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Objective: To assess the frequency of, risk factors for, and adverse outcomes associated with diabetic ketoacidosis (DKA) at delivery hospitalization among individuals with pregestational diabetes (type 1 and 2 diabetes mellitus) and secondarily to evaluate the frequency of and risk factors for antepartum and postpartum hospitalizations for DKA., Methods: We conducted a serial, cross-sectional study using the Agency for Healthcare Research and Quality's Healthcare Cost and Utilization Project Nationwide Readmissions Database from 2010 to 2020 of pregnant individuals with pregestational diabetes hospitalized for delivery. The exposures were 1) sociodemographic and clinical risk factors for DKA and 2) DKA. The outcomes were DKA at delivery hospitalization, maternal morbidity (nontransfusion severe maternal morbidity (SMM), critical care procedures, cardiac complications, acute renal failure, and transfusion), and adverse pregnancy outcomes (preterm birth, hypertensive disorders of pregnancy, and cesarean delivery) and secondarily DKA at antepartum and postpartum hospitalizations., Results: Of 392,796 deliveries in individuals with pregestational diabetes (27.2% type 1 diabetes, 72.8% type 2 diabetes), there were 4,778 cases of DKA at delivery hospitalization (89.1% type 1 diabetes, 10.9% type 2 diabetes). The frequency of DKA at delivery hospitalization was 1.2% (4.0% with type 1 diabetes, 0.2% with type 2 diabetes), and the mean annual percentage change was 10.8% (95% CI, 8.2-13.2%). Diabetic ketoacidosis at delivery hospitalization was significantly more likely among those who had type 1 diabetes compared with those with type 2 diabetes, who were younger in age, who delivered at larger and metropolitan hospitals, and who had Medicaid insurance, lower income, multiple gestations, and prior psychiatric illness. Diabetic ketoacidosis during the delivery hospitalization was associated with an increased risk of nontransfusion SMM (20.8% vs 2.4%, adjusted odds ratio [aOR] 8.18, 95% CI, 7.20-9.29), critical care procedures (7.3% vs 0.4%, aOR 15.83, 95% CI, 12.59-19.90), cardiac complications (7.8% vs 0.8%, aOR 8.87, 95% CI, 7.32-10.76), acute renal failure (12.3% vs 0.7%, aOR 9.78, 95% CI, 8.16-11.72), and transfusion (6.2% vs 2.2%, aOR 2.27, 95% CI, 1.87-2.75), as well as preterm birth (31.9% vs 13.5%, aOR 2.41, 95% CI, 2.17-2.69) and hypertensive disorders of pregnancy (37.4% vs 28.1%, aOR 1.11, 95% CI, 1.00-1.23). In secondary analyses, the overall frequency of antepartum DKA was 3.1%, and the mean annual percentage change was 4.1% (95% CI, 0.3-8.6%); the overall frequency of postpartum DKA was 0.4%, and the mean annual percentage change was 3.5% (95% CI, -1.6% to 9.6%). Of 3,092 antepartum hospitalizations among individuals with DKA, 15.7% (n=485) had a recurrent case of DKA at delivery hospitalization. Of 1,419 postpartum hospitalizations among individuals with DKA, 20.0% (n=285) previously had DKA at delivery hospitalization. The above risk factors for DKA at delivery hospitalization were similar for DKA at antepartum and postpartum hospitalizations., Conclusion: The frequency of DKA at delivery hospitalization and antepartum hospitalizations for DKA increased between 2010 and 2020 among deliveries in individuals with pregestational diabetes in the United States. Diabetic ketoacidosis is associated with an increased risk of maternal morbidity and adverse pregnancy outcomes. Risk factors for DKA at delivery were similar to those for DKA during the antepartum and postpartum periods., Competing Interests: Financial Disclosure Timothy Wen serves as an associate Chief Medical Officer for Delfina Care, Inc. Alexander M. Friedman served on an advisory group for Sage and Biogen and received NIH funding. Cynthia Gyamfi-Bannerman reports receiving payment from Sera. Camile E. Powe's institution received payments from Dexcom, Inc, and Dr. Powe received payment from UpToDate and the American Diabetes Association. The other authors did not report any potential conflicts of interest., (Copyright © 2024 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Background: Gestational diabetes is associated with increased risk of hypertensive disorders of pregnancy, but there are limited data on fetal growth and neonatal outcomes when both conditions are present., Objective: We evaluated the risk of abnormal fetal growth and neonatal morbidity in pregnancies with co-occurrence of gestational diabetes and hypertensive disorders of pregnancy., Study Design: In a retrospective study of 47,093 singleton pregnancies, we compared the incidence of appropriate for gestational age birthweight in pregnancies affected by gestational diabetes alone, hypertensive disorders of pregnancy alone, or both gestational diabetes and hypertensive disorders of pregnancy with that in pregnancies affected by neither disorder using generalized estimating equations (covariates: maternal age, nulliparity, body mass index, insurance type, race, marital status, and prenatal care site). Secondary outcomes were large for gestational age birthweight, small for gestational age birthweight, and a neonatal morbidity composite outcome (stillbirth, hypoglycemia, hyperbilirubinemia, respiratory distress, encephalopathy, preterm delivery, neonatal death, and neonatal intensive care unit admission)., Results: The median (interquartile range) birthweight percentile in pregnancies with both gestational diabetes and hypertensive disorders of pregnancy (50 [24.0-78.0]; N=179) was similar to that of unaffected pregnancies (50 [27.0-73.0]; N=35,833). However, the absolute rate of appropriate for gestational age birthweight was lower for gestational diabetes/hypertensive disorders of pregnancy co-occurrence (78.2% vs 84.9% for unaffected pregnancies). Adjusted analyses showed decreased odds of appropriate for gestational age birthweight in pregnancies with both gestational diabetes and hypertensive disorders of pregnancy compared with unaffected pregnancies (adjusted odds ratio, 0.72 [95% confidence interval, 0.52-1.00]; P=.049), and in pregnancies complicated by gestational diabetes alone (adjusted odds ratio, 0.78 [0.68-0.89]; P<.001) or hypertensive disorders of pregnancy alone (adjusted odds ratio, 0.73 [0.66-0.81]; P<.001). The absolute risk of large for gestational age birthweight was greater in pregnancies with both gestational diabetes and hypertensive disorders of pregnancy (14.5%) than in unaffected pregnancies (8.2%), without apparent difference in the risk of small for gestational age birthweight (7.3% vs 6.9%). However, in adjusted models comparing pregnancies with gestational diabetes/hypertensive disorders of pregnancy co-occurrence with unaffected pregnancies, neither an association with large for gestational age birthweight (adjusted odds ratio, 1.33 [0.88-2.00]; P=.171) nor small for gestational age birthweight (adjusted odds ratio, 1.32 [0.80-2.19]; P=.293) reached statistical significance. Gestational diabetes/hypertensive disorders of pregnancy co-occurrence carried an increased risk of neonatal morbidity that was greater than that observed with either condition alone (gestational diabetes/hypertensive disorders of pregnancy: adjusted odds ratio, 3.13 [2.35-4.17]; P<.001; gestational diabetes alone: adjusted odds ratio, 2.01 [1.78-2.27]; P<.001; hypertensive disorders of pregnancy alone: adjusted odds ratio, 1.38 [1.26-1.50]; P<.001)., Conclusion: Although pregnancies with both gestational diabetes and hypertensive disorders of pregnancy have a similar median birthweight percentile to those affected by neither condition, pregnancies concurrently affected by both conditions have a higher risk of abnormal fetal growth and neonatal morbidity., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Gestational diabetes mellitus (GDM) is one of the most common medical complications of pregnancy. Glycaemic control decreases the risk of adverse pregnancy outcomes for the affected pregnant individual and the infant exposed in utero. One in four individuals with GDM will require pharmacotherapy to achieve glycaemic control. Injectable insulin has been the mainstay of pharmacotherapy. Oral metformin is an alternative option increasingly used in clinical practice. Both insulin and metformin reduce the risk of adverse pregnancy outcomes, but comparative effectiveness data from a well-characterised, adequately powered study of a diverse US population remain lacking. Because metformin crosses the placenta, long-term safety data, in particular, the risk of childhood obesity, from exposed children are also needed. In addition, the patient-reported experiences of individuals with GDM requiring pharmacotherapy remain to be characterised, including barriers to and facilitators of metformin versus insulin use., Methods and Analysis: In a two-arm open-label, pragmatic comparative effectiveness randomised controlled trial, we will determine if metformin is not inferior to insulin in reducing adverse pregnancy outcomes, is comparably safe for exposed individuals and children, and if patient-reported factors, including facilitators of and barriers to use, differ between metformin and insulin. We plan to recruit 1572 pregnant individuals with GDM who need pharmacotherapy at 20 US sites using consistent diagnostic and treatment criteria for oral metformin versus injectable insulin and follow them and their children through delivery to 2 years post partum. More information is available at www.decidestudy.org., Ethics and Dissemination: The Institutional Review Board at The Ohio State University approved this study (IRB: 2024H0193; date: 7 December 2024). We plan to submit manuscripts describing the results of each study aim, including the pregnancy outcomes, the 2-year follow-up outcomes, and mixed-methods assessment of patient experiences for publication in peer-reviewed journals and presentations at international scientific meetings., Trial Registration Number: NCT06445946., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To examine the relationship between gestational glucose intolerance (GGI) and neonatal hypoglycemia., Research Design and Methods: This was a secondary analysis of 8,262 mother-infant dyads, with delivery at two hospitals between 2014 and 2023. We categorized maternal glycemic status as normal glucose tolerance (NGT), GGI, or gestational diabetes mellitus (GDM). We defined NGT according to a normal glucose load test result, GGI according to an abnormal glucose load test result with zero (GGI-0) or one (GGI-1) abnormal value on the 100-g oral glucose tolerance test, and GDM according to an abnormal glucose load test result with two or more abnormal values on the glucose tolerance test. Neonatal hypoglycemia was defined according to blood glucose <45 mg/dL or ICD-9 or ICD-10 diagnosis of neonatal hypoglycemia. We used logistic regression analysis to determine associations between maternal glucose tolerance category and neonatal hypoglycemia and conducted a sensitivity analysis using Δ-adjusted multiple imputation, assuming for unscreened infants a rate of neonatal hypoglycemia as high as 33%., Results: Of infants, 12% had neonatal hypoglycemia. In adjusted models, infants born to mothers with GGI-0 had 1.28 (95% 1.12, 1.65), GGI-1 1.58 (95% CI 1.11, 2.25), and GDM 4.90 (95% CI 3.81, 6.29) times higher odds of neonatal hypoglycemia in comparison with infants born to mothers with NGT. Associations in sensitivity analyses were consistent with the primary analysis., Conclusions: GGI is associated with increased risk of neonatal hypoglycemia. Future research should include examination of these associations in a cohort with more complete neonatal blood glucose ascertainment and determination of the clinical significance of these findings on long-term child health., (© 2024 by the American Diabetes Association.)

Reduced insulin sensitivity (insulin resistance) is a hallmark of normal physiology in late pregnancy and also underlies gestational diabetes mellitus (GDM). We conducted transcriptomic profiling of 434 human placentas and identified a positive association between insulin-like growth factor binding protein 1 gene (IGFBP1) expression in the placenta and insulin sensitivity at ~26 weeks gestation. Circulating IGFBP1 protein levels rose over the course of pregnancy and declined postpartum, which, together with high gene expression levels in our placenta samples, suggests a placental or decidual source. Higher circulating IGFBP1 levels were associated with greater insulin sensitivity (lesser insulin resistance) at ~26 weeks gestation in the same cohort and in two additional pregnancy cohorts. In addition, low circulating IGFBP1 levels in early pregnancy predicted subsequent GDM diagnosis in two cohorts of pregnant women. These results implicate IGFBP1 in the glycemic physiology of pregnancy and suggest a role for placental IGFBP1 deficiency in GDM pathogenesis., (© 2024. The Author(s).)

Purpose: Pregnancy and the postpartum period are increasingly recognised as sensitive windows for cardiometabolic disease risk. Growing evidence suggests environmental exposures, including endocrine-disrupting chemicals (EDCs), are associated with an increased risk of pregnancy complications that are associated with long-term cardiometabolic risk. However, the impact of perinatal EDC exposure on subsequent cardiometabolic risk post-pregnancy is less understood. The Environmental Reproductive and Glucose Outcomes (ERGO) Study was established to investigate the associations of environmental exposures during the perinatal period with post-pregnancy parental cardiometabolic health., Participants: Pregnant individuals aged ≥18 years without pre-existing diabetes were recruited at <15 weeks of gestation from Boston, Massachusetts area hospitals. Participants completed ≤4 prenatal study visits (median: 12, 19, 26, 36 weeks of gestation) and 1 postpartum visit (median: 9 weeks), during which we collected biospecimens, health histories, demographic and behavioural data, and vitals and anthropometric measurements. Participants completed a postpartum fasting 2-hour 75 g oral glucose tolerance test. Clinical data were abstracted from electronic medical records. Ongoing (as of 2024) extended post-pregnancy follow-up visits occur annually following similar data collection protocols., Findings to Date: We enrolled 653 unique pregnancies and retained 633 through delivery. Participants had a mean age of 33 years, 10% (n=61) developed gestational diabetes and 8% (n=50) developed pre-eclampsia. Participant pregnancy and postpartum urinary phthalate metabolite concentrations and postpartum glycaemic biomarkers were quantified. To date, studies within ERGO found higher exposure to phthalates and phthalate mixtures, and separately, higher exposure to radioactive ambient particulate matter, were associated with adverse gestational glycaemic outcomes. Additionally, certain personal care products used in pregnancy, notably hair oils, were associated with higher urinary phthalate metabolite concentrations, earlier gestational age at delivery and lower birth weight., Future Plans: Future work will leverage the longitudinal data collected on pregnancy and cardiometabolic outcomes, environmental exposures, questionnaires, banked biospecimens and paediatric data within the ERGO Study., Competing Interests: Competing interests: CEP is an associate editor of Diabetes Care, receives payments from Wolters Klumer for UpToDate chapters on diabetes in pregnancy, and has received payments for consulting and speaking from Mediflix. All other authors declare no additional actual or perceived competing interests., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Aims/hypothesis: Physiological gestational diabetes mellitus (GDM) subtypes that may confer different risks for adverse pregnancy outcomes have been defined. The aim of this study was to characterise the metabolome and genetic architecture of GDM subtypes to address the hypothesis that they differ between GDM subtypes., Methods: This was a cross-sectional study of participants in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study who underwent an OGTT at approximately 28 weeks' gestation. GDM was defined retrospectively using International Association of Diabetes and Pregnancy Study Groups/WHO criteria, and classified as insulin-deficient GDM (insulin secretion <25th percentile with preserved insulin sensitivity) or insulin-resistant GDM (insulin sensitivity <25th percentile with preserved insulin secretion). Metabolomic analyses were performed on fasting and 1 h serum samples in 3463 individuals (576 with GDM). Genome-wide genotype data were obtained for 8067 individuals (1323 with GDM)., Results: Regression analyses demonstrated striking differences between the metabolomes for insulin-deficient or insulin-resistant GDM compared to those with normal glucose tolerance. After adjustment for covariates, 33 fasting metabolites, including 22 medium- and long-chain acylcarnitines, were uniquely associated with insulin-deficient GDM; 23 metabolites, including the branched-chain amino acids and their metabolites, were uniquely associated with insulin-resistant GDM; two metabolites (glycerol and 2-hydroxybutyrate) were associated with the same direction of association with both subtypes. Subtype differences were also observed 1 h after a glucose load. In genome-wide association studies, variants within MTNR1B (rs10830963, p=3.43×10 -18 , OR 1.55) and GCKR (rs1260326, p=5.17×10 -13 , OR 1.43) were associated with GDM. Variants in GCKR (rs1260326, p=1.36×10 -13 , OR 1.60) and MTNR1B (rs10830963, p=1.22×10 -9 , OR 1.49) demonstrated genome-wide significant association with insulin-resistant GDM; there were no significant associations with insulin-deficient GDM. The lead SNP in GCKR, rs1260326, was associated with the levels of eight of the 25 fasting metabolites that were associated with insulin-resistant GDM and ten of 41 1 h metabolites that were associated with insulin-resistant GDM., Conclusions/interpretation: This study demonstrates that physiological GDM subtypes differ in their metabolome and genetic architecture. These findings require replication in additional cohorts, but suggest that these differences may contribute to subtype-related adverse pregnancy outcomes., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: We compared patient priorities, decisional comfort, and satisfaction with treating gestational diabetes mellitus (GDM) with metformin versus insulin among pregnant individuals with GDM requiring pharmacotherapy., Study Design: We conducted a cross-sectional study of patients' perspectives about GDM pharmacotherapy in an integrated prenatal and diabetes care program from October 19, 2022, to August 24, 2023. The exposure was metformin versus insulin as the initial medication decision. Outcomes included standardized measures of patient priorities, decisional comfort, and satisfaction about their medication decision., Results: Among 144 assessed individuals, 60.4% were prescribed metformin and 39.6% were prescribed insulin. Minoritized individuals were more likely to receive metformin compared with non-Hispanic White individuals (34.9 vs. 17.5%; p  = 0.03). Individuals who were willing to participate in a GDM pharmacotherapy clinical trial were more likely to receive insulin than those who were unwilling (30.4 vs. 19.5%; p  = 0.02). Individuals receiving metformin were more likely to report prioritizing avoiding injections (62.4 vs. 19.3%; adjusted odds ratio [aOR]: 2.83; 95% confidence interval [CI]: 1.10-7.31), wanting to take a medication no more than twice daily (56.0 vs. 30.4%; aOR: 3.67; 95% CI: 1.56-8.67), and believing that both medications can equally prevent adverse pregnancy outcomes (70.9 vs. 52.6%; aOR: 2.67; 95% CI: 1.19-6.03). Conversely, they were less likely to report prioritizing a medication that crosses the placenta (39.1 vs. 82.5%; aOR: 0.09; 95% CI: 0.03-0.25) and needing supplemental insulin to achieve glycemic control (21.2 vs. 47.4%; aOR: 0.36; 95% CI: 0.15-0.90). Individuals reported similarly high (mean score > 80%) levels of decisional comfort, personal satisfaction with medication decision-making, and satisfaction about their conversation with their provider about their medication decision with metformin and insulin ( p ≥ 0.05 for all)., Conclusion: Individuals with GDM requiring pharmacotherapy reported high levels of decision comfort and satisfaction with both metformin and insulin, although they expressed different priorities in medication decision-making. These results can inform future patient-centered GDM treatment strategies., Key Points: · Pregnant individuals with GDM requiring pharmacotherapy expressed a high level of decisional comfort and satisfaction with medication decision making.. · Individuals placed different priorities on deciding to take metformin versus insulin.. · These results can inform interventions aimed at delivering person-centered diabetes care in pregnancy that integrates patient autonomy and knowledge about treatment options.., Competing Interests: None declared., (Thieme. All rights reserved.)

Objective: To examine the accuracy of different periods of continuous glucose monitoring (CGM), hemoglobin A1c (HbA1c), and their combination for estimating mean glycemia over 90 days (AG90)., Research Design and Methods: We retrospectively studied 985 CGM periods of 90 days with <10% missing data from 315 adults (86% of whom had type 1 diabetes) with paired HbA1c measurements. The impact of mean red blood cell age as a proxy for nonglycemic effects on HbA1c was estimated using published theoretical models and in comparison with empirical data. Given the lack of a gold standard measurement for AG90, we applied correction methods to generate a reference (eAG90) that we used to assess accuracy for HbA1c and CGM., Results: Using 14 days of CGM at the end of the 90-day period resulted in a mean absolute error (95th percentile) of 14 (34) mg/dL when compared with eAG90. Nonglycemic effects on HbA1c led to a mean absolute error for average glucose calculated from HbA1c of 12 (29) mg/dL. Combining 14 days of CGM with HbA1c reduced the error to 10 (26) mg/dL. Mismatches between CGM and HbA1c >40 mg/dL occurred more than 5% of the time., Conclusions: The accuracy of estimates of eAG90 from limited periods of CGM can be improved by averaging with an HbA1c-based estimate or extending the monitoring period beyond ∼26 days. Large mismatches between eAG90 estimated from CGM and HbA1c are not unusual and may persist due to stable nonglycemic factors., (© 2024 by the American Diabetes Association.)

Context: Elevated body mass index (BMI) in pregnancy is associated with adverse maternal and fetal outcomes. The placental transcriptome may elucidate molecular mechanisms underlying these associations., Objective: We examined the association of first-trimester maternal BMI with the placental transcriptome in the Gen3G prospective cohort., Methods: We enrolled participants at 5 to 16 weeks of gestation and measured height and weight. We collected placenta samples at delivery. We performed whole-genome RNA sequencing using Illumina HiSeq 4000 and aligned RNA sequences based on the GTEx v8 pipeline. We conducted differential gene expression analysis of over 15 000 genes from 450 placental samples and reported the change in normalized gene expression per 1-unit increase in log2 BMI (kg/m2) as a continuous variable using Limma Voom. We adjusted models for maternal age, fetal sex, gestational age at delivery, gravidity, and surrogate variables accounting for technical variability. We compared participants with BMI of 18.5 to 24.9 mg/kg2 (N = 257) vs those with obesity (BMI ≥30 kg/m2, N = 82) in secondary analyses., Results: Participants' mean ± SD age was 28.2 ± 4.4 years and BMI was 25.4 ± 5.5 kg/m2 in early pregnancy. Higher maternal BMI was associated with lower placental expression of EPYC (slope = -1.94, false discovery rate [FDR]-adjusted P = 7.3 × 10-6 for continuous BMI; log2 fold change = -1.35, FDR-adjusted P = 3.4 × 10-3 for BMI ≥30 vs BMI 18.5-24.9 kg/m2) and with higher placental expression of IGFBP6, CHRDL1, and CXCL13 after adjustment for covariates and accounting for multiple testing (FDR < 0.05)., Conclusion: Our genome-wide transcriptomic study revealed novel genes potentially implicated in placental biologic response to higher maternal BMI in early pregnancy., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: Percent glycated albumin (%GAlb) is a marker of glycemia over the past 2 to 3 weeks in nonpregnant individuals. Longitudinal changes in %GAlb extending throughout pregnancy and postpartum (PP) have not been described. We aimed to describe levels of %GAlb throughout pregnancy and PP and relationships with glycemia., Study Design: Fifty women among those in the Study of Pregnancy Regulation of INsulin and Glucose cohort underwent 75-g oral glucose tolerance tests (OGTTs) at a mean of 13 weeks (V1) and 26 weeks (V2) of gestation and 11 weeks' PP. %GAlb was measured on frozen plasma samples., Results: Total albumin decreased from V1 to V2 and increased PP to levels higher than at V1. %GAlb declined between V1 and V2 ( β  = - 0.63% 95% CI [-0.8, -0.6] p  < 0.001) and remained stable between V2 and PP ( β  = - 0.04% [-0.3, 0.2] p  = 0.78). Body mass index (BMI) was inversely related to %GAlb in pregnancy (V1: rho = - 0.5, p  = 0.0001; V2 rho = - 0.4, p  = 0.006), but not PP (rho = - 0.15, p  = 0.31). The longitudinal changes in %GAlb persisted after adjusting for BMI. Neither glycemia measurements nor hemoglobin A1c were associated with %GAlb at any time point, and adjustments for BMI did not reveal additional associations., Conclusion: %GAlb decreases between early and late gestation and remains decreased PP, despite a PP increase in total albumin above early pregnancy values. Given the lack of correlation with OGTT values or A1c, %GAlb is unlikely to be useful in assessing glycemia in pregnant or PP women., Key Points: · Changes in %GAlb extending to the postpartum period have not been described.. · %GAlb decreases in pregnancy and remains decreased postpartum, despite a postpartum increase in total albumin above early pregnancy values.. · Glycemia measurements nor A1c were associated with %GAlb at any time point, therefore, %GAlb is unlikely to be useful in assessing glycemia in pregnant or postpartum women.., Competing Interests: None declared., (Thieme. All rights reserved.)

Background: Perinatal outcomes vary for women with gestational diabetes mellitus (GDM). The precise factors beyond glycemic status that may refine GDM diagnosis remain unclear. We conducted a systematic review and meta-analysis of potential precision markers for GDM., Methods: Systematic literature searches were performed in PubMed and EMBASE from inception to March 2022 for studies comparing perinatal outcomes among women with GDM. We searched for precision markers in the following categories: maternal anthropometrics, clinical/sociocultural factors, non-glycemic biochemical markers, genetics/genomics or other -omics, and fetal biometry. We conducted post-hoc meta-analyses of a subset of studies with data on the association of maternal body mass index (BMI, kg/m 2 ) with offspring macrosomia or large-for-gestational age (LGA)., Results: A total of 5905 titles/abstracts were screened, 775 full-texts reviewed, and 137 studies synthesized. Maternal anthropometrics were the most frequent risk marker. Meta-analysis demonstrated that women with GDM and overweight/obesity vs. GDM with normal range BMI are at higher risk of offspring macrosomia (13 studies [n = 28,763]; odds ratio [OR] 2.65; 95% Confidence Interval [CI] 1.91, 3.68), and LGA (10 studies [n = 20,070]; OR 2.23; 95% CI 2.00, 2.49). Lipids and insulin resistance/secretion indices were the most studied non-glycemic biochemical markers, with increased triglycerides and insulin resistance generally associated with greater risk of offspring macrosomia or LGA. Studies evaluating other markers had inconsistent findings as to whether they could be used as precision markers., Conclusions: Maternal overweight/obesity is associated with greater risk of offspring macrosomia or LGA in women with GDM. Pregnancy insulin resistance or hypertriglyceridemia may be useful in GDM risk stratification. Future studies examining non-glycemic biochemical, genetic, other -omic, or sociocultural precision markers among women with GDM are warranted., (© 2023. The Author(s).)

Objective: To evaluate changes in insulin physiology in euglycemic pregnancy and gestational diabetes mellitus (GDM)., Research Design and Methods: Participants underwent oral glucose tolerance tests at ≤15 weeks' gestation (early pregnancy), 24-32 weeks' gestation (mid-late pregnancy), and 6-24 weeks postpartum. We evaluated longitudinal changes in insulin secretory response (log Stumvoll first-phase estimate) and insulin sensitivity (log Matsuda index) using linear mixed models. We then evaluated participants who met GDM criteria in early pregnancy (early GDM) and mid-late pregnancy (classic GDM) separately from those without GDM. We derived the pregnancy insulin physiology (PIP) index to quantify β-cell compensation for insulin resistance., Results: Among 166 participants, 21 had early GDM and 24 developed classic GDM. Insulin sensitivity was reduced slightly in early pregnancy (β = -0.20, P < 0.001) and substantially in mid-late pregnancy (β = -0.47, P < 0.001) compared with postpartum. Insulin secretory response (adjusted for insulin sensitivity) was augmented in early pregnancy (β = 0.16, P < 0.001) and mid-late pregnancy (β = 0.16, P = 0.001) compared with postpartum. Compared with postpartum, the PIP index was augmented in early pregnancy (β = 215, P = 0.04) but not mid-late pregnancy (β = 55, P = 0.64). Early GDM was distinguished by a substantial reduction in early pregnancy insulin sensitivity (β = -0.59, P < 0.001) compared with postpartum. Both early and classic GDM lacked evidence of early pregnancy augmentation of insulin secretory response (adjusted for insulin sensitivity) and the PIP index (P > 0.1 vs. postpartum). Early pregnancy PIP index predicted GDM independent of participant characteristics (area under the curve without PIP index 0.70 [95% CI 0.61-0.79], area under the curve with PIP index 0.87 [95% CI 0.80-0.93])., Conclusions: β-Cell function is enhanced in early pregnancy. Deficient first-trimester β-cell function predicts GDM., (© 2023 by the American Diabetes Association.)

Physician parents encounter unique challenges in balancing new parenthood with work responsibilities, especially upon their return from parental leave. We designed a pilot program that incorporated 1:1 parental coaching to expectant and new physician parents and provided stipends for lactation support and help at home. Additional initiatives included launching a virtual new parent group during the COVID-19 pandemic and starting an emergency backup pump supplies program. There was positive feedback for our Parental Wellness Program (PWP), which was used to secure expanded funding. Pilot results showed that our program had a meaningful impact on parental wellness, morale, productivity, and lactation efforts., Competing Interests: The authors have no conflicts of interest to declare., (© The Author(s) 2023.)

Precision medicine is part of the logical evolution of contemporary evidence-based medicine that seeks to reduce errors and optimize outcomes when making medical decisions and health recommendations. Diabetes affects hundreds of millions of people worldwide, many of whom will develop life-threatening complications and die prematurely. Precision medicine can potentially address this enormous problem by accounting for heterogeneity in the etiology, clinical presentation and pathogenesis of common forms of diabetes and risks of complications. This second international consensus report on precision diabetes medicine summarizes the findings from a systematic evidence review across the key pillars of precision medicine (prevention, diagnosis, treatment, prognosis) in four recognized forms of diabetes (monogenic, gestational, type 1, type 2). These reviews address key questions about the translation of precision medicine research into practice. Although not complete, owing to the vast literature on this topic, they revealed opportunities for the immediate or near-term clinical implementation of precision diabetes medicine; furthermore, we expose important gaps in knowledge, focusing on the need to obtain new clinically relevant evidence. Gaps include the need for common standards for clinical readiness, including consideration of cost-effectiveness, health equity, predictive accuracy, liability and accessibility. Key milestones are outlined for the broad clinical implementation of precision diabetes medicine., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Context: The American Diabetes Association (ADA) recommends a 3-day preparatory diet prior to a diagnostic oral glucose tolerance test (OGTT), a test often recommended in postpartum individuals with a history of gestational diabetes (GDM)., Objective: Evaluate the relationship between carbohydrate intake and OGTT glucose in 2 cohorts of postpartum individuals., Methods: We performed analyses of postpartum individuals from 2 prospective studies with recent GDM (Balance after Baby Intervention, BABI, n = 177) or risk factors for GDM (Study of Pregnancy Regulation of INsulin and Glucose, SPRING, n = 104) .We measured carbohydrate intake using 24-hour dietary recalls (SPRING) or Food Frequency Questionnaire (BABI) and performed 2-hour 75-g OGTTs. The main outcome measure was 120-minute post-OGTT glucose., Results: There was no relationship between carbohydrate intake and 120-minute post-OGTT glucose level in either study population (SPRING: β = 0.03, [-5.5, 5.5] mg/dL, P = .99; BABI: β = -3.1, [-9.5, 3.4] mg/dL, P = .35). Adding breastfeeding status to the model did not change results (SPRING β = -0.14, [-5.7, 5.5] mg/dL, P = .95; BABI β = -3.9, [-10.4, 2.7] mg/dL, P = .25). There was, however, an inverse relationship between glycemic index and 120-minute post OGTT glucose (BABI: β = -1.1, [-2.2, -0.03] mg/dL, P = .04)., Conclusion: Carbohydrate intake is not associated with post-OGTT glucose levels among postpartum individuals. Dietary preparation prior to the OGTT may not be necessary in this population., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Maternal obesity is associated with increased risk of offspring obesity and cardiometabolic disease. Altered fetoplacental immune programming is a potential candidate mechanism. Differences in fetal placental macrophages, or Hofbauer cells (HBCs), have been observed in maternal obesity, and lipid metabolism is a key function of resident macrophages that may be deranged in inflammation/immune activation. We sought to test the following hypotheses: 1) maternal obesity is associated with altered HBC density and phenotype in the term placenta and 2) obesity-associated HBC changes are associated with altered placental lipid transport to the fetus. The impact of fetal sex was evaluated in all experiments., Methods: We quantified the density and morphology of CD163-and CD68-positive HBCs in placental villi in 34 full-term pregnancies undergoing cesarean delivery (N = 15, maternal BMI ≥30 kg/m 2 ; N = 19, BMI <30 kg/m 2 ). Antibody-positive cells in terminal villi were detected and cell size and circularity analyzed using a semi-automated method for thresholding of bright-field microscopy images (ImageJ). Placental expression of lipid transporter genes was quantified using RTqPCR, and cord plasma triglycerides (TGs) were profiled using modified Wahlefeld method. The impact of maternal obesity and fetal sex on HBC features, lipid transporters, and cord TGs were evaluated by two-way ANOVA. Spearman correlations of cord TGs, HBC metrics and gene expression levels were calculated., Results: Maternal obesity was associated with significantly increased density of HBCs, with male placentas most affected (fetal sex by maternal obesity interaction p = 0.04). CD163+ HBCs were larger and rounder in obesity-exposed male placentas. Sexually dimorphic expression of placental FATP4, FATP6, FABPPM, AMPKB1 and AMPKG and cord TGs was noted in maternal obesity, such that levels were higher in males and lower in females relative to sex-matched controls. Cord TGs were positively correlated with HBC density and FATP1 expression., Discussion: Maternal obesity is associated with sex-specific alterations in HBC density and placental lipid transporter expression, which may impact umbilical cord blood TG levels and offspring cardiometabolic programming., Competing Interests: Declaration of competing interest D.J.R. reports receiving royalties for authorship on perinatal topics from UpToDate, Cambridge University Press, and AFIP/ARP outside the scope of this work. A.G.E. serves as a consultant for Mirvie, Inc, and receives research funding from Merck Pharmaceuticals outside the scope of this work. L.L.S., K.E.J., C.E.P., R.H·P., K.L.T., P·O.G have no financial disclosures., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objective: To evaluate the risks of large-for-gestational-age birth weight (LGA) and birth weight-related complications in pregnant individuals with gestational glucose intolerance, an abnormal screening glucose loading test result without meeting gestational diabetes mellitus (GDM) criteria., Methods: In a retrospective cohort study of 46,989 individuals with singleton pregnancies who delivered after 28 weeks of gestation, those with glucose loading test results less than 140 mg/dL were classified as having normal glucose tolerance. Those with glucose loading test results of 140 mg/dL or higher and fewer than two abnormal values on a 3-hour 100-g oral glucose tolerance test (OGTT) were classified as having gestational glucose intolerance. Those with two or more abnormal OGTT values were classified as having GDM. We hypothesized that gestational glucose intolerance would be associated with higher odds of LGA (birth weight greater than the 90th percentile for gestational age and sex). We used generalized estimating equations to examine the odds of LGA in pregnant individuals with gestational glucose intolerance compared with those with normal glucose tolerance, after adjustment for age, body mass index, parity, health insurance, race and ethnicity, and marital status. In addition, we investigated differences in birth weight-related adverse pregnancy outcomes., Results: Large for gestational age was present in 7.8% of 39,685 pregnant individuals with normal glucose tolerance, 9.5% of 4,155 pregnant individuals with gestational glucose intolerance and normal OGTT, 14.5% of 1,438 pregnant individuals with gestational glucose intolerance and one abnormal OGTT value, and 16.0% of 1,711 pregnant individuals with GDM. The adjusted odds of LGA were higher in pregnant individuals with gestational glucose intolerance than in those with normal glucose tolerance overall (adjusted odds ratio [aOR] 1.35, 95% CI 1.23-1.49, P <.001). When compared separately with pregnant individuals with normal glucose tolerance, those with either gestational glucose intolerance subtype had higher adjusted LGA odds (gestational glucose intolerance with normal OGTT aOR 1.21, 95% CI 1.08-1.35, P <.001; gestational glucose intolerance with one abnormal OGTT value aOR 1.77, 95% CI 1.52-2.08, P <.001). The odds of birth weight-related adverse outcomes (including cesarean delivery, severe perineal lacerations, and shoulder dystocia or clavicular fracture) were higher in pregnant individuals with gestational glucose intolerance with one abnormal OGTT value than in those with normal glucose tolerance., Conclusion: Gestational glucose intolerance in pregnancy is associated with birth weight-related adverse pregnancy outcomes. Glucose lowering should be investigated as a strategy for lowering the risk of these outcomes in this group., Competing Interests: Financial Disclosure: Camille E. Powe, MD, has received fees and royalties from Mediflix and UpToDate (Wolters Kluwer), respectively, for presentations and articles related to diabetes over which she had full control of content. The other authors did not report any potential conflicts of interest., (Copyright © 2023 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Aim: To evaluate whether pregnancy and birth-related factors are associated with celiac disease (CD) in a large, United States (US)-based mother-child cohort., Methods: We analysed data gathering from the Massachusetts General Hospital Maternal Child Cohort (MMCC) of children born between 1998 and 2016. Data included the mode of delivery, maternal pregnancy and their offspring characteristics. We searched for CD cases by using diagnosis billing codes. Cox proportional hazard regression models were created to identify variables associated with CD., Results: We identified 44 539 mother-child pairs who had at least one encounter by 5 years old and identified 173 children (0.4%) with CD diagnosis; median age at the diagnosis was 6 years. Overall, the adjusted hazard ratio (aHR) of caesarean delivery for CD was 1.39 (95% CI: 0.99, 1.96, p = 0.06) when compared to children born vaginally. After stratifying for the presence of labour, children born by Caesarean delivery without labour had a higher risk of CD (aHR 1.56; 95%CI: 1.01, 2.41; p = 0.046) while infants born by Caesarean delivery with labour did not (aHR 1.26; 95% CI: 0.83, 1.93; p = 0.28)., Conclusion: Being born by Caesarean delivery without labour may be associated with an increased risk for CD in the US children., (© 2023 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

We identified characteristics associated with continuous glucose monitoring (CGM) use in women of reproductive age with type 1 diabetes (T1D) in the T1D Exchange clinic registry from 2015 to 2018. Among 6643 assessed women, the frequency of CGM increased from 2015 to 2018 (20.6% vs. 30.0%; adjusted odds ratios [aOR]: 1.72; confidence interval [95% CI]: 1.51-1.95) and was more likely with recent pregnancy (45.3% vs. 25.8%; aOR: 1.63; 95% CI: 1.23-2.16). Non-Hispanic Black and Hispanic race and ethnicity, younger age, lower educational attainment, lower income, and Medicaid insurance were associated with lower odds of CGM. The use of CGM was associated with lower odds of diabetic ketoacidosis and lower hemoglobin A1c without any difference in the odds of symptomatic severe hypoglycemia. In conclusion, although CGM use was associated with better glycemic control, the majority of reproductive-age women still did not use it. Those who did not use CGM were more likely to be those at greatest risk of adverse pregnancy outcomes.

Background: Administrative data, including International Classification of Diseases codes and birth certificate records, are often used for retrospective gestational diabetes research investigations to describe associations of gestational diabetes with perinatal complications and long-term outcomes, and to determine gestational diabetes prevalence. Research investigating the validity of using International Classification of Diseases codes and birth certificates for gestational diabetes ascertainment shows varying degrees of reliability., Objective: This study aimed to evaluate the accuracy of both International Classification of Diseases codes and birth certificate diagnosis for gestational diabetes ascertainment in a large hospital-based cohort of pregnant individuals, using laboratory criteria for gestational diabetes mellitus as the reference., Study Design: We studied individuals who received prenatal care at an academic hospital and affiliated community health centers between 1998 and 2016. In the setting of universal 2-step screening for gestational diabetes, pregnant individuals were classified as having gestational diabetes if ≥2 oral glucose tolerance test values met or exceeded National Diabetes Data Group thresholds. We calculated the sensitivity, specificity, positive predictive value, and negative predictive value for International Classification of Diseases code and birth certificate ascertainment of gestational diabetes, and their exact binomial 95% confidence intervals., Results: In a cohort of 51,059 pregnancies with complete glucose screening, 1303 (2.6%) met National Diabetes Data Group laboratory criteria for gestational diabetes. Gestational diabetes International Classification of Diseases codes had moderate sensitivity of 70.5% (95% confidence interval, 67.9-72.9), high specificity of 99.3% (95% confidence interval, 99.3-99.4), a positive predictive value of 73.3% (95% confidence interval, 70.8-75.8), and a negative predictive value of 99.2% (95% confidence interval, 99.1-99.3). In the 46,512 pregnancies linked to birth certificate data, birth certificate diagnosis had moderate sensitivity (66.3% [95% confidence interval, 63.6-69.0]), high specificity (98.9% [95% confidence interval, 98.8-99.0]), moderate positive predictive value (62.1% [95% confidence interval, 59.8-64.4]), and high negative predictive value (99.1% [95% confidence interval, 99.0-99.2])., Conclusion: Ascertainment of gestational diabetes using administrative data, including International Classification of Diseases codes or birth certificates, has moderate sensitivity, moderate positive predictive value, high specificity, and high negative predictive value. Our findings provide context for interpreting the validity of studies that depend on administrative data for ascertainment of gestational diabetes and comparing them with prospective studies that use laboratory-based gestational diabetes criteria., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: The rate of gestational diabetes mellitus has increased over the past decade. An age, period, and cohort epidemiologic analysis can be used to understand how and why disease trends have changed over time., Objective: This study aimed to estimate the associations of age (at delivery), period (delivery year), and cohort (birth year) of the pregnant individual with trends in the incidence of gestational diabetes mellitus in the United States., Study Design: We conducted an age, period, and cohort analysis of nulliparous pregnant adults aged 18 to 44 years with singleton live births from the National Vital Statistics System from 2011 to 2019. Generalized linear mixed models were used to calculate the adjusted rate ratios for the incidence of gestational diabetes mellitus for each 3-year maternal age span, period, and cohort group compared with the reference group for each. We repeated the analyses with stratification according to self-reported racial and ethnic group (non-Hispanic Asian-Pacific Islander, non-Hispanic Black, Hispanic, and non-Hispanic White) because of differences in the incidence of and risk factors for gestational diabetes mellitus by race and ethnicity., Results: Among 11,897,766 pregnant individuals, 5.2% had gestational diabetes mellitus. The incidence of gestational diabetes mellitus was higher with increasing 3-year maternal age span, among those in the more recent delivery period, and among the younger birth cohort. For example, individuals aged 42 to 44 years at delivery had a 5-fold higher risk for gestational diabetes mellitus than those aged 18 to 20 years (adjusted rate ratio, 5.57; 95% confidence interval, 5.43-5.72) after adjusting for cohort and period. Individuals who delivered between 2017 and 2019 were at higher risk for gestational diabetes mellitus than those who delivered between 2011 and 2013 (adjusted rate ratio, 1.24; 95% confidence interval, 1.23-1.25) after adjusting for age and cohort. Individuals born between 1999 and 2001 had a 3-fold higher risk for gestational diabetes mellitus than those born between 1969 and 1971 (adjusted rate ratio, 3.12; 95% confidence interval, 2.87-3.39) after adjusting for age and period. Similar age, period, and cohort effects were observed for the assessed racial and ethnic groups, with the greatest period effects observed among Asian and Pacific Islander individuals., Conclusion: Period and birth cohort effects have contributed to the rising incidence of gestational diabetes mellitus in the United States from 2011 to 2019., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: Pregnant individuals are universally screened for gestational diabetes mellitus (GDM). Gestational glucose intolerance (GGI) (an abnormal initial GDM screening test without a GDM diagnosis) is not a recognized diabetes risk factor. We tested for an association between GGI and diabetes after pregnancy., Research Design and Methods: We conducted a retrospective cohort study of individuals followed for prenatal and primary care. We defined GGI as an abnormal screening glucose-loading test result at ≥24 weeks' gestation with an oral glucose tolerance test (OGTT) that did not meet GDM criteria. The primary outcome was incident diabetes. We used Cox proportional hazards models with time-varying exposures and covariates to compare incident diabetes risk in individuals with GGI and normal glucose tolerance., Results: Among 16,836 individuals, there were 20,359 pregnancies with normal glucose tolerance, 2,943 with GGI, and 909 with GDM. Over a median of 8.4 years of follow-up, 428 individuals developed diabetes. Individuals with GGI had increased diabetes risk compared to those with normal glucose tolerance in pregnancy (adjusted hazard ratio [aHR] 2.01 [95% CI 1.54-2.62], P < 0.001). Diabetes risk increased with the number of abnormal OGTT values (zero, aHR 1.54 [1.09-2.16], P = 0.01; one, aHR 2.97 [2.07-4.27], P < 0.001; GDM, aHR 8.26 [6.49-10.51], P < 0.001 for each compared with normal glucose tolerance). The fraction of cases of diabetes 10 years after delivery attributable to GGI and GDM was 8.5% and 28.1%, respectively., Conclusions: GGI confers an increased risk of future diabetes. Routinely available clinical data identify an unrecognized group who may benefit from enhanced diabetes screening and prevention., (© 2022 by the American Diabetes Association.)

Objective: Whether biomarkers may enable early identification of women who develop peripartum cardiomyopathy (PPCM) prior to disease onset remains a question of interest., Study Design: A retrospective nested case-control study was conducted to determine whether first trimester N -terminal pro-B type natriuretic peptide (NT-proBNP) or high sensitivity cardiac troponin I (hs-cTnI) differed among women who developed PPCM versus unaffected pregnancies. Cases were matched to unaffected women by age, race, parity, and gestational age of sample (control A) and then further by blood pressure and pregnancy weight gain (control B)., Results: First trimester NT-proBNP concentrations were numerically higher among women who subsequently developed PPCM (116 pg/mL [83-177]) as compared with women in control A (56.1 pg/mL [38.7-118.7], p  = 0.3) or control B (37.6 [23.3 - 53.8], p <0.05). A higher proportion of women who subsequently developed PPCM (50%) had detectable levels of hs-cTnI as compared with control A (0%, p  = 0.03) or control B (18.8%, p  = 0.52). Among both cases and controls, hs-cTnI values were low and often below the limit of detection., Conclusion: There were differences in first trimester NT-proBNP and hs-cTnI concentrations between women who subsequently developed PPCM and those who did not, raising the possibility the early pregnancy subclinical myocardial dysfunction may be associated with this late-pregnancy disease., Key Points: · First trimester NT-proBNP is numerically higher among women who subsequently develop PPCM.. · First trimester hs-cTnI was nominally higher among women who developed PPCM versus those who did not.. · A significant proportion of normal pregnant women have undetectable hs-cTnI.., Competing Interests: A.A.S. and I.T.G. are supported by an Institutional CRICO Patient Safety Award. J.L.J. reports being a trustee of the American College of Cardiology, receipt of grant support from Novartis Pharmaceuticals and Abbott Diagnostics and honoraria from Abbott, Janssen, Novartis, and Roche Diagnostics, and participation in clinical end point committees and data safety monitoring boards for Abbott, AbbVie, Amgen, Bayer, CVRx, Janssen, and Takeda; he is also supported in part by the Hutter Family Professorship. R.T. reports consultancy agreements with Fresenius Medical Care North America, Thermo Fisher, Moderna, Alnylum, Bayer, Genzyme/Sanofi, Kaneka, FDA, and Novartis; ownership interest in Aggamin LLC and Tvardi; researching funding from National Institutes of Health, Kaneka Corporation, and Genzyme/Sanofi; honoraria from Thermo Fisher, Roche Diagnostics, Pfizer, Merc, Amgen, Genzyme/Sanofi, Bayer, Alnylum, and maternal; patents and inventions with Thermo Fisher and Up-To-Date; and being a scientific advisor or member with Aggamin LLC and Vifor Pharma. M.J.W. reports being a trustee of the American College of Cardiology and on a clinical events committee for Abbvie. C.E.P. is supported by National Institute of Diabetes and Digestive and Kidney Diseases (NIDKK) grant K23-DK-113218 and the Robert Wood Johnson Foundation Harold Amos Medical Faculty Development Program. There are no other author disclosures., (Thieme. All rights reserved.)

Purpose of Review: This review provides an update on gestational diabetes (GDM) and other adverse pregnancy outcomes in individuals with polycystic ovary syndrome (PCOS), one of the most common metabolic disorders and causes of infertility., Recent Findings: Recent studies using Rotterdam diagnostic criteria for PCOS have supported prior literature suggesting that pregnant individuals with PCOS are at an increased risk of GDM. Risk factors for GDM in this population include overweight/obesity, insulin resistance, hyperandrogenism, amenorrhea, and history of miscarriage. It is possible that subtypes of PCOS (metabolic vs. lean/reproductive) pose differential risk. There are no current screening or treatment guidelines specifically for individuals with PCOS for GDM prevention. Although metformin has been studied for GDM prevention in PCOS, there has been no proven benefit. For infertility treatment, assisted reproductive technology and in-vitro fertilization do not appear to increase the risk of GDM in individuals with PCOS desiring pregnancy., Summary: Recent studies of pregnant individuals with PCOS suggest an increased risk of adverse pregnancy outcomes, including GDM. Larger, prospective studies using standardized diagnostic criteria are warranted to determine if the risk is from PCOS generally, or if there are subtypes of PCOS (metabolic vs. lean/reproductive) at a higher risk of GDM than others., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To estimate short-term maternal and neonatal outcomes with one-compared with two-step testing for gestational diabetes mellitus (GDM)., Data Sources: A systematic review of randomized controlled trials (RCTs) and observational studies comparing one-step and two-step GDM testing strategies before September 2021 was conducted. We searched Ovid Medline (1946-), EMBASE (1947-), Scopus (1960-), Cochrane Central, and ClinicalTrials.gov . The primary outcome was rate of large-for-gestational age (LGA) neonates. Secondary outcomes were clinically relevant outcomes for GDM that were selected a priori., Methods of Study Selection: Titles, abstracts, and manuscripts were screened, selected, and reviewed by the first two authors. Four RCTs (24,966 patients) and 13 observational studies (710,677 patients) were analyzed., Tabulation, Integration, and Results: Pooled relative risks (RRs) were calculated with 95% CIs using random-effects models and were plotted graphically with forest plots. Study heterogeneity was evaluated using Cochran Q and Higgins I 2 tests. The quality of studies that met the inclusion criteria was evaluated with the Downs and Black checklist. Publication bias was assessed by using asymmetry of funnel plots and Harbord's test. There was no difference in the rate of LGA neonates (pooled RR 0.95; 95% CI 0.88-1.04) by testing strategy among RCTs, but patients who underwent one-step testing were more likely to be diagnosed with GDM (pooled RR 2.13; 95% CI 1.61-2.82) and treated with diabetes medications (pooled RR 2.24; 95% CI 1.21-4.15). One-step testing was associated with higher rates of neonatal intensive care unit (NICU) admission (pooled RR 1.12; 95% CI 1.00-1.26) and neonatal hypoglycemia (pooled RR 1.23; 95% CI 1.13-1.34). In analysis of high-quality RCTs and observational studies, one-step testing was associated with a lower rate of LGA neonates (pooled RR 0.97; 95% CI 0.95-0.98), but higher rates of GDM diagnosis, treatment, NICU admission, and neonatal hypoglycemia., Conclusion: Despite a significant increase in GDM diagnosis and treatment with one-step testing, there is no difference in rate of LGA neonates compared with two-step testing among RCTs., Systematic Review Registration: PROSPERO, CRD42021252703., Competing Interests: Financial Disclosure Jeannie C. Kelly reports that money was paid to her institution from PEW, the Barnes Jewish Foundation, and Doris Duke. Ebony Carter's institution received payment from the American Diabetes Association NIH/NIMH Robert Wood Johnson Foundation. She received payment as part of Carter Expert Strategic Consulting and from Affinia Healthcare (board advisor, Mother Goose). The other authors did not report any potential conflicts of interest., (Copyright © 2022 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Objective: This cross-sectional study characterized associations between sex, role misidentification, and burnout among surgical and nonsurgical residents., Summary Background Data: Limited evidence suggests that female resident physicians are more likely to be misidentified as nonphysician team members, with potential negative implications for wellbeing. The prevalence and impact of role misidentification on the trainee experience in surgical as compared to nonsurgical specialties is unknown., Methods: An anonymous electronic survey was distributed to fourteen different residency programs at 2 academic medical centers in August 2018. The survey included questions about demographics, symptoms of burnout, the frequency of misidentification as another member of the care team, and the effect of misidentification on respondents' well-being. Results: Two-hundred sixty out of 419 (62.1% response rate) resident physicians completed the survey, of whom 184 (77.3%) reported being misidentified as a nonphysician at least weekly. Female sex was associated with a significantly increased odds of being misidentified at least weekly (adjusted OR 23.7, 95% CI 10.9-51.5; P < 0.001), as was training in a surgical program (adjusted OR 3.7, 95% CI 1.7-8.0; P = 0.001). Frequent role misidentification was associated with burnout (OR 2.6, 95% CI 1.2-5.5; P = 0.01). In free-text responses, residents reported that being misidentified invoked a sense of not belonging, caused emotional exhaustion, and interfered with patient communication., Conclusions: Role misidentification is more prevalent among female residents and surgical residents, compared to male residents and nonsurgical residents, respectively. Physician role misidentification is associated with burnout and has negative implications for resident wellbeing; interventions to reduce role misidentification are needed., Competing Interests: The authors report no conflicts of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Importance: Role misidentification of resident physicians occurs frequently and is associated with decreased well-being., Objective: To evaluate the role misidentification and burnout rates among resident physicians after disbursement of role identity badges., Design, Setting, and Participants: This quality improvement study was conducted during the 2018 to 2019 academic year. Residents in 13 surgical and nonsurgical residency programs at 2 large academic medical centers (Massachusetts General Hospital and Brigham and Women's Hospital) were eligible to receive the intervention and complete 2 surveys (before and after the intervention). Data were analyzed from December 4, 2021, to February 7, 2022., Intervention: Role identity badges that displayed "Doctor" and could be attached to mandatory hospital identification badges were distributed to residents in August 2018 at Massachusetts General Hospital and in March 2019 at Brigham and Women's Hospital. Residents were not required to wear the badge., Main Outcomes and Measures: The primary outcome was self-reported role misidentification at least once per week during the previous 3 months. The change from pre- to post-badge distribution surveys was assessed with McNemar's test. A secondary outcome was any reduction in the frequency of role misidentification after badge distribution. Multivariable logistic regression was used to assess the association between reduced frequency of role misidentification and demographic characteristics. A separate analysis evaluated the change in self-reported burnout after badge distribution., Results: A total of 161 residents (39%) completed both surveys, which included 79 men (49%), 72 (45%) who were younger than 30 years, 20 (12%) with an underrepresented in medicine status, and 74 (46%) who were in surgical specialties. The proportion of residents reporting at least weekly role misidentification decreased from 50% (n = 81 of 161) before badge distribution to 35% (n = 57 of 161; P < .001) after badge distribution. Female residents were more likely to report reduced role misidentification frequency after receiving a badge compared with male residents (adjusted odds ratio, 2.32; 95% CI, 1.18-4.63; P = .01). Residents who wore badges demonstrated no change in burnout before vs after badge distribution (39% [n = 33 of 85] vs 34% [29 of 85]; P = .87) compared with an increase among residents who did not wear a badge (27% [n = 15 of 55] vs 45% [n = 25 of 55]; P = .03)., Conclusions and Relevance: This study found that the distribution of role identity badges was associated with less frequent perception of role misidentification among resident physicians across specialties, particularly among female residents. Role identity badges were a well-received, low-cost intervention that could be used to reduce role misidentification and address burnout among residents.

The Endocrine Society recognizes racism as a root cause of the health disparities that affect racial/ethnic minority communities in the United States and throughout the world. In this policy perspective, we review the sources and impact of racism on endocrine health disparities and propose interventions aimed at promoting an equitable, diverse, and just healthcare system. Racism in the healthcare system perpetuates health disparities through unequal access and quality of health services, inadequate representation of health professionals from racial/ethnic minority groups, and the propagation of the erroneous belief that socially constructed racial/ethnic groups constitute genetically and biologically distinct populations. Unequal care, particularly for common endocrine diseases such as diabetes, obesity, osteoporosis, and thyroid disease, results in high morbidity and mortality for individuals from racial/ethnic minority groups, leading to a high socioeconomic burden on minority communities and all members of our society. As health professionals, researchers, educators, and leaders, we have a responsibility to take action to eradicate racism from the healthcare system. Achieving this goal would result in high-quality health care services that are accessible to all, diverse workforces that are representative of the communities we serve, inclusive and equitable workplaces and educational settings that foster collaborative teamwork, and research systems that ensure that scientific advancements benefit all members of our society. The Endocrine Society will continue to prioritize and invest resources in a multifaceted approach to eradicate racism, focused on educating and engaging current and future health professionals, teachers, researchers, policy makers, and leaders., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Oral glucose tolerance test (OGTT)-based measures of insulin secretory response have not been validated in pregnancy., Methods: In a secondary analysis of a longitudinal study, participants were studied prepregnancy (n = 40), in early pregnancy (n = 36; 12-14 weeks' gestation), and in late pregnancy (n = 36; 34-36 weeks' gestation). Participants underwent an OGTT, an intravenous glucose tolerance test (IVGTT), and a hyperinsulinemic-euglycemic clamp at each timepoint. We calculated homeostatic model assessment of beta-cell function (HOMA-2B), insulinogenic index (IGI), corrected insulin response (CIR), ratio of the area under the insulin curve and the area under the glucose curve (AUCins/AUCglu), and Stumvoll first-phase estimate (Stumvoll) from OGTT insulin and glucose levels. We used Pearson correlation to compare measures from OGTT and IVGTT. We used mixed effects models to examine longitudinal changes in insulin secretory response., Results: Stumvoll was the only OGTT-based measure that was significantly correlated with first-phase insulin response prior to and across gestation (prepregnancy: r = 0.44, P = 0.01; early pregnancy: r = 0.67, P = 0.0001; late pregnancy: r = 0.67, P = 0.0001). In early and late pregnancy, AUCins/AUCglu had the strongest correlation with first-phase insulin response (early pregnancy: r = 0.79, P < 0.0001; late pregnancy: r = 0.69, P < 0.0001) but was not significantly correlated prepregnancy. IGI and CIR were significantly correlated with first-phase insulin response prepregnancy (IGI: r = 0.50, P = 0.005; CIR r = 0.47, P = 0.008) and in late pregnancy (IGI: r = 0.68, P = 0.0001; CIR r = 0.57, P = 0.002) but not in early pregnancy. HOMA-2B was the weakest correlate of first-phase insulin response. Stumvoll and AUCins/AUCglu recapitulated the longitudinal changes in insulin secretory response observed by IVGTT., Conclusions: Stumvoll and AUCins/AUCglu are valid OGTT-based insulin secretory response measures for pregnancy studies., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Importance: Gestational diabetes, which increases the risk of adverse pregnancy outcomes, has been increasing in frequency across all racial and ethnic subgroups in the US., Objective: To assess whether the frequency of adverse pregnancy outcomes among those in the US with gestational diabetes changed over time and whether the risk of these outcomes differed by maternal race and ethnicity., Design, Setting, and Participants: Exploratory serial, cross-sectional, descriptive study using US National Center for Health Statistics natality data for 1 560 822 individuals with gestational diabetes aged 15 to 44 years with singleton nonanomalous live births from 2014 to 2020 in the US., Exposures: Year of delivery and race and ethnicity, as reported on the birth certificate, stratified as non-Hispanic American Indian, non-Hispanic Asian/Pacific Islander, non-Hispanic Black, Hispanic/Latina, and non-Hispanic White (reference group)., Main Outcomes and Measures: Maternal outcomes of interest included cesarean delivery, primary cesarean delivery, preeclampsia or gestational hypertension, intensive care unit (ICU) admission, and transfusion; neonatal outcomes included large for gestational age (LGA), macrosomia (>4000 g at birth), small for gestational age (SGA), preterm birth, and neonatal ICU (NICU) admission, as measured by the frequency (per 1000 live births) with estimation of mean annual percentage change (APC), disparity ratios, and adjusted risk ratios., Results: Of 1 560 822 included pregnant individuals with gestational diabetes (mean [SD] age, 31 [5.5] years), 1% were American Indian, 13% were Asian/Pacific Islander, 12% were Black, 27% were Hispanic/Latina, and 48% were White. From 2014 to 2020, there was a statistically significant increase in the overall frequency (mean APC per year) of preeclampsia or gestational hypertension (4.2% [95% CI, 3.3% to 5.2%]), transfusion (8.0% [95% CI, 3.8% to 12.4%]), preterm birth at less than 37 weeks (0.9% [95% CI, 0.3% to 1.5%]), and NICU admission (1.0% [95% CI, 0.3% to 1.7%]). There was a significant decrease in cesarean delivery (-1.4% [95% CI, -1.7% to -1.1%]), primary cesarean delivery (-1.2% [95% CI, -1.5% to -0.9%]), LGA (-2.3% [95% CI, -2.8% to -1.8%]), and macrosomia (-4.7% [95% CI, -5.3% to -4.0%]). There was no significant change in maternal ICU admission and SGA. In comparison with White individuals, Black individuals were at significantly increased risk of all assessed outcomes, except LGA and macrosomia; American Indian individuals were at significantly increased risk of all assessed outcomes except cesarean delivery and SGA; and Hispanic/Latina and Asian/Pacific Islander individuals were at significantly increased risk of maternal ICU admission, preterm birth, NICU admission, and SGA. Differences in adverse outcomes by race and ethnicity persisted through these years., Conclusions and Relevance: From 2014 through 2020, the frequency of multiple adverse pregnancy outcomes in the US increased among pregnant individuals with gestational diabetes. Differences in adverse outcomes by race and ethnicity persisted.

Importance: A growing body of evidence suggests that adverse pregnancy outcomes (APOs), including hypertensive disorders of pregnancy, gestational diabetes (GD), preterm birth, and intrauterine growth restriction, are associated with increased risk of cardiometabolic disease and cardiovascular disease (CVD) later in life. Adverse pregnancy outcomes may therefore represent an opportunity to intervene to prevent or delay onset of CVD. The objective of this review was to summarize the current evidence for targeted postpartum interventions and strategies to reduce CVD risk in women with a history of APOs., Observations: A search of PubMed and Ovid for English-language randomized clinical trials, cohort studies, descriptive studies, and guidelines published from January 1, 2000, to April 30, 2021, was performed. Four broad categories of interventions were identified: transitional clinics, lifestyle interventions, pharmacotherapy, and patient and clinician education. Observational studies suggest that postpartum transitional clinics identify women who are at elevated risk for CVD and may aid in the transition to longitudinal primary care. Lifestyle interventions to increase physical activity and improve diet quality may help reduce the incidence of type 2 diabetes in women with prior GD; less is known about women with other prior APOs. Metformin hydrochloride may prevent development of type 2 diabetes in women with prior GD. Evidence is lacking in regard to specific pharmacotherapies after other APOs. Cardiovascular guidelines endorse using a history of APOs to refine CVD risk assessment and guide statin prescription for primary prevention in women with intermediate calculated 10-year CVD risk. Research suggests a low level of awareness of the link between APOs and CVD among both patients and clinicians., Conclusions and Relevance: These findings suggest that transitional clinics, lifestyle intervention, targeted pharmacotherapy, and clinician and patient education represent promising strategies for improving postpartum maternal cardiometabolic health in women with APOs; further research is needed to develop and rigorously evaluate these interventions. Future efforts should focus on strategies to increase maternal postpartum follow-up, improve accessibility to interventions across diverse racial and cultural groups, expand awareness of sex-specific CVD risk factors, and define evidence-based precision prevention strategies for this high-risk population.

Aims/hypothesis: Despite recommendations to screen women with diabetes risk factors for hyperglycaemia in the first trimester, criteria for normal glucose values in early pregnancy have not been firmly established. We aimed to compare glucose levels in early pregnancy with those later in gestation and outside of pregnancy in women with diabetes risk factors., Methods: In pregnant women (N = 123) followed longitudinally through the postpartum period, and a separate cohort of non-pregnant women (N = 65), we performed 75 g oral glucose tolerance tests. All participants had one or more risk factors for diabetes. Using linear regression, we tested for differences in glucose levels between non-pregnant and pregnant women at early (7-15 weeks) and mid-late (24-32 weeks) gestation as well as postpartum, with adjustment for maternal age, parity, marital status and BMI. In a longitudinal analysis using mixed-effects models, we tested for differences in glucose levels across early and mid-late pregnancy compared with postpartum. Differences are expressed as β (95% CI)., Results: Fasting glucose was lower in pregnant compared with non-pregnant women by 0.34 (0.18, 0.51) mmol/l (p < 0.0001) in early pregnancy and by 0.45 (0.29, 0.61) mmol/l (p < 0.0001) in mid-late pregnancy. In longitudinal models, fasting glucose was lower by 0.13 (0.04, 0.21) mmol/l (p = 0.003) in early pregnancy and by 0.16 (0.08, 0.25) mmol/l (p = 0.0003) in mid-late pregnancy compared with the same women postpartum. Early pregnancy post-load glucose levels did not differ from those in non-pregnant women or the same women postpartum. In mid-late pregnancy, compared with non-pregnant women, elevations in 1 h post-load glucose level (0.60 [-0.12, 1.33] mmol/l, p = 0.10) and 2 h post-load glucose (0.49 [-0.21, 1.19] mmol/l, p = 0.17) were not statistically significant. However, in longitudinal analyses, 1 h and 2 h post-load glucose levels were higher in mid-late pregnancy (by 0.78 [0.35, 1.21] mmol/l, p = 0.0004, and 0.67 [0.30, 1.04] mmol/l, p = 0.0005, respectively) when compared with postpartum., Conclusions/interpretation: In women with diabetes risk factors, fasting glucose declines in the first trimester. Post-load glucose increases later in pregnancy. These findings may inform criteria for diagnosing hyperglycaemia early in pregnancy., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Women with gestational glucose intolerance, defined as an abnormal initial gestational diabetes mellitus screening test, are at risk of adverse pregnancy outcomes even if they do not have gestational diabetes mellitus. Previously, we defined the physiological subtypes of gestational diabetes mellitus based on the primary underlying physiology leading to hyperglycemia and found that women with different subtypes had differential risks of adverse outcomes. Physiological subclassification has not yet been applied to women with gestational glucose intolerance., Objective: We defined the physiological subtypes of gestational glucose intolerance based on the presence of insulin resistance, insulin deficiency, or mixed pathophysiology and aimed to determine whether these subtypes are at differential risks of adverse outcomes. We hypothesized that women with the insulin-resistant subtype of gestational glucose intolerance would have the greatest risk of adverse pregnancy outcomes., Study Design: In a hospital-based cohort study, we studied women with gestational glucose intolerance (glucose loading test 1-hour glucose, ≥140 mg/dL; n=236) and normal glucose tolerance (glucose loading test 1-hour glucose, <140 mg/dL; n=1472). We applied homeostasis model assessment to fasting glucose and insulin levels at 16 to 20 weeks' gestation to assess insulin resistance and deficiency and used these measures to classify women with gestational glucose intolerance into subtypes. We compared odds of adverse outcomes (large for gestational age birthweight, neonatal intensive care unit admission, pregnancy-related hypertension, and cesarean delivery) in each subtype to odds in women with normal glucose tolerance using logistic regression with adjustment for age, race and ethnicity, marital status, and body mass index., Results: Of women with gestational glucose intolerance (12% with gestational diabetes mellitus), 115 (49%) had the insulin-resistant subtype, 70 (27%) had the insulin-deficient subtype, 40 (17%) had the mixed pathophysiology subtype, and 11 (5%) were uncategorized. We found increased odds of large for gestational age birthweight (primary outcome) in women with the insulin-resistant subtype compared with women with normal glucose tolerance (odds ratio, 2.35; 95% confidence interval, 1.43-3.88; P=.001; adjusted odds ratio, 1.74; 95% confidence interval, 1.02-3.48; P=.04). The odds of large for gestational age birthweight in women with the insulin-deficient subtype were increased only after adjustment for covariates (odds ratio, 1.69; 95% confidence interval, 0.84-3.38; P=.14; adjusted odds ratio, 2.05; 95% confidence interval, 1.01-4.19; P=.048). Among secondary outcomes, there was a trend toward increased odds of neonatal intensive care unit admission in the insulin-resistant subtype in an unadjusted model (odds ratio, 2.09; 95% confidence interval, 0.99-4.40; P=.05); this finding was driven by an increased risk of neonatal intensive care unit admission in women with the insulin-resistant subtype and a body mass index of <25 kg/m 2 . Infants of women with other subtypes did not have increased odds of neonatal intensive care unit admission. The odds of pregnancy-related hypertension in women with the insulin-resistant subtype were increased (odds ratio, 2.09; 95% confidence interval, 1.31-3.33; P=.002; adjusted odds ratio, 1.77; 95% confidence interval, 1.07-2.92; P=.03) compared with women with normal glucose tolerance; other subtypes did not have increased odds of pregnancy-related hypertension. There was no difference in cesarean delivery rates in nulliparous women across subtypes., Conclusion: Insulin-resistant gestational glucose intolerance is a high-risk subtype for adverse pregnancy outcomes. Delineating physiological subtypes may provide opportunities for a more personalized approach to gestational glucose intolerance., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objectives: To estimate the prevalence of pre-existing diabetes in pregnancy from studies published during 2010-2020., Methods: We searched PubMed, CINAHL, Scopus and other sources for relevant data sources. The prevalence of overall pre-existing, type 1 and type 2 diabetes, by country, region and period of study was synthesised from included studies using the inverse-variance heterogeneity model and the Freeman-Tukey transformation. Heterogeneity was assessed using the I 2 statistic and publication bias using funnel plots., Results: We identified 2479 records, of which 42 data sources with a total of 78 943 376 women, met the eligibility criteria. The included studies were from 17 countries in North America, Europe, the Middle East and North Africa, Australasia, Asia and Africa. The lowest prevalence was in Europe (0.5%, 95 %CI 0.4-0.7) and the highest in the Middle East and North Africa (2.4%, 95 %CI 1.5-3.1). The prevalence of pre-existing diabetes doubled from 0.5% (95 %CI 0.1-1.0) to 1.0% (95 %CI 0.6-1.5) during the period 1990-2020. The pooled prevalences of pre-existing type 1 and type 2 diabetes were 0.3% (95 %CI 0.2-0.4) and 0.2% (95 %CI 0.0-0.9) respectively., Conclusion: While the prevalence of pre-existing diabetes in pregnancy is low, it has doubled from 1990 to 2020., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Context: Individuals with monogenic diabetes due to inactivating glucokinase (GCK) variants typically do not require treatment, except potentially during pregnancy. In pregnancy, fetal GCK genotype determines whether treatment is indicated, but noninvasive methods are not clinically available., Objective: This work aims to develop a method to determine fetal GCK genotype noninvasively using maternal cell-free fetal DNA., Methods: This was a proof-of-concept study involving 3 pregnant women with a causal GCK variant that used information from 1) massive parallel sequencing of maternal plasma cell-free DNA, 2) direct haplotype sequences of maternal genomic DNA, and 3) the paternal genotypes to estimate relative haplotype dosage of the pathogenic variant-linked haplotype. Statistical testing of variant inheritance was performed using a sequential probability ratio test (SPRT)., Results: In each of the 3 cases, plasma cell-free DNA was extracted once between gestational weeks 24 and 36. The fetal fraction of cell-free DNA ranged from 21.8% to 23.0%. Paternal homozygous alleles that were identical to the maternal GCK variant-linked allele were not overrepresented in the cell-free DNA. Paternal homozygous alleles that were identical to the maternal wild-type-linked allele were significantly overrepresented. Based on the SPRT, we predicted that all 3 cases did not inherit the GCK variant. Postnatal infant genotyping confirmed our prediction in each case., Conclusion: We have successfully implemented a noninvasive method to predict fetal GCK genotype using cell-free DNA in 3 pregnant women carrying an inactivating GCK variant. This method could guide tailoring of hyperglycemia treatment in pregnancies of women with GCK monogenic diabetes., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Competing Interests: Financial Disclosure The authors did not report any potential conflicts of interest.

Aims: Evaluate the relationship between self-reported carbohydrate intake and oral glucose tolerance test (OGTT) results in pregnancy., Methods: We measured carbohydrate intake using 24-hour dietary recall and performed a 2-hour 75-gram OGTT in 95 pregnant women with risk factors for gestational diabetes (GDM) at a median of 26 weeks' gestation. We tested for associations between carbohydrate intake in the 24 hours preceding the OGTT and 60-minute OGTT glucose, glucose at other timepoints, and glucose area under the curve (AUC) using linear regression, with adjustment for potential confounders., Results: We observed an inverse linear relationship between carbohydrate intake (median 237 grams [interquartile range: 196, 303]) and 60-minute OGTT glucose. For every 50 gram reduction in carbohydrate intake, there was an 8.9 mg/dl increase in 60-minute OGTT glucose (P < 0.01) in an adjusted model. Lower carbohydrate intake was also associated with higher 30-minute (adjusted β = -6.5 mg/dl, P < 0.01) and 120-minute OGTT glucose (adjusted β = -8.1 mg/dl, P = 0.01) and AUC (adjusted β = -767, P < 0.01)., Conclusions: Carbohydrate intake in the day preceding an OGTT in pregnancy is associated with post-load glucose values, with lower carbohydrate intake predicting higher glucose levels and higher carbohydrate intake predicting lower glucose levels. Carbohydrate restriction or excess before an OGTT may affect GDM diagnosis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)