bluuebunny/crossref_metadata_2025_split huggingface dataset:
139-OR: GIP Regulates Fatty Acid and Glycerol Synthesis in Human Adipocytes
Authors: MILLIGAN PAUL L. , ROTH KENNETH D. , HU HAITAO , MOYERS JULIE , RUAN XIAOPING , ROELL WILLIAM C. , REGMI AJIT 
Published: June 2019

Activation of GIP (glucose-dependent insulinotropic peptide) receptor (GIPR) in combination with GLP-1 receptor has demonstrated reduced adiposity and bodyweight in mice. Although the incretin action of GIP in pancreatic beta cells is well characterized, its regulation of adipose tissue metabolism are incompletely understood. Using differentiated human adipocytes we demonstrated GIP suppression of insulin stimulated [14C] glucose and [14C] acetate incorporation into the cellular lipid fraction suggesting GIP/insulin co-regulation of de novo lipogenesis. To further investigate these findings, we employed an NMR and mass spec strategy. Briefly, human adipocytes were differentiated then incubated with [13C] glucose or [13C] acetate overnight in the presence GIP, insulin, GIP + insulin, or control followed by lysate preparation for mass spec and NMR analysis. Isotope label incorporation in lysate fatty acids were determined by HPLC-MS detection of base-hydrolyzed lipids. GIP significantly reduced incorporation of labeled acetate and labeled glucose in fatty acids, both in the presence and absence of insulin. Sample analysis by NMR demonstrated a GIP regulated increase in glycerol production from labeled glucose both in the presence and absence of insulin with little to no acetate incorporation into glycerol under all conditions tested. These findings demonstrate GIP signaling in adipocytes reduces de novo fatty acid synthesis while increasing glycerol formation. This suggests a model whereby GIP suppresses generation of new fatty acids from substrate but enhances appropriate storage capacity of dietary fatty acids by increasing production of glycerol required for triglyceride generation. Further studies will be required to elucidate this potential benefit of GIP to improve nutrient partitioning.

Disclosure
P.L. Milligan: Employee; Self; Eli Lilly and Company. K.D. Roth: Employee; Self; Eli Lilly and Company. H. Hu: None. J. Moyers: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company. X. Ruan: Employee; Self; Eli Lilly and Company. W.C. Roell: Employee; Self; Eli Lilly and Company. A. Regmi: Employee; Self; Eli Lilly and Company.
1392-P: The Potential Role of Placental α2-Adrenergic Receptors in the High Risk of Preeclampsia in Diabetes
Authors: CHOW REBECCA P. , ZHAO JIAWU , CURTIS TIM , LYONS TIMOTHY , YU JEREMY 
Published: June 2019

Preeclampsia is a life-threatening complication of pregnancy that occurs four times more frequently in the presence of maternal diabetes. The anti-angiogenic factor soluble fms-like tyrosine kinase-1 (sFlt1), released from the placenta, plays a crucial role in PE development. Alpha 2-adrenoceptor (A2AR) dysfunction has been reported in diabetes, and is implicated in the development of vascular complications. Furthermore, A2AR agonist antihypertensive agents are frequently used to treat patients with preeclampsia, whether they have a disease-modifying role is unclear. We hypothesized that A2AR dysfunction could underlie up-regulation of placental sFlt1 expression, thus ‘driving’ preeclampsia in diabetes. We treated cultured human trophoblasts (HTR8/SVneo) with a stressor often present in the diabetic vasculature, ‘heavily oxidized, glycated’ low-density lipoproteins (HOG-LDL), vs. native LDL (at 100 µg protein/ml) with or without the A2AR agonist, clonidine, and antagonist, yohimbine (24h; both drugs at 10 μM and 100 μM). We determined α2A-, α2B- and α2C-AR mRNA expression (RT-PCR) and immunostaining; sFlt1 mRNA expression and protein release (ELISA); and cell viability (Cell Counting Kit-8 assay). Experiments were repeated three times independently. We found that all three A2AR subtypes were expressed in human trophoblasts. HOG- vs. N-LDL increased sFlt1 mRNA expression (2.0-fold, p&lt;0.001) and protein release (2.5-fold, p&lt;0.01), but neither clonidine nor yohimbine had any effect at either dose. Neither HOG- nor N-LDL altered A2AR expression or cell viability. Overall, the data confirm that modified lipoproteins may promote PE development in women with diabetes via upregulation and release of sFlt1, but do not provide clear evidence that A2ARs are implicated in this process. Further work will investigate whether A2ARs may be modified by other stressors of diabetes, and whether they may affect non-sFlt1 mechanisms for PE.

Disclosure
R.P. Chow: None. J. Zhao: None. T. Curtis: None. T. Lyons: None. J. Yu: None.
1395-P: Maternal Exercise during Pregnancy Affects Offspring Adiposity through One Carbon Metabolism Cycle
Authors: BOONPATTRAWONG NICHA , MEHRAN ARYA , LAHER ISMAIL , DEVLIN ANGELA M. 
Published: June 2019

Maternal obesity during pregnancy can adversely affect adult offspring adiposity and insulin resistance. The goal of this study was to determine if maternal exercise mitigates the adverse effects of maternal obesity on offspring health. Female (C57BL/6NJ) mice were fed from weaning a control diet (10%kcal fat; MC n=18) or western diet (45% kcal fat; MW n=15) to induce excess adiposity. After 13 weeks, the mice were bred and maintained on the diets, with (E) and without (S) access to a running wheel (exercise), throughout pregnancy and lactation. Offspring were weaned onto the control diet and fed for 13 weeks; male offspring were studied. Offspring from MWE dams had greater (p&lt;0.05) retroperitoneal and mesenteric adipose tissue than offspring from MWS dams. This was not observed in offspring from dams fed the control diet. Offspring from exercised dams had lower glucose-stimulated insulin secretion compared to those from sedentary dams, independent of maternal diet. No differences in glucose and insulin tolerance were observed. One carbon metabolism is required for several physiological processes including DNA synthesis, amino and lipid metabolism, and the generation of methyl groups. Disturbances in one carbon metabolism occur in obesity. We hypothesized that maternal exercise mitigates the adverse effects of maternal obesity on offspring adiposity through changes in one carbon metabolism. MCE offspring had lower serum total homocysteine (6.3μmol/L) compared to MCS offspring (9.4μmol/L). This was not observed in the offspring from western diet-fed dams. Offspring from western diet-fed dams had higher hepatic methylenetetrahydrofolate reductase (Mthfr) mRNA expression compared to offspring from control diet-fed dams. Offspring from dams that exercised also had higher hepatic Mthfr mRNA; the highest expression was observed in MWE offspring. The findings from this study suggest that one carbon metabolism may play a role in developmental programing of offspring adiposity.

Disclosure
N. Boonpattrawong: None. A. Mehran: None. I. Laher: None. A.M. Devlin: None.

Funding
Canadian Institutes of Health Research
1409-P: Using Fasting Venous Plasma Glucose (FVPG) to Stratify Risk in Women with Gestational Diabetes (GDM)
Authors: MCINTYRE DAVID , GIBBONS KRISTEN S. , MADSEN LENE R. , MA RONALD C. , SACKS DAVID A. , TAM WING H. , CATALANO PATRICK 
Published: June 2019

Powe et al described variable “defects” (defined as parameter values &lt;25th centile for non GDMs) in OGTT derived insulin secretion (Isecr) and sensitivity (Isens) estimates in GDM. They reported that pregnancy complications relate primarily to low Isens. To explore applicability to routine OGTT data, an analogous but simplified analysis was undertaken, classifying IADPSG GDM women according to FVPG &lt; or ≥ 75th centile for non GDM women (cut-off 4.6 mmol/L - near the cohort mean (SD) of 4.5(0.4) mmol/L). Our multi-ethnic cohort included a diverse group of 6128 untreated women from 5 centers in the blinded epidemiologic HAPO study. Analyses compared outcome frequencies (LGA, excess neonatal (NN) adiposity, NN hypoglycemia, NN hyperinsulinemia, preterm birth, primary C section) with non GDM women and between GDM-FVPG groups using χ2 tests and logistic regression analyses adjusted for maternal age, height, smoking, FH diabetes, BMI at OGTT visit and ethnicity (Table 1). The 25% of GDM women with FVPG &lt; 4.6 mmol/L were at much lower risk of adverse outcomes. Although “mechanistic” classification considering Isecr and Isens may offer insights for treatment, a simpler classification by FVPG performs better and appears simpler for routine use. A modified “two-step” approach for detection and classification of pregnancy hyperglycemia, using FVPG as the first step, deserves consideration.

Disclosure
D. McIntyre: None. K.S. Gibbons: None. L.R. Madsen: None. R.C. Ma: Advisory Panel; Self; Boehringer Ingelheim International GmbH. Research Support; Self; AstraZeneca, Bayer AG, Pfizer Inc. Stock/Shareholder; Self; GemVCare. Other Relationship; Self; AstraZeneca. D.A. Sacks: None. W.H. Tam: None. P. Catalano: None.

Funding
National Institutes of Health
1415-P: Gestational Diabetes Mellitus after Delivery: The Need for Continued Vigilance
Authors: KAUL PADMA , SAVU ANAMARIA , MOORE LINN E. , YEUNG ROSEANNE O. , RYAN EDMOND A. 
Published: June 2019

Despite guideline recommendations, there are currently limited data on the extent and yield of repeat postpartum glucose testing of women with gestational diabetes mellitus (GDM). Accordingly, we examined these issues in a large population-based cohort of women in Alberta, Canada, who gave birth between 10/01/2008-06/30/2013, were diagnosed with GDM, and followed-up until 12/31/2015 (n=10520). The study population included the 4625 (44%) women who underwent glucose testing within 6 months (m) after delivery. Laboratory data were used to identify rates of repeat testing between 6-18 m postpartum. Diabetes Canada thresholds were used to identify women who converted to diabetes mellitus (DM). A total of 211 (4.6%) women had overt DM, i.e., DM within 6 m of delivery. Among 4414 women with GDM who had a normal glucose test within 6 m, 1656 (37.5%) underwent repeat testing between 6-18 m. Of these, 77 (4.6%) were diagnosed with DM. This latter group was older, more likely multiparous, had higher rates of gestational hypertension and C-section, more likely to have been on insulin therapy during pregnancy, and had the highest rates of large for gestational age (LGA) babies (Table). While early postpartum glucose screening is likely to identify women with overt diabetes, continued monitoring, despite initial normal screens, is necessary to ensure early detection of DM and other chronic disease in women with GDM.

Disclosure
P. Kaul: None. A. Savu: None. L.E. Moore: None. R.O. Yeung: Advisory Panel; Self; Sanofi. Consultant; Self; Novo Nordisk Inc. Research Support; Self; AstraZeneca. Speaker's Bureau; Self; Novo Nordisk Inc., Sanofi. E.A. Ryan: None.

Funding
Canadian Institutes of Health Research
1421-P: Associations of Sleep Disturbances Before and During Early Pregnancy with Increased Risk of Gestational Diabetes
Authors: BADON SYLVIA E. , XU FEI , FERRARA ASSIAMIRA , HEDDERSON MONIQUE M. 
Published: June 2019

Women with sleep disturbances before or during pregnancy may be at high risk for gestational diabetes (GDM) due to poor sleep-related increases in insulin resistance. To estimate associations of habitual snoring and other sleep disturbances before and during early pregnancy with GDM risk, we combined data collected as part of two prospective pregnancy cohort studies at Kaiser Permanente Northern California that used the same sleep questionnaires (N=3,646, 2011-2018). In early pregnancy (7-22 weeks gestation) participants self-reported snoring frequency in the 12 months before becoming pregnant and since becoming pregnant. Snoring most or some of the time was considered habitual snoring. Participants also reported if they had trouble falling asleep in early pregnancy. Three hundred four (8%) women were diagnosed with GDM based on laboratory glucose values meeting the Carpenter and Coustan criteria. Forty-four percent of women reported habitual snoring prior to pregnancy and 45% in early pregnancy. Thirty-one percent of women reported trouble falling asleep in early pregnancy. In logistic regression models adjusted for maternal age, race/ethnicity, pre-pregnancy BMI, and parity, habitual snoring prior to pregnancy was associated with a 33% greater odds of GDM (OR [95% CI]: 1.33 [1.00, 1.77]) compared to no snoring. Habitual snoring in early pregnancy was not statistically significantly associated with GDM (1.14 [0.84, 1.53]). Trouble falling asleep in early pregnancy was borderline significantly associated with greater GDM risk (1.27 [0.98, 1.66]). Our findings suggest that snoring prior to pregnancy and other sleep disturbances during early pregnancy are associated with greater risk of GDM. Studies with objective measures of sleep are needed to confirm these findings and prior to designing interventions to reduce sleep disturbances to decrease risk for GDM.

Disclosure
S.E. Badon: None. F. Xu: None. A. Ferrara: None. M.M. Hedderson: None.

Funding
National Institute of Diabetes and Digestive and Kidney Diseases (T32DK11668401 to S.E.B.)
1425-P: A Translational Diabetes Prevention Program (DPP)-based Lifestyle Intervention in Women with GDM Improves Postpartum Lifestyle Behaviors
Authors: HEDDERSON MONIQUE M. , BROWN SUSAN D. , FENG JUANRAN , QUESENBERRY CHARLES , FERRARA ASSIAMIRA 
Published: June 2019

Women with GDM are 7 times more likely to develop type 2 diabetes later in life than parous women without GDM. Thus, interventions to improve lifestyle behaviors among women with GDM are urgently needed. In a randomized controlled trial, we tested a DPP-based intervention to help women with GDM make long-term healthy lifestyle changes and manage weight after pregnancy. Of 352 participants, 178 were randomized to standard care and 174 were randomized to a lifestyle intervention of individual sessions with a coach trained in motivational interviewing, which provided specific diet, physical activity and weight goals. The intervention consisted of a pregnancy phase (1 in-person session and 2 telephone sessions), an early postpartum phase (2 in-person sessions and 11 telephone sessions up to 6 months postpartum), and a late postpartum phase (6 maintenance newsletters up to 12 months postpartum). Participants were followed from pregnancy (shortly after GDM diagnosis) to 24 months postpartum. On average, over the 24-month postpartum period, women in the intervention reported greater reductions in daily total energy intake (mean changes [95% CI]: 103.5 [-206.8 to -0.2] kcal) and percent of calories from fat (-1.6 [-2.7 to -0.4]) than women in standard care. Women in the intervention also reported greater increases in MET hours/week of moderate-intensity sports activity at 6 months postpartum (1.98 [-0.24 to 4.20]); however, this difference did not persist at 24 months postpartum (1.00 [-1.64 to 3.65]). On average, over the 24-month postpartum period, there was no difference between conditions in mean weight change (-0.09 [-1.12 to 0.94] kg). A 12-month, translational DPP-based intervention delivered primarily via telephone improved diet and physical activity, but did not impact weight, at 24 months postpartum.

Disclosure
M.M. Hedderson: None. S.D. Brown: None. J. Feng: None. C. Quesenberry: None. A. Ferrara: None.

Funding
National Institutes of Health
1427-P: Plasma Phospholipid MUFA Biomarkers and Gestational Diabetes Mellitus: A Longitudinal Study in a Multiracial Cohort
Authors: TSOI KIT YING , ZHU YEYI , WU JING , SUN QI , LI MENGYING , HINKLE STEFANIE , AJJARAPU APARNA , MA RONALD C. , ZHANG CUILIN 
Published: June 2019

Previous studies on circulating monounsaturated fatty acids (MUFAs) and the risk of gestational diabetes (GDM) are limited although MUFAs have been implicated outside of pregnancy in glucose homeostasis. The aim of this study was to prospectively investigate levels of total and individual MUFAs (16:1n-7c, 18:1n-9, 20:1n-9, 24:1n-9) in plasma phospholipids in relation to risk of GDM. This was a case-control study nested in the NICHD Fetal Growth Studies-Singletons (2009-2013), a prospective study of 2,802 low risk pregnant women. A total of 107 GDM cases were ascertained using the Carpenter and Coustan criteria, and 214 non-GDM controls were selected on a 1:2 ratio and individually matched on age, race/ethnicity, and gestational week (GW) of blood collection. Blood samples were collected at GW 10-14, 15-26, 23-31 and 33-39. Spearman’s correlation coefficient was used to assess the association of circulating MUFAs with indices of glucose homeostasis (e.g., insulin, C-peptide, and HOMA-IR). Conditional logistic regression models adjusted for risk factors of GDM including pre-pregnancy BMI were used to assess the associations of circulating MUFAs with subsequent GDM risk. Total MUFAs (p=0.015) and 18:1n-9 (p=0.012) were significantly lower in GDM cases than controls at GW 15-26. 16:1n-7c was significantly higher in GDM cases than controls at GW 10-14 (p=0.008) and 15-26 (p=0.048). Total MUFAs and 18:1n-9 at GW 15-26 were significantly associated with a lower GDM risk; the adjusted ORs (95% CIs) comparing highest vs. lowest quartiles were 0.15 (0.05-0.44) and 0.14 (0.05-0.45), respectively. Total MUFAs and 18:1n-9 at GW10-14 were inversely correlated with insulin, HOMA-IR, c-peptide at GW 15-26. No significant associations were observed for other individual MUFAs at GW 10-14 or 15-26 with GDM risk.
In conclusion, higher plasma concentrations of MUFAs, especially 18:1n-9, at GW 15-26 were prospectively related to a reduced risk of GDM.

Disclosure
K. Tsoi: None. Y. Zhu: None. J. Wu: None. Q. Sun: Consultant; Self; Emavant Solutions GmbH. M. Li: None. S. Hinkle: None. A. Ajjarapu: None. R.C. Ma: Advisory Panel; Self; Boehringer Ingelheim International GmbH. Research Support; Self; AstraZeneca, Bayer AG, Pfizer Inc. Stock/Shareholder; Self; GemVCare. Other Relationship; Self; AstraZeneca. C. Zhang: None.

Funding
Eunice Kennedy Shriver National Institute of Child Health and Human Development; American Recovery and Reinvestment Act (HHSN275200800013C, HHSN275200800002I, HHSN27500006, HHSN275200800003IC, HHSN275200800014C, HHSN275200800012C, HHSN275200800028C, HHSN275201000009C, HHSN275201000001Z)
1433-P: Does Physician Counseling Regarding Lifestyle Choices Impact Postpartum Visit Attendance among Pregnant Women with Diabetes?
Authors: MANIN EMILY , HERRICK CYNTHIA J. , DUCKHAM HILLARY E. , WOOLFOLK CANDICE L. , CARTER EBONY B. 
Published: June 2019

Objective: To determine whether physician lifestyle counseling during prenatal care for patients with diabetes is associated with increased attendance at postpartum visit.
Study Design: We performed a retrospective cohort study of pregnant women with type 1, type 2 and gestational diabetes who received prenatal care at Barnes-Jewish Hospital from June 2009- December 2017. Medical records were reviewed to determine whether the physician documented counseling the patient regarding exercise, diet, weight gain, and whether the patient saw a diabetes educator for at least one visit during the course of prenatal care. Logistic regression was used to identify the association between physician counseling and 6-week postpartum visit attendance after controlling for age, race, employment, education, number of prenatal visits, delivery complications, and delivery mode.
Results: Of 638 patients in the cohort, 319 (50%) were documented to have received lifestyle counseling from their physician: 82 (26%) on exercise, 277 (87%) on diet, and 100 (31%) on recommended gestational weight gain. Most patients (87%) saw a diabetes educator. Demographic characteristics were similar between women who received lifestyle counseling and those who did not. Seventy-three percent of patients attended the 6-week postpartum visit and women with documentation of lifestyle counseling were nearly twice as likely to attend as those without (aOR 1.87; 95% CI 1.18-2.98). There were no differences in postpartum visit attendance based on consultation with a diabetes educator.
Conclusion: Physician documentation of lifestyle counseling for pregnant women with diabetes is associated with improved rates of postpartum visit attendance, but documentation of counseling remains low. Further study is needed to determine the content/quality of physician lifestyle counseling and its impact on pregnancy and postpartum outcomes among women with pregnancies complicated by diabetes.

Disclosure
E. Manin: None. C.J. Herrick: Stock/Shareholder; Spouse/Partner; Cardinal Health. H.E. Duckham: None. C.L. Woolfolk: None. E.B. Carter: None.

Funding
Robert Wood Johnson Foundation (74250)
1436-P: Gestational Diabetes Pregnancy by Pregnancy
Authors: GIULIANI CHIARA , BITTERMAN OLIMPIA , AMOROSI FRANCESCA ROMANA , FESTA CAMILLA , NAPOLI ANGELA 
Published: June 2019

Gestational diabetes mellitus (GDM) is a risk factor for GDM in next pregnancies.The aims of this observational study are to measure GDM recurrence rate in post index pregnancy of women with prior GDM and to compare maternal and neonatal outcomes and pancreatic beta cells function in two consecutive pregnancies.
Methods: Longitudinal observational study in 68 women with GDM in index pregnancy (G1), followed by a post index pregnancy (G2) and normal glucose tolerance in-between [G1 vs. G2: age 32,1±4,6 vs. 35,5±4,7 years, BMI 24,5 (19,2-42,7) vs. 24,7 (17,5-42,2) kg/m2, ns]. GDM diagnosis according to IADPSG criteria. Statistics: SPSS.
Results: significantly earlier first visit gestational age in G2 [17 (6-36) weeks] than in G1 [28,5 (8-35) weeks] (p&lt;0,001). GDM recurrence rate was 85,3% (n58) 3,32±1,8 years after index pregnancy: of these women, n31 (45,6%) [36.5±4 years; BMI 24.7 (19.3-42.1) Kg/m2] developed GDM in early pregnancy (16-18 weeks), while n27 (39,7%) [35.66±4 years; BMI 25.26 (17.6-42.2) Kg/m2] at the end of second trimester (24-28 weeks). Women who reported a negative OGTT at both time-points (n10, 14,7%) [33.7±5.5 years; BMI 20.45 (17.5-25.4) Kg/m2;] showed a significantly lower BMI (p&lt;0,0015) and a higher disposition index (p=0.07) than those with positive OGTT. In women who did not relapse GDM, no significant inter-pregnancy weight gain was observed and GDM diagnosis in G1 was performed by post-load OGTT points. Lower 24-28thOGTT post load blood glucose levels and AUCglucose were found in G2 (p&lt;0,02, Wilcoxon). No pancreatic beta cells function deterioration was recorded in post index pregnancy. We found a lower rate of cumulative neonatal adverse outcomes in G2 (30,2% in G1 vs. 25,7% in G2, p&lt;0,04) and a reduced maternal hypertension rate even though it did not reach the level of significance (4vs8).
Conclusions: GDM relapsed in the majority of women with previous GDM with no weight gain between pregnancies and no pancreatic function deterioration. However, a normal OGTT in second pregnancy was found in normoweight women.

Disclosure
C. Giuliani: None. O. Bitterman: None. F. Amorosi: None. C. Festa: None. A. Napoli: None.