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.

Recent Immigrants with Inflammatory Bowel Disease Have Significant Health-Care Utilization from Preconception to Postpartum: A Population Cohort Study.

BACKGROUND: Immigrants with inflammatory bowel disease (IBD) may have increased health-care utilization during pregnancy compared to non-immigrants, though this remains to be confirmed. We aimed to characterize this between these groups. METHODS: We accessed administrative databases to identify women (age 18-55) with IBD with a singleton pregnancy between 2003-2018. Immigration status was defined as recent (< 5 years of date of conception), remote (≥ 5 years since date of conception), and none. Differences in ambulatory, emergency department (ED), hospitalization, endoscopic, and prenatal visits during 12-months preconception, pregnancy and 12-months postpartum were characterized. Region of immigration origin was ascertained. Multivariable negative binomial regression was performed for adjusted incidence rate ratios (aIRR) with 95% confidence intervals (95% CI). RESULTS: 8880 pregnancies were included, 8304 in non-immigrants, 96 in recent immigrants, 480 in remote immigrants. Compared to non-immigrants, recent immigrants had the highest rates of IBD-specific ambulatory visits during preconception (aIRR 3.06, 95% CI, 1.93-4.85), pregnancy (aIRR 2.15, 95% CI, 1.35-3.42), and postpartum (aIRR 2.21, 1.37-3.57) and the greatest rates of endoscopy visits during preconception (aIRR 2.69, 95% CI, 1.64-4.41) and postpartum (aIRR 2.01, 95% CI, 1.09-3.70). There were no differences in ED and hospitalization visits between groups though those arriving from the Americas were the most likely to be hospitalized for any reason. All immigrants with IBD were less likely to have a first trimester prenatal visit. CONCLUSION: Recent immigrants were more likely to have IBD-specific ambulatory care but less likely to receive adequate prenatal care during pregnancy.

The presence of polycystic ovary syndrome increases the risk of maternal but not neonatal complications in women with type 2 diabetes in pregnancy.

AIMS: Our aims were, in the setting of type 2 diabetes mellitus (T2DM) in pregnancy, to investigate the association of polycystic ovary syndrome (PCOS) with perinatal outcomes and to examine whether treatment with metformin had a differential effect in those with and without PCOS. MATERIALS AND METHODS: We performed a retrospective cohort study using the metformin in women with type 2 diabetes in pregnancy (MiTy) trial data. We examined differences in maternal and neonatal outcomes among MiTy participants with and without PCOS using linear and logistic regression to adjust for potential confounders. We additionally examined the relative difference in the effect of metformin treatment on pregnancy outcomes among MiTy participants with PCOS versus those without PCOS. RESULTS: Among women with T2DM in pregnancy, PCOS was significantly associated with higher excess gestational weight gain (unadjusted 12.0 vs. 11.4 kg, adjusted mean difference 2.1 kg [0.3, 3.9], p = 0.021) and higher total insulin dose at 34-36 weeks (unadjusted 172 vs. 124 units per day, adjusted mean difference 44 units [15, 73], p = 0.004), but no difference was seen in neonatal outcomes. Unlike the non-PCOS subgroup, metformin treatment versus placebo in the PCOS subgroup was associated with an increase in extremely large-for-gestational-age infants (28.6 vs. 14.0%, p = 0.008 for interaction) and an increase in worsened pre-existing maternal hypertension (16.7 vs. 4.5%, p = 0.046 for interaction). CONCLUSIONS: Clinicians should be alerted to the potential for high insulin requirements and excess weight gain in pregnant patients with T2DM and comorbid PCOS. Moreover, metformin may not be as beneficial in this population as previously understood.

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

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

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

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

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

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

Differences in Healthcare Utilization in Women with and without Inflammatory Bowel Diseases During Preconception, Pregnancy and Postpartum: A Population-Based Cohort Study.

BACKGROUND AND AIMS: Compared to those without inflammatory bowel disease [IBD], women with IBD may have increased healthcare utilization during pregnancy and postpartum, though this remains to be confirmed. We aimed to characterize this healthcare use between these groups. METHODS: Administrative databases were accessed to identify women [aged 18-55 years] with and without IBD who had a live, singleton pregnancy between 2003 and 2018. Differences in emergency department [ED] visits, hospitalizations and prenatal care during 12 months preconception, pregnancy and 12 months postpartum were characterized. Multivariable negative binomial regression was performed to report incidence rate ratios [IRRs] with 95% confidence intervals [95% CIs]. Covariates included maternal age at conception, location of residence, socioeconomic status and maternal comorbidity. RESULTS: In total, 6163 women with IBD [9158 pregnancies] and 1091 013 women without IBD [1729 411 pregnancies] were included. Women with IBD were more likely to visit the ED [IRR 1.13, 95% CI 1.08-1.18] and be hospitalized [IRR 1.11, 95% CI 1.01-1.21] during pregnancy, and visit the ED [IRR 1.21, 95% CI 1.15-1.27] and be hospitalized [IRR 1.18, 95% CI 1.05-1.32] during postpartum. On unadjusted analysis, women with IBD were more likely to be hospitalized for venous thromboembolic events. There was no difference in healthcare use in preconception. Finally, women with IBD also had a greater number of prenatal visits during pregnancy and were more likely to receive a first-trimester prenatal visit. CONCLUSION: Women with IBD have increased healthcare utilization during pregnancy and postpartum. Efforts should be made to increase ambulatory care access during this period, which in turn may reduce this health-services utilization.

The association between immigration status and the development of type 2 diabetes in women with a prior diagnosis of gestational diabetes: A population-based study.

AIMS: The aim of this study was to examine the influence of immigration status and region of origin on the risk of type 2 diabetes in women with prior gestational diabetes (GDM). METHODS: This retrospective population-based cohort study included women with gestational diabetes (GDM) aged 16 to 50 years in Ontario, Canada, who gave birth between 2006 and 2014. We compared the incidence of type 2 diabetes after delivery between long-term residents and immigrants-overall, by time since immigration and by region of-using Cox regression adjusted for age, year, neighbourhood income, rurality, infant birth weight and presence of hypertensive disorders of pregnancy (HDP). RESULTS: Among 38,515 women with prior GDM (42% immigrants), immigrants had a significantly higher risk of type 2 diabetes compared with long-term residents (adjusted hazard ratio [HR] 1.19, 95% confidence interval [CI] 1.13-1.26), with no meaningful difference based on time since immigration. The highest adjusted relative risks of type 2 diabetes compared with long-term residents were found for immigrants from Sub-Saharan Africa (HR 1.63, 95% CI 1.40-1.90), Latin America/Caribbean (HR 1.44, 95% CI 1.28-1.62) and South Asia (HR 1.34, 95% CI 1.25-1.44). CONCLUSIONS: Immigration is associated with a significantly higher risk of type 2 diabetes after GDM, particularly for women from certain low- and middle-income countries. Diabetes prevention strategies will need to consider the unique needs of immigrants from these regions.

The Antioxidant Capacity of Breast Milk and Plasma of Women with or without Gestational Diabetes Mellitus.

Women with gestational diabetes (GD) have reduced antioxidant capacity; however, the relationship between maternal diet, maternal biochemical capacity, breast milk concentration, and infant intake has not been adequately explored in the literature. An exploration of underlying mechanism(s) is warranted, particularly for nutrient antioxidants impacted by maternal intake. These nutrients may provide a means for modifying maternal and infant antioxidant capacity. Oxygen radical absorbance capacity (ORAC), alpha-tocopherol, ascorbic acid, and beta-carotene concentrations were measured in breast milk of women with and without GD. Plasma, three-day diet records, and breast milk were collected at 6 to 8 weeks postpartum. Student's t-test was used to compare breast milk ORAC, nutrient antioxidant concentration and plasma ORAC between women with and without GD. Pearson correlations were used to determine associations among antioxidant concentrations in breast milk and dietary antioxidant intake. Breast milk antioxidant concentrations were associated with maternal intake of beta-carotene (r = 0.629, p = 0.005). Breast milk and plasma ORAC and antioxidant vitamin concentrations were not significantly different between GD and NG women. Breast milk ORAC associated with breast milk alpha-tocopherol for NG (r = 0.763, p = 0.010), but not GD women (r = 0.385, p = 0.35), and with breast milk ascorbic acid for GD (r = 0.722, p = 0.043) but not NG women (r = 0.141, p = 0.70; interaction p = 0.041). In GD participants, breast milk ORAC was significantly associated with plasma ORAC (r = 0.780, p = 0.039). ORAC and antioxidant vitamin concentrations in breast milk in women with GD were comparable to women with NG; however, the relationships between breast milk ORAC and vitamin concentrations differed in GD versus NG women for alpha-tocopherol and ascorbic acid.

Real-world use of Control-IQ™ technology automated insulin delivery in pregnancy: A case series with qualitative interviews.

BACKGROUND: Most commercially available automated insulin delivery (AID) systems are not approved for pregnancy use. Information regarding use of the Tandem t:slim X2 insulin pump with Control-IQ™ technology in pregnancy is lacking. AIMS: This case series aimed to explore glycaemic and qualitative experiences of four early adopters of Control-IQ technology in pregnancy. METHODS: Participants used Control-IQ technology in pregnancy and postpartum and consented to analysis of glycaemic data and semi-structured interviews. RESULTS: Case 1 began Control-IQ technology at 10 weeks gestation. Her pregnancy glucose time-in-range (3.5-7.8 mmol/L [63-140 mg/dL]) increased from 58.7% to 73.3% by third trimester. Cases 2-4 began using Control-IQ technology 0-2 months preconception. Pregnancy time-in-range glucose increased from 73.4% to 78.7%, 78% to 83.6%, and 46.5% to 71.9% between first and third trimesters, respectively. A mid-pregnancy decline in time-in-range glucose was observed in two of the four participants related to suboptimal pump setting adjustments and delays in sensor and infusion set replacement. No diabetic ketoacidosis or severe hypoglycaemia occurred. All participants reported reduced diabetes management burden and improved sleep with Control-IQ technology use. CONCLUSIONS: Early adopters of Control-IQ technology safely used this system off-label in pregnancy and reported reduced diabetes management burden and improved sleep. The largest glycaemic improvements were observed among those with the lowest pregnancy time-in-range glucose at the beginning of pregnancy. Participants with low pregnancy glucose time-in-range increased their time-in-range with Control-IQ technology use and participants with high pregnancy glucose time-in-range maintained and increased their time-in-range with less diabetes management burden.

Outcomes in children of women with type 2 diabetes exposed to metformin versus placebo during pregnancy (MiTy Kids): a 24-month follow-up of the MiTy randomised controlled trial.

BACKGROUND: Metformin is increasingly being used during pregnancy, with potentially adverse long-term effects on children. We aimed to examine adiposity in children of women with type 2 diabetes from the Metformin in Women with Type 2 Diabetes in Pregnancy (MiTy) trial, with and without in-utero exposure to metformin, up to 24 months of age. METHODS: MiTy Kids is a follow-up study that included infants of women who participated in the MiTy randomised controlled trial, receiving either oral 1000 mg metformin twice daily or placebo. Caregivers and researchers remained masked to the type of medication (metformin or placebo) mothers received during their pregnancy. Anthropometric measurements, including weight, height, and skinfold thicknesses, were taken at 3, 6, 12, 18, and 24 months. At 24 months, linear regression was used to compare the BMI Z score and sum of skinfolds in the metformin versus placebo groups, adjusted for confounders. Fractional polynomials were used to assess growth trajectories. This study is registered with ClinicalTrials.gov, NCT01832181. FINDINGS: Of the 465 eligible children, 283 (61%) were included from 19 centres in Canada and Australia. At 24 months, there was no difference between groups in mean BMI Z score (0·84 [SD 1·52] with metformin vs 0·91 [1·38] with placebo; mean difference 0·07 [95% CI -0·31 to 0·45], p=0·72) or mean sum of skinfolds (23·0 mm [5·2] vs 23·8 mm [5·4]; mean difference 0·8 mm [-0·7 to 2·3], p=0·31). Metformin was not a predictor of BMI Z score at 24 months of age (mean difference -0·01 [95% CI -0·42 to 0·37], p=0·92). There was no overall difference in BMI trajectory but, in males, trajectories were significantly different by treatment (p=0·048); BMI in the metformin group was higher between 6 and 24 months. Children of women with type 2 diabetes were approximately 1 SD heavier than the WHO reference population. INTERPRETATION: Anthropometrics were similar in children exposed and those not exposed to metformin in utero; hence, overall, data are reassuring with regard to the use of metformin during pregnancy in women with type 2 diabetes and the long-term health of their children. FUNDING: Canadian Institute for Health Research.

Existing standardised questionnaires do not adequately capture quality-of-life outcomes of greatest importance for those living with type 1 diabetes in pregnancy.

BACKGROUND: No standardised questionnaires have been specifically developed to assess the considerable demands of managing type 1 diabetes (T1D) during pregnancy. AIMS: This study aimed to explore what domains of measurement are important to quality of life during pregnancy with TID and to assess if standardised questionnaires, used by previous researchers, adequately capture patients' reported experience of TID in pregnancy. METHODS: A qualitative inquiry was conducted using semi-structured focus groups with Canadian women who have experienced T1D in pregnancy. Participants were asked open-ended questions about experiences managing T1D during pregnancy and whether options on standardised tools captured their pregnancy experiences. Audio from focus groups was transcribed verbatim. Two researchers independently analysed the transcripts using inductive thematic analysis. Salient ideas, experiences and key words were coded iteratively and grouped into broader themes and subsequently reviewed by five participants. RESULTS: The sample included nine participants. Emergent themes included changes in day-to-day routines to manage T1D in pregnancy, fear of hyperglycaemia during pregnancy and of hypoglycaemia postpartum. Participants felt that existing options on standardised questionnaires did not adequately quantify diabetes interference in work, family time, planned activities and sleep, and did not address hyperglycaemia fear. CONCLUSIONS: Existing standardised questionnaires do not adequately capture patient-reported outcomes of greatest importance for those living with T1D in pregnancy. Future research assessing the impact of therapies on quality-of-life measures in TID pregnancies should quantify their influence on day-to-day activities, adjust measures of sleep quality and capture fear of hyperglycaemia in pregnancy and hypoglycaemia postpartum.

Insulin degludec versus insulin detemir, both in combination with insulin aspart, in the treatment of pregnant women with type 1 diabetes (EXPECT): an open­label, multinational, randomised, controlled, non-inferiority trial.

BACKGROUND: Insulin degludec (degludec) is a second-generation basal insulin with an improved pharmacokinetic-pharmacodynamic profile compared with first-generation basal insulins, but there are few data regarding its use during pregnancy. In this non-inferiority trial, we aimed to compare the efficacy and safety of degludec with insulin detemir (detemir), both in combination with insulin aspart (aspart), in pregnant women with type 1 diabetes. METHODS: This open-label, multinational, randomised, controlled, non-inferiority trial (EXPECT) was conducted at 56 sites (hospitals and medical centres) in 14 countries. Women aged at least 18 years with type 1 diabetes who were between gestational age 8 weeks (+0 days) and 13 weeks (+6 days) or planned to become pregnant were randomly assigned (1:1), via an interactive web response system, to degludec (100 U/mL) once daily or detemir (100 U/mL) once or twice daily, both with mealtime insulin aspart (100 U/mL), all via subcutaneous injection. Participants who were pregnant received the trial drug at randomisation, throughout pregnancy and until 28 days post-delivery (end of treatment). Participants not pregnant at randomisation initiated the trial drug before conception. The primary endpoint was the last planned HbA1c measurement before delivery (non-inferiority margin of 0·4% for degludec vs detemir). Secondary endpoints included efficacy, maternal safety, and pregnancy outcomes. The primary endpoint was assessed in all randomly assigned participants who were pregnant during the trial. Safety was assessed in all randomly assigned participants who were pregnant during the trial and exposed to at least one dose of trial drug. This study is registered with ClinicalTrials.gov, NCT03377699, and is now completed. FINDINGS: Between Nov 22, 2017, and Nov 8, 2019, from 296 women screened, 225 women were randomly assigned to degludec (n=111) or detemir (n=114). Mean HbA1c at pregnancy baseline was 6·6% (SD 0·6%; approximately 49 mmol/mol; SD 7 mmol/mol) in the degludec group and 6·5% (0·8%; approximately 48 mmol/mol; 9 mmol/mol) in the detemir group. Mean last planned HbA1c measurement before delivery was 6·2% (SE 0·07%; approximately 45 mmol/mol; SE 0·8 mmol/mol) in the degludec group and 6·3% (SE 0·07%; approximately 46 mmol/mol; SE 0·8 mmol/mol) in the detemir group (estimated treatment difference -0·11% [95% CI -0·31 to 0·08]; -1·2 mmol/mol [95% CI: -3·4 to 0·9]; pnon-inferiority<0·0001), confirming non-inferiority. Compared with detemir, no additional safety issues were observed with degludec. INTERPRETATION: In pregnant women with type 1 diabetes, degludec was found to be non-inferior to detemir. FUNDING: Novo Nordisk.

The association between offspring birthweight and future risk of maternal diabetes: A population-based study.

AIMS: As an indicator of maternal cardiometabolic health, newborn birthweight may be an important predictor of maternal type 2 diabetes mellitus (diabetes). We evaluated the relation between offspring birthweight and onset of maternal diabetes after pregnancy. METHODS: This retrospective cohort study used linked population-based health databases from Ontario, Canada. We included women aged 16-50 years without pre-pregnancy diabetes, and who had a live birth between 2006 and 2014. We used Cox proportional hazard regression to evaluate the association between age- and sex-standardized offspring birthweight percentile categories and incident maternal diabetes, while adjusting for maternal age, parity, year, ethnicity, gestational diabetes (GDM) and hypertensive disorders of pregnancy (HDP). Results were further stratified by the presence of GDM in the index pregnancy. RESULTS: Of 893,777 eligible participants, 14,329 (1.6%) women were diagnosed with diabetes over a median (IQR) of 4.4 (1.5-7.4) years of follow-up. There was a continuous positive relation between newborn birthweight above the 75th percentile and maternal diabetes. Relative to a birthweight between the 50th and 74.9th percentiles, women whose newborn had a birthweight between the 97th and 100th percentiles had an adjusted hazards ratio (aHR) of diabetes of 2.30 (95% CI 2.16-2.46), including an aHR of 2.01 (95% CI 1.83-2.21) among those with GDM, and 2.59 (2.36-2.84) in those without GDM. CONCLUSIONS: A higher offspring birthweight signals an increased risk of maternal diabetes, offering another potentially useful way to identify women especially predisposed to diabetes.

Validation of Algorithms to Identify Gestational Diabetes From Population-level Health-care Administrative Data.

OBJECTIVES: Our aim in this study was to determine the test characteristics of algorithms using hospitalization and physician claims data to predict gestational diabetes (GDM). METHODS: Using population-level health-care administrative data, we identified all pregnant women in Ontario in 2019. The presence of GDM was determined based on glucose screening laboratory results. Algorithms using hospitalization records and/or physician claims were tested against this "gold standard." The selected algorithm was applied to administrative data records from 1999 to 2019 to determine GDM prevalence in each year. RESULTS: Identifying GDM based on either a diabetes mellitus code on the delivery hospitalization record, OR at least 1 physician claim with a diabetes diagnosis code with a 90-day lookback before delivery yielded a sensitivity of 95.9%, a specificity of 99.2% and a positive predictive value of 87.6%. The prevalence of GDM increased from 4.2% of pregnancies in 1999 to 12.0% in 2019. CONCLUSION: Algorithms using hospitalization or physician claims administrative data can accurately identify GDM.

Associations Among Biomarkers of Inflammation, Tubular Injury and Lipid Metabolism With Gestational Diabetes Mellitus Status, Microalbuminuria and Retinopathy in the Microalbuminuria and Retinopathy in Gestational Diabetes Study.

OBJECTIVES: Pregnancy may be complicated by gestational diabetes mellitus (GDM) and/or microvascular complications like albuminuria, retinopathy and pre-eclampsia. In this study we aimed to identify whether mechanistic pathways associated with microvascular complications are active in pregnant women with GDM or microvascular disease. METHODS: Urinary albumin excretion and biomarkers of inflammation, lipoprotein metabolism and tubular injury were quantified in 355 pregnant women with and without GDM. Participants underwent fundus photography graded for retinopathy. Adjusted associations between individual biomarkers and each outcome variable of interest, including GDM status, albuminuria and retinopathy, were performed using logistic regression. RESULTS: After adjusting for age, systolic blood pressure, body mass index and ethnicity, significant associations between GDM status and apolipoprotein A1, interleukin (IL)-6, IL-8, soluble tumour necrosis factor receptor-I and -II (sTNFR-I and -II), vascular endothelial growth factor and von Willebrand factor were observed. Increased high-sensitivity C-reactive protein (hsCRP) and sTNFR-II were associated with higher levels of albuminuria. hsCRP and previous GDM were associated with retinopathy. CONCLUSION: Mechanistic pathways associated with microvascular complications appear to be active in pregnant women with GDM or microvascular disease.

Continuous Glucose Monitoring Metrics and Birth Weight: Informing Management of Type 1 Diabetes Throughout Pregnancy.

OBJECTIVE: To determine gestational weekly changes in continuous glucose monitoring (CGM) metrics and 24-h glucose profiles and their relationship to infant birth weight in pregnant women with type 1 diabetes. RESEARCH DESIGN AND METHODS: An analysis of >10.5 million CGM glucose measures from 386 pregnant women with type 1 diabetes from two international multicenter studies was performed. CGM glucose metrics and 24-h glucose profiles were calculated for each gestational week, and the relationship to normal (10-90th percentile) and large (>90th percentile) for gestational age (LGA) birth weight infants was determined. RESULTS: Mean CGM glucose concentration fell and percentage of time spent in the pregnancy target range of 3.5-7.8 mmol/L (63-140 mg/dL) increased in the first 10 weeks of pregnancy and plateaued until 28 weeks of gestation, before further improvement in mean glucose and percentage of time in range until delivery. Maternal CGM glucose metrics diverged at 10 weeks of gestation, with significantly lower mean CGM glucose concentration (7.1 mmol/L; 95% CI 7.05-7.15 [127.8 mg/dL; 95% CI 126.9-128.7] vs. 7.5 mmol/L; 95% CI 7.45-7.55 [135 mg/dL; 95% CI 134.1-135.9]) and higher percentage of time in range (55%; 95% CI 54-56 vs. 50%; 95% CI 49-51) in women who had normal versus LGA. The 24-h glucose profiles were significantly higher across the day from 10 weeks of gestation in LGA. CONCLUSIONS: Normal birth weight is associated with achieving significantly lower mean CGM glucose concentration across the 24-h day and higher CGM time in range from before the end of the first trimester, emphasizing the need for a shift in clinical management, with increased focus on using weekly CGM glucose targets for optimizing maternal glycemia from early pregnancy.