Diagnosis and Treatment of Hyperglycemia in Pregnancy: Type 2 Diabetes Mellitus and Gestational Diabetes.

Hyperglycemia in pregnancy due to pre-existing Type 2 diabetes mellitus (T2DM) and gestational diabetes mellitus (GDM) is rising globally with increasing rates of risk factors for metabolic disease. This review summarizes current evidence and recommendations from national and international guidelines for diagnosis and management of T2DM and GDM to optimize maternal and neonatal outcomes.

Real-world data on the Minimed 780G advanced hybrid closed-loop system use during type 1 diabetes pregnancy: One centre observational study.

Aim The efficacy of hybrid closed-loop systems (HCLs) in managing glycemic control in pregnant women with type 1 diabetes remains inadequately characterized. We evaluated the use of the Medtronic Minimed 780G HCLs. METHODS: The retrospective observational study analyzed the glycemic and perinatal outcomes of pregnant women using the HCLs, followed at our tertiary centre. Independent t-tests were employed to compare data among trimesters based on pre-pregnancy HbA1c. The associations between glycemic parameters and perinatal outcomes were explored using Spearman rho. RESULTS: Among the 21 women (age: 33.5 ± 4.2 years, diabetes duration: 21.2 ± 7.6 years, pre-pregnancy HbA1c 7.0 ± 1.1 % (52.9 ± 11.9 mmol/mol)) time in range (pTIR, 63-140 mg/dl; 3.5-7.8 mmol/l) increased progressively throughout pregnancy (trimesters: first: 64.0 ± 9.0 %; second:71.3 ± 11.8 %; third: 75.7 ± 8.1 %). Simultaneously, mean sensor glucose decreased (trimesters: first: 130 ± 10.4 mg/dl (7.2 ± 0.6 mmol/l); second: 120.9 ± 13.4 mg/dl (6.7 ± 0.7 mmol/l); third: 117.3 ± 9.1 mg/dl (6.5 ± 0.5 mmol/l)). Although a majority of women achieved the target pTIR until the third trimester, this did not consistently prevent the delivery of a large-for-gestational-age baby. Notably, one ketoacidosis event occurred, and there were no reported instances of severe hypoglycemia. CONCLUSION: Use of the Minimed 780G HCLs enabled the attainment of recommended pregnancy glycemic targets for most women with type 1 diabetes in a real-world setting.

Correlation between newborn weight and serum BCAAs in pregnant women with diabetes.

BACKGROUND: Branched-chain amino acids (BCAAs), including leucine, isoleucine, and valine, are essential amino acids for mammals. Maternal BCAAs during pregnancy have been associated with newborn development. Meanwhile, BCAAs have been tightly linked with insulin resistance and diabetes in recent years. Diabetes in pregnancy is a common metabolic disorder. The current study aims to assess the circulating BCAA levels in pregnant women with diabetes and their relationship with neonatal development. METHODS: The serum concentrations of BCAAs and their corresponding branched-chain α-keto acids (BCKAs) catabolites in 33 pregnant women with normal glucose tolerance, 16 pregnant women with type 2 diabetes before pregnancy (PDGM), and 15 pregnant women with gestational diabetes mellitus (GDM) were determined using a liquid chromatography system coupled to a mass spectrometer. The data were tested for normal distribution and homogeneity of variance before statistical analysis. Correlations were computed with the Pearson correlation coefficient. RESULTS: The maternal serum BCAAs and BCKAs levels during late pregnancy were higher in women with PGDM than those in healthy women. Meanwhile, the circulating BCAAs and BCKAs showed no significant changes in women with GDM compared with those in healthy pregnant women. Furthermore, the circulating BCAA and BCKA levels in women with PGDM were positively correlated with the weight of the newborn. The circulating leucine level in women with GDM was positively correlated with the weight of the newborn. BCAA and BCKA levels in healthy pregnant women showed no correlation with newborn weight. CONCLUSIONS: The serum BCAAs in pregnant women with diabetes, which was elevated in PGDM but not GDM, were positively correlated with newborn weight. These findings highlight potential approaches for early identification of high-risk individuals and interventions to reduce the risk of adverse pregnancy outcomes.

Pregnancy Outcomes in Women with Poorly Controlled Pregestational Diabetes Mellitus.

BACKGROUND: The prevalence of pregestational diabetes mellitus (PGDM) in women of reproductive age has surged globally, contributing to increased rates of adverse pregnancy outcomes. Hemoglobin A1c (HbA1c) is a crucial marker for diagnosing and monitoring PGDM, with periconceptional levels influencing the risk of congenital anomalies and complications. OBJECTIVES: To evaluate the association between periconceptional HbA1c levels and perinatal complications in pregnant women with poorly controlled PGDM. METHODS: We conducted a retrospective analysis of prospectively collected data of pregnancies between 2010 and 2019, HbA1c > 6% at 3 months prior to conception or during the first trimester. Outcomes of periconceptional HbA1c levels were compared. RESULTS: The cohort included 89 women: 49 with HbA1c 6-8%, 29 with HbA1c 8-10%, and 11 with HbA1c > 10%. Higher HbA1c levels were more prevalent in type 1 diabetics and were associated with increased end-organ damage risk. Women with elevated HbA1c levels tended toward unbalanced glucose levels during pregnancy. The cohort exhibited high rates of preterm delivery, hypertensive disorders, cesarean delivery, and neonatal intensive care unit admission. Overall live birth rate was 83%. While a significant correlation was found between HbA1c levels and preterm delivery, no consistent association was observed with other adverse outcomes. CONCLUSIONS: Periconceptional glycemic control in PGDM pregnancies is important. Elevated HbA1c levels are associated with increased risks of adverse outcomes. Beyond a certain HbA1c level, risks of complications may not proportionally escalate.

Comparing advanced hybrid closed loop therapy and standard insulin therapy in pregnant women with type 1 diabetes (CRISTAL): a parallel-group, open-label, randomised controlled trial.

BACKGROUND: Advanced hybrid closed loop (AHCL) therapy can improve glycaemic control in pregnant women with type 1 diabetes. However, data are needed on the efficacy and safety of AHCL systems as these systems, such as the MiniMed 780G, are not currently approved for use in pregnant women. We aimed to investigate whether the MiniMed 780G can improve glycaemic control with less hypoglycaemia in pregnant women with type 1 diabetes. METHODS: CRISTAL was a double-arm, parallel-group, open-label, randomised controlled trial conducted in secondary and tertiary care specialist endocrinology centres at 12 hospitals (11 in Belgium and one in the Netherlands). Pregnant women aged 18-45 years with type 1 diabetes were randomly assigned (1:1) to AHCL therapy (MiniMed 780G) or standard insulin therapy (standard of care) at a median of 10·1 (IQR 8·6-11·6) weeks of gestation. Randomisation was done centrally with minimisation dependent on baseline HbA1c, insulin administration method, and centre. Participants and study teams were not masked to group allocation. The primary outcome was proportion of time spent in the pregnancy-specific target glucose range (3·5-7·8 mmol/L), measured by continuous glucose monitoring (CGM) at 14-17 weeks, 20-23 weeks, 26-29 weeks, and 33-36 weeks. Key secondary outcomes were overnight time in target range, and time below glucose range (<3·5 mmol/L) overall and overnight. Analyses were conducted on an intention-to-treat basis. This trial is registered with ClinicalTrials.gov (NCT04520971). FINDINGS: Between Jan 15, 2021 and Sept 30, 2022, 101 participants were screened, and 95 were randomly assigned to AHCL therapy (n=46) or standard insulin therapy (n=49). 43 patients assigned to AHCL therapy and 46 assigned to standard insulin therapy completed the study. At baseline, 91 (95·8%) participants used insulin pumps, and the mean HbA1c was 6·5% (SD 0·6). The mean proportion of time spent in the target range (averaged over four time periods) was 66·5% (SD 10·0) in the AHCL therapy group compared with 63·2% (12·4) in the standard insulin therapy group (adjusted mean difference 1·88 percentage points [95% CI -0·82 to 4·58], p=0·17). Overnight time in the target range was higher (adjusted mean difference 6·58 percentage points [95% CI 2·31 to 10·85], p=0·0026), and time below range overall (adjusted mean difference -1·34 percentage points [95% CI, -2·19 to -0·49], p=0·0020) and overnight (adjusted mean difference -1·86 percentage points [95% CI -2·90 to -0·81], p=0·0005) were lower with AHCL therapy than with standard insulin therapy. Participants assigned to AHCL therapy reported higher treatment satisfaction. No unanticipated safety events occurred with AHCL therapy. INTERPRETATION: In pregnant women starting with tighter glycaemic control, AHCL therapy did not improve overall time in target range but improved overnight time in target range, reduced time below range, and improved treatment satisfaction. These data suggest that the MiniMed 780G can be safely used in pregnancy and provides some additional benefits compared with standard insulin therapy; however, it will be important to refine the algorithm to better align with pregnancy requirements. FUNDING: Diabetes Liga Research Fund and Medtronic.

Hemoglobin A1c Trajectories During Pregnancy and Adverse Outcomes in Women With Type 2 Diabetes: A Danish National Population-Based Cohort Study.

OBJECTIVE: To identify and characterize groups of pregnant women with type 2 diabetes with distinct hemoglobin A1c (HbA1c) trajectories across gestation and to examine the association with adverse obstetric and perinatal outcomes. RESEARCH DESIGN AND METHODS: This was a retrospective Danish national cohort study including all singleton pregnancies in women with type 2 diabetes, giving birth to a liveborn infant, between 2004 and 2019. HbA1c trajectories were identified using latent class linear mixed-model analysis. Associations with adverse outcomes were examined with logistic regression models. RESULTS: A total of 1,129 pregnancies were included. Three HbA1c trajectory groups were identified and named according to the glycemic control in early pregnancy (good, 59%; moderate, 32%; and poor, 9%). According to the model, all groups attained an estimated HbA1c <6.5% (48 mmol/mol) during pregnancy, with no differences between groups in the 3rd trimester. Women with poor glycemic control in early pregnancy had lower odds of having an infant with large-for-gestational-age (LGA) birth weight (adjusted odds ratio [aOR] 0.57, 95% CI 0.40-0.83), and higher odds of having an infant with small-for-gestational age (SGA) birth weight (aOR 2.49, 95% CI 2.00-3.10) and congenital malformation (CM) (aOR 4.60 95% CI 3.39-6.26) compared with women with good glycemic control. There was no evidence of a difference in odds of preeclampsia, preterm birth, and caesarean section between groups. CONCLUSIONS: Women with poor glycemic control in early pregnancy have lower odds of having an infant with LGA birth weight, but higher odds of having an infant with SGA birth weight and CM.

Efficacy of automated insulin delivery in pregnant women with type 1 diabetes: a meta-analysis and trial sequential analysis of randomized controlled trials.

BACKGROUND: Automated insulin delivery (AID) devices have shown to be a promising treatment to improve glycemic control in patients with type 1 diabetes mellitus (T1DM). However, its efficacy in pregnant women with T1DM remains uncertain. METHODS: PubMed, Scopus, Cochrane Central and ClinicalTrials.gov were systematically searched for randomized controlled trials (RCTs) comparing AID to standard care (SC), defined as use of sensor-augmented pump and multiple daily insulin injections. Outcomes included time in range (TIR), nocturnal TIR, time in hypoglycemic and hyperglycemic ranges, among others. Sensitivity and trial sequential analyses (TSA) were performed. PROSPERO ID: CRD42023474398. RESULTS: We included five RCTs with a total of 236 pregnant women, of whom 117 (50.6%) received AID. There was a significant increase in nocturnal TIR (mean difference [MD] 12.69%; 95% CI 8.74-16.64; p < 0.01; I2 = 0%) and a decrease in glucose variability (standard deviation of glucose; MD -2.91; 95% CI -5.13 to -0.69; p = 0.01; I2 = 0%). No significant differences were observed for TIR, HBGI, LGBI, mean glucose and time spent in hyperglycemia and hypoglycemia. Regarding TSA, the statistical significance obtained in nocturnal TIR was conclusive and with minimal risk of a type I error. CONCLUSION: Our findings suggest that AID systems can significantly improve nocturnal glycemic control and potentially reduce glycemic variability in pregnant women with T1DM, with no effect in the risk of hypoglycemia and hyperglycemia compared with current insulin treatments.

Glycemic control assessed by continuous glucose monitoring during pregnancy in women with type 1 diabetes and its association with preeclampsia, an observational Swedish cohort study.

INTRODUCTION: Women with type 1 diabetes have an increased risk of preeclampsia (PE), but it is not fully understood if degree of glycemic control is associated with this risk. The aim of this study was to assess glycemic control during pregnancy analyzed by continuous glucose monitoring (CGM) in women with and without PE and to investigate if glycemic control is associated with increased risk of PE. MATERIAL AND METHODS: A total of 120 pregnant Swedish women with type 1 diabetes using CGM were included. Background factors and pregnancy outcomes were collected from medical records. CGM data were collected via the internet-based platform Diasend. Mean glucose, standard deviation of mean glucose, percentage of time in target, time below target, and time above target were presented for each trimester in women who did or did not develop PE. Associations between CGM-derived metrics and PE were analyzed with logistic regression and adjusted for confounders. RESULTS: Twenty-two women (18.3%) developed PE. There were no significant differences in maternal characteristics between women with and without PE. Glycemic control improved in each trimester but was suboptimal in both groups. Time in target increased from 59% in the non-PE group and 54% in the PE group in the first trimester to 65% in both groups in the third trimester. There were no significant associations between glycemic control and PE after adjustment for confounders. CONCLUSIONS: Degree of glycemic control during pregnancy assessed by CGM was not associated with development of PE in women with type 1 diabetes. However, more research is needed to understand the role of glycemic control in relation to development of PE.

Continuous Glucose Monitoring Metrics for Pregnancies Complicated by Diabetes: Critical Appraisal of Current Evidence.

Ascertaining the utility of continuous glucose monitoring (CGM) in pregnancy complicated by diabetes is a rapidly evolving area, as the prevalence of type 1 diabetes (T1D), type 2 diabetes (T2D), and gestational diabetes mellitus (GDM) escalates. The seminal randomized controlled trial (RCT) evaluating CGM use added to standard care in pregnancy in T1D demonstrated significant improvements in maternal glycemia and neonatal health outcomes. Current clinical guidance recommends targets for percentage time in range (TIR), time above range (TAR), and time below range (TBR) during pregnancy complicated by T1D that are widely used in clinical practice. However, the superiority of CGM over blood glucose monitoring (BGM) is still questioned in both T2D and GDM, and whether glucose targets should be different than in T1D is unknown. Questions requiring additional research include which CGM metrics are superior in predicting clinical outcomes, how should pregnancy-specific CGM targets be defined, whether CGM targets should differ according to gestational age, and if CGM metrics during pregnancy should be similar across all types of diabetes. Limiting the potential for CGM to improve pregnancy outcomes may be our inability to maintain TIR > 70% throughout gestation, a goal achieved in the minority of patients studied. Adverse pregnancy outcomes remain high in women with T1D and T2D in pregnancy despite CGM technology, and this review explores the potential reasons and questions yet to be investigated.

Continuous subcutaneous insulin infusion versus multiple daily injection therapy in pregnant women with type 1 diabetes.

INTRODUCTION: The study aimed to compare glycemic control and pregnancy outcomes in women with type 1 diabetes mellitus (T1DM) using multiple daily injection therapy (MDI) and continuous subcutaneous insulin infusion (CSII) and to compare outcomes of women treated with long-acting insulin or neutral protamine Hagedorn (NPH). METHODS: This multicenter prospective cohort study involved women with pregestational T1DM treated with MDI and CSII. Primary outcome was glycated hemoglobin (HbA1c) before and during pregnancy. Secondary outcomes included maternal and neonatal outcomes and quality of life. RESULTS: Of the 121 studied women, the average age was 28.48 years, and the average body mass index was 21.29 kg/m2 at conception and 26.32 kg/m2 at delivery. Of the studied women, 78.51% had planned pregnancy. Women treated with MDI and CSII had comparable HbA1c before pregnancy or in the first and second trimesters. In the third trimester, women on CSII therapy had significantly lower HbA1c (6.07 ± 0.62 vs 6.20 ± 0.88%, p = .017), higher HbA1c on-target rate (71.43% vs 64.62%, p = .030), and greater decline of HbA1c from preconception to the third trimester (-0.65 vs -0.30%, p = .047). Fewer daily insulin requirements were observed in those used CSII compared with MDI-treated women (0.60 ± 0.22 vs 0.73 ± 0.25 U/kg/day, p = .004). Newborns born of mothers treated with the CSII method were more likely to have neonatal jaundice (adjusted odds ratio [OR] 2.76, 95% confidence interval [CI] 1.16-6.57) and neonatal intensive care unit (adjusted OR 3.73, 95%CI 1.24-11.16), and women on CSII had lower scores in patient-reported quality of life (p = .045). In the MDI group, those receiving long-acting insulin had nonsignificant lower HbA1c and higher HbA1c on-target rate in the second and third trimesters, compared with those treated with NPH. CONCLUSIONS: Insulin pump users may achieve better glycemic control than multiple daily insulin injections, which did not substantially improve pregnancy outcome.

Association between extrapolated time in range and large for gestational age infants in pregnant women with type 1 diabetes.

AIMS: To evaluate the association between extrapolated time in range (eTIR), measured by self-monitoring of blood glucose (SMBG), and large-for-gestational-age (LGA) infants in pregnancies with type 1 diabetes (T1D). METHODS: Retrospective cohort analysis including singleton pregnancies with T1D who started antenatal care before 20 gestational weeks and delivered live newborns at a Brazilian hospital between 2010 and 2019, with LGA fetuses as the main outcome. Glycemic records acquired using SMBG were categorized as eTIR, extrapolated time below range (eTBR), and extrapolated time above range (eTAR). Women were divided into two groups (LGA and adequate for gestational age [AGA]) and compared regarding clinical characteristics, obstetric outcomes, and frequencies of eTIR, eTBR, and eTAR. Logistic regression analysis verified the independent predictive variables for LGA infants. RESULTS: Data from 125 pregnancies were analyzed. For the first, second and third trimesters, each 1 % increase in eTIR was associated with a decreased risk of LGA by 2.9 % (OR: 0.971; 95%CI: 0.945-0.998), 2.5 % (OR: 0.975; 95%CI: 0.951-0.999) and 2.3 % (OR: 0.977; 95%CI: 0.955-0.998) and each 1 % increase in eTAR was associated with an increased risk of LGA by 2.7 % (OR: 1.027; 95%CI: 1.005-1.050), 3.9 % (OR: 1.039; 95%CI: 1.014-1.063) and 4.6 % (OR: 1.046; 95%CI: 1.018-1.075), respectively. CONCLUSION: The concept of TIR can be extrapolated to patients undergoing SMBG to assess the risk of LGA infants in pregnant women with T1D.

Discrete glucose profiles identified using continuous glucose monitoring data and their association with adverse pregnancy outcomes.

BACKGROUND: Continuous glucose monitoring has facilitated the evaluation of dynamic changes in glucose throughout the day and their effect on fetal growth abnormalities in pregnancy. However, studies of multiple continuous glucose monitoring metrics combined and their association with other adverse pregnancy outcomes are limited. OBJECTIVE: This study aimed to (1) use machine learning techniques to identify discrete glucose profiles based on weekly continuous glucose monitoring metrics in pregnant individuals with pregestational diabetes mellitus and (2) investigate their association with adverse pregnancy outcomes. STUDY DESIGN: This study analyzed data from a retrospective cohort study of pregnant patients with type 1 or 2 diabetes mellitus who used Dexcom G6 continuous glucose monitoring and delivered a nonanomalous, singleton pregnancy at a tertiary center between 2019 and 2023. Continuous glucose monitoring data were collapsed into 39 weekly glycemic measures related to centrality, spread, excursions, and circadian cycle patterns. Principal component analysis and k-means clustering were used to identify 4 discrete groups, and patients were assigned to the group that best represented their continuous glucose monitoring patterns during pregnancy. Finally, the association between glucose profile groups and outcomes (preterm birth, cesarean delivery, preeclampsia, large-for-gestational-age neonate, neonatal hypoglycemia, and neonatal intensive care unit admission) was estimated using multivariate logistic regression adjusted for diabetes mellitus type, maternal age, insurance, continuous glucose monitoring use before pregnancy, and parity. RESULTS: Of 177 included patients, 90 (50.8%) had type 1 diabetes mellitus, and 85 (48.3%) had type 2 diabetes mellitus. This study identified 4 glucose profiles: (1) well controlled; (2) suboptimally controlled with high variability, fasting hypoglycemia, and daytime hyperglycemia; (3) suboptimally controlled with minimal circadian variation; and (4) poorly controlled with peak hyperglycemia overnight. Compared with the well-controlled profile, the suboptimally controlled profile with high variability had higher odds of a large-for-gestational-age neonate (adjusted odds ratio, 3.34; 95% confidence interval, 1.15-9.89). The suboptimally controlled with minimal circadian variation profile had higher odds of preterm birth (adjusted odds ratio, 2.59; 95% confidence interval, 1.10-6.24), cesarean delivery (adjusted odds ratio, 2.76; 95% confidence interval, 1.09-7.46), and neonatal intensive care unit admission (adjusted odds ratio, 4.08; 95% confidence interval, 1.58-11.40). The poorly controlled profile with peak hyperglycemia overnight had higher odds of preeclampsia (adjusted odds ratio, 2.54; 95% confidence interval, 1.02-6.52), large-for-gestational-age neonate (adjusted odds ratio, 3.72; 95% confidence interval, 1.37-10.4), neonatal hypoglycemia (adjusted odds ratio, 3.53; 95% confidence interval, 1.37-9.71), and neonatal intensive care unit admission (adjusted odds ratio, 3.15; 95% confidence interval, 1.20-9.09). CONCLUSION: Discrete glucose profiles of pregnant individuals with pregestational diabetes mellitus were identified through joint consideration of multiple continuous glucose monitoring metrics. Prolonged exposure to maternal hyperglycemia may be associated with a higher risk of adverse pregnancy outcomes than suboptimal glycemic control characterized by high glucose variability and intermittent hyperglycemia.

Performance of the Dexcom G7 Continuous Glucose Monitoring System in Pregnant Women with Diabetes.

Background: We evaluated accuracy and safety of a seventh-generation real-time continuous glucose monitoring (CGM) system during pregnancy. Materials and Methods: Evaluable data for accuracy analysis were obtained from 96 G7 sensors (Dexcom, Inc.) worn by 96 of 105 enrolled pregnant women with type 1 (n = 59), type 2 (n = 21), or gestational diabetes (n = 25). CGM values were compared with arterialized venous glucose values from the YSI comparator instrument during 6-h clinic sessions at different time points throughout the sensors' 10-day wear period. The primary endpoint was the proportion of CGM values in the 70-180 mg/dL range within 15% of comparator glucose values. Secondary endpoints included the proportion of CGM values within 20% or 20 mg/dL of comparator values ≥ or <100 mg/dL, respectively (the %20/20 agreement rate). Results: Of the 1739 pairs with CGM in the 70-180 mg/dL range, 83.2% were within 15% of comparator values. The lower bound of the 95% confidence interval was 79.8%. Of the 2102 pairs with CGM values in the 40-400 mg/dL range, the %20/20 agreement rate was 92.5%. Of the 1659 pairs with comparator values in the 63-140 mg/dL range, the %20/20 agreement rate was 92.3%. The %20/20 agreement rates on days 1, 4 and 7, and 10 were 78.6%, 96.3%, and 97.3%, respectively. Consensus error grid analysis showed 99.8% of pairs in the clinically acceptable A and B zones. There were no serious adverse events. The sensors' 10-day survival rate was 90.3%. Conclusion: The G7 system is accurate and safe during pregnancies complicated by diabetes and does not require confirmatory fingerstick testing. Clinical Trial Registration: clinicaltrials.gov NCT04905628.

Clinical Effectiveness of Continuous Glucose Monitoring in Pregnancies Affected by Type 1 Diabetes.

Background: Continuous glucose monitoring (CGM) improves neonatal outcomes in type 1 diabetes pregnancies; however, its effectiveness has not been assessed in a real-world setting in the United States. Objective: The Triple C Study aimed to examine the clinical effectiveness, assessed through maternal glucose control and gestational health outcomes, of CGM use compared with self-monitoring of blood glucose (SMBG) in pregnancies associated with type 1 diabetes in a real-world setting. Research Design and Methods: We retrospectively identified 160 type 1 diabetes pregnancies at the Barbara Davis Center for Diabetes managed with CGM therapy (n = 109) or SMBG (n = 51) over a 6.5-year period (2014-2020). Obstetric care was provided at multiple practices. CGM use was defined as ≥60% wear in the second and third trimesters of pregnancy. Data were obtained from the electronic medical record system, hospital records, and vital statistics departments (Colorado and Wyoming). We used Student's t-test for continuous variables and chi-square test for categorical variables to compare outcomes between groups. Results: The CGM group had more participants meeting trimester-specific hemoglobin A1C (HbA1c) goals throughout pregnancy and postpartum (P < 0.01 in each time period). The CGM group had fewer participants never meeting HbA1c goals in any trimester than the SMBG group (P < 0.001). There were no significant differences in neonatal outcomes between groups, other than for macrosomia (12.8% CGM vs. 29.4% SMBG, P = 0.01). Infants of CGM users required a neonatal intensive care unit admission less often (52.9% CGM vs. 68.3% SMBG, P = 0.0989). Conclusions: CGM use was associated with improved maternal glucose levels in a diverse real-world cohort.

Randomized Trial of Assisted Hybrid Closed-Loop Therapy Versus Sensor-Augmented Pump Therapy in Pregnancy.

Objective: Examine gestational safety, glycemic and health outcomes, of a hybrid closed-loop (HCL) system without pregnancy-specific glucose targets. Research Design: This was a pilot feasibility investigator-initiated, two-site, single-blind, randomized controlled trial of sensor-augmented pump therapy (SAPT) versus HCL therapy in type 1 diabetes pregnancies. Participants were enrolled in the first trimester and randomized at 14-18 weeks of gestation and used SAPT or HCL until 4-6 weeks postpartum. We compared continuous glucose monitoring (CGM) metrics, severe hypoglycemia (SH), diabetic ketoacidosis (DKA), adverse skin reactions, and pregnancy outcomes between groups. Results: Baseline characteristics were similar between groups (n = 11 HCL and n = 12 SAPT). There was no SH or DKA episode after randomization. Time spent <54 mg/dL did not differ between groups. Time spent <63 mg/dL decreased in both groups, significantly in the HCL group (3.5% [1.3% standard error] second trimester and 2.8% [1.3%] third trimester vs. 7.9% [1.3%] run-in phase, P < 0.05 for both). Mean sensor glucose was lower with SAPT compared to HCL therapy in the third trimester (119 [4] mg/dL SAPT vs. 132 [4] mg/dL HCL, P < 0.05). Third trimester time-in-range (TIR; 63-140 mg/dL) increased with SAPT (68.2% [3.1%] vs. 64.3% [3.1%] run-in phase, P < 0.05). Gestational health outcomes did not differ between groups. The HCL group used assistive techniques, such as fake carbohydrate boluses and exiting HCL overnight. Conclusions: CGM within group differences were seen for time <63 mg/dL favoring HCL therapy and TIR favoring SAPT (third trimester vs. baseline). Safety and adverse pregnancy outcomes were similar between groups.

Mean Glucose and Gestational Weight Gain as Predictors of Large-for-Gestational-Age Infants in Pregnant Women with Type 1 Diabetes Using Continuous Glucose Monitoring.

Aims/hypothesis: To compare glycemic metrics during pregnancy between women with type 1 diabetes (T1D) delivering large-for-gestational-age (LGA) and appropriate-for-gestational-age (AGA) infants, and to identify predictors of LGA infants. Materials and Methods: A cohort study including 111 women with T1D using intermittently scanned continuous glucose monitoring from conception until delivery. Average sensor-derived metrics: mean glucose, time in range in pregnancy (TIRp), time above range in pregnancy, time below range in pregnancy, and coefficient of variation throughout pregnancy and in pregnancy intervals of 0-10, 11-21, 22-33, and 34-37 weeks were compared between women delivering LGA and AGA infants. Predictors of LGA infants were sought for. Infant growth was followed until 3 months postdelivery. Results: In total, 53% (n = 59) delivered LGA infants. Mean glucose decreased during pregnancy in both groups, with women delivering LGA infants having a 0.4 mmol/L higher mean glucose from 11-33 weeks (P = 0.01) compared with women delivering AGA infants. Mean TIRp >70% was obtained from 34 weeks in women delivering LGA infants and from 22-33 weeks in women delivering AGA infants. Independent predictors for delivering LGA infants were mean glucose throughout pregnancy and gestational weight gain. At 3 months postdelivery, infant weight was higher in infants born LGA compared with infants born AGA (6360 g ± 784 and 5988 ± 894, P = 0.04). Conclusions/interpretations: Women with T1D delivering LGA infants achieved glycemic targets later than women delivering AGA infants. Mean glucose and gestational weight gain were independent predictors for delivering LGA infants. Infants born LGA remained larger postdelivery compared with infants born AGA.

Real-World Evidence of Off-Label Use of Commercially Automated Insulin Delivery Systems Compared to Multiple Daily Insulin Injections in Pregnancies Complicated by Type 1 Diabetes.

Aims: To compare glycemic control and maternal-fetal outcomes of women with type 1 diabetes (T1D) using hybrid closed loop (HCL) versus multiple daily insulin injections (MDI) plus continuous glucose monitoring. Methods: Multicenter prospective cohort study of pregnant women with T1D in Spain. We evaluated HbA1c and time spent within (TIR), below (TBR), and above (TAR) the pregnancy-specific glucose range of 3.5-7.8 mmol/L. Adjusted models were performed for adverse pregnancy outcomes, including baseline maternal characteristics and center. Results: One hundred twelve women were included (HCL n = 59). Women in the HCL group had a longer duration of diabetes and higher rates of prepregnancy care. There was no between-group difference in HbA1c in any trimester. However, in the second trimester, MDI users had a greater decrease in HbA1c (-6.12 ± 9.06 vs. -2.16 ± 7.42 mmol/mol, P = 0.031). No difference in TIR (3.5-7.8 mmol/L) and TAR was observed between HCL and MDI users, but with a higher total insulin dose in the second trimester [+0.13 IU/kg·day)]. HCL therapy was associated with increased maternal weight gain during pregnancy (ßadjusted = 3.20 kg, 95% confidence interval [CI] 0.90-5.50). Regarding neonatal outcomes, newborns of HCL users were more likely to have higher birthweight (ßadjusted = 279.0 g, 95% CI 39.5-518.5) and macrosomia (ORadjusted = 3.18, 95% CI 1.05-9.67) compared to MDI users. These associations disappeared when maternal weight gain or third trimester HbA1c was included in the models. Conclusions: In a real-world setting, HCL users gained more weight during pregnancy and had larger newborns than MDI users, while achieving similar glycemic control in terms of HbA1c and TIR.

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.).