diet, BMI, weight gain) and perinatal complications (pre-eclampsia, large for gestational age [LGA], neonatal hypoglycaemia, hyperinsulinism) in the Continuous Glucose Monitoring in Women with Type 1 Diabetes in Pregnancy Trial (CONCEPTT). METHODS: A total of 174 CONCEPTT participants gave ≥1 non-fasting serum sample for the biorepository at 12 gestational weeks (147 women), 24 weeks (167 women) and 34 weeks (160 women) with cord blood from 93 infants. Results from untargeted metabolite analysis (ultrahigh performance LC-MS) are presented as adjusted logistic/linear regression of maternal and cord blood metabolites, risk factors and perinatal complications using a modified Bonferroni limit of significance for dependent variables. RESULTS: Maternal continuous glucose monitoring time-above-range (but not BMI or excessive gestational weight gain) was associated with increased triacylglycerols in maternal blood and increased carnitines in cord blood. LGA, adiposity, neonatal hypoglycaemia and offspring hyperinsulinism showed distinct metabolite profiles. LGA was associated with increased carnitines, steroid hormones and lipid metabolites, predominantly in the third trimester. However, neonatal hypoglycaemia and offspring hyperinsulinism were both associated with metabolite changes from the first trimester, featuring triacylglycerols or dietary phenols. Pre-eclampsia was associated with increased abundance of phosphatidylethanolamines, a membrane phospholipid, at 24 weeks. CONCLUSIONS/INTERPRETATION: Altered lipid metabolism is a key pathophysiological feature of type 1 diabetes pregnancy. New strategies for optimising maternal diet and insulin dosing from the first trimester are needed to improve pregnancy outcomes in type 1 diabetes.

Management of type 1 diabetes in pregnancy: update on lifestyle, pharmacological treatment, and novel technologies for achieving glycaemic targets.

Glucose concentrations within target, appropriate gestational weight gain, adequate lifestyle, and, if necessary, antihypertensive treatment and low-dose aspirin reduces the risk of pre-eclampsia, preterm delivery, and other adverse pregnancy and neonatal outcomes in pregnancies complicated by type 1 diabetes. Despite the increasing use of diabetes technology (ie, continuous glucose monitoring and insulin pumps), the target of more than 70% time in range in pregnancy (TIRp 3·5-7·8 mmol/L) is often reached only in the final weeks of pregnancy, which is too late for beneficial effects on pregnancy outcomes. Hybrid closed-loop (HCL) insulin delivery systems are emerging as promising treatment options in pregnancy. In this Review, we discuss the latest evidence on pre-pregnancy care, management of diabetes-related complications, lifestyle recommendations, gestational weight gain, antihypertensive treatment, aspirin prophylaxis, and the use of novel technologies for achieving and maintaining glycaemic targets during pregnancy in women with type 1 diabetes. In addition, the importance of effective clinical and psychosocial support for pregnant women with type 1 diabetes is also highlighted. We also discuss the contemporary studies examining HCL systems in type 1 diabetes during pregnancies.

Interventions to enhance pre-pregnancy care for women with type 2 diabetes: A systematic review of the literature.

AIMS: The aim of the study was to examine the content and impact of interventions that have been used to increase the uptake of pre-pregnancy care for women with type 2 diabetes, and their impact on maternal and fetal outcomes. METHODS: A systematic search of multiple databases was conducted in November 2021, and updated July 2022, to identify studies assessing interventions to enhance pre-pregnancy care for women with type 2 diabetes. Over 10% of articles were screened by two reviewers at title and abstract phase, after which all selected full-text articles were screened by two reviewers. Quality assessment was conducted using the Critical Appraisal Skills Programme checklist for cohort studies. Meta-analysis was not possible due to study heterogeneity; therefore, narrative synthesis was conducted. RESULTS: Four eligible cohort studies were identified. The conclusions able to be drawn by this review were limited as women with type 2 diabetes (n = 800) were in the minority in all four studies (35%-40%) and none of the interventions were exclusively tailored for them. The uptake of pre-pregnancy care was lower in women with type 2 diabetes (8%-10%) compared with other participant groups in the studies. Pregnancy preparation indicators generally improved among all groups exposed to pre-pregnancy care, with varying impact on pregnancy outcomes. CONCLUSIONS: This review demonstrates that previous interventions have had a limited impact on pre-pregnancy care uptake in women with type 2 diabetes. Future studies should focus on tailored interventions for improving pre-pregnancy care for women with type 2 diabetes, particularly those from ethnic minorities and living in poorer communities.

Healthcare professionals' views about how pregnant women can benefit from using a closed-loop system: Qualitative study.

BACKGROUND: Interest is growing in how closed-loop systems can support attainment of within-target glucose levels amongst pregnant women with type 1 diabetes. We explored healthcare professionals' views about how, and why, pregnant women benefitted from using the CamAPS FX system during the AiDAPT trial. METHODS: We interviewed 19 healthcare professionals who supported women using closed-loop during the trial. Our analysis focused on identifying descriptive and analytical themes relevant to clinical practice. RESULTS: Healthcare professionals highlighted clinical and quality-of-life benefits to using closed-loop in pregnancy; albeit, they attributed some of these to the continuous glucose monitoring component. They emphasised that the closed-loop was not a panacea and that, to gain maximum benefit, an effective collaboration between themselves, the woman and the closed-loop was needed. Optimal performance of the technology, as they further noted, also required women to interact with the system sufficiently, but not excessively; a requirement that they felt some women had found challenging. Even where healthcare professionals felt that this balance was not achieved, they suggested that women had still benefitted from using the system. Healthcare professionals reported difficulties predicting how specific women would engage with the technology. In light of their trial experiences, healthcare professionals favoured an inclusive approach to closed-loop rollout in routine clinical care. CONCLUSIONS: Healthcare professionals recommended that closed-loop systems be offered to all pregnant women with type 1 diabetes in the future. Presenting closed-loop systems to pregnant women and healthcare teams as one pillar of a three-party collaboration may help promote optimal use.

Rollout of Closed-Loop Technology to Pregnant Women with Type 1 Diabetes: Healthcare Professionals' Views About Potential Challenges and Solutions.

Aims: To explore healthcare professionals' views about the training and support needed to rollout closed-loop technology to pregnant women with type 1 diabetes. Methods: We interviewed (n = 19) healthcare professionals who supported pregnant women using CamAPS FX closed-loop during the Automated insulin Delivery Amongst Pregnant women with Type 1 diabetes (AiDAPT) trial. Data were analyzed descriptively. An online workshop involving (n = 15) trial team members was used to inform recommendations. Ethics approvals were obtained in conjunction with those for the wider trial. Results: Interviewees expressed enthusiasm for a national rollout of closed-loop, but anticipated various challenges, some specific to use during pregnancy. These included variations in insulin pump and continuous glucose monitoring expertise and difficulties embedding and retaining key skills, due to the relatively small numbers of pregnant women using closed-loop. Inexperienced staff also highlighted difficulties interpreting data downloads. To support rollout, interviewees recommended providing expert initial advice training, delivered by device manufacturers together with online training resources and specific checklists for different systems. They also highlighted a need for 24 h technical support, especially when supporting technology naive women after first transitioning onto closed-loop in early pregnancy. They further recommended providing case-based meetings and mentorship for inexperienced colleagues, including support interpreting data downloads. Interviewees were optimistic that if healthcare professionals received training and support, their long-term workloads could be reduced because closed-loop lessened women's need for glycemic management input, especially in later pregnancy. Conclusions: Interviewees identified challenges and opportunities to rolling-out closed-loop and provided practical suggestions to upskill inexperienced staff supporting pregnant women using closed-loop. A key priority will be to determine how best to develop mentorship services to support inexperienced staff delivering closed-loop. Clinical Trials Registration: NCT04938557.