Search

Background: The Continuous Glucose Monitoring in Women with Type 1 Diabetes in Pregnancy Trial (CONCEPTT) found improved health outcomes for mothers and their infants among those randomized to self-monitoring of blood glucose (SMBG) with continuous glucose monitoring (CGM) compared with SMBG alone. In this study, we evaluated whether CGM or standard SMBG was more or less costly from the perspective of a third-party payer., Methods: We conducted a posthoc analysis of data from the CONCEPTT trial (Mar. 25, 2013, to Mar. 22, 2016). Health care resource data from 215 pregnant women, randomized to CGM or SMBG, were collected from 31 hospitals in 7 countries. We determined resource costs posthoc based on prices from hospitals in 3 Canadian provinces (Ontario, British Columbia, Alberta). The primary outcome was the difference between groups in the mean total cost of care for mother and infant dyads, paid by each government (i.e., the third-party payer) from randomization to hospital discharge (time horizon). The secondary outcome included CGM and SMBG costs not paid by governments (e.g., glucose monitoring devices and supplies)., Results: The mean total cost of care was lower in the CGM group compared with the SMBG group in each province (Ontario: $13 270.25 v. $18 465.21, difference in mean total cost [DMT] -$5194.96, 95% confidence interval [CI] -$9841 to -$1395; BC: $13 480.57 v. $18 762.17, DMT -$5281.60, 95% CI -$9964 to -$1382; Alberta: $13 294.39 v. $18 674.45, DMT -$5380.06, 95% CI -$10 216 to -$1490). There was no difference in the secondary outcome., Interpretation: Government health care costs are lower when CGM is paid by the patient, driven by lower costs from reduced use of the neonatal intensive care unit in the CGM group; however, when governments pay for CGM equipment, there is no overall cost difference between CGM and SMBG. Governments should consider paying for CGM, as it results in improved maternal and neonatal outcomes with no added overall cost., Trial Registration: ClinicalTrials.gov, no. NCT01788527., Competing Interests: Competing interests: Rashid Ahmed received grant support from the Centre for Clinical Trial Support, Sunnybrook Research Institute, Toronto, Canada, from a grant funded by the Juvenile Diabetes Research Foundation (JDRF) and grants under the JDRF Canadian Clinical Trial Network. Helen Murphy reports personal fees from Medtronic, Novo Nordsik, Roche and Dexcom. She also reports acting as a board member of the Medtronic European Scientific Advisory Board, all outside the submitted work. Denice Feig reports receiving grant support from the JDRF Canadian Clinical Trials Network and advisory board and speaker fees from Medtronic, outside the submitted work. No other competing interests were declared., (© 2021 CMA Joule Inc. or its licensors.)

Objective: To compare glycemic control, quality of life, and pregnancy outcomes of women using insulin pumps and multiple daily injection therapy (MDI) during the Continuous Glucose Monitoring in Women With Type 1 Diabetes in Pregnancy Trial (CONCEPTT)., Research Design and Methods: This was a prespecified analysis of CONCEPTT involving 248 pregnant women from 31 centers. Randomization was stratified for pump versus MDI and HbA 1c . The primary outcome was change in HbA 1c from randomization to 34 weeks' gestation. Key secondary outcomes were continuous glucose monitoring (CGM) measures, maternal-infant health, and patient-reported outcomes., Results: At baseline, pump users were more often in stable relationships ( P = 0.003), more likely to take preconception vitamins ( P = 0.03), and less likely to smoke ( P = 0.02). Pump and MDI users had comparable first-trimester glycemia: HbA 1c 6.84 ± 0.71 vs. 6.95 ± 0.58% (51 ± 7.8 vs. 52 ± 6.3 mmol/mol) ( P = 0.31) and CGM time in target (51 ± 14 vs. 50 ± 13%) ( P = 0.40). At 34 weeks, MDI users had a greater decrease in HbA 1c (-0.55 ± 0.59 vs. -0.32 ± 0.65%, P = 0.001). At 24 and 34 weeks, MDI users were more likely to achieve target HbA 1c ( P = 0.009 and P = 0.001, respectively). Pump users had more hypertensive disorders ( P = 0.011), mainly driven by increased gestational hypertension (14.4 vs. 5.2%; P = 0.025), and more neonatal hypoglycemia (31.8 vs. 19.1%, P = 0.05) and neonatal intensive care unit (NICU) admissions >24 h (44.5 vs. 29.6%; P = 0.02). Pump users had a larger reduction in hypoglycemia-related anxiety ( P = 0.05) but greater decline in health/well-being ( P = 0.02)., Conclusions: In CONCEPTT, MDI users were more likely to have better glycemic outcomes and less likely to have gestational hypertension, neonatal hypoglycemia, and NICU admissions than pump users. These data suggest that implementation of insulin pump therapy is potentially suboptimal during pregnancy., (© 2018 by the American Diabetes Association.)

Purpose of Review: The purpose of the study is to discuss emerging technologies available in the management of type 1 diabetes in pregnancy., Recent Findings: The latest evidence suggests that continuous glucose monitoring (CGM) should be offered to all women on intensive insulin therapy in early pregnancy. Studies have additionally demonstrated the ability of CGM to help gain insight into specific glucose profiles as they relate to glycaemic targets and pregnancy outcomes. Despite new studies comparing insulin pump therapy to multiple daily injections, its effectiveness in improving glucose and pregnancy outcomes remains unclear. Sensor-integrated insulin delivery (also called artificial pancreas or closed-loop insulin delivery) in pregnancy has been demonstrated to improve time in target and performs well despite the changing insulin demands of pregnancy. Emerging technologies show promise in the management of type 1 diabetes in pregnancy; however, research must continue to keep up as technology advances. Further research is needed to clarify the role technology can play in optimising glucose control before and during pregnancy as well as to understand which women are candidates for sensor-integrated insulin delivery.

We consider situations, which are common in medical statistics, where we have a number of sets of response data, from different individuals, say, potentially under different conditions. A parametric model is defined for each set of data, giving rise to a set of random effects. Our goal here is to efficiently explore a range of possible 'population' models for the random effects, to select the most appropriate model. The range of possible models is potentially vast, because the random effects may depend on observed covariates, and there may be multiple credible ways of partitioning their variability. Here, we consider pharmacokinetic (PK) data on insulin aspart, a fast acting insulin analogue used in the treatment of diabetes. PK models are typically nonlinear (in their parameters), often complex and sometimes only available as a set of differential equations, with no closed-form solution. Fitting such a model for just a single individual can be a challenging task. Fitting a joint model for all individuals can be even harder, even without the complication of an overarching model selection objective. We describe a two-stage approach that decouples the population model for the random effects from the PK model applied to the response data but nevertheless fits the full, joint, hierarchical model, accounting fully for uncertainty. This allows us to repeatedly reuse results from a single analysis of the response data to explore various population models for the random effects. This greatly expedites not only model exploration but also cross-validation for the purposes of model criticism. © 2015 The Authors. Statistics in Medicine published by John Wiley & Sons Ltd., (© 2015 The Authors. Statistics in Medicine published by John Wiley & Sons Ltd.)

Objective: To examine the changes in glycemic excursions that occur during pregnancy using continuous glucose monitoring and to compare patterns of glycemia in pregnant women with type 1 and type 2 diabetes., Research Design and Methods: An observational data analysis was performed from a prospective randomized study of continuous glucose monitoring in 57 women with pregestational type 1 (n = 40) or type 2 (n = 17) diabetes with 7-day continuous glucose monitoring system profiles during each trimester. Serial glucose measurements were divided into periods of euglycemia (70-140 mg/dl), hyperglycemia (>140 mg/dl), and hypoglycemia (<70 mg/dl). Generalized linear mixed effects models were fitted to the repeated measures data to determine how these glycemic characteristics varied during gestation and by diabetes type., Results: A total of 180 continuous glucose profiles were examined (140 type 1 diabetes, 40 type 2 diabetes), providing 20,433 h of data for analysis (16,117 h type 1 diabetes, 4,316 type 2 diabetes). Women with type 2 diabetes spend approximately 33% less time hyperglycemic throughout pregnancy than women with type 1 diabetes (P = 0.005), with a significantly more rapid reduction in time spent hyperglycemic in early pregnancy (P = 0.02). Although women with type 2 diabetes spend less overall time hypoglycemic (P = 0.04), their risk of nocturnal hypoglycemia is equivalent to that of women with type 1 diabetes (blood glucose level <70 mg/dl, P = 0.9; blood glucose level <50 mg/dl, P = 0.2)., Conclusions: Continuous glucose monitoring reveals clear differences in the level of glycemic control that exist in women with type 1 and type 2 diabetes. These data will guide therapeutic interventions aimed at optimizing glycemic control and improving the pregnancy outcomes of both type 1 and type 2 diabetes.

Background: The number of women of childbearing age with Type 2 diabetes(T2DM) is increasing, and they now account for > 50% of pregnancies in women with pre-existing diabetes. Diabetes pregnancies without adequate pre-pregnancy care have higher risk for poor outcomes (miscarriages, birth-defects, stillbirths) and are associated with increased complications (caesarean deliveries, macrosomic babies, neonatal intensive-care admissions). The risks and costs of these pregnancies can be reduced with pregnancy preparation (HbA1c, ≤ 6.5%, 5 mg folic acid and stopping potentially harmful medicines). However, 90% of women with T2DM, most of whom are based in primary care, are not adequately prepared for pregnancy. This study will evaluate a programme of primary care-based interventions (decision-support systems; pre-pregnancy care-pathways; pregnancy-awareness resources; professional training; and performance monitoring) to improve pregnancy preparation in women with T2DM. Methods: The study aims to optimise the programme interventions and estimate their impact on pregnancy preparation, pre-pregnancy care uptake and pregnancy outcomes. To evaluate this multimodal intervention, we will use a multi-method research design following Complex Adaptive Systems (CAS) theory, refining the interventions iteratively during the study. Thirty GP practices with ≥ 25 women with T2DM of reproductive age (18–45 years) from two South London boroughs will be exposed to the intervention. This will provide > 750 women with an estimated pregnancy incidence of 80–100 to study. The research involves: a clinical audit of processes and outcomes; a process evaluation informing intervention feasibility, implementation, and behaviour change; and a cost-consequences analysis informing future economic evaluation. Performance data will be collected via audits of GP systems, hospital antenatal clinics and pregnancy outcomes. Following CAS theory, we will use repeated measurements to monitor intervention impact on pregnancy preparation markers at 4-monthly intervals over 18-months. We will use performance and feasibility data to optimise intervention effects iteratively. The target performance for the intervention is a 30% increase in the proportion of women meeting pre-pregnancy care criteria. Discussion: The primary output will be development of an integrated programme of interventions to improve pregnancy preparation, pre-pregnancy care uptake, and reduce adverse pregnancy outcomes in women with T2DM. We will also develop an implementation plan to support the introduction of the interventions across the NHS. Trial registration: ISRCTN47576591; February 8, 2022. [ABSTRACT FROM AUTHOR]

Similarly, in late pregnancy, women with type 2 diabetes were more likely to have anxiety symptoms (31 vs 11%; I P i =0.002) and depressive symptoms (23 vs 4%; I P i =0.002) compared to women without diabetes. Compared to women without diabetes, those with type 2 diabetes were more likely to have both anxiety symptoms (36 vs 6%; I P i <0.001) and depressive symptoms (14 vs 2%; I P i =0.003) in early pregnancy. Conclusions While mean sensor glucose over 24 h and overnight were similar between IS-CGM and RT-CGM, time below range overnight was higher when assessed using IS-CGM compared to masked RT-CGM in early pregnancy. The manuscripts chosen for this yearbook address key controversies in the screening and detection of gestational diabetes mellitus (GDM), glycemic metrics using intermittent and continuous glucose monitoring (CGM) in type 1 diabetes and the theory of beta-cell regeneration. [Extracted from the article]

Background: Offspring of women with type 1 diabetes are at increased risk of fetal growth patterns which are associated with perinatal morbidity. Our aim was to compare rates of large- and small-for-gestational age (LGA; SGA) defined according to different criteria, using data from the Continuous Glucose Monitoring in Type 1 Diabetes Pregnancy Trial (CONCEPTT).Methods: This was a pre-specified analysis of CONCEPTT involving 225 pregnant women and liveborn infants from 31 international centres ( ClinicalTrials.gov NCT01788527; registered 11/2/2013). Infants were weighed immediately at birth and GROW, INTERGROWTH and WHO centiles were calculated. Relative risk ratios, sensitivity and specificity were used to assess the different growth standards with respect to perinatal outcomes, including neonatal hypoglycaemia, hyperbilirubinaemia, respiratory distress, neonatal intensive care unit (NICU) admission and a composite neonatal outcome.Results: Accelerated fetal growth was common, with mean birthweight percentiles of 82.1, 85.7 and 63.9 and LGA rates of 62, 67 and 30% using GROW, INTERGROWTH and WHO standards respectively. Corresponding rates of SGA were 2.2, 1.3 and 8.9% respectively. LGA defined according to GROW centiles showed stronger associations with preterm delivery, neonatal hypoglycaemia, hyperbilirubinaemia and NICU admission. Infants born > 97.7th centile were at highest risk of complications. SGA defined according to INTERGROWTH centiles showed slightly stronger associations with perinatal outcomes.Conclusions: GROW and INTERGROWTH standards performed similarly and identified similar numbers of neonates with LGA and SGA. GROW-defined LGA and INTERGROWTH-defined SGA had slightly stronger associations with neonatal complications. WHO standards underestimated size in preterm infants and are less applicable for use in type 1 diabetes.Trial Registration: This trial is registered with ClinicalTrials.gov . number NCT01788527 . Trial registered 11/2/2013. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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, HbA1c 8.0% [1.1], and BMI 26.6 [4.4] kg/m2) to an open-label, randomized, crossover trial. Participants completed 28 days of closed-loop and sensor-augmented pump (SAP) insulin delivery separated by a washout period. Afterward, participants could continue to use the closed-loop system up to 6 weeks postpartum. The primary end point was the proportion of time with glucose levels within the target range (63-140 mg/dL).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. [ABSTRACT FROM AUTHOR]

Gestational diabetes mellitus (GDM) is defined as hyperglycaemia that is diagnosed for the first time in the second or third trimester of pregnancy. It occurs in one in seven pregnancies worldwide and is associated with increased risk of adverse perinatal outcome, in particular, infant birth weight that is large for gestational age, increased infant adiposity, preeclampsia and preterm delivery, and increased delivery by caesarean section. This review focuses on the controversy regarding screening and diagnosis of GDM following development of the International Association of Diabetes and Pregnancy Study Groups (IADPSG) guidelines and the National Institute of Clinical Excellence (NICE) 2015 guidelines. It reviews the most recent research in to diet and exercise modification in prevention and management of GDM, pharmacological management and post-partum management to delay and/or prevent progression to type 2 diabetes. [ABSTRACT FROM AUTHOR]

Objective: To determine whether fetal overgrowth precedes the diagnosis of gestational diabetes mellitus (GDM) and to quantify the interrelationships among fetal overgrowth, GDM, and maternal obesity.Research Design and Methods: We conducted a prospective cohort study of unselected nulliparous women and performed ultrasonic measurement of the fetal abdominal circumference (AC) and head circumference (HC) at 20 and 28 weeks of gestational age (wkGA). Exposures were diagnosis of GDM ≥28 wkGA and maternal obesity. The risk of AC >90th and HC-to-AC ratio <10th percentile was modeled using log-binomial regression, adjusted for maternal characteristics.Results: Of 4,069 women, 171 (4.2%) were diagnosed with GDM at ≥28 wkGA. There was no association between fetal biometry at 20 wkGA and subsequent maternal diagnosis of GDM. However, at 28 wkGA, there was an increased risk of AC >90th percentile (adjusted relative risk 2.05 [95% CI 1.37-3.07]) and HC-to-AC ratio <10th percentile (1.97 [1.30-2.99]). Maternal obesity showed similar associations at 28 wkGA (2.04 [1.62-2.56] and 1.46 [1.12-1.90], respectively). The combination of GDM and obesity was associated with an approximately fivefold risk of AC >90th (4.52 [2.98-6.85]) and approximately threefold risk of HC-to-AC ratio <10th percentile (2.80 [1.64-4.78]) at 28 wkGA. Fetal AC >90th percentile at 28 weeks was associated with an approximately fourfold risk of being large for gestational age at birth.Conclusions: Diagnosis of GDM is preceded by excessive growth of the fetal AC between 20 and 28 wkGA, and its effects on fetal growth are additive with the effects of maternal obesity. [ABSTRACT FROM AUTHOR]

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 multidisci-plinary obstetric clinics for diabetes in the U.K. and Denmark. LGA was defined as birth weight S90th 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 midmorn-ing (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. [ABSTRACT FROM AUTHOR]

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/m², 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% (50100%) 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. [ABSTRACT FROM AUTHOR]

OBJECTIVE--To assess random venous blood glucose (RBG) measurement at antenatal booking to detect "overt diabetes in pregnancy" (ODIP). RESEARCH DESIGN AND METHODS--A retrospective analysis of regional hospital obstetric data from 2004-2008 was performed. Universal RBG screening was included at booking. Oral glucose tolerance test (OGTT) was administered if RBG >7.0 mmol/L or other indications, e.g., if a 50-g glucose challenge test was >7.7 mmol/L at 26-28 weeks. ODIP was based upon World Health Organization plasma glucose criteria for diabetes. RESULTS--RBG data were collected from 17,852/26,369 (67.7%) pregnancies around the initial antenatal visit; 3,007 women had an OGTT. The receiver operator curve area under the curve for RBG to detect ODIP was 0.86 (0.80-0.92) (assuming women without an OGTT did not have ODIP). CONCLUSIONS--RBG at booking may provide a sufficiently sensitive screening tool for the detection of ODIP. We recommend further studies and comparison with fasting glucose and HbA1c. [ABSTRACT FROM AUTHOR]

The article discusses research done on intermittent real-time continuous glucose monitoring (CGM) in pregnant women with diabetes. It references a study by A. L. Secher and colleagues, published in the 2013 issue. The researchers focused on the prevention of nocturnal hypoglycemia. They concluded that intermittent use of real-time CGM failed to improve glycemic control or neonatal morbidity.