bluuebunny/crossref_metadata_2025_split huggingface dataset:
1173-P: Maternally Supplemented PQQ Targets Ceramide Metabolism in Offspring to Blunt Developmental Programming of NAFLD
Authors: MANDALA ASHOK , TEAGUE APRIL M. , JANSSEN RACHEL , PATIL NIKHIL , JOSHI ADITYA D. , FRIEDMAN JACOB E. , JONSCHER KAREN R. 
Published: June 2023

Maternal obesity is a key risk factor for pediatric nonalcoholic fatty liver disease (NAFLD). Using a mouse model of Western-style diet (WD)-induced maternal obesity, we studied effects of supplementing dams with pyrroloquinoline quinone (PQQ; a potent dietary antioxidant) during gestation and lactation on hepatic lipid metabolism and fibrosis in offspring at postnatal day (PND) 14 and at 16 wks after a 4 wk WD challenge. Maternal PQQ (mWDPQQ) decreased neonatal hepatic triglycerides (30%, P=0.0012) and altered bioactive sphingolipids in adult offspring compared with those exposed to maternal WD (mWD), with no change in weight gain. mWDPQQ increased very long chain ceramides (VLCer; 219%, P=0.0002), associated with protection from fibrosis, concomitant with decreased expression of genes promoting ceramide degradation (Asah2, P=0.0014 and Acer3, P=0.02). Expression of Scd1, a desaturase regulating triglyceride biosynthesis, was attenuated in mWDPQQ offspring at PND14 (P=0.0009) and at 16 wks (P=0.0012), while expression of Elovl3, an enzyme promoting elongation of saturated fatty acids and ceramide production, was increased (P=0.0026). Comparative pathway analysis of RNASeq data showed enrichment of pathways in fatty acid metabolism, hepatic fibrosis and, unexpectedly, signaling through the aryl hydrocarbon receptor (AHR; a ligand-activated transcription factor regulating immune function and hepatoxicity). Chromatin IP in mWDPQQ liver showed increased AHR binding to the Cyp1a1 promoter, its canonical target, as compared with mWD, suggesting AHR signaling may be activated by mWDPQQ. AHR binding to the Scd1 promoter, a known AHR target, was increased, as was binding to Asah2 and Acer3, putative new AHR targets regulating long-chain ceramide degradation. These findings suggest that maternal PQQ has both short and long-term effects on blunting steatosis/fibrosis and promoting VLCer increase through novel AHR targets, protecting offspring from NAFLD.

Disclosure
A.Mandala: None. A.M.Teague: None. R.Janssen: None. N.Patil: None. A.D.Joshi: None. J.E.Friedman: None. K.R.Jonscher: None.

Funding
National Institutes of Health (1R01DK121951)
1176-P: Maternal Hyperglycemia Leads to Distinct Differences in Metabolism and Pancreatic Beta-Cell Function in Male and Female Offspring
Authors: O'HARA STEPHANIE E. , GEMBUS KELLY M. , CLARKE GEORGIA S. , PAGE AMANDA J. , NICHOLAS LISA M. 
Published: June 2023

Maternal hyperglycemia is a major risk factor for future T2D risk in the offspring. To better understand T2D pathogenesis in this context, we used a mouse model of hyperglycemia induced by high-fat, high-sugar (HFHS) feeding from before mating through to weaning. This resulted in increased adiposity, reduced insulin sensitivity, hyperinsulinemia and impaired glucose tolerance pre-pregnancy. Pregnancy further worsened the metabolic health of dams resulting in reduced insulin levels in addition to glucose intolerance at gestational day 16. By weaning, HFHS-fed dams had fasting hyperglycemia. Maternal hyperglycemia had no impact on offspring body weight and composition at postnatal day 2. However, male offspring of HFHS-fed dams experienced decelerated postnatal growth in the first 2 weeks of life followed by catch-up growth by weaning. Despite comparable body weight, relative fat mass was increased and relative lean mass decreased from 3 to 8 weeks of age in exposed offspring. In males, this was not linked to changes in food intake and metabolic activity measured at 7 weeks. In contrast, daily energy expenditure was increased in female offspring of hyperglycemic dams. At 8 weeks old, despite normal glucose tolerance and insulin sensitivity, male offspring of HFHS-fed dams were hyperinsulinemic during a glucose tolerance test. In contrast, female offspring had reduced insulin sensitivity and higher plasma insulin concentration at baseline and 45 min. Interestingly, insulin secretion was increased only in islets from male offspring characterised by a marked increase in 1st phase and a trend towards higher 2nd phase secretion. Insulin secretion in response to potassium chloride was also increased in these islets. Thus, our data suggest that there are sex-specific mechanisms contributing to future T2D risk in offspring exposed to maternal hyperglycemia with primary hyperinsulinemia being an early feature in males and insulin resistance in females.

Disclosure
S.E.O'hara: None. K.M.Gembus: None. G.S.Clarke: None. A.J.Page: None. L.M.Nicholas: None.

Funding
National Health and Medical Research Council of Australia (GNT1092158)
1181-P: Substituting Protein for Fat Lowers Postprandial Glycemic Response in Gestational Diabetes
Authors: ROSENBERG EMILY A. , THAWEETHAI TANAYOTT , JAMES KAITLYN , KELTY ESTELLE , AZEVEDO ROBIN L. , NELSON STACEY , GARRY JAMIE L. , SEELY ELLEN W. , POWE CAMILLE E. 
Published: June 2023

Background: Dietary guidelines in gestational diabetes mellitus (GDM) focus on carbohydrate without regard to other macronutrients. We tested the impact of fat and protein on postprandial glycemia in GDM and analyzed whether the physiology underlying GDM influenced this response.
Methods: In a pilot crossover trial, participants ate two isocaloric breakfast meals with the same carbohydrate content and different protein and fat content (High protein meal: 390 kCal, 35 g protein, 9 g fat, 45 g carb, High fat meal: 411 kCal, 15 g protein, 19 g fat, 46 g carb) on subsequent days in a random order. We measured peak postprandial glucose (primary outcome) using continuous glucose monitors. We used homeostatic model assessment to determine if participants had insulin resistant (IR) or insulin deficient (ID) GDM. We used paired t-tests to test if glycemic response to the meals differed and linear regression to test if differential response to meals was influenced by having IR vs ID GDM.
Results: We studied 16 women with diet-controlled GDM (median [IQR] 31 [30-33] weeks’ gestation). Mean [SD] peak glucose after the high fat meal (146 [20] mg/dl) was higher than after the high protein meal (137 [21] mg/dl) (P=0.03), but individuals varied in their differential response to the meals (range: 25 mg/dl higher after high protein meal to 35 mg/dl higher after high fat meal). Median time to peak glucose (IQR) was 72 (63-74) minutes after the high protein meal and 65 (60-73) minutes after the high fat meal (P=0.11). There was no difference in differential glycemic response to the meals in IR (n=8) vs ID (n=4) GDM (P=0.98); age (median [IQR] 36 [33-38] yrs) and BMI (median [IQR] 27 [24-30]) adjustment did not change results (P=0.82).
Conclusion: On average, women with GDM have lower post prandial glucose levels after a high protein meal compared to a high fat meal with equivalent carbohydrate content. This may inform GDM dietary recommendations and motivate research on determinants of individual-level response to macronutrients.

Disclosure
E.A.Rosenberg: None. T.Thaweethai: None. K.James: None. E.Kelty: None. R.L.Azevedo: None. S.Nelson: None. J.L.Garry: None. E.W.Seely: None. C.E.Powe: Consultant; Mediflix, Inc., Other Relationship; Wolters Kluwer Health.

Funding
Robert Wood Johnson Foundation; National Institutes of Health (5F32DK12634302); Endocrine Fellows Foundation
1183-P: Association of Community-Level Social Determinants of Health and Pregestational and Gestational Diabetes
Authors: FIELD CHRISTINE P. , GROBMAN WILLIAM , WU JIQIANG , LYNCH COURTNEY , VENKATESH KARTIK K. 
Published: June 2023

Objective: To determine whether community-level adverse social determinants of health are associated with increased risk of pregestational and gestational diabetes (DM, GDM).
Methods: We conducted a secondary analysis from the prospective cohort Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-To-Be. We evaluated three community-level exposures using home addresses geocoded at the census-tract level: 1) socioeconomic disadvantage by 2015 Area Deprivation Index (ADI); 2) food insecurity by USDA Food Access Research Atlas; and 3) walkability by EPA National Walkability Score. The outcomes were DM and GDM.
Results: Of 9,155 assessed individuals, 33.6% were in the highest tertile (T3) of ADI, 24.4% lived in a food-insecure community, and 33.7% lived in a less walkable neighborhood; 1.5% (n=137) had DM and 4.2% (n=380) developed GDM. Individuals living in a community in the highest tertile of ADI were more likely to have DM (aOR: 2.49; 95% CI: 1.48, 4.18) and GDM (aOR: 1.49; 95% CI: 1.13, 1.97). Individuals living in a food-insecure community (aOR: 1.49; 95% CI: 1.17, 1.89) and living in a less walkable neighborhood (aOR: 1.29; 95% CI: 1.03, 1.62) were more likely to have GDM, but not DM.
Conclusions: Multiple measures of community-level adverse social determinants of health were associated with an increased risk of developing GDM. Only socioeconomic disadvantage was associated with DM.

Disclosure
C.P.Field: None. W.Grobman: None. J.Wu: None. C.Lynch: None. K.K.Venkatesh: None.

Funding
Eunice Kennedy Shriver National Institute of Child Health and Human Development
1184-P: No Increased Risk of Gestational Diabetes Mellitus (GDM) Diagnosis after COVID-19 Vaccination
Authors: VESCO KIMBERLY K. , DENOBLE ANNA , LIPKIND HEATHER S. , KHARBANDA ELYSE , DESILVA MALINI B. , DALEY MATTHEW F. , GETAHUN DARIOS , ZERBO OUSSENY , NALEWAY ALLISON , JACKSON LISA , WILLIAMS JOSHUA , BOYCE THOMAS G. , FULLER CANDACE , VAZQUEZ BENITEZ GABRIELA 
Published: June 2023

Background: Hyperglycemia and possible accelerated onset of de novo diabetes have been reported following COVID-19 vaccination in nonpregnant adults. The objective of this study was to examine the risk of GDM after COVID-19 vaccination in pregnancy.
Methods: Using data from 8 integrated health care systems participating in the Vaccine Safety Datalink, we performed a retrospective analysis among 42,140 pregnancies resulting in livebirth from 1/27/21 -1/25/22. Diagnosis of GDM was defined as two outpatient or one inpatient ICD-10 codes for GDM at or beyond 22 weeks’ gestation. GDM diagnoses were compared between individuals who received one or two COVID-19 vaccine doses prior to 22 weeks’ gestation and those who did not receive a COVID-19 vaccine during pregnancy. We used generalized estimating equations with robust variance and inverse probability weighting to estimate the adjusted relative risk (aRR) and 95% Confidence Interval (CI) of GDM, accounting for baseline differences between vaccinated and unvaccinated individuals.
Results: Of the 42,140 pregnancies, 38% identified as Hispanic, 33% non-Hispanic White, 15.6% non-Hispanic Asian, 8.8% non-Hispanic Black, and 4.4% other or unknown; 25.6% received one or more COVID-19 vaccine doses prior to 22 weeks’ gestation. Individuals who were vaccinated were older (mean age 32.0 ± 4.6 vs 29.5 ± 5.3 years) and more likely to be of non-Hispanic White (37.4% vs 31.7%) or Asian background (25.7% vs 12.1%) than those who were unvaccinated. The rate of GDM was 11.9 per 100 among those who received a COVID-19 vaccine and 10.6 per 100 among those who did not. There was no increased risk of GDM diagnosis associated with receipt of a COVID-19 vaccine during pregnancy, aRR 1.00 (95% CI 0.90-1.10).
Conclusion: Data from this large cohort did not identify an increased risk of GDM associated with receipt of a COVID-19 vaccine prior to 22 weeks’ gestation. These results further support emerging evidence regarding the safety of COVID-19 vaccination in pregnancy.

Disclosure
K.K.Vesco: Research Support; Pfizer Inc. L.Jackson: None. J.Williams: None. T.G.Boyce: None. C.Fuller: Research Support; Pfizer Inc., Johnson & Johnson. G.Vazquez benitez: Research Support; AbbVie Inc., Sanofi. A.Denoble: None. H.S.Lipkind: Other Relationship; Pfizer Inc., Research Support; Centers for Disease Control and Prevention, Patient-Centered Outcomes Research Institute, National Institutes of Health. E.Kharbanda: None. M.B.Desilva: None. M.F.Daley: None. D.Getahun: None. O.Zerbo: None. A.Naleway: None.

Funding
Centers for Disease Control and Prevention (200-2012-53526)
1185-P: Maternal Exposure to Per- and Polyfluoroalkyl Substances and Risk of Adiposity in Offspring at Birth and Early Childhood—A Longitudinal Birth Cohort Study
Authors: YANG AIMIN , TAM CLAUDIA H. , OZAKI RISA , LOWE WILLIAM L. , METZGER BOYD E. , TAM WING H. , WONG CHRIS K. , MA RONALD C. 
Published: June 2023

Introduction: Per- and polyfluoroalkyl substances (FPAS) are a class of man-made chemicals that cross the placenta. We examined the associations of maternal exposure to PFAS mixture with risk of adiposity in offspring at birth and childhood.
Methods: In the perspective Hyperglycaemia-and-Adverse-Pregnancy-Outcome (HAPO) study, we measured serum concentrations of six PFAS biomarkers using high-performance LC-MS-MS in 1601 mothers who had joined the Hong Kong centre in 2002-2004 and 922 children at seven years old. We estimated PFAS burden score for each mother and child using concentrations of individual PFAS and exposure patterns of PFAS mixture. Adiposity in the offspring was defined by the ponderal-index (PI) at birth and sum-of-skinfold-thickness in mm at birth and childhood. We used linear regression to estimate associations of maternal exposure to PFAS mixture with adiposity risk.
Results: PFAS burden score in pregnancy was positively associated with PI (β=0.50, 95% CI: 0.02, 0.97) and negatively associated with skinfold thickness (β=-0.61, 95% CI: -0.96, -0.27) in offspring at birth. The correlation of PFAS burden score in mothers and children at seven years old was weak (r=0.07). After adjusting for PFAS burden score of childhood, maternal PFAS burden score was negatively associated with skinfold-thickness in childhood (β=-2.29, 95% CI: -3.97, -0.62). Sex-specific analyses showed similar associations with PI in boys and girls at birth. In contrast, significant negative associations with skinfold thickness were observed in girls but not in boys at childhood.
Conclusions: Maternal exposure to PFAS mixture is independently associated with risk of adiposity in offspring at birth. Its effect on childhood adiposity was apparent only in girls, not boys.

Disclosure
A.Yang: None. C.H.Tam: None. R.Ozaki: None. W.L.Lowe: None. B.E.Metzger: None. W.H.Tam: None. C.K.Wong: None. R.C.Ma: Advisory Panel; AstraZeneca, Merck & Co., Inc., Other Relationship; Bayer Inc., Boehringer-Ingelheim, Research Support; Tricida, Inc., Roche Diagnostics, Novo Nordisk.

Funding
Health and Medical Research Fund (13140761); Eunice Kennedy Shriver National Institute of Child Health and Human Development/National Institute of Diabetes and Digestive and Kidney Diseases (R01HD34242, R01HD34243); Research Grants Council of Hong Kong (473408, 471713)
1187-P: Early Pregnancy Hyperglycemia and Glycemic Status at 24–28 Weeks in Indian Women
Authors: HANNAH WESLEY , DEEPA MOHAN , SHIVASHRI CHOCKALINGAM , SAITE HEMAVATHY , RAM UMA , MOHAN ANJANA RANJIT , GHEBREMICHAEL-WELDESELASSIE YONAS , SARAVANAN PONNUSAMY , MOHAN VISWANATHAN 
Published: June 2023

Introduction: Early pregnancy hyperglycemia threshold (FPG ≥92mg/dl (≥5.1mmol/l)) suggested by International Association of Diabetes and Pregnancy Study Groups (IADPSG) is debateable. There is no evidence of their glycemic status at 24-28 weeks in Indians.
Aim: To understand the 24-28 weeks glycemic status in women with early pregnancy hyperglycemia.
Methods: STratification of Risk of Diabetes in Early pregnancy (STRiDE) study, designed to identify the role of HbA1c in early pregnancy on incident GDM, recruited 2703 pregnant women from 7 centres in south India and 566 (20.9%) women had early pregnancy hyperglycemia. Of these 477 women underwent 24-28 weeks screening (OGTT n=150, FPG n=327)
Results: Abnormal glucose values were present in 32.7% of women at 24-28 weeks (high FPG or GDM by OGTT). These women had higher weight, BMI, waist circumference, family history of diabetes, FPG, and HbA1c at booking compared to women who were normoglycaemic. In multiple regression analysis, early pregnancy FPG ≥95mg/dl (5.3mmol/l) was independently associated with abnormal glucose values at 24-28 weeks (aOR: 1.9; 95% CI: 1.3-3.0, p &lt;0.001), adjusted for key covariates.
Conclusion: Majority of women who had early pregnancy hyperglycaemia became normoglycaemic at 24-28 weeks. HAPO study FPG threshold for the adverse outcomes with aOR: 2.0 was ≥95mg/dl. It may be prudent to classify Indian women with this threshold in early pregnancy as abnormal.

Disclosure
W.Hannah: None. M.Deepa: None. C.Shivashri: None. H.Saite: None. U.Ram: None. R.Anjana: None. Y.Ghebremichael-weldeselassie: None. P.Saravanan: Other Relationship; Novo Nordisk, Research Support; Novo Nordisk, Amgen Inc., Abbott. V.Mohan: None.

Funding
Medical Research Council, UK (MR/N006232/1)
1189-P: The Project Wellness Pilot Feasibility Randomized Controlled Trial, a Behavioral Physical Activity Intervention for Gestational Glucose Intolerance and Gestational Diabetes
Authors: EHRLICH SAMANTHA F. , RAND BETHANY G. , ZITE NIKKI , FORTNER KIMBERLY B. , PAUDEL ALISSA M. , CROUTER SCOTT E. , MAPLES JILL M. 
Published: June 2023

Introduction: Animal evidence suggests that maternal exercise improves metabolic health in the offspring. The offspring of individuals with gestational glucose intolerance (GGI) or gestational diabetes mellitus (GDM) are at increased risk for large for gestational age, shoulder dystocia, obesity, and diabetes. Maternal physical activity (PA) is indicated for these pregnancies, though PA levels tend to be suboptimal and decline over pregnancy. This pilot feasibility randomized controlled trial explored the effects of a behavioral counseling intervention on late pregnancy maternal PA and neonatal anthropometrics.
Methods: Twenty individuals with GGI or GDM were enrolled. Those randomized to the behavioral PA intervention met weekly with a lifestyle coach via Zoom for at least 5 sessions (10-20 minutes per session). Participants completed surveys and wore ActiGraph CentrePoint PA monitoring devices on their dominant wrist for a 7-day period, at both baseline and follow-up. The TwoRegressions algorithm estimated minute by minute metabolic equivalents of task (METs) for periods in which the devices were worn, and minutes per day at ≥ 3.0 METs, indicative of moderate to vigorous intensity PA (MVPA), were totaled. Neonatal measurements (n = 17) occurred within 3 days of birth.
Results: Those in the PA intervention decreased MVPA less than controls [i.e., -4.0 minutes per day (95% CI -14.5, 6.5) vs. -23.5 minutes per day (95% CI -34.9, -12.1), P = .02]. Neonates born to those in the PA intervention were smaller than control neonates, however no difference attained statistical significance (e.g., weight, neonatal fat mass, total skinfolds). There was the suggestion of significant effect on subscapular skinfold (P = .07).
Conclusion: A behavioral PA counseling intervention mitigated late pregnancy declines in PA in GGI or GDM, and could reduce upper-trunk adiposity in their neonates.

Disclosure
S.F.Ehrlich: None. B.G.Rand: None. N.Zite: Other Relationship; Merck & Co., Inc. K.B.Fortner: Other Relationship; Pfizer Inc. A.M.Paudel: None. S.E.Crouter: None. J.M.Maples: None.

Funding
National Institutes of Health (K01DK105106)
119-LB: Preliminary Accuracy Analysis of a Noninvasive Optical Glucose Sensing Prototype
Authors: GEISER LUKE , MAN COLMAN LEUNG HO , BERGET CARI , GONG CHENGYUE , LIU QIANG , ZHOU XIA , FORLENZA GREGORY P. 
Published: June 2023

Background: As the use of CGM in type 1 Diabetes (T1D) becomes more prevalent, it is important to develop less invasive technologies to improve diabetes health outcomes and reduce burden. Optical glucose sensing (OGS) offers a non-invasive option to measure sub-dermal glucose levels by shining a laser beam of light onto the skin. The aim of this study was to gather preliminary data on the accuracy of OGS technology using a prototype device.
Methods: Eighteen adults with T1D (32 ± 11yrs.; 83% white, 17% Latinx) using Dexcom G6 or Libre CGM used an OGS prototype device for 5 days, scanning the palm of their hand up to eight times per day to measure glucose levels. Paired CGM values obtained from Clarity or Libreview CSV files were used for comparison. Outliers due to user-error were removed by leave-one-out cross-validation (20% of values).
Results: Paired CGM and OGS values (n=599) resulted in a MARD of 19% ±13% with 99% of values within the Clarke Error Grid A&B Zones (Figure 1). The % within 15/15, 20/20, or 30/30 were 44%, 59%, and 80%, respectively.
Discussion: OGS may be a promising, non-invasive alternative to current CGM devices on the market. Further research and development of the sensing algorithm is needed to lower the MARD closer to current factory calibrated CGMs. In addition, increased recruitment of people with diabetes who have darker skin tones is needed to evaluate accuracy across all populations.

Disclosure
L. Geiser: None. H. Leung: None. C. Berget: Consultant; Insulet Corporation, Dexcom, Inc. Other Relationship; Tandem Diabetes Care, Inc. C. Gong: None. Q. Liu: None. X. Zhou: None. G. P. Forlenza: Advisory Panel; Medtronic. Research Support; Medtronic, Abbott. Consultant; Dexcom, Inc. Research Support; Dexcom, Inc. Consultant; Insulet Corporation. Research Support; Insulet Corporation. Consultant; Tandem Diabetes Care, Inc. Research Support; Tandem Diabetes Care, Inc. Consultant; Lilly Diabetes.

Funding
National Science Foundation (ECCS-2037267)
1190-P: Dose-Dependency of Prevention of Cesarean Section and Macrosomia by Glycemic Control—A Meta-analysis
Authors: KODAMA SATORU , YAGYUDA NORIKO , YAMADA TAKAHO , NISHIJIMA KOJI , YOSHIHARA KOSUKE , FUJIHARA KAZUYA , YACHI YOKO , IWANAGA MIDORI , KATO KIMINORI , SONE HIROHITO 
Published: June 2023

Observational studies have shown an association of poor glycemic control (GC) with various adverse pregnancy outcomes in patients with diabetes mellitus. To examine whether improving GC reduces risk of maternal/fetal complications, we did a meta-analysis of the quantitative relationship between reductions in glucose levels and individual complication risks. MEDLINE and EMBASE were used to identify randomized controlled trials of the effect of intensified glucose management (i.e., glucose monitoring and/or strict glycemic goals, additional glucose-lowering drugs) on both antepartum glucose levels and incidence of any maternal/fetal complication. Fifty-two eligible trials were retrieved from 2724 articles published until Aug.31, 2022. Focusing on cesarean section (CS) and macrosomia (including large for gestational age if data were unavailable), which are frequent complications, meta-regression analyses indicated that a 1% reduction in HbA1c resulted in a 45% reduction in CS (r=0.59, p=0.002) and a 72% reduction in macrosomia (r=0.43, p=0.005). The intercept (i.e., relative risk at 0 of HbA1c reduction) was almost 1 (1.05 (p=0.46) for CS; 1.02 (p=0.89) for macrosomia) (Figure). In trials of patients with only gestational diabetes, results were unchanged. We conclude that preventing CS and macrosomia depended on the extent to which antenatal cares improved GC.

Disclosure
S.Kodama: None. H.Sone: Research Support; Novo Nordisk, Astellas Pharma Inc., Kyowa Kirin Co., Ltd., Taisho Pharmaceutical Holdings Co., Ltd., Ono Pharmaceutical Co., Ltd., Eisai Co., Ltd., Takeda Pharmaceutical Co., Ltd. N.Yagyuda: None. T.Yamada: None. K.Nishijima: None. K.Yoshihara: None. K.Fujihara: None. Y.Yachi: None. M.Iwanaga: None. K.Kato: None.