bluuebunny/crossref_metadata_2025_split huggingface dataset:
1410-P: High Prevalence of Gestational Diabetes among Women in Rural District of North-Eastern Tanzania
Authors: GRUNNET LOUISE , HJORT LINE , NIELSEN BIRGITTE B. , MINJA DANIEL T. , MSEMO OMARI ABDUL , LUSINGU JOHN P. , PRASAD RASHMI B. , GROOP LEIF , THEANDER THOR G. , SCHMIEGELOW CHRISTENTZE , BYGBJERG IB C. , CHRISTENSEN DIRK L. 
Published: June 2019

Background and Aims: The prevalence of gestational diabetes mellitus (GDM) is increasing world-wide and it complicates around 1-10% of all pregnancies. GDM is associated with increased risk of long-term metabolic health consequences for both mother and child. In Tanzania, GDM prevalence increased from 0% in 1991 to 19.5% in 2016. Furthermore, the prevalence seems to be dependent on the living conditions, thus an overall GDM prevalence of 5.9% was found in urban areas and 1.0% in rural areas in Tanzania. We aimed to examine the prevalence of GDM in a rural district of North-Eastern Tanzania based upon an oral glucose tolerance test (OGTT) with subsequent fasting blood samples.
Methods: The participants were included in a large population-based pre-pregnancy study named ”FOETALforNCD - Foetal Exposure and Epidemiological Transition: The Role of Anaemia in Early Life for Non-Communicable Diseases in Later Life." In total, 538 women were included in the pregnancy study; hereof 403 women were screened with an OGTT at week 32-34 of gestation, after 12 hours of fasting. GDM was diagnosed according to the WHO 2013 guidelines.
Results: The OGTT results showed that 153 women had GDM, i.e., a prevalence of 39.0%. The majority (94.1%) were diagnosed based on the fasting blood sample. When examine the blood samples from the follow-up of the 153 women diagnosed with GDM, 41 had a confirmed GDM diagnosis (39 had repeated fasting blood sample and 2 had a repeated OGTT. In the remaining 112 women. GDM could not be validated. 40 women had repeated fasting blood samples, 43 had random blood samples, 3 had a repeated OGTT and 26 had no further blood samples taken.
Conclusion: A very high prevalence of GDM was found in this part of Tanzania. In view of the laborious, costly and patient unfriendly OGTT, in low and middle-income countries alternative methods should be considered to be used to diagnose GDM.

Disclosure
L. Grunnet: None. L. Hjort: None. B.B. Nielsen: None. D.T. Minja: None. O.A. Msemo: None. J.P. Lusingu: None. R.B. Prasad: None. L. Groop: None. T.G. Theander: None. C. Schmiegelow: None. I.C. Bygbjerg: None. D.L. Christensen: None.

Funding
Danish Council for Strategic Research (1309-00003B)
1411-P: Glycated Hemoglobin A1c Levels during Pregnancy and Risk of Autism in Offspring
Authors: XIANG ANNY , CHOW TING , MARTINEZ MAYRA P. , GETAHUN DARIOS , PAGE KATHLEEN A. , BUCHANAN THOMAS A. , FELDMAN R. KLARA 
Published: June 2019

Children exposed in utero to pre-existing type 1, type 2 diabetes or gestational diabetes diagnosed by second trimesters are at increased risk of developing autism spectrum disorders (ASD). Here we assessed the role of maternal glycemic levels using hemoglobin A1c. Data were from 35,819 singleton children born in 2012 and 2013 with maternal HbA1c measured during the first two trimesters of pregnancy (median=9.0 weeks, interquartile range (IQR) 6.7-11.4 weeks). All children were from an integrated healthcare system and enrolled in the health plan by age one. Children were tracked from age one until December 31, 2017. Risk of ASD associated with maternal HbA1c levels were estimated by hazard ratio (HR) using Cox regression. Potential confounding by maternal age, maternal obesity, parity, education, race/ethnicity, history of comorbidity, and sex of the child were assessed. During a median of 4.5 (IQR of 4.0-5.0) years after birth, 707 (2.0%) children were diagnosed with ASD. Univariately, the HR of ASD associated with each 1% increase of HbA1c was 1.23 (95% CI 1.08-1.41; p=0.002). When analyzed categorically, compared to exposure to HbA1c &lt;5.7% (n=30,419), the HR (95% CI) associated with exposure to HbA1c 5.7% to 5.9% (n=4,172), 6.0% to 6.5% (n=871) and &gt;6.5% (n=357) were 1.24 (1.01-1.54; p=0.04), 0.98 (0.61-1.59; p=0.94) and 2.17 (1.30-3.62; p=0.003) respectively. None of the potential confounders changed the model estimates by more than 10% except for maternal pre-pregnancy BMI and race/ethnicity. Adjusting for both reduced the corresponding HRs to 1.08 (0.87-1.35; p=0.46), 0.79 (0.48-1.28; p=0.33) and 1.79 (1.06-3.00; p=0.03) respectively. Thus, exposure to hyperglycemia defined by HbA1c &gt;6.5% in the first two trimesters was associated with an increased ASD risk in offspring. Improving glycemic control during pregnancy may reduce the risk of ASD in children, and monitoring HbA1c may assist in identifying at-risk children for early intervention to reduce ASD disabilities.

Disclosure
A. Xiang: None. T. Chow: None. M.P. Martinez: None. D. Getahun: Research Support; Self; Bayer AG. K.A. Page: None. T.A. Buchanan: Research Support; Self; Allergan, Apollo EndoSurgery. R. Feldman: None.
1416-P: Impact of Birth Weight Category on Early Childhood Growth in the Offspring of Women with Diabetes
Authors: FEGHALI MAISA N. , CARITIS STEVE , SCIFRES CHRISTINA M. 
Published: June 2019

Maternal diabetes mellitus (DM) affects fetal growth and we sought to examine the impact of birth weight category on growth in the first 3 years of life. We conducted a retrospective cohort study of 787 women with gestational (n=629) or pre-gestational DM (n=158). Maternal characteristics and perinatal outcomes, as well as childhood height and weight through age 3, were collected. Bivariate and multivariable linear regression analyses were used to assess factors associated with early childhood growth.
We compared weight z-scores and BMI at 6 months, 1, 2, and 3 years of age among those born small for gestational status (SGA) (n=71), adequate for gestational age (AGA) (n=619) and large for gestational age (LGA) (n=97). Weight z-scores and BMI at all time points were higher in infants born LGA and lower among those with SGA birth weight. BMI &gt;85th percentile at age 3 was more common in offspring born LGA compared to those born AGA or SGA (44.57 vs. 21.09 vs. 12.9%, p&lt;0.001). After adjusting for covariates, birth weight category remained significantly associated with BMI at ages 2 and 3 (Table).
Our findings suggest that birth weight category is a significant predictor of early childhood growth, and interventions that reduce the prevalence of LGA birth weight or optimize early childhood nutrition may impact long-term obesity risks.

Disclosure
M.N. Feghali: None. S. Caritis: None. C.M. Scifres: None.

Funding
National Institutes of Health (K23HD092893)
142-OR: Unique Role of the a4 Component for S6-Kinase Activity in Metabolic Regulation and Anti-apoptotic Effect in Brown Adipose Tissue
Authors: SAKAGUCHI MASAJI , OKAGAWA SHOTA , KITANO SAYAKA , KONDO TATSUYA , ARAKI EIICHI 
Published: June 2019

Insulin and IGF1 signaling regulate function of brown and white adipose tissues. Recently we created adipocyte-specific inducible IR/IGF1R knockout mouse (Ai-DKO) and demonstrated the critical role of insulin signaling in maintenance of BAT and WAT. To further investigate downstream targets of these hormones regulating adipose tissue mass in adult animals, we compared gene expression patterns in WAT and BAT by using Ai-DKO mice, and found α4 expression was significantly reduced in Ai-DKO BAT but not in WAT compared with those of control. Knockdown of α4 in brown preadipocytecell lines using shRNA did not affect insulin-stimulated phosphorylation of IR, IRS1 or Akt; however, phosphorylation of ribosomal S6 protein was significantly increased in α4 KD cells after insulin stimulation. To investigate the impact of α4in mature adipocytesin vivo, we created inducible adipocyte-specific knockout of α4 gene (Ai-α4 KO) using floxed mice and mice carrying a tamoxifen-inducible Cre-ERT2transgene on the adiponectin promoter. Within 7 days, Ai-α4KO displayed an apparent decrease in SC-WAT and BAT mass, but not a significant effect on PG-WAT mass. Ai-α4 KO revealed extensive losses of adipocytes in SC-WAT and BAT depots with a significant increase in stromovascular cells in histological analysis with elevation of F4/80, TNF-α and IL-6, while no apparent changes were observed in PG-WAT. This appears to be due to a rapid development of an apoptotic process with increased TUNEL and cleaved caspase-3.Interestingly, Ai-α4KO showed marked reduction of BAT-associated functional gene UCP1 as well as PRDM16, Tfam and PGC1α mRNA compared to control. Consistent with these changes in mRNA and the decrease in BAT mass, Ai-α4 KO mice showed marked cold intolerance, glucose intolerance and insulin resistance. Thus, α4 is one of the components in control of insulin signaling and preferentially BAT mass, and has a unique role in regulating anti-apoptotic effect in brown adipocytes.

Disclosure
M. Sakaguchi: None. S. Okagawa: None. S. Kitano: None. T. Kondo: None. E. Araki: Research Support; Self; Astellas Pharma Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo Company, Limited, Novo Nordisk Inc., Takeda Pharmaceutical Company Limited. Speaker's Bureau; Self; Astellas Pharma Inc., Merck & Co., Inc., Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd., Sanofi.

Funding
Japan Society for the Promotion of Science; Takeda Foundation; MSD Foundation; Kenzou Suzuki Foundation; Ono Foundation; Motida Foundation
1420-P: Improvements in Contraception Uptake and Reduced Pregnancy Rates in Women with Type 1 Diabetes after Changes to the Running of a Tertiary Centre Diabetes Transition Clinic
Authors: SIMMONS DAVID , OSUAGWU UCHECHUKWU L. , GUPTA AKHIL , RATNAWEERA MANJULA 
Published: June 2019

Objective: Unplanned pregnancies among young women with diabetes are associated with hyperglycaemia related fetopathy. We have evaluated whether introducing a structured approach to contraception and pregnancy planning in the clinic was associated with greater uptake of contraception and reduced pregnancy rates.
Methods: Repeat retrospective reviews before (2012-2016) and after (2017- 2018) the introduction of a proforma including documentation of contraception uptake, provision of educational materials, reserved waiting area space and early evening clinic slots in a tertiary hospital diabetes transition clinic (for those aged 17-25 years). Between clinic telephone support continued unchanged.
Results: The pre-/post-change reviews included 43 and 48 women with type 1 diabetes (T1DM) respectively. Age at diagnosis (10-11 years), time between first and last clinic attendance (25-26 months), diabetes duration (10-12 years), CSII use (23%) and HbA1c (9.5-9.7%) on first attendance were similar. Number of clinic attendances dropped from 6.8±4.1 to 5.0±3.7 (p=0.01). HbA1c reduction since first attendance (0.1±1.8 vs. 1.2±3.0%, p&lt;0.001) was greater, and episodes of diabetic ketoacidosis (55.8% vs. 14.6% p&lt;0.001) and severe hypoglycaemia (18.6% vs. 2.1% 0.01) were less, in the ‘after’ group. Metformin use increased from 2.3% to 18.4% (p&lt;0.05). Use of CGMS increased from 0% to 39.6% (p&lt;0.001). Documented advice on contraception increased from 0% to 95.8% (p&lt;0.001). Use of contraception increased from 25.6% to 43.8% (p&lt;0.001: implants 7 to 15%, OCPs 16 to 27%). Prior/current pregnancy rates were less (18.6% vs. 8.3% respectively; p=0.03).
Conclusions: Introduction of more proactive approaches to diabetes management including contraception awareness and advice were associated with improved glycaemia and a reduced risk of pregnancy in younger women with T1DM.

Disclosure
D. Simmons: Speaker's Bureau; Self; Sanofi-Aventis. Other Relationship; Self; Medtronic. U.L. Osuagwu: None. A. Gupta: None. M. Ratnaweera: None.
1423-P: Diagnostic Performance of Fasting Glucose, Insulin, and HOMA-IR in the First and Second Trimesters in Predicting Gestational Diabetes
Authors: ZHU YEYI , HEDDERSON MONIQUE M. , FENG JUANRAN , QUESENBERRY CHARLES , FERRARA ASSIAMIRA 
Published: June 2019

The International Association of Diabetes and Pregnancy Study Groups recommend early testing for gestational diabetes (GDM) using fasting glucose (FG) of 5.1-6.9 mmol/L at the first prenatal visit. Nonetheless, the optimal approach to diagnosing GDM remains debatable given the limited data on glycemia in the first half of pregnancy. We evaluated the diagnostic performance of FG, insulin, and HOMA-IR in the first and second trimesters in prediction of GDM diagnosis in the third trimester. In a nested case-control study within the prospective Pregnancy Environment and Lifestyle Study (PETALS) pregnancy cohort, 193 GDM cases were diagnosed at gestational weeks 24-28 using the Carpenter-Coustan criteria and matched to 386 controls on age and race/ethnicity. FG, insulin and HOMA-IR were assessed at gestational weeks 10-13 and 16-19, respectively. The mean (SD) of FG and insulin were 4.4 (0.4) mmol/L and 8.4 (10.9) µU/mL at weeks 10-13, and 4.4 (0.5) mmol/L and 11.5 (18.3) µU/mL at weeks 16-19, respectively. The sensitivity of GDM diagnosis using FG of 5.1-6.9 mmol/L was 0.25 (95% CI 0.19-0.32) at gestational weeks 10-13, 0.29 (0.22-0.36) at weeks 16-19, and 0.39 (0.32-0.47) at either weeks 10-13 or 16-19; the corresponding specificity was 0.97 (0.94-0.98), 0.94 (0.91-0.96), and 0.91 (0.88-0.94). By lowering the cutoff to 4.9 mmol/L (90th percentile among controls) for FG, the corresponding sensitivity was 0.38 (0.31-0.45), 0.42 (0.35-0.49), and 0.54 (0.46-0.61) at gestational weeks 10-13, 16-19, or either, with specificity ranging from 0.81-0.90. Diagnostic performance of GDM was not enhanced by using fasting insulin or HOMA-IR. Our data show that only 25% or 29% of GDM can be diagnosed using FG ≥5.1 mmol/L at gestational weeks 10-13 or 16-19 and thus do not support a single FG value of 5.1-6.9 mmol/L in the first or second trimester as the criteria for GDM diagnosis. It is still imperative to conduct an OGTT at gestational weeks 24-28 to confirm or rule out GDM.

Disclosure
Y. Zhu: None. M.M. Hedderson: None. J. Feng: None. C. Quesenberry: None. A. Ferrara: None.

Funding
National Institutes of Health
1424-P: Changes in Device Uptake and Glycemic Control among Pregnant Women with Type 1 Diabetes: Data from the T1D Exchange
Authors: LEVY CAROL J. , FOSTER NICOLE C. , DUBOSE STEPHANIE , AGARWAL SHIVANI , LYONS SARAH , PETERS ANNE L. , UWAIFO GABRIEL I. , DIMEGLIO LINDA , SHERR JENNIFER , POLSKY SARIT 
Published: June 2019

We examined characteristics of pregnant women aged 16-40 years with type 1 diabetes (T1D) enrolled in the T1D Exchange clinic registry. We compared characteristics of 3 cohorts of women with data collection periods from: 2010-12 (N=4651), 2011-13 (N=3355), and 2016-18 (N=2818). 2.9%, 2.2%, and 1.7% of women reported being pregnant during 2010-12, 2011-13, and 2016-18, respectively. For pregnant women, there was a trend for a decrease in HbA1c over the 3 time periods from 6.8% to 6.7% to 6.4% (P=0.13 adjusted for age, race/ethnicity, frequency of glucose monitoring, and use of CGM). Self-reported use of CGM while pregnant increased more than 2-fold over the time period (P=0.001 adjusted for age, duration, race/ethnicity, insurance status, and use of pump); conversely, self-reported pump use while pregnant remained unchanged (adjusted P=0.38) (Table). Severe hypoglycemia (seizure/loss of consciousness) was similar across cohorts (adjusted P=0.38).We found in a real-world population of pregnant women in the U.S., lower HbA1c levels compared to those pregnant 5-6 years ago. CGM use in pregnancy appears to have increased over time, with relatively low but stable participant-reported insulin pump use. Further explorations of these findings, ongoing assessment of real-world pregnancy outcomes and comparisons with data on T1D pregnant women from other large registries are needed.

Disclosure
C.J. Levy: Advisory Panel; Self; Novo Nordisk A/S, Sanofi. Employee; Spouse/Partner; Allergan. N.C. Foster: None. S. DuBose: None. S. Agarwal: None. S. Lyons: None. A.L. Peters: Advisory Panel; Self; Abbott, Becton, Dickinson and Company, Bigfoot Biomedical, Eli Lilly and Company, Lexicon Pharmaceuticals, Inc., Livongo Health, MannKind Corporation, Medscape, Merck & Co., Inc., Omada Health, Inc., OptumRx, Inc., Sanofi US, Zafgen, Inc. Research Support; Self; AstraZeneca, Dexcom, Inc., Jaeb Center for Health Research, MannKind Corporation, National Institute of Diabetes and Digestive and Kidney Diseases. Speaker's Bureau; Self; Novo Nordisk Inc. G.I. Uwaifo: None. L. DiMeglio: Research Support; Self; Amgen Inc., Caladrius Biosciences, Inc., Janssen Research & Development, Medtronic, Sanofi. Other Relationship; Self; Dexcom, Inc. J. Sherr: Advisory Panel; Self; Bigfoot Biomedical, Eli Lilly and Company, Insulet Corporation. Consultant; Self; Lexicon Pharmaceuticals, Inc., Medtronic, Sanofi. Research Support; Self; Dexcom, Inc., Insulet Corporation. S. Polsky: Consultant; Self; Jaeb Center for Health Research. Research Support; Self; Barbara Davis Center for Diabetes, Children's Diabetes Foundation, Dexcom, Inc., Eli Lilly and Company, JDRF, Leona & Harry Helmsley Charitable Trust, National Institute of Diabetes and Digestive and Kidney Diseases, Sanofi US.

Funding
The Leona M. and Harry B. Helmsley Charitable Trust
1435-P: Impaired Early-Phase Suppression of Glucagon Secretion after Glucose Load Associated with Insulin Need during Pregnancy in Gestational Diabetes
Authors: HORIE ICHIRO , HARAGUCHI AI , ABIRU NORIO , KAWAKAMI ATSUSHI 
Published: June 2019

Aims: The prevalence of gestational diabetes mellitus (GDM) has recently increased all over the world. It is hard to predict insulin need during pregnancy even if the insulin secretory capacity is evaluated when studying 75-g OGTT to screen for GDM. The role of glucagon abnormality has remarked in pathogenesis of type 2 diabetes, however, still unknown in GDM. This study was aimed to evaluate glucagon responses in GDM and to investigate whether measurement of glucagon is useful to anticipate insulin need during pregnancy.
Methods: Forty-nine women diagnosed with GDM based on IADPSG criteria were enrolled into the study and re-studied OGTT during mid-gestation to evaluate glucagon responses. Plasma glucagon levels were measured before and 30, 60, 120 min after glucose load using a sandwich ELISA kit. Insulin treatment was initiated when either a fasting glucose &gt;95 mg/dL or postprandial 2-h glucose &gt;120 mg/dL continues for more than a week after starting diet therapy.
Results: Of 49 patients, fifteen were required insulin (defined as GDM/Insulin) and 34 could be treated with diet therapy alone until delivery (defined as GDM/Diet). GDM/Insulin was started insulin treatment at 29.6±3.6 weeks of gestation and the maximum insulin dose was 39.0±24.8 units/day. There were no significant differences in maternal age, pre-gravid BMI and insulin secretory responses during OGTT between the groups. Although fasting glucagon levels were not different between the groups, paradoxical increases in early-phase glucagon secretion after glucose load were observed in GDM/Insulin but not in GDM/Diet. The changes in glucagon levels (pg/mL) from 0 min to 30 min were significantly different between the groups (1.3±8.1 in GDM/Insulin vs. -4.2±4.0 in GDM/Diet, p&lt;0.01), and the ROC analysis of the value to predict insulin need was -2.01 pg/mL.
Conclusions: Impaired early-phase glucagon suppression might be useful to predict for insulin need during pregnancy in GDM.

Disclosure
I. Horie: None. A. Haraguchi: None. N. Abiru: None. A. Kawakami: None.
1447-P: Epistatic Interactions of Known Gene Variants for Glycated Hemoglobin: Evidence from the Long Life Family Study
Authors: AN PING , THYAGARAJAN BHARAT , LEE JOSEPH H. , SCHUPF NICOLE , ZMUDA JOSEPH M. , PROVINCE MICHAEL 
Published: June 2019

HbA1c, an index of chronic glycemic status relevant to IR and T2D, is associated with aging, cognitive performance and mortality. To identify epistatic interactions, we assessed 65 published SNPs associated with levels of HbA1c (n=4,090) and change in HbA1c levels over time (n=2,054) among nondiabetic participants of European ancestry who had complete data from 2 exams collected 7 years apart in the LLFS, a multicenter family study with a clustering of healthy aging and exceptional survival. Both traits were adjusted for age, sex, BMI, field center and principal components, with correction for familial membership. HbA1c change over time was derived using growth curve modeling, taking into account baseline HbA1c. A knowingly more powerful Bayesian approach was used to test SNP association searching for significant (Bayes Factor, BF&gt;3) single SNPs and best (top 1) combinations of interacting SNPs followed by MIXED regression reconfirmation (p&lt;0.05 for main and interaction terms). HK1-rs17476364 (BF=7.8), GCK-rs4607517 (BF=5.7), HK1-rs16926246 (BF=4.8), SPTA1-rs12041363 (BF=4.5), G6PC2-rs560887 (BF=3.6) and SPTA1-rs857691 (BF=3.0) were individually associated with baseline HbA1c. Their best and significant 2-SNP association was found between HK1-rs17476364 and GCK (BF=13.5; p=0.000015, 0.0038 and 0.0093 for main and interaction terms, respectively). The emerged best 3 and 4 SNP combinations were HK1-GCK-SPTA1 (BF=18.1) and HK1-GCK-SPTA1-G6PC2 (BF=22.0), respectively. For HbA1c change over time, no single SNPs were significant; their best SNP combination involved G6PC2, ADCY5, SLC30A8, HK1, PHB2 and FN3KRP. Glucokinase (GCK product) and hexokinase (HK1 product) are isozymes that interactively and uniquely phosphorylate glucose to make G6P, an important intermediate enabling the coordination of the rate of glycolysis. Together, HK1-GCK interaction for HbA1c was observed first in a large family data with familial clustering of exceptional longevity.

Disclosure
P. An: None. B. Thyagarajan: None. J.H. Lee: None. N. Schupf: None. J.M. Zmuda: None. M. Province: None.

Funding
National Institutes of Health