bluuebunny/crossref_metadata_2025 huggingface dataset:
1334-P: Hyperglycemia-Induced Eye Malformations through Dysregulation of Autophagy in the Mouse Embryo
Authors: LU WENHUI , YANG PEIXIN
Published: June 2020

Accumulating evidence indicates that autophagy is essential for development and its dysregulation is involved in maternal diabetes-induced fetal malformations. Maternal diabetes induces fetal eye defects by reducing macular thickness and macular volume. We utilized the Streptozotocin-induced type 1 diabetes model to investigate the role of autophagy in maternal diabetes-induced embryonic eye defects. We found that maternal diabetes induced eye defects in the embryonic day (E15) embryos including anophthalmia, microphthalmia. The Haematoxylin Eosin staining showed some severe defects: coloboma, smaller lens, and smaller volume of eyes. In some cases, there were failures to fully develop eye structures. In these embryonic eye defects, the thickness of retinal was significantly thinner than that in the nondiabetic group. Our hypothesis is that maternal diabetes induces embryonic eye malformations by suppressing autophagy. Maternal diabetes increased cell apoptosis and suppressed cell proliferation in retinal of the eye. We found that autophagy-related genes (ATGs) was robustly expressed in the lens and retina of the eyes of mouse embryos and was suppressed by maternal diabetes. Maternal diabetes suppressed the expression of pax6, a key gene in visual system development. Taken together, our data demonstrates that autophagy is important for eye development and maternal diabetes induces embryonic eye defects by inhibiting autophagy.

Disclosure

W. Lu: None. P. Yang: None.

Funding

National Institutes of Health (R01DK083243, R01DK101972, R01HL131737, R01HL134368, R01DK103024)
1338-P: Second Heart Field-Specific Deletion of Dnmt3a and Dnmt3b Ameliorates Maternal Diabetes-Cardiac Septation Defects, but Increases Hypoplastic Left Heart Syndrome
Authors: YE FEI , YANG PEIXIN
Published: June 2020

Maternal diabetes is a common risk factor for congenital heart defects (CHDs) in infants, suggesting hyperglycemia disrupts specific morphogenesis events in the embryonic heart. DNA methylation plays important roles in embryonic development. Our previous study demonstrated that global DNA methylation is significantly increased in early stage embryos from diabetic pregnancy compared to that from nondiabetic pregnancy. Isl1 marks the second heart field cardiac progenitor population, which contribute to outflow tract, right ventricle, and much of the atria. We hypothesize that conditional knockout of Dnmt3a and Dnmt3b will ameliorate maternal diabetes-induced CHDs derived from the defects of the second heart field. We used the well-established type 1 diabetic embryopathy mouse model, in which diabetes was induced by streptozotocin for our in vivo studies. To determine if conditional deletion of Dnmt3a and/or Dnmt3b in the second heart field progenitors ameliorates specific CHDs in diabetic pregnancy, we induced diabetic embryopathy in Dnmt3af/f/3bf/f female mice, which bred with Dnmt3af/w/Dnmt3bf/w;Isl1-Cre male mice, embryos were harvested at embryonic day 12.5 (E12.5) to determine DNA methylation activity and at E17.5 for the presence of CHDs. Embryos of diabetic dams had a 50% CHDs, double deletion of Dnmt3a and Dnmt3b significantly ameliorated CHDs derived from the defect of the second heart field from 27% to 0%, while dramatically enhanced CHD derived from the first heart field incidence 23% to 50%, mainly Hypoplastic left heart syndrome (HLHS). Our study demonstrates that DNA methylation plays an important role in the regulation of diabetic pregnancies. CHD of SHF are rescued by dKO of Dnmt3a/3b, while CHD of SHF enhanced. This suggests that targeting of DNA methylation may be a viable strategy for suppression of congenital heart defects in fetuses of diabetic pregnancies.

Disclosure

F. Ye: None. P. Yang: None.

Funding

National Institutes of Health (1R01134368)
1345-P: Long-Term Follow-Up of Children with Intrauterine Glyburide Exposure
Authors: RODENSTEIN MARISSA S. , BIANCO MONICA E. , RAMCHAL MAEGAN , SILTON REBECCA L. , MURIAS MICHAEL , JOSEFSON JAMI L.
Published: June 2020

Outcome data in children exposed to glyburide for maternal treatment of gestational diabetes mellitus (GDM) is lacking. Insulin is the standard of care for GDM medical management, yet glyburide use is increasing and this medication crosses the placenta. The study objective was to evaluate physical and neurodevelopmental outcomes of 5-10 year old children born to GDM mothers treated with glyburide or insulin. Children had anthropometric measures including body composition with air displacement plethysmography, and underwent a neurodevelopmental assessment with performance-based tests to evaluate executive functions of working memory and inhibition. Analysis included paired t-tests, chi-square test, and multivariate analysis of variance (MANOVA). Participants, n=51, 25 glyburide-exposed, 26 insulin-exposed were age and sex-matched between groups. Mean age was 7.7 years and 45% were female. Ethnicity and maternal education differed between groups: glyburide-exposed were primarily Hispanic (80%) and had lower maternal education level compared to insulin-exposed (50% Hispanic). Anthropometric means were: BMI 18.8 kg/m2 (sd 5.1), BMI%ile 67.7% (32.3), waist circumference z-score 0.6 (1.1), body fat 21.9% (11.6), triceps z-score 0.8 (1.2), subscapular z-score 1.1 (1.1), sum of 3 skinfolds, triceps, subscapular, iliac crest 39.3 mm (26.0), systolic bp 101 (10.1), diastolic bp 63 (8.2). Among participants, 17.6% had an overweight BMI and 23.5% had an obese BMI. No significant differences were identified in these measures or rates of overweight/obese BMI between groups. A MANOVA with maternal education as a covariate showed that the glyburide-exposed group had significantly lower scores on a visual-spatial working memory test compared to the insulin-exposed group (p=0.03). No differences were observed on an inhibition test.

In summary, children with intrauterine glyburide exposure had reduced spatial working memory yet similar physical measurements compared to children with insulin exposure.

Disclosure

M.S. Rodenstein: None. M.E. Bianco: None. M. Ramchal: None. R.L. Silton: None. M. Murias: None. J.L. Josefson: None.

Funding

Evergreen Invitational and Institute for Innovations in Developmental Sciences
1346-P: Glyburide vs. Insulin for the Treatment of Gestational Diabetes in an Integrated Health Care System
Authors: HEDDERSON MONIQUE M. , FERRARA ASSIAMIRA , REGENSTEIN ANNE , NEUGEBAUER ROMAIN
Published: June 2020

Almost 30% of women with gestational diabetes (GDM) fail to achieve glycemic control with lifestyle modification alone and require medication treatment. Currently, the American Diabetes Association recommends insulin as the first line medication treatment for women with GDM. However, oral agents have several advantages including ease of use and acceptance among patients. The safety and efficacy of glyburide for the treatment of GDM remains controversial. We aimed to compare the effectiveness of glyburide and insulin in improving perinatal outcomes. We used rigorous causal inference methods with time-varying exposures and machine learning to evaluate perinatal outcomes of exposure to glyburide versus insulin during pregnancy in a retrospective cohort study of 11,321 women diagnosed with GDM who required medication treatment to achieve glycemic control in Kaiser Permanente Northern California from 2007-2017. For each outcome, Inverse Probability Weighting (IPW) estimation was used to separately compare several perinatal outcomes between glyburide versus insulin initiators. This approach combined with Super Learning for propensity score estimation can account for both baseline and time-dependent confounding in per protocol analyses to evaluate the effect of continuous exposure to the same therapy. Women who used glyburide versus insulin had similar rates of macrosomia, hypoglycemia, hyperbilirubinemia, and cesarean delivery; significantly lower rates of a NICU admission (risk difference -0.03 [95%CI:-0.06;-0.002]) or respiratory distress syndrome (-0.02 [-0.04;-0.001]) and suggestive higher rates of an appropriately sized for gestational age infant (0.04 [-0.002;0.08]) after adjusting for baseline and time-varying covariates. Using data from a real-world clinical setting we find no evidence to suggest that adverse outcomes were higher among glyburide users compared with insulin users.

Disclosure

M.M. Hedderson: None. A. Ferrara: None. A. Regenstein: None. R. Neugebauer: None.

Funding

Permanente Medical Group
1348-P: Social Adaptability Index and Pregnancy Outcomes in Women with Diabetes during Pregnancy
Authors: PALATNIK ANNA , THAKKAR MADHULI Y. , WALKER REBEKAH J. , EGEDE LEONARD E.
Published: June 2020

Objective: The social adaptability index (SAI) is a composite indicator capturing an individual’s social adaptability within society and socioeconomic status in order to predict overall health outcomes. The objective of this analysis was to examine whether the SAI is an independent risk factor for adverse pregnancy outcomes in women whose pregnancy is complicated by diabetes.

Methods: Data from the 2011-2017 National Survey of Family Growth were analyzed using cross-sectional methodology. Women with a singleton gestation age 18-44 were included. Maternal diabetes was defined as either presence of pre-gestational diabetes or diagnosis of gestational diabetes. The SAI was developed from the following maternal variables: education level, employment status, income, marital status and substance abuse. Higher score indicates lower risk. Multivariable logistic regression models were run to assess the association between SAI and pregnancy outcomes associated with diabetes, including cesarean delivery, macrosomia (birthweight >4000g) and preterm delivery (<37 weeks), stratified by maternal diabetes. All analyses were weighted.

Results: A total of 18,304 women were included in the analysis, with 1,965 (10.7%) having diabetes during pregnancy. The SAI was lower in women with diabetes during pregnancy, compared to controls (6.7±0.2 vs. 7.2±0.1, p<0.001). In the univariable analysis, the SAI had a significant association with the outcomes of preterm delivery (OR=0.94, p<0.001) and was not significantly associated with cesarean delivery or macrosomia. In adjusted multivariable analysis, controlling for maternal race/ethnicity, insurance status, body mass index, age and partner support of the index pregnancy, SAI remained to be independently associated with preterm delivery among women with diabetes during pregnancy (aOR=0.83, 95% CI 0.77-0.94).

Conclusion: Among women with diabetes during pregnancy, a higher SAI is independently associated with a lower risk of preterm delivery.

Disclosure

A. Palatnik: None. M.Y. Thakkar: None. R.J. Walker: None. L.E. Egede: None.
1351-P: Association of Muscle/Fat Mass Ratio in the First Trimester with Gestational Diabetes Mellitus in Chinese Subjects
Authors: LI PING , LIN SHUO , FAN JIANHUI , ZENG LONGYI
Published: June 2020

This study aims to evaluate the association of muscle/fat mass ratio in the first trimester with gestational diabetes mellitus (GDM) in Chinese subjects. A total of 3011 pregnant women were recruited from our hospital, Guangzhou, China, from Jan 2017 to Dec 2017. The muscle/fat mass ratio (< 13+6 weeks’ gestation) and 75-g OGTT (24-28 weeks’ gestation) were measured in each subject. The muscle/fat mass ratio was assessed by bioelectrical impedance analysis. GDM was diagnosed according the IADPSG guideline (2010). All subjects had average age 29 years (interquartile range:27-32 years), mean pregestational body mass index 20.7±2.6kg/m2, muscle/fat mass ratio 2.64±0.65. Five hundred and forty eight subjects (17.9%) were diagnosed as GDM. The prevalence of GDM were 25.9%, 20.4%, 14.1%, and 11.3% among subjects with muscle/fat mass ratio in 1st quartile (≤2.15), 2nd quartile (2.16-2.61), 3rd quartile (2.62-3.08), and 4th quartile(≥3.09), respectively. The prevalence of GDM decreased while muscle/fat mass ratio increased. The area under ROC curve was 0.612 (0.595-0.630) for the muscle/fat mass ratio in predicting GDM (P<0.0001) and the threshold of 2.59 yielded the highest combination of sensitivity (63.2%) and specificity (55.7%). This study suggested the muscle/fat mass ratio in the first trimester may be used as an index to predict GDM in Chinese subjects.

Disclosure

P. Li: None. S. Lin: None. J. Fan: None. L. Zeng: None.

Funding

Science and Technology Planning Project of Guangdong Province (2017A020215026); Medical Scientific Research Foundation of Guangdong Province (A2017314)
1356-P: Can First-Trimester Glycated Hemoglobin Predict Gestational Diabetes Diagnosis?
Authors: FARO FERNANDA , RAMALHO RODRIGO F. , PRIETO WESLEY H. , PEREIRA MARIANA , SALLES JOAO E. , ROSA PEDRO S. , TELES MILENA G. , TAVARES RUSSO PEDRO DE SÁ
Published: June 2020

Background: diagnostic criteria for gestational diabetes mellitus (GDM) have been controversial. Although Oral Glucose Tolerant Test (OGTT) is generally proposed, it requires an extensive preparation, is uncomfortable and lacks reproducibility. In contrast, Glycated Hemoglobin test (A1C) is more convenient and accurate, however, its use for GDM diagnosis has not been recommended yet. The aim of this study was to evaluate whether a first trimester A1C predicts an abnormal second trimester OGTT.

Methods: This was an observational retrospective study that included Brazilian women screened with A1C until 14 weeks of gestation between January 2009 and March 2019. Data were collected from a laboratory center. A1C was measured by high-performance liquid chromatography. Exclusion criteria were first trimester glycemia ≥ 92 mg/dL or A1C ≥ 6.5% and use of antidiabetic drugs or insulin. Primary outcome was association between A1C value and diagnosis of GDM, according to 75g or 100g OGTT, as defined by American Diabetes Association (ADA).

Results: a total of 373 women were included, 106 were diagnosed with GDM by OGTT. General characteristics of the groups with and without GDM were, respectively: mean age 35.1 ±3.5 and 34.1 ± 3.5 years, mean Body Mass Index (BMI) 24.2 ± 4.8 and 25.4 ± 3.7 Kg/m², mean first trimester glycemia 81.8 ± 5.1 and 81.2 ± 5.2 mg/dL and mean A1C 5.1 ± 0.3 and 5.0 ± 0.3%. OGTT values in the GDM group were: fasting 80.1 ± 6.6, 1st hour 171.6 ± 25.7 and 2nd hour 152 ± 27.1. For women without GDM, the results were: fasting 78.1 ± 5.7, 1st h 143.4 ± 29.5 and 2nd h 123.1 ± 28.3. There was no significant statistical difference of A1C values between groups with or without GDM (P=0.26, Wilcoxon test).

Conclusion: A1C could not predict women who would develop GDM in this population. Ethnicity and different criteria for OGTT interpretation may have contributed for these findings. The limitations of this study were lack of data about previous history of GDM, family history of diabetes and weight gain during pregnancy.

Disclosure

F. Faro: None. R.F. Ramalho: None. W.H. Prieto: None. M. Pereira: None. J.E. Salles: Board Member; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Lilly Diabetes, Novo Nordisk Inc. P.S. Rosa: None. M.G. Teles: None. P. de Sá Tavares Russo: None.
1361-P: Rapid Development of Hypoglycemia and Hypoglycemia Unawareness in a Pregnant Patient with Cystic Fibrosis Related Diabetes (CFRD) on a Basal-Predominant Insulin Regimen
Authors: LITVIN MARINA
Published: June 2020

Background: Patients with CF are at risk for gestational diabetes/CFRD, which is challenging to treat. Traditional insulin regiments with fixed prandial and high basal insulin increase hypoglycemia.

Case: A 23 year old woman with CF was diagnosed with gestational diabetes and started on NPH 18 units qAM/8 at HS, and Lispro 6 units TID. She had a blood glucose of 36 mg/dL in clinic, with which she was asymptomatic, suggesting hypoglycemia unawareness. NPH was discontinued and a 1:12 carb ratio was started, reducing glycemic excursions and hypoglycemia.

Discussion: Patient rapidly developed hypoglycemia on a basal-predominant regimen. By decreasing basal insulin and targeting prandial insulin coverage we more closely approximated CFRD physiology, improving glycemic excursions and hypoglycemia.

Conclusion: Due to physiology of CFRD, basal-predominant regiments may cause fasting hypoglycemia and post-prandial hyperglycemia. Providers should be aware that patients with gestational diabetes/CFRD have minimal basal insulin requirements and glycemic control should focus on flexible prandial coverage of their high in carbohydrates diet.

Disclosure

M. Litvin: None.
137-OR: Trends in Lipid Levels Relative to Lipid-Lowering Drug Use among Danish Type 2 Diabetes Subjects
Authors: AMADID HANAN , DUNBAR MARIA BEKKER-NIELSEN , RØNN PERNILLE F. , KNUDSEN JAKOB S. , CARSTENSEN BENDIX , PERSSON FREDERIK , JØRGENSEN MARIT E.
Published: June 2020

Background: Lipid-lowering treatment is crucial in preventing cardiovascular disease in type 2 diabetes subjects. It is unknown how well treatment guidelines translate into clinical practice. We examined measured lipid levels in relation to use of lipid-lowering drugs among type 2 diabetes subjects in Denmark from 2010 to 2017.

Methods: The study population consisted of 404,389 subjects with type 2 diabetes living in Denmark between 1996 and 2017 identified using the Danish Diabetes Register. Redemptions of prescribed lipid-lowering drugs were ascertained from the nationwide Register of Medicinal Products Statistics. Data on lipid levels was sourced from the National Laboratory Database containing detailed information on laboratory measurements at major clinical laboratories since 2010. A drug-exposure function was developed and applied to examine follow-up of lipid-lowering drug coverage at any given time based on the redeemed amount and dose of lipid-lowering drugs. Annual mean lipid levels were obtained by calculating the mean lipid measurement value per subject, per calendar year, and per lipid type. Proportions of subjects within LDL thresholds were calculated according to thresholds defined by 2019 European Society of Cardiology dyslipidemia guidelines.

Results: In total, 64% of subjects redeemed at least two prescriptions of lipid-lowering drugs during the study period. A decline in levels of total-cholesterol and LDL was observed in the years from 2010 to 2017 in users and non-users of lipid-lowering drugs. Annual mean LDL levels were lower among lipid-lowering drug users compared with non-users (in 2017: 1.84 and 2.57 mmol/L, respectively). A greater fraction of lipid-lowering drug users achieved the LDL goal of <1.8 mmol/L compared with non-lipid-lowering drug users (in 2017: 51.7% and 19%, respectively).

Conclusions: Lipid-lowering drug use and LDL levels are far from optimal in the Danish type 2 diabetes population and constitute a large potential for improvement.

Disclosure

H. Amadid: None. M. Bekker-Nielsen Dunbar: None. P.F. Rønn: Research Support; Self; Amgen, Danish Diabetes Academy. Stock/Shareholder; Spouse/Partner; Novo Nordisk A/S. J.S. Knudsen: None. B. Carstensen: Stock/Shareholder; Self; Novo Nordisk A/S. F. Persson: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Novo Nordisk A/S. Research Support; Self; Amgen, AstraZeneca, Novo Nordisk A/S. Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Merck Sharp & Dohme Corp., Mundipharma International, Novo Nordisk A/S. M.E. Jørgensen: Research Support; Self; Amgen, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Sanofi-Aventis. Stock/Shareholder; Self; Novo Nordisk A/S.

Funding

Amgen Inc.
1371-P: Effect of Omega-3 Supplementation in Pregnant Women with Obesity on Offspring Growth and Body Composition
Authors: MONTHE-DREZE CARMEN , ENSTAD SAMANTHA , SEN SARBATTAMA , DE MOUZON SYLVIE HAUGUEL , CATALANO PATRICK
Published: June 2020

Background: Maternal obesity is a growing health burden associated with adverse cardiometabolic health outcomes in the offspring. Higher omega-3 polyunsaturated fatty acids (n3 PUFA) status in pregnancy is associated with higher birthweight. However, the effect of n3 supplementation, specifically in pregnant women with overweight and obesity, on fetal growth and adiposity has not been explored.

Objective: To examine the effect of n-3 supplementation in overweight and obese pregnancy on offspring anthropometry and body composition.

Methods: A secondary analysis of a double-blind randomized controlled trial of pregnant women with pre-pregnancy BMI≥ 25 randomized to daily DHA plus EPA (2 g/d) or placebo (wheat germ oil) from 10-16 weeks gestation to delivery. We compared the following newborn outcomes i) birthweight z-score derived from anthropometrics, ii) % adiposity, fat-mass and fat-free mass using PeaPodTM and skin fold thickness measurement, by randomization group using Student T-test and Wilcoxon rank-sum for bivariate analyses, and linear regression adjusting for gestational age (GA) and sex.

Results: For the 46 mother-child dyads with complete exposure and outcome data, median (IQR) maternal BMI was 30.2 (27.9, 35.5) kg/m2. Gestation was longer in the treatment vs. placebo group (40 (38.6,40.1) vs. 38.9 (38.0,39.4) weeks, p=0.009). Sex- and GA- specific birthweight z-score (-0.2 ± 0.7 vs. -0.6 ± 0.6-unit, p =0.035), but not birth length z-score (-0.3 ± 0.7 vs. -0.6 ± 0.6-unit, p =0.21), was higher in the treatment vs. placebo group. N-3 treatment was associated with higher fat-free mass (β 131.4g higher for treatment vs. control, 95% CI 3.1, 259.7) by skinfolds but not %bodyfat or fat mass at birth.

Conclusion: n-3 supplementation early in pregnancy in women with obesity increased birthweight, but this results from increased fetal lean mass accrual. Future investigations should explore the long-term impact of this intervention on offspring cardiometabolic health.

Disclosure

C. Monthe-Dreze: None. S. Enstad: None. S. Sen: None. S. Hauguel de Mouzon: None. P. Catalano: None.

Funding

National Institutes of Health (RHD057236); Case Western Reserve University/Cleveland Clinic Clinical and Translational Science Award (UL1RR024989)
1374-P: Association between Number of Abnormal Glucose Values and Severity of Fasting Plasma Glucose in IADPSG Criteria and Pregnancy Outcomes in Pregnant Women in South India
Authors: BALAJI BHAVADHARINI , ANJANA RANJIT MOHAN , DEEPA MOHAN , RAJENDRA PRADEEPA , RAM UMA , SARAVANAN PONNUSAMY , MOHAN VISWANATHAN
Published: June 2020

Background: International Association for Diabetes in Pregnancy Study Group (IADPSG) criteria recommends single step OGTT for diagnosis of gestational diabetes mellitus (GDM). The main concerns with IADPSG criteria are i) only one abnormal value is required and ii) fasting plasma glucose (FPG) cut point is too low. We report on association between number of abnormal glucose values and levels of FPG with pregnancy outcomes.

Methods: Pregnant women (n=1,044) were screened for GDM using IADPSG criteria. OGTT’s were classified based on the number of abnormal glucose values (any one value vs. more than one value), and FPG values (<92mg/dl,92-100mg/dl,>100mg/dl) and correlated with pregnancy outcomes. Odds Ratios were adjusted for age, BMI, family history of diabetes, history of GDM, birth weight, gestational week at diagnosis and delivery. For macrosomia, birth weight was not included.

Results: For caesarean sections, risk was higher in women with any one abnormal glucose value (OR:1.53;95%CI:1.08-2.16) and it increased further in those with more than one abnormal value (OR:1.58;95%CI:0.99-2.52), compared to women with normal glucose tolerance (NGT). Risk of caesarean section was also higher in women with FPG (92-100mg/dl) (OR:1.36;95%CI:0.86-2.15) and even higher in women with FPG >100mg/dl (OR:1.88;95%CI:1.08-3.29) when compared to FPG <92mg/dl. For macrosomia, women with any one abnormal value (OR:1.49;95%CI:0.96-2.33) and with more than one abnormal value (OR:1.07;95%CI:0.57-2.03) had higher risk compared to women with NGT. Risk of macrosomia was also higher in women who had FPG 92-100mg/dl (OR:1.04;95%CI:0.56-1.95) and FPG >100mg/dl (OR:1.61;95%CI:0.83-3.10) compared to FPG<92mg/dl.

Conclusion: The risk for poor pregnancy outcomes starts in those with one abnormal value in the OGTT or with FPG >92mg/dl and the risk further increases with higher abnormal values.

Disclosure

B. Balaji: None. R. Anjana: None. M. Deepa: None. P. Rajendra: None. U. Ram: None. P. Saravanan: None. V. Mohan: None.
1378-P: Are Nutritional Habits Equally Associated with the Risk of Gestational Diabetes and Gestational Glucose Intolerance?
Authors: YABACI MERVE , SATMAN ILHAN , IDIZ CEMILE , TURKER FULYA , YUKSEL ATIL , OMER BEYHAN , DEMIREL BIRSEN , OZER EMEL
Published: June 2020

Objective: The aim of this study is to investigate the relationships between the nutritional characteristics of pregnant women and the risk of gestational diabetes mellitus (GDM) and Gestational Glucose Intolerance (GGIT).

Materials and Method: Women were investigated for GDM during the 24th to 28th weeks of pregnancy. According to the two-step diagnostic approach, women with normal glucose tolerance (normal), those with only 1 high glucose (GGIT) and those with at least 2 high values (GDM) in OGTT were included in the study. There was 60 pregnant women in each group (mean age 31.6±5.4; range 19-46 years). Demographic and clinical characteristics of the participants were questioned and a 3-day food consumptions record were evaluated with BEBIS program.

Results: The mean weight, BMI and daily fiber intake in GDM group were significantly higher than the normal group. In the GDM and GGIT groups, the mean age, weight, daily carbohydrate (CHO) and protein intakes, and family history of diabetes were higher than those with normal group. Moreover, in the GDM group, daily fat intake was also significantly higher than the normal and GGIT groups. According to the separate models of logistic regression analysis; the age; daily protein, CHO and fat consumptions; having the first pregnancy and higher pre-pregnancy BMI (>25 kg/m2) were associated with increased likelihood of GDM. Similarly, the age, daily protein consumption, history of giving birth to a macrosomic baby and current smoking were positively linked with the risk of GGIT.

Conclusion: Women’s nutritional habits (excessive CHO, fat and especially protein consumptions), phenotypic characteristics, family history of diabetes and poor obstetric history are similarly related to the risk of developing GDM and GGIT. Our results showed that in all women, particularly in those at high-risk for GDM who are planning pregnancy, a special attention should be given to general health and balanced diet, starting from pre-pregnancy.

Disclosure

M. Yabaci: None. I. Satman: None. C. Idiz: None. F. Turker: None. A. Yuksel: None. B. Omer: None. B. Demirel: None. E. Ozer: None.

Funding

Istanbul University
1379-P: Insufficient and Excessive Gestational Weight Gain across Midpregnancy to Delivery Are Associated with Multiple Adverse Maternal–Infant Outcomes: From the Camden Study
Authors: CHEN XINHUA , SCHOLL THERESA O.
Published: June 2020

Retrospective studies on the relationship of gestational weight gain (GWG) with pregnancy outcomes such as preterm delivery and preeclampsia are inconsistent. We examined the association of longitudinally assessed GWG above (excessive) and below (insufficient) the IOM guidelines with maternal-infant outcomes from the Camden study - a large prospective cohort in young pregnant women (n=2,444, African-American 38%, Hispanic 45%, Caucasian 17%, age 22 ± 5.2 yr., BMI 26 ± 6 kg/m2). All of the analyses were multivariable adjusted. Excessive GWG was 48%, 53%, 56% and 58% in all pregnancies and insufficient GWG was 25%, 27%, 23%, 21% assessed at gestational week of 24, 28, 32 and at delivery, respectively. At delivery, insufficient GWG was associated with increased risk of preterm delivery (<37 weeks’ gestation) (AOR 2.14, 95% CI 1.55-2.95) and small for gestational age (SGA, AOR 1.64, 95% CI 1.27-2.11). Excessive GWG was associated with higher risk of preeclampsia (AOR 1.56, 95% CI 1.08-2.27), large for gestational age (LGA, AOR 2.49, 95% CI 1.58-3.94) and a decreased risk of SGA (AOR 0.49, 95% CI 0.33-0.73). There was no significant difference in GDM. Similar results between insufficient or excessive GWG and risk of LGA, preeclampsia and SGA were observed in GWG assessed at week 24, 28, and 32, but no significant difference for preterm delivery. Significant linear trends among insufficient, adequate and excessive GWG at delivery with infant birth weight, birth length, chest and head circumferences were observed (p<0.001 to p<0.0001 for each). The relationship persisted and found as early as gestational week 24. Insufficient or excessive GWG across mid pregnancy to delivery are significantly associated with increased risk of several adverse maternal-infant outcomes. Maintaining adequate GWG from early pregnancy are important to improve the prognosis of maternal infant outcomes.

Disclosure

X. Chen: None. T.O. Scholl: None.

Funding

National Institutes of Health (R01MD007828)
1380-P: Pregravid A1C and Glucose Measurements to Rule Out Gestational Diabetes and Reduce the Need for Oral Glucose Tolerance Testing in Pregnancy
Authors: RETNAKARAN RAVI , SHAH BAIJU R.
Published: June 2020

The recommendation of universal screening for gestational diabetes (GDM) by oral glucose tolerance test (OGTT) in pregnancy may pose a resource challenge for healthcare systems. In light of growing recognition that women who develop GDM have chronic metabolic dysfunction that predates their pregnancy, we hypothesized that pre-gravid measurement of A1c and glucose may provide the capacity to rule out GDM in low-risk women and thereby reduce the overall OGTT burden in pregnancy. To test this hypothesis, we identified all women in Ontario, Canada, with singleton live-birth pregnancies between January 2008 and December 2015 (n=1,001,006, of which 47,180 had GDM), and created derivation and validation cohorts (each n=500,503). In the derivation cohort, pre-gravid A1c (OR=9.72, 95%CI 8.76-10.79), fasting glucose (OR=3.32, 95%CI 3.13-3.51) and random glucose (OR=1.70, 95%CI 1.65-1.75) each predicted subsequent GDM. Area-under-receiver-operating-characteristic curve (AROC) was higher for A1c (0.684) than for fasting glucose (0.647) or random glucose (0.625). Test characteristics revealed that the negative predictive value (NPV) for ruling out GDM was optimized (NPV=98.7%) at pre-gravid A1c ≤4.3%. However, when evaluated in the validation cohort, this pre-gravid A1c threshold would only reduce the need for antepartum OGTT in 0.11% of women. Conversely, if test sensitivity for predicting GDM were set at 95.1% in the derivation cohort, the resultant threshold of pre-gravid A1c ≤5.0% would reduce the need for antepartum OGTT in 7.2% of women but at the cost of missing 2.5% of GDM diagnoses in the validation cohort.

In conclusion, pre-gravid A1c and glucose levels can predict a woman’s future risk of GDM. However, their test characteristics are clinically not acceptable for reducing the need for GDM screening by OGTT in pregnancy.

Disclosure

R. Retnakaran: Consultant; Self; Eli Lilly and Company, Novo Nordisk Inc., Sanofi. Research Support; Self; Boehringer Ingelheim International GmbH, Novo Nordisk Inc. B.R. Shah: None.
1381-P: Association of Implementation of a Comprehensive Peripregnancy Management Plan with Pregnancy Outcomes among Chinese Pregnant Women with Type 1 Diabetes
Authors: ZHENG XUEYING , YANG DAIZHI , LUO SIHUI , YAN JINHUA , WENG JIANPING
Published: June 2020

Background: Risk of adverse pregnancy outcomes (APOs) remains high among pregnant women with type 1 diabetes (T1D). We aimed to investigate whether implementation of a comprehensive evidence-based peri-pregnancy management plan was associated with lower rates of APOs among these women.

Methods: This is a nationwide observational cohort study. A comprehensive evidence-based peri-pregnancy management plan for T1D was launched in 11 centers from 8 cities in China. During 2015-2017 we prospectively collected data from all pregnant women with T1D attending these centers. We compared pregnancy outcomes in this prospective cohort (PC) with two comparison populations. These populations were constructed by compiling data from medical records: the first was a retrospective cohort (RC) of pregnant women with T1D attending the same centers during 2012-2014 before the management plan, and the second was a comparison cohort (CC) of pregnant women with T1D receiving routine care during 2015-2017 in the comparison centers. The comparison centers were another 11 centers from 7 cities with matched socio-economic variables and medical facilities. The main outcome was severe APO comprising maternal mortality, neonatal death, congenital malformation(s), miscarriage in the 2nd trimester, and stillbirth.

Results: We included a PC of 133 pregnant women with TID who received the comprehensive management during 2015-2017; a RC of 153 TID pregnancies out of 137544 pregnancies during 2012-2014; and a CC of 116 TID pregnancies out of 165493 pregnancies during 2015-2017. The rate of severe APO was significantly lower in the PC (6.02%) than either the RC (18.30%, adjusted odds ratio[aOR] 0.31, 95% CI 0.13-0.74, P<0.01) or the CC (25.00%, aOR 0.22, 95% CI 0.09-0.52, P<0.001).

Conclusions: Implementation of the comprehensive evidence-based peri-pregnancy management plan is associated with lower risk of APOs among Chinese pregnant women with T1D.

Disclosure

X. Zheng: None. D. Yang: None. S. Luo: None. J. Yan: None. J. Weng: None.

Funding

National Health and Family Planning Commission of the People’s Republic of China; Foundation for Public Welfare Industry Research Project (201502011); World Diabetes Foundation (WDF14-921)
139-OR: Superior Effect of 1-Year Treatment with GLP-1 Receptor Agonist and Exercise on Weight Loss Maintenance and Body Composition after a Very Low-Calorie Diet: The S-LITE Randomized Trial
Authors: JANUS CHARLOTTE , LUNDGREN JULIE R. , JENSEN SIMON , OLSEN LISA M. , JUHL CHRISTIAN RIMER , BLOND MARTIN B. , CHRISTENSEN RASMUS M. , BOJSEN-MOLLER KIRSTINE N. , SVANE MARIA S. , BANDHOLM THOMAS , JENSEN JENS-ERIK B. , STALLKNECHT BENTE , HOLST JENS J. , MADSBAD STEN , TOREKOV SIGNE S.
Published: June 2020

Background: Weight loss decreases energy expenditure and increases appetite, leading to weight regain. Energy expenditure can be targeted with exercise, and appetite with the glucagon-like peptide-1 (GLP-1) receptor agonist, liraglutide.The objective was to investigate 1-year weight loss maintenance and change in body composition with liraglutide, exercise, and the combination in individuals with obesity after a very low-calorie diet (VLCD).

Methods: Double-blinded, randomized placebo-controlled trial. Following 8-weeks of VLCD (800 kcal/day), inducing a body weight loss of ≥ 5%, the participants were randomized to 1-year of treatment with 1) liraglutide 3.0 mg/day (LIRA), 2) exercise 150 min/week + placebo (EX), 3) exercise 150 min/week + liraglutide 3.0 mg/day (LIRA + EX), or 4) placebo (PLA).

Results: Participants with obesity were included (n = 215, 64% women, age 42 years (IQR 30.7 to 51.9), BMI 36.6 kg/m2 (34.5 to 39.2)). See Table 1 for all results.

Conclusion: The combination of liraglutide and exercise was superior to placebo and exercise alone, and numerically better to liraglutide, in weight loss maintenance and further weight reduction. Fat percentage loss with the combination treatment was superior to liraglutide and exercise alone, supporting the combined treatment for healthy weight loss maintenance.

Disclosure

C. Janus: Research Support; Spouse/Partner; Mercodia, Novo Nordisk A/S. Research Support; Self; Novo Nordisk Foundation. Research Support; Spouse/Partner; Novo Nordisk Foundation. Speaker’s Bureau; Spouse/Partner; Merck Sharp & Dohme Corp. J.R. Lundgren: None. S. Jensen: None. L.M. Olsen: None. C. Juhl: None. M.B. Blond: None. R.M. Christensen: None. K.N. Bojsen-Moller: None. M.S. Svane: None. T. Bandholm: Employee; Spouse/Partner; Novo Nordisk A/S. Stock/Shareholder; Spouse/Partner; Novo Nordisk A/S. J.B. Jensen: None. B. Stallknecht: None. J.J. Holst: Advisory Panel; Self; AstraZeneca, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Zealand Pharma A/S. Other Relationship; Spouse/Partner; Antag Therapeutics. S. Madsbad: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi-Aventis. Research Support; Self; Boehringer Ingelheim International GmbH, Novo Nordisk A/S. Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Novo Nordisk A/S. S.S. Torekov: Research Support; Self; Novo Nordisk Inc.

Funding

Novo Nordisk Foundation (NNF16OC0019968); Novo Nordisk Center for Metabolic Research; Helsefonden
1391-P: Geographic Disparities in the Receipt of Reproductive Health Care among Young Women with Diabetes
Authors: WISK LAUREN E. , NOURBAKHSH POURANDOKHT S. , KRANSDORF LISA N.
Published: June 2020

We sought to examine disparities in realized access to guideline-recommended reproductive health services (e.g., preconception counseling) for young women with type 1 or 2 diabetes mellitus (DM) compared to peers without DM and to determine if/how such disparities varied by geography. We included over 1 million young women (ages 13-39) both with and without DM, using over 2 million person-years of data from Virginia’s All-Payer Claims Data (covering 40% of commercially and 95% of publicly insured people in the state) from 2016-2018. Multivariate regression modeled receipt of reproductive care by DM status and county of residence, adjusting for age, payer, race/ethnicity, and year. We identified 2.4 million visits for reproductive care (mean of 1.17 visits per person per year), including 657K for routine gynecological exams, 824K for contraception management, and 1.05M for STI screening and treatment. Compared to women with DM, those without DM had higher odds of receiving routine gynecological exams (OR:1.20, 95%CI: 1.18-1.22) and visits for contraceptive management (OR:1.05, 95%CI: 1.04-1.07); but among those receiving care, women with DM averaged slightly more visit per year (gynecological exam β=0.06, p<0.01; contraception management β=0.09, p<0.01). County-specific prevalence of DM ranged from 5% to 17% and DM prevalence was higher in smaller counties (pop<20K) compared to medium (20-100K) or large counties (pop>100K). Overall, there were no differences in receipt of reproductive care by DM status in large counties but disparities manifested for those living in medium and smaller counties. Differences by payer and race/ethnicity were also identified. Given the acute health threats for women with DM who do not receive appropriate preventive reproductive services, observed disparities are worrisome. As disparities were exacerbated in counties with the highest prevalence of DM, more work needs to be done to ensure equitable access to care in areas that have a higher disease burden.

Disclosure

L.E. Wisk: None. P.S. Nourbakhsh: None. L.N. Kransdorf: None.

Funding

National Institute of Diabetes and Digestive and Kidney Diseases (1K01DK116932-01 to L.E.W.); University of California, Los Angeles (to L.E.W.)
1395-P: Practical Triage in Women with Gestational Diabetes According to Their Risk Category for Insulin Therapy
Authors: YAMASHITA HIROSHI , YASUHI ICHIRO , SUGA SACHE , ISOKAWA SATOSHI , FUKUOKA MISAO , KOGA MEGUMI , YAMAGUCHI JUNKO , SUGIMI SO , UMEZAKI YASUSHI , FUKUDA MASASHI , KUSUDA NOBUKO
Published: June 2020

Objective: We investigated efficacy of the risk category system in the triage of patients to insulin therapy in a prospective cohort of women with gestational diabetes (GDM).

Study Design: In a previous retrospective study, we developed a risk category system for insulin therapy (≥20 U/day), in which we found two risk factors including prepregnancy BMI ≥24 and fasting plasma glucose ≥84 mg/dl. In the current study, we investigated the validity of the risk categories for triage to insulin therapy in a new prospective cohort. We included women with GDM diagnosed at 24-32 weeks of gestation according to the IADPSG criteria in a single tertiary perinatal care center between June 2015 and March 2018. After the diagnosis, all patients underwent self-monitoring of blood glucose (SMBG) under nutrition therapy. Insulin therapy was indicated, if SMBG did not achieve 80% of the target glucose values. Multivariate analysis adjusted for confounders were performed to examine the association between risk categories and insulin therapy (≥20 U/day and ≥30 U/day).

Results: Among 240 patients with GDM, 119 (50%) had at least one risk category. Insulin therapy ≥20 U/day and ≥30 U/day was indicated in 86 (35.8%) and 61 (25.4%) patients, respectively. In comparison to women without risk factor, patients with at least one risk factor were significantly at risk for insulin therapy ≥20 and ≥30 U/day with adjusted odds ratio of 3.8 (95%CI 1.7-8.7) and 16.4 (4.9-75.6), PPV of 0.51 and 0.39, and NPV of 0.79 and 0.88, respectively.

Conclusion: With keeping SMBG triage first, the risk category system seems to be effective, especially for the triage of patients without risk categories to less intensive care, because of the high negative predictive value.

Disclosure

H. Yamashita: None. I. Yasuhi: None. S. Suga: None. S. Isokawa: None. M. Fukuoka: None. M. Koga: None. J. Yamaguchi: None. S. Sugimi: None. Y. Umezaki: None. M. Fukuda: None. N. Kusuda: None.
14-LB: Overnight Hypoglycemia Prediction for CGM Users
Authors: WEXLER YDO , GOLDNER DAN , MERCHANT GINA , HIRSCH ASHLEY , HUDDLESTON BRIAN , DACHIS JEFF
Published: June 2020

Background: Knowing at bedtime whether hypoglycemia is likely to occur while sleeping could empower people with diabetes to take preventive action, and could reduce concerns about either being awoken by a continuous glucose monitor (CGM) alarm, or sleeping through the alarm and not being able to respond. We used CGM and self-care data collected in the One Drop app to predict the occurrence of overnight hyperglycemia.

Method: Over 500,000 person-nights of sleep, blood glucose (BG), self-care and contextual data from over 3000 app users with CGMs were pooled and used to train and test a supervised learning model to predict, as of bedtime, the minimum BG value for the coming night. A related model was trained to predict the probability of any BG value being lower than 70 mg/dL during the night.

Results: Test-set predictions of minimum overnight BG value had a mean absolute relative deviation (MARD) of 18.6%. For test-set predictions of the probability of BG lower than 70 mg/dL, the area under the receiver operating characteristic curve (AUC) was 82.2%. About 30% of predictions could be identified at prediction time as having higher accuracy. For those, test-set minimum BG prediction MARD was 15.4%, and probability of BG lower than 70 mg/dL prediction AUC was 87.0%.

Conclusion: Pooling sleep, BG, behavioral and self-care data from thousands of One Drop app users who also use CGM accurately predicts the probability of overnight hypoglycemia. Having such predictions at bedtime can facilitate preventative action, reduce anxiety and improve both sleep and quality of life.

Disclosure

Y. Wexler: Employee; Self; One Drop. D. Goldner: Employee; Self; One Drop. G. Merchant: Employee; Self; One Drop. A. Hirsch: Employee; Self; Informed Data Systems Inc. B. Huddleston: Employee; Self; One Drop. Stock/Shareholder; Self; One Drop. J. Dachis: Board Member; Self; One Drop. Employee; Self; One Drop. Stock/Shareholder; Self; One Drop.
14-OR: Piloting a Video-Based Telehealth Intervention to Reduce Distress and Depression in Parents of Schoolagers with Type 1 Diabetes (T1D)
Authors: PATTON SUSANA R. , MARKER ARWEN M. , MONZON ALEXANDRA , NELSON EVE-LYNN , CLEMENTS MARK A.
Published: June 2020

Parents of school-agers (5-12 years) with T1D play an important role in their child’s T1D management and may be vulnerable to T1D distress and depressive symptoms. We present pilot data from a new group-based video telehealth intervention to reduce depressive symptoms and distress in parents of youth with T1D. Currently, 40 families enrolled in the Cognitive Adaptations to Reduce Emotional Stress (CARES) intervention and 27 completed treatment (both parents participated from two families for N=29; Age = 41.1±6.7 years; Child age = 10.1±1.5 years, 48% girls). CARES uses a cognitive behavioral framework to help parents identify maladaptive thoughts and promote healthy coping through behavioral activation and mindfulness. Parents participated in weekly CARES sessions via a HIPAA-compliant video-based telehealth platform. We measured feasibility and acceptability of 12-session and 8-session versions of the CARES intervention. We used paired t-tests to assess preliminary efficacy based on pre- and post-intervention changes in parent T1D-Distress (PAID-PR) and depressive symptoms (CESD-R), and exploratory changes in child HbA1c. Parents attended 89% of the 12-version sessions (N=14) and 84% of the 8-version sessions (N=15), suggesting adequate feasibility. Parents reported satisfaction with CARES across both versions. In the 12-session version, parents noted significant reductions in CESD-R scores (p=0.046) and T1D-Distress (immediate, p=0.007; theory, p=0.004), whereas in the 8-session version parents only noted reductions in T1D-Distress (immediate, p=0.018; theory, p=0.024). For both the 12- and 8-session versions, we found no difference in child HbA1c (p=0.497 and p=0.146, respectively). Our preliminary data suggest feasibility and efficacy for using video-based telehealth to deliver a group-based intervention to reduce parent distress, but only our 12-session version achieved a significant reduction in parent depression.

Disclosure

S.R. Patton: None. A.M. Marker: None. A. Monzon: None. E. Nelson: None. M.A. Clements: Consultant; Self; Glooko, Inc. Other Relationship; Self; Glooko, Inc.

Funding

National Institute of Diabetes and Digestive and Kidney Diseases (R01DK100779)
1402-P: Impact of Diabetes Duration on Functional and Clinical Status in Older Adults with Type 1 Diabetes
Authors: MUNSHI MEDHA , SLYNE CHRISTINE , SIFRE KAYLA , O’DONNELL RACHEL , ATAKOV-CASTILLO ASTRID , TOSCHI ELENA
Published: June 2020

Background: Adults with type 1 diabetes (T1D) are aging more successfully than ever. However, in this older, heterogeneous population, diabetes duration can vary widely, as people may have been diagnosed many decades ago in early childhood or as recently as late adulthood. There is little information about the impact of diabetes duration on psychosocial factors and functional status as patients with T1D age.

Methods: We evaluated a cohort of older adults (age≥65 years) with T1D. All participants completed surveys regarding demographics, medical history, overall health (Short Form 36; SF-36), hypoglycemia awareness (Clarke Score), and hypoglycemia fear (HFSII). Laboratory A1C was measured, and Montreal Cognitive Assessment (MoCA) was performed to assess cognitive function.

Results: We evaluated 148 older adults, mean age 71 ± 5 years, 55% female, 97% white, mean A1C 7.4 ± 0.9%, mean diabetes duration 39 ± 17 years, with 20% of participants living alone. The participants were divided into tertiles of diabetes duration; ≤30 years (n=48), 31-49 years (n=54) years, and ≥50 years (n=46). Comparison of the shortest and longest tertiles of diabetes duration showed that participants of the group with the shortest duration had significantly less depression (35% vs. 59%; p=0.02), less hypoglycemia unawareness (31% vs. 61%; p=0.008), fewer recent falls in the prior 6 months (5 vs. 12; p=0.05), fewer daily medications (9 vs. 11; p=0.02), and fewer comorbidities (8 vs. 9; p=0.05). Additionally, the overall health survey (SF-36) showed that the group with longer duration reported more difficulty and limitation in daily activities due to physical health. The two groups did not differ in age, A1C, cognitive dysfunction (MoCA score <26), or hypoglycemia fear.

Conclusion: In older adults with T1D, duration of diabetes impacts clinical and functional status, and should be kept in consideration when developing management strategies for maximum safety and success.

Disclosure

M. Munshi: Consultant; Self; Eli Lilly and Company, Sanofi. C. Slyne: None. K. Sifre: None. R. O’Donnell: None. A. Atakov-Castillo: None. E. Toschi: None.

Funding

National Institutes of Health (1DP3DK112214-01)