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Aims/hypothesis: This study aimed to describe the relationship between breastfeeding episodes and maternal glucose levels, and to assess whether this differs with closed-loop vs open-loop (sensor-augmented pump) insulin therapy. Methods: Infant-feeding diaries were collected at 6 weeks, 12 weeks and 24 weeks postpartum in a trial of postpartum closed-loop use in 18 women with type 1 diabetes. Continuous glucose monitoring (CGM) data were used to identify maternal glucose patterns within the 3 h of breastfeeding episodes. Generalised mixed models adjusted for breastfeeding episodes in the same woman, repeat breastfeeding episodes, carbohydrate intake, infant age at time of feeding and early pregnancy HbA1c. This was a secondary analysis of data collected during a randomised trial (ClinicalTrials.gov registration no. NCT04420728). Results: CGM glucose remained above 3.9 mmol/l in the 3 h post-breastfeeding for 93% (397/427) of breastfeeding episodes. There was an overall decrease in glucose at nighttime within 3 h of breastfeeding (1.1 mmol l−1 h−1 decrease on average; p=0.009). A decrease in nighttime glucose was observed with open-loop therapy (1.2 ± 0.5 mmol/l) but was blunted with closed-loop therapy (0.4 ± 0.3 mmol/l; p<0.01, open-loop vs closed-loop). Conclusions/interpretation: There is a small decrease in glucose after nighttime breastfeeding that usually does not result in maternal hypoglycaemia; this appears to be blunted with the use of closed-loop therapy. [ABSTRACT FROM AUTHOR]

Summary: Polycystic ovary syndrome (PCOS) is a common endocrine disorder in females. Modest weight loss improves reproductive and metabolic PCOS features. While lifestyle modifications and pharmacotherapies remain first‐line weight loss strategies, bariatric surgery is emerging as a potentially effective treatment. We performed a systematic review and meta‐analysis of published literature to examine the impact of bariatric surgery in PCOS to inform the 2023 International PCOS Evidence‐based Guidelines. Electronic databases were searched for observational studies and trials comparing pharmacologic or lifestyle treatments to bariatric surgery in women with PCOS or bariatric surgery in women with or without PCOS. Anthropometric, reproductive, hormonal, and metabolic outcomes were included and, where possible, meta‐analyzed using random‐effects models. Risk of bias and evidence quality were assessed. Ten studies were included involving 432 women with and 590 women without PCOS. Comparisons between bariatric surgery and pharmacologic or lifestyle treatments were only reported in one study each, and most reproductive outcomes were limited to a single study; therefore, meta‐analyses could not be performed. Meta‐analysis found that women with PCOS experience similar improvements in anthropometric, hormonal, and metabolic outcomes after bariatric surgery compared to those without PCOS. Existing research is limited and of low quality with high risk of bias, especially in comparison to existing PCOS treatments and with respect to reproductive outcomes including pregnancy, highlighting the need for additional studies to inform clinical recommendations. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

A systematic review is a rigorous process that involves identifying, selecting, and synthesizing available evidence pertaining to an a priori–defined research question. The resulting evidence base may be summarized qualitatively or through a quantitative analytic approach known as meta-analysis. Systematic review and meta-analysis (SRMAs) have risen in popularity across the scientific realm including diabetes research. Although well-conducted SRMAs are an indispensable tool in informing evidence-based medicine, the proliferation of SRMAs has led to many reviews of questionable quality and misleading conclusions. The objective of this article is to provide up-to-date knowledge and a comprehensive understanding of strengths and limitations of SRMAs. We first provide an overview of the SRMA process and offer ways to identify common pitfalls at key steps. We then describe best practices as well as evolving approaches to mitigate biases, improve transparency, and enhance rigor. We discuss several recent developments in SRMAs including individual-level meta-analyses, network meta-analyses, umbrella reviews, and prospective meta-analyses. Additionally, we outline several strategies that can be used to enhance quality of SRMAs and present key questions that authors, editors, and readers should consider in preparing or critically reviewing SRMAs. [ABSTRACT FROM AUTHOR]

This year's diabetes pregnancy manuscripts, three for each of type 1 diabetes (T1D), type 2 diabetes (T2D), and gestational diabetes mellitus (GDM), were chosen from over 3500 published articles. Data were collected on pregnant women with diabetes (any type) with DKA events (cases) and pregnant women with diabetes without DKA (controls) from 194 maternity units between April 2019 and September 2020. Another concerning finding is the prevalence of diabetic ketoacidosis (DKA) during pregnancy in all types of diabetes. Seventy DKA events (85%) occurred in women with T1D (incidence 16.6/100,000; 95% CI, 13.0-20.9), 5 DKA events (6%) in women with T2D (incidence 1.1/100,000; 95% CI, 0.4-2.5), and 7 (9%) in women diagnosed with GDM. [Extracted from the article]

Background: There is limited information regarding the association between missed appointments and neonatal outcomes for diabetes in pregnancy. Study Methods: This retrospective live birth cohort included pregnant women with Type 1 or 2 diabetes who attended specialized clinics from 2008 to 2020. The association between at least one missed antenatal diabetes appointments and outcomes were assessed using logistic regression and reported as adjusted odds ratios (aOR) (95% confidence interval). Mediation analyses were conducted to examine if above target HbA1c mediated these relationships. Results: The cohort included 407 and 902 women with Type 1 and 2 diabetes, respectively, of whom 25.1% and 34.5% missed at least one appointment. Women with Type 1 diabetes who missed an appointment were more likely to have a caesarean section (aOR 1.95 [1.15, 3.31]) and their babies more likely to be admitted to the neonatal intensive care unit (aOR 2.25 [1.35, 3.75]). Women with Type 2 diabetes who missed an appointment were more likely to have a large‐for‐gestational‐age infant (aOR 1.61 [1.13, 2.28]), and an extreme large‐for‐gestational‐age infant (aOR 1.69 [1.02, 2.81]) compared with women who did not miss appointments. Above target HbA1c mediated the relationship between missed appointments and caesarean delivery in Type 1 diabetes and large‐for‐gestational age and extreme large‐for‐gestational age in Type 2 diabetes. Conclusion: In individuals with Type 1 and 2 diabetes, there are differences in neonatal outcomes between those who missed an appointment compared to those who did not. It remains unclear if missed diabetes appointments are causative or a marker of other health behaviours or risk factors leading to neonatal morbidity. [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]

Aims/hypothesis: Controversy exists over whether gestational diabetes increases the risk of stillbirth. The aim of this review was to examine the association between gestational diabetes and stillbirth. Methods: We performed searches of the published literature to May 2021. Study selection and data extraction were performed in duplicate by independent reviewers. Meta-analyses of summary measures were conducted using random-effect models for cohort and case–control studies separately. The study protocol was registered in PROSPERO (registration ID CRD42020166939). Results: From 9981 citations, 419 were identified for full-text review and 73 met inclusion criteria (n = 70,292,090). There was no significant association between gestational diabetes and stillbirth in cohort studies (pooled OR 1.04 [95% CI 0.90, 1.21]; I2 86.1%) or in case–control studies (pooled OR 1.57 [95% CI 0.83, 2.98]; I2 94.8%). Gestational diabetes was associated with lower odds of stillbirth among cohort studies presenting with an adjusted OR (pooled OR 0.78 [95% CI 0.68, 0.88]; I2 42.7%). Stratified analyses by stillbirth ≥28 weeks' gestation, studies published prior to 2013 and studies identified as low quality demonstrated a significantly higher odds of stillbirth in meta-regression (p = 0.016, 0.023 and 0.005, respectively). Egger's test for all included cohort studies (p = 0.018) suggests publication bias for the main meta-analysis. Conclusions/interpretation: Given the substantial heterogeneity across studies, there are insufficient data to define the relationship between stillbirth and gestational diabetes adequately. In the main analyes, gestational diabetes was not associated with an increased risk of stillbirth. However, heterogeneity across studies means this finding should be interpreted cautiously. [ABSTRACT FROM AUTHOR]

Aims: (1) To determine the likelihood of full breastfeeding at 3 months postpartum in women with and without diabetes in pregnancy (DiP); (2) to explore the associations between diabetes management practices and infant feeding practices in those who had DiP and (3) to examine women's experiences of feeding their infants after having DiP. Methods: The quantitative study used data from Alberta Pregnancy Outcomes and Nutrition (APrON) cohort study. Participants who had DiP (n = 62) were matched 1:3 to participants without DiP for pre‐pregnancy BMI, parity, mode of delivery and pre‐term birth. Infant feeding questionnaires, prospective breastfeeding diaries and medical chart data were analysed to determine likelihood of fully breastfeeding at 3 months postpartum. For the qualitative study, interviews were conducted with postpartum women who had DiP to explore the experiences of infant feeding. Interviews were thematically analysed, and the results were compared between women who were categorized as 'full breast feeders' or 'mixed feeders'. Results: The odds of fully breastfeeding were 50% lower in women with DiP than women without DiP (OR: 0.50, 95% CI 0.25–0.99, p = 0.04). Qualitative interviews identified that although all women showed resilience in the face of infant feeding challenges, those who were fully breastfeeding reported seeking out external infant feeding supports, for example, classes or Doula's. Mixed Feeders perceived there was a lack of infant feeding information and support given to them prior to giving birth. Conclusion: Women with DiP may require additional prenatal and postnatal infant feeding support to be better prepared to overcome feeding challenges they may face. [ABSTRACT FROM AUTHOR]

Purpose Of Review: To review the current evidence for the use of metformin in pregnancy for women with type 2 diabetes.Recent Findings: A large, multicenter, double-blind randomized controlled trial found that women with type 2 diabetes in pregnancy treated with metformin as an adjunct to insulin therapy had less gestational weight gain, insulin requirements, caesarian sections, macrosomia, and neonatal adiposity, but more neonates were small for gestational age (SGA) compared with insulin alone. It is unclear if the higher number of SGA infants are a direct result of metformin exposure or mediated through other effects such as less gestational weight gain and improved glycemic control. Additional follow-up studies of offspring exposed to metformin in utero are required. Metformin may be a useful adjunctive treatment for women with type 2 diabetes in pregnancy to help meet glycemic targets if there are no concerns for or indications of SGA. [ABSTRACT FROM AUTHOR]

Results Case 1 presented at 4-weeks gestation in her second pregnancy, having had a previous miscarriage at 7-weeks gestation. They encompass improvements in our understanding of continuous glucose monitoring (CGM) in pregnancy, early data on the first commercially available closed-loop system used (off-license) during pregnancy, and advancements in our understanding of screening for GDM. As CGM in pregnancy continues to gain more widespread use, identifying these patterns using FDA may not only aid in the understanding of the pathophysiology of various glycemic-related complications but also help diabetes clinicians and women with diabetes identify and target patterns to reduce adverse outcomes. The manuscripts chosen for this year's article on technology and pregnancy demonstrated advances in our understanding of type 1, type 2, and gestational diabetes (GDM) in pregnant women. [Extracted from the article]

Background: Women with hypothyroidism before pregnancy often require an increase in their levothyroxine dosage to maintain a euthyroid state during pregnancy. The objectives of this study were to investigate: (i) the frequency and distribution of thyrotropin (TSH) testing and levothyroxine dosage adjustment by gestational age, (ii) the magnitude of levothyroxine increase by the underlying etiology of hypothyroidism, and (iii) the relationship of overtreatment or undertreatment during pregnancy with adverse pregnancy outcomes among women using thyroid replacement before pregnancy. Methods: A retrospective cohort study of pregnancies in women on thyroid replacement before pregnancy in Alberta, Canada, was performed. Women using thyroid replacement anytime during the two years before pregnancy who delivered between October 2014 and September 2017 were included. Delivery records, physician billing, and laboratory and pharmacy administrative data were linked. Outcomes included characteristics of TSH testing, levothyroxine dosing, and pregnancy outcomes. The frequency and gestational timing of TSH testing and levothyroxine adjustments were calculated. Multiple logistic regression was used to test whether pregnancies with TSH <0.10 mIU/L (overtreatment) or TSH ≥10.00 mIU/L (undertreatment) compared with control pregnancies (TSH 0.10–4.00 mIU/L) were associated with adverse pregnancy and neonatal outcomes. Results: Of the 10,680 deliveries, 8774 (82.2%) underwent TSH testing at least once during pregnancy, at a median gestational age of six weeks. An adjustment of levothyroxine dosage was made for 4321 (43.7%) during pregnancy. TSH in pregnancy below 0.10 mIU/L increased the odds of preterm delivery when compared with control pregnancies (adjusted odds ratio, 2.14 [95% confidence interval 1.51–2.78]). TSH ≥10.00 mIU/L during pregnancy was not associated with any adverse pregnancy or neonatal outcomes in the multivariable analysis. Conclusions: Although most women on thyroid replacement before conception had TSH measured at some point during pregnancy, it is concerning that 17.8% did not. Levothyroxine overtreatment in pregnancy was associated with preterm delivery. These findings suggest that clinicians should be careful to avoid overtreatment with levothyroxine in pregnancy. [ABSTRACT FROM AUTHOR]

In recent years, continuous glucose monitoring (CGM) has become increasingly available with the introduction of devices that are specifically approved for use during pregnancy. Evidence in the form of randomized-controlled trials and cohort studies continues to build support for the use of CGM during pregnancy to improve measures of maternal glycemia as well as obstetric and neonatal outcomes. Based on data from the CGM in pregnant women with type 1 diabetes (CONCEPTT) trial alongside a Swedish cohort study of real-world outcomes of pregnant women with type 1 diabetes, the UK National Institute for Health and Clinical Excellence (NICE) guidelines now recommend that real-time CGM be offered to all pregnant women with type 1 diabetes. Based on these guidelines, all pregnant individuals in the United Kingdom with type 1 diabetes will receive government-funded real-time CGM for a 12-month duration. These guidelines are a game-changer and will continue to facilitate more widespread access to CGM use in the United Kingdom and beyond. This review describes the role of CGM in the management of diabetes in pregnancy, discusses contemporary maternal glucose levels and their relationship with outcomes in diabetes pregnancies, and examines the high-quality, randomized-controlled trial and the real-world clinical data evaluating the impact of CGM use. [ABSTRACT FROM AUTHOR]

Objective: The optimal method of monitoring glycemia in pregnant women with type 1 diabetes remains controversial. This study aimed to assess the predictive performance of HbA1c, continuous glucose monitoring (CGM) metrics, and alternative biochemical markers of glycemia to predict obstetric and neonatal outcomes.Research Design and Methods: One hundred fifty-seven women from the Continuous Glucose Monitoring in Women With Type 1 Diabetes in Pregnancy Trial (CONCEPTT) were included in this prespecified secondary analysis. HbA1c, CGM data, and alternative biochemical markers (glycated CD59, 1,5-anhydroglucitol, fructosamine, glycated albumin) were compared at ∼12, 24, and 34 weeks' gestation using logistic regression and receiver operating characteristic (ROC) curves to predict pregnancy complications (preeclampsia, preterm delivery, large for gestational age, neonatal hypoglycemia, admission to neonatal intensive care unit).Results: HbA1c, CGM metrics, and alternative laboratory markers were all significantly associated with obstetric and neonatal outcomes at 24 weeks' gestation. More outcomes were associated with CGM metrics during the first trimester and with laboratory markers (area under the ROC curve generally <0.7) during the third trimester. Time in range (TIR) (63-140 mg/dL [3.5-7.8 mmol/L]) and time above range (TAR) (>140 mg/dL [>7.8 mmol/L]) were the most consistently predictive CGM metrics. HbA1c was also a consistent predictor of suboptimal pregnancy outcomes. Some alternative laboratory markers showed promise, but overall, they had lower predictive ability than HbA1c.Conclusions: HbA1c is still an important biomarker for obstetric and neonatal outcomes in type 1 diabetes pregnancy. Alternative biochemical markers of glycemia and other CGM metrics did not substantially increase the prediction of pregnancy outcomes compared with widely available HbA1c and increasingly available CGM metrics (TIR and TAR). [ABSTRACT FROM AUTHOR]

Background: Screening in pregnancy for subclinical hypothyroidism, often defined as thyroid-stimulating hormone (TSH) greater than 2.5 mIU/L or greater than 4.0 mIU/L, is controversial. We determined the frequency and distribution of TSH testing by gestational age, as well as TSH values associated with treatment during pregnancy and the frequency of postpartum continuation of thyroid hormone therapy.Methods: We performed a retrospective cohort study of pregnancies in Alberta, Canada. We included women without thyroid disease who delivered between October 2014 and September 2017. We used delivery records, physician billings, and pharmacy and laboratory administrative data. Our key outcomes were characteristics of TSH testing and the initiation and continuation of thyroid hormone therapy. We calculated the proportion of pregnancies with thyroid testing and the frequency of each specific thyroid test.Results: Of the 188 490 pregnancies included, 111 522 (59.2%) had at least 1 TSH measurement. The most common time for testing was at gestational week 5 to 6. Thyroid hormone therapy was initiated at a median gestational age of 7 (interquartile range 5-12) weeks. Among women with first TSH measurements of 4.01 to 9.99 mIU/L who were not immediately treated, the repeat TSH measurement was 4.00 mIU/L or below in 67.9% of pregnancies. Thyroid hormone was continued post partum for 44.6% of the women who started therapy during their pregnancy.Interpretation: The findings of our study suggest that current practice patterns may contribute to overdiagnosis of hypothyroidism and overtreatment during pregnancy and post partum. [ABSTRACT FROM AUTHOR]

The manuscripts chosen for this year's technology and pregnancy article provide new insights into fetal exposure to maternal glucose during pregnancies complicated by gestational diabetes, and type 1 diabetes. Data relating continuous glucose monitoring (CGM) in type 1 diabetes pregnancy to neonatal outcomes are scarce. Healthcare providers and women with diabetes can focus on increasing CGM time in range during the latter half of pregnancy to reduce the risk of neonatal hypoglycemia. Women with gestational diabetes were more likely to develop type 2 diabetes or prediabetes than women without gestational diabetes (adjusted OR 3.44 [95% CI 2.84, 4.14]). [Extracted from the article]

Aims/hypothesis: We performed a systematic review and meta-analysis to determine whether exposure to maternal pre-existing diabetes in pregnancy is associated with neurocognitive or behavioural outcomes in offspring. Methods: We searched MEDLINE, EMBASE, PsychINFO, the Cochrane Database of Systematic Reviews and Scopus for studies that examined any neurocognitive or behavioural outcomes in offspring of mothers with pre-existing diabetes in pregnancy in accordance with a published protocol (PROSPERO CRD42018109038). Title and abstract review, full-text review and data extraction were performed independently and in duplicate. Risk of bias was assessed using the Newcastle–Ottawa scale. Meta-analyses of summary measures were performed using random-effects models. Results: Nineteen articles including at least 18,681 exposed and 2,856,688 control participants were identified for inclusion. Exposure to maternal pre-existing diabetes in pregnancy was associated with a lower pooled intelligence quotient in the offspring (pooled weighted mean difference −3.07 [95% CI −4.59, −1.55]; I2 = 0%) and an increased risk of autism spectrum disorders (effect estimate 1.98 [95% CI 1.46, 2.68]; I2 = 0%). There was also an increased risk of attention deficit/hyperactivity disorder (pooled HR 1.36 [95% CI 1.19, 1.55]; I2 = 0%), though this was based on only two studies. Although most studies were found to be high quality in terms of participant selection, in many studies, comparability of cohorts and adequacy of follow-up were sources of bias. Conclusions/interpretation: There is evidence to suggest that in utero exposure to maternal pre-existing diabetes is associated with some adverse neurocognitive and behavioural outcomes. It remains unclear what the role of perinatal factors is and the degree to which other environmental factors contribute to these findings. [ABSTRACT FROM AUTHOR]

Background: Population-, assay-, and trimester-specific reference intervals for thyroid function tests are necessary to assess thyroid status accurately and manage thyroid disease throughout pregnancy. This study's objective was to verify if the manufacturer's recommended trimester-specific reference intervals for thyroid tests and the American Thyroid Association's recommended total thyroxine (TT4) pregnancy reference intervals were verifiable and appropriate for use in the authors' multicultural population. Methods: Blood samples were obtained from the following sources: stored frozen surplus blood from women undergoing routine aneuploidy screening (first- and second-trimester samples, n = 274), women participating in an observational cohort study (second- and third-trimester samples, n = 135), and blood collected from women presenting for assessment to the labor and delivery ward (third-trimester samples, n = 35). Exclusions included thyroid medication or disease and positive thyroid peroxidase antibodies (anti-TPO). Samples were analyzed for thyrotropin (TSH), free T4 (fT4), free triiodothyronine (fT3), TT4, and anti-TPO using the Roche Cobas 8000 Modular e602 electrochemiluminescence immunoassay. Results: Nine percent of the aneuploidy screening samples were excluded prior to thyroid testing due to maternal use of thyroid medication. Six percent of analyzed samples were excluded: 5.9% with positive anti-TPO and one with a TSH >10 mIU/L. The manufacturer's recommended trimester-specific reference intervals for TSH were not verified by described standardized methods. Therefore, 95th percentile reference intervals were determined using a minimum number of samples. Reference intervals for TSH and fT4 were as follows: 9–12 weeks, 0.18–2.99 mIU/L and 11–19.2 pmol/L; second trimester, 0.11–3.98 mIU/L and 10.5–18.2 pmol/L; and third trimester, 0.48–4.71 mIU/L and 9.0–16.1 pmol/L, respectively. The TT4 reference interval after 19 weeks' gestation was 77–186 nmol/L. Conclusions: This study provides a simple approach to verify or establish trimester-specific thyroid function reference intervals in local populations. The TT4 reference interval was lower than the interval proposed by the American Thyroid Association, suggesting the need for further study of TT4 in pregnancy and reliance on locally established fT4 reference intervals after 19 weeks, especially when there are no equivalent reference intervals for TT4. [ABSTRACT FROM AUTHOR]

The article offers information on some key advances in the field of diabetes technology that is increasingly used in the clinical management of diabetes before and during pregnancy. It mentions the real-world data are becoming increasingly important to health-care providers and regulators; and also mentions metabolomic data from the Great Britain describe the metabolite disturbances in obese women 10 weeks prior to gestational diabetes mellitus (GDM) diagnosis.

Objective To determine in women with subclinical hypothyroidism diagnosed in pregnancy whether levothyroxine treatment compared with control, impacts important obstetrical or childhood outcomes (specifically IQ) in randomised controlled trials. Design Systematic review and meta-analysis. study eligibility criteria Randomised trials which met all the following were included: (1) reported original data of women with subclinical hypothyroidism diagnosed in pregnancy (by any prespecified study definition); (2) randomised to either levothyroxine or control (placebo or no treatment); (3) reported obstetrical outcomes and/or childhood neurodevelopmental outcomes and (4) published from 1980 to January 2018 in either English or French language. Data sources Medline, EMBASE, CINAHL, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials and ClinicalTrials.gov. Outcome measures Obstetrical, neonatal and childhood outcomes including: miscarriage, gestational hypertension, pre-eclampsia, preterm delivery, mode of delivery, neonatal intensive care unit admission, birth weight, gestational age at delivery, childhood IQ and neurodevelopmental scores. risk of bias assessment Cochrane Risk of Bias Tool (Modified) for Quality Assessment of Randomised Controlled Trials results Three trials of low to unclear risk of bias with 1837 participants were included. Two studies were meta-analysed for maternal and neonatal outcomes and two studies for childhood IQ. No statistically significant differences were found for any clinical outcomes with levothyroxine therapy compared with control. Limitations Only three trials were identified for inclusion. Conclusions This review, based on three randomised trials in women with subclinical hypothyroidism diagnosed in pregnancy, found no evidence of benefit of levothyroxine therapy on obstetrical, neonatal, childhood IQ or neurodevelopmental outcomes. Current trial evidence does not support the treatment of subclinical hypothyroidism diagnosed in pregnancy. PrOsPErO registration number CRD4201707980. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: Medical nutrition therapy is a mainstay of gestational diabetes mellitus (GDM) treatment. However, data are limited regarding the optimal diet for achieving euglycemia and improved perinatal outcomes. This study aims to investigate whether modified dietary interventions are associated with improved glycemia and/or improved birth weight outcomes in women with GDM when compared with control dietary interventions.Research Design and Methods: Data from published randomized controlled trials that reported on dietary components, maternal glycemia, and birth weight were gathered from 12 databases. Data were extracted in duplicate using prespecified forms.Results: From 2,269 records screened, 18 randomized controlled trials involving 1,151 women were included. Pooled analysis demonstrated that for modified dietary interventions when compared with control subjects, there was a larger decrease in fasting and postprandial glucose (-4.07 mg/dL [95% CI -7.58, -0.57]; P = 0.02 and -7.78 mg/dL [95% CI -12.27, -3.29]; P = 0.0007, respectively) and a lower need for medication treatment (relative risk 0.65 [95% CI 0.47, 0.88]; P = 0.006). For neonatal outcomes, analysis of 16 randomized controlled trials including 841 participants showed that modified dietary interventions were associated with lower infant birth weight (-170.62 g [95% CI -333.64, -7.60]; P = 0.04) and less macrosomia (relative risk 0.49 [95% CI 0.27, 0.88]; P = 0.02). The quality of evidence for these outcomes was low to very low. Baseline differences between groups in postprandial glucose may have influenced glucose-related outcomes. As well, relatively small numbers of study participants limit between-diet comparison.Conclusions: Modified dietary interventions favorably influenced outcomes related to maternal glycemia and birth weight. This indicates that there is room for improvement in usual dietary advice for women with GDM. [ABSTRACT FROM AUTHOR]

Objective: The objective of the study is to assess the impact of maternal glycaemic control and large-for-gestational-age (LGA) infant size on the risk of developing neonatal hypoglycaemia in offspring of women with type 1 diabetes and to determine possible predictors of neonatal hypoglycaemia and LGA.Research Methods and Design: This retrospective cohort study evaluated pregnancies in 161 women with type 1 diabetes mellitus at a large urban centre between 2006 and 2010. Mean trimester A1c values were categorized into five groups. Multiple logistic regression analyses were used to examine predictors of neonatal hypoglycaemia and large-for-gestational-age (LGA).Results: Hypoglycaemia occurred in 36.6% of neonates. There was not a linear association between trimester specific A1c and LGA. After adjusting for maternal age, body mass index (BMI), smoking and premature delivery, neonatal hypoglycaemia was not linearly associated with A1c in the first, second or third trimesters. LGA was the only significant predictor for neonatal hypoglycaemia (OR, 95% CI 2.51 [1.10, 5.70]) in logistic regression analysis that adjusted for glycaemic control, maternal age, smoking, prematurity and BMI. An elevated third trimester A1c increased the odds of LGA (1.81 [1.03, 3.18]) after adjustment for smoking, parity and maternal BMI.Conclusions: Large-for-gestational-age imparts a 2.5-fold increased odds of hypoglycaemia in neonates of women with type 1 diabetes and may be a better predictor of neonatal hypoglycaemia than maternal glycaemic control. Our data suggest that LGA neonates of women with type 1 diabetes should prompt increased surveillance for neonatal hypoglycaemia and that the presence of optimum maternal glycaemic control should not reduce this surveillance. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Aims: We assessed metabolomic signatures in maternal and cord blood associated with suboptimal outcomes in the continuous glucose monitoring in women with type 1 diabetes in pregnancy trial (CONCEPTT). Methods: Serum samples from 162 mothers (12, 24 and 34 weeks' gestation) and 93 cord blood samples were analysed for 1049 metabolites and 1041 lipids using ultra-performance liquid chromatography-tandem mass spectroscopy. We used adjusted and unadjusted logistic regression of metabolomic variables using adjudicated outcomes: extremely-large-for-gestational-age (ELGA; >97.5th centile), pre-eclampsia and neonatal hypoglycaemia with modified Bonferroni false discovery rate p≤0.001. Results: All materno-fetal complications studied were associated with reliance on non-carbohydrate sources of fuel. Lipids through beta oxidation were the main fuel source in ELGA (24 and 34 weeks), neonatal hypoglycaemia (12 weeks only) and pre-eclampsia (12 and 24 weeks). Marked protein catabolism was evident in neonatal hypoglycaemia (34 weeks) and pre-eclampsia (24 and 34 weeks). Cord blood in ELGA infants showed evidence of simultaneous beta oxidation and de novo lipogenesis, a biologically futile cycle of creating and destroying lipids, which consumes excess energy and substrate. Cord blood from infants with neonatal hypoglycaemia showed evidence of pronounced protein catabolism providing glucogenic amino acids for gluconeogenesis. Conclusions: Reliance on lipid or protein sources for fuel was associated with ELGA, neonatal hypoglycaemia and pre-eclampsia. Carbohydrate metabolism was insufficient to meet cellular energy demands, possibly due to insufficient insulin, insufficient dietary carbohydrate or both. Improving outcomes in type 1 diabetes pregnancy may require greater focus on normalising carbohydrate metabolism through optimal carbohydrate intake and matched insulin dosing. Disclosure: C. L. Meek: None. Z. Stewart: None. S. Furse: None. J. M. Yamamoto: None. D. Feig: Advisory Panel; Self; Novo Nordisk. A. Koulman: None. H. R. Murphy: None. Funding: JDRF (17/2011/533, 80/2010/585); Diabetes UK (DUK-HKF 17/0005712, DUK-PG 17/0005633.BBSRC BB/M027252/1) [ABSTRACT FROM AUTHOR]

Purpose Of Review: To review the latest evidence for dietary interventions for treatment of gestational diabetes (GDM).Recent Findings: High-quality systematic reviews demonstrate no major advantages between the low-carbohydrate or calorie-restricted diets. However, the low glycemic index (GI) diet, characterized by intake of high-quality, complex carbohydrates, demonstrated lower insulin use and reduced risk of macrosomia in multiple reviews. Recent evidence suggests the Mediterranean diet is safe in pregnancy, though trials are needed to determine its efficacy over conventional dietary advice. Currently, there are insufficient data to support the safety of the ketogenic diet for the treatment of GDM. The low GI diet may improve maternal and neonatal outcomes in GDM. The liberalized carbohydrate intake is less restrictive, culturally adaptable, and may improve long-term maternal adherence. Further research is needed to establish the optimal, most sustainable, and most acceptable medical nutrition therapy for management of women with GDM. [ABSTRACT FROM AUTHOR]

Aims/Objectives: To describe the maternal-fetal metabolomic and lipidomic profiles and examine associations with neonatal birthweight in type 1 diabetes pregnancy. Methods: A longitudinal prospective study of 162 CONCEPTT mothers. 1049 maternal metabolites and 1041 lipids were analyzed at 12, 24 and 34 weeks gestation, in addition to 93 cord-blood samples using ultra-performance liquid chromatography-tandem mass spectroscopy. The effects on neonatal birth weight, classified as appropriate for gestational age (AGA) 10-90th percentile, large for gestational age (LGA) >90th percentile and extreme LGA (ELGA) >97.7th percentile were examined through ANOVA, principle component analysis and hierarchical clustering, adjusting for maternal BMI. Results: Significant gestational changes in the maternal metabolome and lipidomic profiles were observed. Metabolite changes associated with birthweight were modest in LGA, albeit more apparent in ELGA. At 24 and 34 weeks, glucose levels were significantly elevated and 1,5-anhydroglucitol (1,5-AG) significantly reduced in ELGA mothers. Triglycerides did not differ between AGA and LGA. Throughout pregnancy, many lipid classes were lower in LGA mothers, with modest increases in free fatty acids and acylcarnitine species at 34 weeks in ELGA. The distribution of lipid classes was significantly different between maternal and cord-blood samples, with most cord-blood lipids comparable between AGA, LGA and ELGA. There were some differences in the cord-blood steroid hormones and acylcarnitine species of ELGA neonates. Conclusions: Gestational changes in maternal-fetal metabolomic and lipidomic profiles are largely conserved across birthweight categories. Some differences in glucose handling, lipid homeostasis, steroid hormones and acylcarnitine species were apparent in maternal-fetal samples of ELGA neonates. Disclosure: Z.A. Stewart: None. J.M. Yamamoto: None. C.L. Meek: None. J. Sanchez: None. D. Feig: Advisory Panel; Self; Medtronic. Speaker's Bureau; Self; Medtronic. H.R. Murphy: Advisory Panel; Self; Medtronic MiniMed, Inc. Funding: Diabetes UK; JDRF [ABSTRACT FROM AUTHOR]

Type 1 diabetes (T1D) in pregnancy is associated with increased neonatal morbidity, which improves with optimal glycemic control. Aim: To compare lab and CGM glucose summary measures as predictors of neonatal outcomes in T1D pregnancy. Methods: 225 CONCEPTT participants had 6-day CGM and blood analysis of glycemic markers in 1st trimester, 24 and 34 weeks (Average glucose; % time in target 63-140 mg/dl, coefficient of variation (CV)); HbA1c; glycated CD59 (gCD59); 1,5-anhydroglucitol (1,5AG); glycated albumin). Outcomes: large for gestational age (LGA), neonatal hypoglycemia (NH) and neonatal intensive care unit (NICU) admission. Statistics: Unadjusted logistic regression. Results: All glucose summary measures excluding CV predicted neonatal outcomes (Table). Glycemic control at all timepoints from 1st trimester was important for LGA, but emerged later for NH (24 and 34 weeks) and NICU (mainly 24 weeks). Both CGM time in target and average glucose and lab markers HbA1c, 1,5AG and gCD59 predicted all three outcomes studied. Time in target was the best CGM predictor. The best lab predictors were HbA1c, 1,5AG and gCD59. HbA1c was the strongest predictor of LGA and NH, but only predicted NICU admission late in pregnancy. Conclusions: In women with T1D, both CGM and lab glucose summary measures can predict neonatal outcomes from 1st trimester. Disclosure: C.L. Meek: None. D. Tundidor: None. H.R. Murphy: Advisory Panel; Self; Medtronic MiniMed, Inc. J.M. Yamamoto: None. E.M. Scott: Advisory Panel; Self; Abbott. Speaker's Bureau; Self; Abbott, Eli Lilly and Company. D. Ma: None. J. Halperin: Stock/Shareholder; Self; Mellitus, LLC. D. Feig: Advisory Panel; Self; Medtronic. Speaker's Bureau; Self; Medtronic. R. Corcoy: None. Funding: JDRF; Canadian Clinical Trials Network; National Institute for Health Research; European Foundation for the Study of Diabetes/Sanofi; Diabetes UK (17/0005712 to C.L.M.); Asahi Kasei Pharma Corporation; GlycoMark, Inc. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]