bluuebunny/crossref_metadata_2025_split huggingface dataset:
1323-P: Frequency of Diabetes Team Contacts in Children and Adolescents Using Insulin Pumps
Authors: BABALOLA FUNMBI , MILLER MICHAEL , ENS ANDREA , GALLEGO PATRICIA H. , STEIN ROBERT I. , CLARSON CHERIL 
Published: June 2020

Type 1 diabetes (T1D) management has become increasingly technologically advanced with the use of insulin pumps, continuous glucose monitoring and diabetes data management software. These technologies are underutilized although there is evidence for improvement in A1C when adults review blood glucose trends with their diabetes team in between clinic visits. The primary objective of this study was to assess if a correlation exists between A1C within target (≤ 7.5%) and frequency of contact of pediatric patients with the diabetes team between clinic visits. Secondary objectives included determining barriers to contact and change in A1C from baseline to end of study. T1D patients using an insulin pump for one year or more were approached to participate. Participants completed a questionnaire to assess diabetes management over the past year. A1C and contact with the diabetes team between clinic visits for insulin adjustments in the past year were collected. One hundred and seventy six participants were enrolled, 46% female, with a mean age of 12.9 (± 3.8) years. Mean duration of T1D was 6.7 (± 3.7) years with a mean duration of pump use of 4.5 (± 3.1) years. Mean A1C at baseline was 8.1% (± 1). One hundred and sixteen (66%) patients contacted the diabetes team for insulin adjustments between clinic visits with a mean of 1.2 (± 1.7) contacts, 90% by e-mail. There was no significant relation between target A1C and frequency of contact (p&gt;0.05). Decreased frequency of contact was associated with increased age (r=0.20, p = 0.01) and longer duration of pump use (r=0.17, p = 0.02). Barriers to contact included being too busy (41%) and technical problems with software (39%).
In conclusion, there was no significant relationship between frequency of contact of pediatric patients with the diabetes team and A1C. The low frequency of contact raises the importance of defining strategies to increase patient contact which has the potential to improve diabetic control.

Disclosure
F. Babalola: None. A. Ens: None. P.H. Gallego: None. R.I. Stein: None. C. Clarson: None.
1325-P: Study on the Mechanism of Activating Macrophages TGR5 on Glucose Metabolism during Pregnancy
Authors: LI JUNXIAN , LIU FANG 
Published: June 2020

Purpose: To explore a new mechanism of improving glucose homeostasis in pregnancy through activation of Takeda G protein-coupled receptor 5 (TGR5) in bone marrow derived macrophages (BMDM) from gestational diabetes mellitus (GDM) model mouse and observation the changes of macrophages migration, inflammatory factors and chemokines expression and secretion, and the expression of Proprotein Convertase 1/3 (PC1/3).
Methods: INT-777 was used as TGR5 agonist and LPS was used as inducer for macrophage polarization to M1. Primary bone marrow cells were extracted from GDM model mouse and were induced into macrophages. The macrophages activity and migration were detected by cck-8 tests and Transwell assay respectively when macrophages were treated with INT-777. The expression and secretion levels of inflammatory factors and chemokines in macrophages were detected by real-time PCR, cytometric bead array and ELISA, and the expression levels of PC1/3 was detected by Western blot when macrophages were treated both with INT-777 and lipopolysaccharide (LPS).
Results: TGR5 activation of macrophages by INT-777 increased cell activity (P &lt; 0.01) and decreased cell migration (P &lt; 0.001). Moreover, the mRNA levels of inflammatory cytokines and chemokines including IL-1β, IL-6, TNF-α, CCL2, CCL4, CCL5 and CCL7 mRNA were significantly decreased (All P &lt; 0.05), the secretion levels of inflammatory cytokines and chemokines including IL-6, TNF-α, MCP-1, CCL2, CCL3 and CCL4 were significantly decreased (All P &lt; 0.05) and the expression of PC1/3 was increased (P &lt; 0.05) in INT-777 + LPS treated macrophages, compared with LPS treated macrophages only.
Conclusions: Activation of TGR5 in BMDM can effectively inhibit the macrophage polarization to M1, including inhibiting inflammatory factors expression and secretion. Moreover, activation of TGR5 can inhibit macrophage chemokine expression and secretion, cell migration and can upregulate PC1/3 expression.

Disclosure
J. Li: None. F. Liu: None.

Funding
National Natural Science Foundation of China (81770802)
1327-P: Maternal Diabetes Suppresses Neural Tube Closure Gene Shroom3 through DNA Hypermethylation and Thus Disrupts Planar Cell Polarity
Authors: XU CHENG , YANG PEIXIN 
Published: June 2020

Neural Tube Defects (NTDs) are among the most frequent and severe malformations associated with maternal diabetes. DNA hypermethylation inhibits gene expression. Our recent studies have revealed a group of neural tube closure-related genes are downregulated by maternal diabetes. Planar cell polarity (PCP) is conserved in metazoans and is essential for development, deficiencies of PCP genes result in NTDs. Shroom3 encodes a PDZ-domain-containing protein that regulates cell shape in epithelium. Shroom3 interacts with PCP genes, loss of function of Shroom3 leads to NTDs. We hypothesize that DNA hypermethylation induced by maternal diabetes is responsible for the downregulation of Shroom3, which disrupts the PCP pathway leading to NTD formation. We found global DNA methylation levels were increased about 3 times and all 3 DNA methyltransferase levels were increased in the embryos from diabetic dams compared to the nondiabetic control group. Conditional double knockout of Dnmt3a/Dnmt3b gene in the developing neuroepithelium ameliorated maternal diabetes-induced NTDs, while overexpression Dnmt3b in the neuroepithelium induced NTDs in a dose dependent manner. Expression levels of PCP genes and Shroom3 were reduced by maternal diabetes and Dnmt3b transgenic overexpression. Similarly, PCP protein subcellular expression patterns were also disrupted. DNA methyl-sequencing revealed maternal diabetes-induced hypermethylation in the Shromm3 gene promoter. De-methylation rescued Shroom3 promoter activity suppressed by high glucose. Our study reveals that diabetes-induced DNA hypermethylation inhibits Shroom3 gene expression and Shroom3 deficiency mediates the teratogenic effect of maternal diabetes by disrupting PCP and resulting in NTDs. Since de-methylation can rescue Shroom3 activity, our findings suggest that targeting DNA hypermethylation could be therapeutically effective in treating maternal diabetes-induced NTDs.

Disclosure
C. Xu: None. P. Yang: None.

Funding
National Institutes of Health (R01DK083243, R01DK101972, R01HL131737, R01HL134368, R01DK103024)
1332-P: Lactation Improves Glucose Homeostasis by Enhancing ß-Cell Mass and Function through Serotonin Production
Authors: MOON JOON HO , KIM HYEONGSEOK , JANG HAK CHUL , KIM HAIL 
Published: June 2020

Parous women who did not lactate have increased risk of diabetes compared to nulliparous women, but this risk is normalized by lactating for &gt;3 months. However, the mechanism of the beneficial effects of lactation has not been elucidated. Therefore, we compared metabolic phenotypes including β cell characteristics in lactating and non-lactating humans and mice. For the human study, we recruited gestational diabetes and gestational impaired glucose tolerance women, and performed 75 g oral glucose tolerance test at postpartum 2 months and annually thereafter. Both lactating and non-lactating women showed normal glucose tolerance after 2 months of lactation. However, after a mean 3.6 years from delivery, lactated women maintained similar glucose tolerance whereas glucose tolerance deteriorated over time in non-lactated women. The Disposition index was improved in previously lactated women, suggesting improved β cell function after several years of delivery. For the mouse study, nine-week-old female C57BL/6J mice were mated to give birth and pups were either left (Lactating) or removed (Non-lactating) from the cage at the day of delivery. At 3 weeks after delivery, lactating mice had improved glucose tolerance and increased β cell mass compared to non-lactating mice. Lactating mice maintained high serum prolactin levels, which induced serotonin production in β cell via PRLR-STAT5-TPH1 cascade. Serotonin facilitated β cell proliferation and enhanced β cell function in lactating mice. Amelioration of glucose tolerance and β cell function were maintained for several months after the cessation of lactation in mice. These beneficial effects of lactation, however, were diminished in β cell-specific Tph1 knockout mice. We demonstrated a novel mechanism of 5-HT derivatives acting as a direct anti-oxidant to enhance β cell survival upon oxidative stress.
In conclusion, serotonin contributes to the beneficial metabolic effects of lactation by enhancing β cell mass and function.

Disclosure
J. Moon: None. H. Kim: None. H. Jang: Speaker’s Bureau; Self; Daiichi Sankyo, Handok, Pfizer Inc., Takeda Pharmaceutical Company Limited. H. Kim: None.

Funding
National Research Foundation of Korea (2017H1A2A1042095, 2013H1A8A1003985, 2018R1A6A3A01012333, 2015M3A9B3028218, 2018R1A2A3074646)
1335-P: Hepatic Prolactin Receptor Signaling Is Critical for Protecting against Gestational Diabetes
Authors: ZHU CUILING , YAMAUCHI JUN , PAN CHENGLIN , GAO JINGYANG , QU SHEN , BANERJEE RONADIP R. , DONG H. HENRY 
Published: June 2020

Gestational diabetes mellitus (GDM) is characterized by fasting hyperglycemia and glucose intolerance during pregnancy, but with poorly understood mechanisms. We found that prolactin receptor (Prlr) is markedly upregulated in liver of pregnant female mice. These findings have spurred the hypothesis that hepatic Prlr signaling is pivotal for physiological adaptation of hepatic metabolism to gestation. To address this hypothesis, we generated liver-conditional L-Prlr-KO mice, followed by determination of glucose and lipid metabolism in female L-Prlr-KO vs. age-matched female WT mice prior to and during gestation. Hepatic Prlr depletion did not impact glucose and lipid metabolism in virgin L-Prlr-KO mice. However, pregnant L-Prlr-KO mice developed GDM, as evidenced by the induction of glucose intolerance, fasting hyperglycemia, higher HOMA-IR levels and abnormal glucose-stimulated insulin secretion at gestational day 15.5. We reproduced these findings in female L-Prlr-KO mice in the 1st, 2nd and 3rd pregnancy, with the severity of GDM exacerbated by transient high fat feeding prior to conception in female L-Prlr-KO mice. Hepatic Prlr depletion did not affect litter size, but pups born to L-Prlr-KO mice had significantly lower birth weight. We recapitulated this finding in newborns derived from the 1st, 2nd and 3rd pregnancy in L-Prlr-KO mice. Hepatic Prlr depletion also resulted in increased triglyceride and cholesterol levels in liver, characteristic of nonalcoholic fatty liver disease and consistent with increased insulin resistance in pregnant L-Prlr-KO mice. Multiparous L-Prlr-KO mice developed postpartum prediabetes. Our studies unveiled an unprecedented role of hepatic Prlr signaling in regulating maternal hepatic metabolism to protect against GDM.

Disclosure
C. Zhu: None. J. Yamauchi: None. C. Pan: None. J. Gao: None. S. Qu: None. R.R. Banerjee: None. H. Dong: None.

Funding
National Key Research and Development Program of China (2018YFC1314100); National Natural Science Foundation of China (81970677)
1341-P: Comparison of the Effects of Metformin and Exenatide on Pregnancy Rate and Outcomes in Overweight or Obese PCOS Women
Authors: LI RENYUAN , ZHENG SIYUAN , MAI TINGTING , XUE JIAO , ZHANG YING 
Published: June 2020

The majority of PCOS are overweight or obese (OW/OB) with increased infertility and risk of pregnancy complications. Evidences show that in PCOS, metformin and exenatide have impact on insulin resistance and body weight with seldom information about pregnancy and its outcome. This study was designed directly to compare the effect of two treatments on pregnancy rate and outcomes in OW/OB PCOS. This prospective clinical trial randomized 160 OW/OB PCOS with infertility, without diabetes into metformin and exenatide treatment for the first 12 weeks. Afterward, all were treated with metformin alone until week 52. If patients failed spontaneous pregnancy during the second 12 weeks, assisted reproduction technique (ART) could be offered until week 52. The spontaneous and total pregnancy rates were recorded within 52 weeks. Pregnancy outcomes were followed until the deliveries. Baseline characteristics were similar between two groups. At week 24, higher spontaneous pregnancy rate was observed in exenatide group, although at week 52, the total pregnancy rates were similar between two groups. Meanwhile, no significant difference of pregnancy outcomes was implicated between two groups (Table 1). In OW/OB PCOS, 12 weeks exenatide treatment had improved spontaneous pregnancy rate compared with metformin treatment, without benefit effects on total pregnancy rate and overall pregnancy outcomes.

Disclosure
R. Li: None. S. Zheng: None. T. Mai: None. J. Xue: None. Y. Zhang: None.

Funding
National Natural Science Foundation of China (81200607)
1347-P: Contraception Preferences in Women with Diabetes
Authors: WALKER SHANNON L. , ANGUZU RONALD , EGEDE LEONARD E. , PALATNIK ANNA 
Published: June 2020

Objective: Effective contraception use in women with diabetes until glucose control is achieved is one of the key factors for optimizing pregnancy outcomes in this high-risk population. The objective of this analysis was to examine whether contraception utilization varied by presence of maternal diabetes.
Methods: Data from the 2011-2017 National Survey of Family Growth were analyzed using cross-sectional methodology. Women age 18-44 were included in the analysis. Maternal diabetes was defined as either the presence of pre-gestational diabetes or diagnosis of gestational diabetes. Bivariate and multivariable logistic regression analyses were run to evaluate the association between the use of contraception by contraception type (sterilization, long-acting reversible contraception (LARC), other hormonal method, barrier method and none) and maternal diabetes status.
Results: A total of 28,454 women were included in the analysis, with 3,003 (10.5%) women with diabetes during pregnancy. Women with diabetes were less likely to use LARC (7.2% vs. 10.7%) or barrier methods (14.4% vs. 17.6%) compared to controls (p&lt;0.001 for both comparisons). The utilization rates of sterilization and other hormonal methods did not differ between the groups. In multivariable logistic regression, controlling for maternal age, race/ethnicity, body mass index, insurance, education, marital status, family income and diagnosis of sexually transmitted infection, maternal diabetes remained to be significantly associated with lower utilization rates of LARC (aOR=0.73, 95% CI 0.55-0.97) and barrier methods (aOR=0.76, 95% CI 0.59-0.97).
Conclusions: In this cohort, women with diabetes were less likely to choose LARC and barrier methods for contraception. As LARC is one of the more effective and safest options of contraception in this high-risk population, further research is required to understand the causes behind this variation in contraception utilization.

Disclosure
S.L. Walker: None. R. Anguzu: None. L.E. Egede: None. A. Palatnik: None.
1349-P: Incidence of Diabetes in Women with Gestational Diabetes Mellitus Diagnosed by the IADPSG vs. Two-Step Criteria
Authors: BALAJI BHAVADHARINI , READ STEPHANIE , BERGER HOWARD , FEIG DENICE , SHAH BAIJU R. , LIPSCOMBE LORRAINE 
Published: June 2020

Background: In Canada, the 2-step approach for the diagnosis of gestational diabetes (GDM) continues to be used, due to uncertain treatment benefit at the lower diagnostic thresholds recommended by the International Association of Diabetes and Pregnancy Study Groups (IADPSG). GDM diagnosed by 2 step criteria is associated with an elevated risk of subsequent diabetes; however, the impact of GDM based on IADPSG criteria on future diabetes risk is unknown.
Aim: To evaluate the risk of future diabetes associated with a GDM diagnosis using the 2 step and IADPSG criteria.
Methods: Using Ontario population-based databases, we evaluated the incidence of diabetes in women with a live birth recorded between April 2011 and March 2014 and available prenatal glucose tolerance test records. Women were categorized according to their prenatal glucose tolerance results as no GDM, GDM based on 2-step criteria, and GDM based on IADPSG criteria (positive by IADPSG, negative by 2 step criteria). They were followed until April 2018 for a diagnosis of diabetes. Risk of diabetes associated with GDM based on each definition was compared to no GDM using a multivariable Cox proportional hazards model.
Results: Of the 104,942 women included in the study, 5,371 (5.1%) had GDM by 2 step criteria and 2,436 (2.3%) had GDM based on IADPSG criteria. There were 821 (0.78%) diabetes cases over 329 771 person-years of follow-up. After adjusting for age, body-mass index, history of GDM, gestational weight gain, birth weight, income, and ethnicity, diabetes risk was significantly higher for both GDM women by 2 step criteria (HR 14.1; 95% CI 11.7-16.9) and for GDM based on IADPSG criteria alone (HR 3.1; 95% CI:2.0-4.7) compared to no GDM.
Conclusion: While the relative risk of diabetes compared to normal glucose tolerance is higher for women diagnosed with GDM using the conventional 2 step criteria, GDM based on IADPSG criteria also confers a significant 3-fold increase in diabetes risk.

Disclosure
B. Balaji: None. S. Read: None. H. Berger: None. D. Feig: Advisory Panel; Self; Novo Nordisk A/S. Speaker’s Bureau; Self; Medtronic. B.R. Shah: None. L. Lipscombe: None.
135-OR: The Effect of Fixed-Dose Combination of Insulin Degludec and Liraglutide on Serum Lipoprotein Metabolism in Patients with Type 2 Diabetes Mellitus
Authors: PAPPA ELENI , KOSTARA CHRISTINA , TELLIS CONSTANTINOS , TSELEPIS ALEXANDROS D. , BAIRAKTARI ELENI , TSIMIHODIMOS VASILIS 
Published: June 2020

Aim: Administration of fixed-dose combination of Insulin Degludec and Liraglutide (IDegLira) has been associated with changes in the lipid-profile of diabetic patients. We assessed the effect of IDegLira on serum apolipoproteins, apoB-containing lipoprotein subclasses and HDL lipidome in patients with type 2 diabetes mellitus (T2DM).
Methods: Sixty uncontrolled patients with T2DM on oral antidiabetic drugs were included. Of them, thirty received IDegLira and the remaining Insulin Degludec(IDeg). Lipid and carbohydrate metabolism parameters were assessed before and following 3-month-treatment. ApoB-containing lipoprotein subclasses levels were measured by LDL-Lipoprint method, whereas HDL lipidomic analysis via 1H-NMR spectroscopy.
Results: Administration of IDegLira resulted in a significant reduction of total (TC) and LDL cholesterol (LDLC) by 14.68mg/dl and 10.45mg/dl, respectively. ApoA1 and apoB decreased in patients treated with IDegLira. A non-significant change in small-dense LDLC (sdLDL-C) levels was observed that was significantly correlated with changes in TG levels (r=0.468, p=0.007). Furthermore, IDegLira administration resulted in significant enrichment of HDL particles’ core in esterified cholesterol and depletion of TGs content. IDegLira induced an atheroprotective shift in fatty acid pattern of HDLs characterized by a statistically significant lower content in saturated and higher in unsaturated fatty acids (linoleic acid, eicosapentaenoic and arachidonic acids and docosahexaenoic acid). No significant changes were observed in the IDeg group.
Conclusions: Administration of IDegLira is accompanied by changes in HDL lipdome, a decrease in TC, LDLC, apoA1 and B, while the levels of sdLDL were only reduced in patients experiencing a decrease in TGs. The contribution of these changes to cardiovascular risk reduction after treatment with liraglutide in clinical trials cannot be excluded.

Disclosure
E. Pappa: None. C. Kostara: None. C. Tellis: None. A.D. Tselepis: None. E. Bairaktari: None. V. Tsimihodimos: None.
1358-P: Point of Care OGTT for the Screening of Gestational Diabetes: A Feasible Proposal for Low-Resource Settings
Authors: GALLARDO HECTOR , LOMELIN-GASCON JULIETA , MARTINEZ LUIS A. , MONTOYA ALEJANDRA , REYES-MUÑOZ ENRIQUE , TAPIA-CONYER ROBERTO C. 
Published: June 2020

Due to the ubiquity of risk factors associated with gestational diabetes (GDM) in Mexican women and the low availability of the Oral Glucose Tolerance Test (OGTT), we compared the efficacy of two point of care (POC) models for GDM detection against the plasmatic 2hr OGTT-75gr in primary health care clinics in Mexico. We evaluated 328 pregnant women without previous diabetes diagnosis from a prospective cohort study “Cuido mi embarazo”; all of them were tested with the gold standard plasmatic 2hr OGTT-75gr for the diagnosis of GDM based on the ADA 2019 criteria. Simultaneously, we measured with a glucometer (ACCU-CHEK instant®) the glucose concentration either by capillary whole blood (172 measures) or from venous whole blood (156 measures). We evaluated the diagnostic accuracy by calculating the sensitivity, specificity, and ROC curve of each of the glucometer test results compared to the plasmatic test. For the first model, POC venous OGTT, the incidence of GDM was 41.66% compared to 7.05% of the plasmatic test. The ROC area under the curve for GDM prediction was 0.81 (95% CI 0.77-0.85), with a sensitivity of 100% and specificity of 62.8%. The low specificity is dependent on the fasting venous value of 64% since it was compared to 95% and 97% specificity of the 1hr and 2hr values, respectively. The second model, POC capillary OGTT, had an incidence of GDM of 30.23% compared to 8.13% of the plasmatic test. It had lower sensitivity (78.57%) and higher specificity (74.1%) compared to the first model, having an overall 0.76 (95% CI 0.65-0.88) ROC area under the curve for GDM prediction. We propose POC venous OGTT as a feasible diagnostic alternative for low resource settings where laboratory infrastructure is not available. Its positive bias could be beneficial since the treatment and control of early cases is related to better health outcomes for the moms and their babies. Further analysis is needed to improve GDM, POC screening interventions.

Disclosure
H. Gallardo: None. J. Lomelin-Gascon: Other Relationship; Self; Lilly Global Health Partnership. L.A. Martinez: Other Relationship; Self; Lilly Global Health Partnership. A. Montoya: None. E. Reyes-Muñoz: None. R.C. Tapia-Conyer: None.

Funding
Eli Lilly and Company