bluuebunny/crossref_metadata_2025_split huggingface dataset:
Subclinical Inflammation and Lymphocytes in Subcutaneous and Visceral Adipose Tissue—The Influence of Pregnancy and Gestational Diabetes Mellitus
Authors: CINKAJZLOVA ANNA , ANDERLOVÁ KATEřINA , SIMJAK PATRIK , LACINOVÁ ZDENA , KLOUCKOVA JANA , KRATOCHVILOVA HELENA , KREJCI HANA , MRAZ MILOS , HALUZIK MARTIN , KRSEK MICHAL 
Published: June 2018

Obesity and type 2 diabetes mellitus are accompanied by low-grade inflammation and changed immune cell composition in adipose tissue. However, little is known about subclinical inflammation in gestational diabetes mellitus (GDM). The aim of our study was to analyse lymphocyte populations in subcutaneous (SAT) and visceral adipose tissue (VAT) together with systemic levels and mRNA expression of selected inflammatory markers in these depots and placenta. Thirty-seven pregnant females - 21 with GDM (GDM group) and 16 without GDM (P group) - were included into the study. Blood samples were taken in 28th-32th and 36th-38th gestational week and 6-12 months after delivery and SAT, VAT and placental samples were obtained during delivery. Lymphocytes were assessed as percent of CD45+ cells measured by flow cytometry. In both groups CD45+ lymphocytes were higher in VAT compared to SAT (19.2 ± 2.2 vs. 6.5 ± 0.7%, p&lt;0.001 for GDM and 18.3 ± 3.4 vs.7.8 ±1.6, p=0.0for P, respectively). In GDM group T helper (CD4+) cells were higher in SAT compared to VAT (37.6 ± 2.4 vs. 28.6 ± 2.6%, p=0.019), resulting in a higher ratio of CD4+/CD8+ cells. Similarly, the amount of B (CD19+) and NKT (CD16/56+CD3+) cells was higher in SAT relative to VAT in GDM group, but not in P group. In contrast, NK (CD15/56+CD3-) cells were increased in VAT compared with SAT in GDM group (17.9 ± 3.1 vs. 9.1 ± 1.3%, p=0.015), while no difference was seen in P group. CRP levels did not differ between GDM and P group, while TNF-α concentrations were higher in GDM throughout the study (7.92 ± 0.69 vs. 4.59 ± 0.61 pg/ml, p=0.001). Placental mRNA expression of IL-10 and IL-8 was elevated in GDM vs. P group with no difference between SAT and VAT depots. Taken together GDM is associated with increased systemic TNF-α levels and changed lymphocyte content in different adipose tissue depots. These changes could be in part responsible for increased risk of complications for both mother and child during and after pregnancy.

Disclosure
A. Cinkajzlova: None. K. Anderlová: None. P. Simjak: None. Z. Lacinová: None. J. Klouckova: None. H. Kratochvilova: None. H. Krejci: None. M. Mraz: None. M. Haluzik: None. M. Krsek: None.
The Association of Pregnancy Number and Outcome with Mortality in Type 1 Diabetes
Authors: COSTACOU TINA , RUBINSTEIN DEBRA , ORCHARD TREVOR J. 
Published: June 2018

Women with type 1 diabetes are at greater risk of adverse pregnancy outcomes and complications compared with the general population. Whether the number and outcome of pregnancies predict mortality risk, however, is not well studied. We thus assessed this hypothesis among women with childhood-onset type 1 diabetes. Female participants (n=325, mean age 28 and duration 19 years) of the Pittsburgh Epidemiology of Diabetes Complications (EDC) study, a prospective investigation of childhood onset type 1 diabetes, were selected for study. Pregnancy data were available for 320 women (98.5%). During 25 years of follow-up, 25.9% died (n=83). Excluding women (n=4) with twin pregnancies, no differences were observed in the proportion having been pregnant or in the number of pregnancies by mortality status. However, among those with at least one pregnancy (and adjusting for the total number of pregnancies), deceased were more likely to have had fewer live births and induced abortions but a greater number of spontaneous abortions and stillbirths (all p≤0.05). In multivariable Cox models adjusting for traditional baseline risk factors, having ever been pregnant was associated with a borderline inverse mortality risk (HR=0.65, p=0.07). In addition, among women with at least one pregnancy, adjusting (among other risk factors) for the total number of pregnancies, ≥ 2 spontaneous abortions (HR=3.5, p=0.03); ≥ 2 stillbirths (HR=9.1, p=0.02); and ≥ 2 occurrences of any adverse pregnancy outcome (i.e., tubal/ectopic pregnancies, spontaneous abortions, stillbirths; HR=3.9, p=0.007) were associated with an increased risk of death. Women whose pregnancy outcomes were all spontaneous abortions were at tenfold increased risk for mortality (p=0.004) whereas those with all preterm births were 76% less likely to die (HR=0.24, p=0.06).
In conclusion, adverse pregnancy outcomes among women with type 1 diabetes are associated with a greater mortality risk even after adjustment for traditional risk factors and diabetes control.

Disclosure
T. Costacou: None. D. Rubinstein: None. T.J. Orchard: None.
Comparison of Cardiometabolic Risk Factors in Offspring of Diabetic Mothers (ODM) and Nondiabetic Mothers (ONDM) in India
Authors: WAGLE SONALI S. , KUMARAN KALYANARAMAN , LADKAT RASIKA , BHAT DATTATRAY , YAJNIK PALLAVI C. , YAJNIK CHITTARANJAN S. 
Published: June 2018

Background: Maternal diabetes is a risk factor for obesity and glucose intolerance in the child, and contributes to the escalating epidemic of diabesity. This could have both a genetic and fetal programming basis. Only sparse data is available in India. We followed children born to diabetic and nondiabetic mothers 2-26 years after delivery to assess their cardio-metabolic risk factors.
Methods: Of 861 women diagnosed and treated for diabetes in pregnancy (1986-2014), we traced 346 and studied 200 children (ODM). We also studied 177 children of nondiabetic mothers (ONDM), matched for age, gender and socioeconomic status. We measured anthropometry, body composition (DXA) and a capillary blood glucose (&lt;10y, 119 ODM, 93 ONDM) or a 1.75g/kg OGTT with venous blood (&gt;10y, 81 ODM, 84 ONDM). Overweight+obesity was diagnosed by IOTF (≤18y) or WHO criteria (&gt;18y). Glucose tolerance was classified by the ADA 2014 criteria. We compared cardio-metabolic risk factors in ODM and ONDM by calculating age and gender specific SD scores (reference ONDM).
Results: Three (4%) ODM were known diabetic (diagnosed at 16, 14 and 23y, 2 receiving OHA and 1 insulin), one was diagnosed on testing. ODM had higher BMI, skinfolds, body fat percent, and circulating glucose, insulin, total and LDL cholesterol, and triglyceride concentrations. ODM had higher HOMA-IR and pulse rate but lower disposition index (HOMA-β/HOMA-IR) and diastolic blood pressure. Prediabetes (IFG+IGT) (37 vs. 20%, p=0.005) and overweight+obesity (24 vs. 15%, p=0.014) were more common in ODM compared to ONDM.
Conclusions: We confirm elevated risk of obesity, adiposity, diabetes and other cardio-metabolic risk factors in children of Indian diabetic mothers. Despite following the current standards of practice for GDM management, the offspring continue to have high risk of diabesity. This suggests a need for reevaluation of current standards of care which overlook the peri-conceptional window of fetal programming.

Disclosure
S.S. Wagle: None. K. Kumaran: None. R. Ladkat: None. D. Bhat: None. P.C. Yajnik: None. C.S. Yajnik: None.
Maternal Postprandial Triglycerides in the Home Setting
Authors: BARRETT HELEN L. , DEKKER MARLOES NITERT , DE JERSEY SUSAN J. , D'EMDEN MICHAEL C. , CALLAWAY LEONIE , DAVID MCINTYRE H. 
Published: June 2018

Background and Aims: Elevated maternal triglycerides (TG) have been associated with adverse pregnancy outcomes including an increased risk of preeclampsia and macrosomia. Maternal TG are primarily measured in the fasting state and at single time points during pregnancy. Temporal and prandial changes in TG levels during pregnancy are not well described. The purpose of this study was to examine flux of capillary glucose and TG in late pregnancy, how they are influenced by high and low fat meals, and whether they relate to infant body composition.
Materials and Methods: Women in the third trimester of pregnancy completed 4 days of home capillary glucose and TG monitoring (4 times a day (fasting and two hours post each meal)). Using the Roche Accutrend Plus meter. Each woman consumed an isocaloric high fat (41%) and a low fat (25%) breakfast meal on different days during the study period. Area under the curve (AUC) for the capillary glucose and TG measures after the standardized meals was calculated using trapezoidal approximation. AUC for women with and without GDM was compared for each meal and metabolic measure. Infant body fat % was measured by air displacement plethysmography.
Results: To date, thirteen women, 7 with GDM and 6 normoglycaemic have completed the study. Median capillary glucose levels: fasting 5.0 (95% CI 4.6-5.2) mmol/L and postprandial 6.0 (95% CI 5.7-6.2) mmol/L. Median capillary TG: fasting 3.3 (95% CI 2.9-3.8) mmol/L and postprandial 3.6 (95% CI 3.2-3.8) mmol/L. Mean infant body fat % 10.6 (SD4.9)%. There were no significant differences in capillary glucose or triglycerides between the meals although capillary glucose trended higher with the low fat meal. GDM status did not affect the AUC glucose or AUC triglycerides for either meal.
Conclusion: This study demonstrates that capillary triglycerides can be monitored at home in a similar fashion to capillary glucose. Capillary triglyceride levels were not related to infant anthropometry and did not vary significantly with meal fat content. Recruitment is ongoing.

Disclosure
H.L. Barrett: None. M. Dekker: Speaker's Bureau; Self; Abbott. Other Relationship; Self; Nestlé. S.J. de Jersey: None. M.C. d'Emden: Advisory Panel; Self; AstraZeneca. Speaker's Bureau; Self; AstraZeneca. Advisory Panel; Self; Eli Lilly and Company. Speaker's Bureau; Self; Eli Lilly and Company, Boehringer Ingelheim GmbH. Advisory Panel; Self; Sanofi. Speaker's Bureau; Self; Sanofi, Novo Nordisk A/S, Novartis Pharmaceuticals Corporation. L. Callaway: None. H. McIntyre: Speaker's Bureau; Self; Novo Nordisk Inc.. Research Support; Self; Danish Diabetes Academy.
Maternal Metabolites during Pregnancy Are Associated with Newborn Outcomes
Authors: KADAKIA RACHEL , NODZENSKI MICHAEL , TALBOT OCTAVIOUS , KUANG ALAN , BAIN JAMES R. , MUEHLBAUER MICHAEL , ILKAYEVA OLGA , O'NEAL SARA K. , LOWE LYNN P. , METZGER BOYD E. , SCHOLTENS DENISE , LOWE WILLIAM ,   HAPO STUDY COOPERATIVE RESEARCH GROUP
Published: June 2018

The maternal metabolome serves as a proxy for the fetus’s metabolic environment, but its impact on newborn outcomes is largely unknown. To address this, we determined the association of maternal metabolites with newborn adiposity and hyperinsulinemia in a multiethnic cohort of mother-newborn dyads. Targeted and nontargeted metabolomics assays were performed on fasting and 1 hour serum samples from 1600 mothers in four ancestry groups (Northern European, Afro-Caribbean, Mexican-American, and Thai) who participated in the Hyperglycemia and Adverse Pregnancy Outcome Study, underwent an OGTT at ∼28 weeks gestation, and whose newborns had anthropometric measurements at birth. Maternal metabolite-newborn phenotype associations were investigated using 1) per-metabolite analyses within and across ancestries and 2) network analyses to identify interconnected metabolites associated with phenotypes. Meta-analyses demonstrated more associations of maternal 1 hour vs. fasting metabolites with newborn outcomes. At fasting, maternal triglycerides, valine, pyruvate, and acylcarnitine (AC) C20 were associated with newborn birthweight, cord C-peptide, and/or sum of skinfolds (SSF). At 1 hour, several amino acids (AAs), ACs, fatty acids (FA), and lipid metabolites were associated with one or more of these same outcomes in models adjusted for maternal BMI or glucose. For example, the branched-chain amino acid valine and its carnitine ester AC C4/Ci4 were associated with cord C-peptide at 1 hour independent of maternal BMI or glucose. Network analyses revealed clusters of fasting ACs, AAs, FA and lipid metabolites associated with cord C-peptide and SSF, with the addition of branched-chain and aromatic amino acids at 1 hour. Maternal metabolites during pregnancy, particularly 1 hour post glucose, are associated with fetal adiposity and hyperinsulinemia, independent of maternal BMI and glycemia, and provide insight into the interrelationship between maternal metabolism and newborn size.

Disclosure
R. Kadakia: None. M. Nodzenski: None. O. Talbot: None. A. Kuang: None. J.R. Bain: None. M. Muehlbauer: None. O. Ilkayeva: None. S.K. O'Neal: None. L.P. Lowe: None. B.E. Metzger: None. D. Scholtens: None. W. Lowe: None.
Maternal Central Obesity and Birth Size—A Mendelian Randomization Analysis
Authors: HUANG TAO , GENG TINGTING 
Published: June 2018

Background: Observational studies have illustrated that maternal central obesity is associated with birth size,including of birth weight, birth length and head circumference, but the causal nature of these associations remains unclear.
Objective: To test the causal effect of maternal central obesity on birth size and puberty height growth using a Mendelian randomization (MR) analysis.
Methods: We performed two-sample MR using summary-level genome-wide public data from the Genetic Investigation of Anthropometric Traits (GIANT) Consortium and the Early Growth Genetics Consortium (EGG). Thirty-five single nucleotide polymorphisms (SNPs), 25 SNPs and 41SNPs were selected as instrumental variables for waist-to-hip ratio adjust BMI (WHRadjBMI), waist circumference adjust BMI (WCadjBMI) and hip circumference adjust BMI (HIPadjBMI), respectively to test the causal effects of maternal central obesity on birth size and puberty height using an inverse-variance-weighted approach.
Results: In this MR analysis, we found no evidence between genetic instrumental variables for waist circumference (WC)or waist-to-hip ratio (WHR) and the outcomes. We observed one standard deviation (SD) increase in hip circumference (HC) was associated with a 0.392 SD increase in birth length (p=1.1×10-6) and a 0.168 SD increase in birth weight (p=7.1×10-5), respectively.In addition, higher genetically predicted maternal HP was strongly associated with the puberty heights (0.835 SD, p=8.4×10-10). However,HP was not associated with head circumference(p=0.172).
Conclusion: A genetic predisposition to higher maternal HC was causally associated with larger offspring birth weight,higher birth length, and puberty height independent of maternal BMI. However, we found no evidence of a causal association between maternal WC, WHR and birth size.

Disclosure
T. Huang: None. T. Geng: None.
Nocturnal Insulin Requirements Are Higher in Pregnant Hispanic Women with Type 2 DM
Authors: EHRIG JESSICA C. , ALLSHOUSE AMANDA A. , BARBOUR LINDA A. 
Published: June 2018

T2DM is rapidly rising in pregnancy, especially in Hispanic women (HW). Classically, OBGYNs are taught to manage T2DM with a split dose NPH/Regular, especially if cost is a concern. OBGyn textbooks advise that 2/3 of total NPH be given in the am; 1/3 in pm based on historical data in Caucasians with T1DM. However, HW often display greater fasting glucoses (FBG) secondary to hepatic insulin resistance. We tested the hypothesis that more HW who are adequately controlled would require &gt;50% of their NPH at night compared to non-Hispanic (NHW). All 667 pregnant women with T2DM at our county hospital from 2010-2016 were evaluated for inclusion (insulin treatment by 22 weeks, ≥5 prenatal visits, and ≥4/7 FBG≤95 mg/dl and A1C &lt;6.5 by term). Our primary endpoint was tested with χ2; differences over time with generalized linear mixed-effects modeling. Inclusion criteria were met by 102 (81 HW and 21 NHW). Mean A1C decreased from baseline to term (7.7 to 5.9; 7.2 to 5.9 respectively). By term, more HW required &gt;50% of NPH at night (51% vs. 19%, p=0.009). Fig. 1 shows at each prenatal visit, significantly more HW required &gt;50% NPH at night (p&lt; 0.05). Hispanic women require a higher % of NPH at night throughout gestation and at term to achieve adequate control. This novel finding questions the efficacy of traditional split dosing of NPH/Reg in HW and could lead to a change in dosing strategies and earlier FBG control, essential to improve outcomes.

Disclosure
J.C. Ehrig: None. A.A. Allshouse: None. L.A. Barbour: None.
Predicting Diabetes in the First Two Years Postpartum among Women with Recent Gestational Diabetes—The Linda-Brasil Study
Authors: CASTILHOS CRISTINA D. , LADWIG RUBEN , DREHMER MICHELE , DUNCAN BRUCE B. , FACANHA CRISTINA , SCHMIDT MARIA I. 
Published: June 2018

Background: GDM is a strong risk factor for early development of diabetes. Yet, adherence to protocols for testing at postpartum is usually low. We investigated the main predictors of diabetes up to two years post-partum among women with recent GDM participating in the LINDA-Brasil cohort.
Methods: We recruited potential participants with GDM for an ongoing clinical trial of postpartum diabetes prevention, LINDA-Brasil. We ascertained diabetes by OGTT. We estimated relative risks and 95% CIs, and area under the ROC curve (AUC) for diabetes postpartum through logistic regression.
Results: We recruited 27women with GDM, of whom 1482 (55%) underwent OGTT testing postpartum. Among these, mean (SD) pre-pregnancy BMI was 30.2 (6.4) kg/m2 and mean age, 32.0 (6.3) years; 316 (21.3%) used insulin during pregnancy, an additional 314 (21.2%) oral hypoglycemic agents (OHAs). During follow-up, 163 (11%) developed diabetes. Use of insulin during pregnancy predicted a six-fold higher crude risk of developing diabetes postpartum (RR 6.7; 95% CI 4.7-9.4) and of OHAs, a two-fold risk (RR=2.0; 95% CI 1.4-2.9). The inclusion of just these two variables yielded an AUC of 0.754; adding fasting and 2h plasma glucose at the diagnosis of GDM increased it to 0.810; further addition of age and pre-pregnancy BMI increased it minimally (0.813), and age was not statistically significant. Most incident cases used insulin (59%) or OHAs alone (20%) during pregnancy, thus, 79% of all cases (sensitivity) could be identified as being at high risk just by this information. Stated as post-test probabilties, 20% of those using antidiabetic medication during pregnancy but only 4% of those not using medication developed diabetes.
Conclusions: Simple clinical or administrative information can be effectively used to prioritize screening and counselling for diabetes prevention in the initial years following pregnancy complicated by GDM.

Disclosure
C.D. Castilhos: None. R. Ladwig: None. M. Drehmer: None. B.B. Duncan: Research Support; Self; Eli Lilly and Company. Research Support; Spouse/Partner; Eli Lilly and Company. C. Facanha: None. M.I. Schmidt: Research Support; Self; Eli Lilly and Company. Research Support; Spouse/Partner; Eli Lilly and Company.
White Coat Hypertension in Early Pregnancy Is Prevalent in Women with Type 1 and Type 2 Diabetes
Authors: VESTGAARD MARIANNE , ÁSBJÖRNSDÓTTIR BJÖRG , RINGHOLM LENE , JENSEN DORTE M. , TORVIN ANDERSEN LISE LOTTE , DAMM PETER , MATHIESEN ELISABETH R. 
Published: June 2018

Aim: Verifying the diagnosis of hypertension in pregnancy by home blood pressure (BP) or 24-h BP measurements is recommended (ACOG, 2013) to avoid over-treatment of white coat hypertension. In pregnancy a threshold of 140/90 mmHg measured by office BP is normally used, but in our center, we use a threshold of ≥135/85 mmHg for antihypertensive therapy in women with diabetes. The prevalence of white coat hypertension in pregnant women with diabetes is unknown. We explored the prevalence of white coat hypertension in early pregnancy in women with type 1 (T1DM) and type 2 (T2DM) diabetes.
Methods: Home BP was measured for 3 days (18 measurements in total) at median 67 gestational days (range 33-139), within a week of office BP measurement. The women were divided in groups: treated hypertension, white coat hypertension (office BP ≥135/85 mmHg and mean home BP &lt;130/80 mmHg), true new-onset hypertension (office BP ≥135/85 mmHg and mean home BP ≥130/80 mmHg), masked hypertension (office BP &lt;135/85 mmHg and home BP ≥130/80 mmHg) and normotension (office BP &lt;135/85 mmHg and mean home BP &lt;130/80 mmHg).
Results: In total 178 (72%) out of 244 consecutive pregnant women with diabetes were included: 107 women with T1DM and 71 women with T2DM with mean age 31±5 and 34±5 years and mean BMI 27±6 and 34±5 kg/m2, respectively. Treated hypertension was present in 11 (6%). In total 20/27 (74%) of the remaining women with hypertension measured by office BP ≥135/85 mmHg had white coat hypertension (85% (12/14) of women with T1DM and 62% (8/13) in women with T2DM). Among women with office BP ≥140/90 mmHg 8/9 (89%) had white coat hypertension (home BP &lt;135/85 mmHg). True new onset hypertension was seen in 7 (4%). One women had masked hypertension and the remaining 139 (78%) were normotensive.
Conclusion: White coat hypertension in early pregnancy is prevalent in women with T1DM and T2DM. These data support routine home BP measurement before initiating antihypertensive therapy in this population.

Disclosure
M. Vestgaard: None. B. ásbjörnsdóttir: None. L. Ringholm: None. D.M. Jensen: None. L. Andersen: None. P. Damm: Advisory Panel; Self; Novo Nordisk A/S. Other Relationship; Self; Novo Nordisk A/S. E.R. Mathiesen: Speaker's Bureau; Self; Novo Nordisk A/S. Other Relationship; Self; Novo Nordisk A/S, Novo Nordisk Foundation, Novo Nordisk A/S.
Medical Nutrition Therapy for Gestational Diabetes Mellitus (GDM) Based on Mediterranean Diet Principles
Authors: DURAN ALEJANDRA , ASSAF-BALUT CARLA , DE LA TORRE NURIA GARCIA , FUENTES MANUEL , BORDIU ELENA , VALLE LAURA DEL , BARABASH ANA M. , CUESTA MARTIN , RUBIO MIGUEL A. , CALLE ALFONSO L. 
Published: June 2018

Background: Medical nutrition therapy (MNT) is the first-line therapy to achieve glycemic control in women with gestational diabetes mellitus (GDMw). It has been associated with better pregnancy outcomes. Whether MNT can make pregnancy outcomes like women without GDM remains unknown.
Objective: To assess if a Mediterranean-diet-based medical nutrition therapy (MNT) facilitates near-normoglycemia (determined by HbA1c levels) at 36-38 gestational weeks in GDMw, and observe its effects on adverse pregnancy outcomes.
Study Design: A sub-analysis of the St Carlos GDM Prevention Study. It was conducted between January-December 2015 in the Hospital Clínico San Carlos (Madrid, Spain). One thousand consecutive normoglycemic women were included before 12th gestational weeks, and 874 included in the final analysis: 177 were diagnosed with GDM (IADPSG criteria) and 697 had normal glucose tolerance. GDMw received Mediterranean diet-based MNT, with a daily intake of ≥40 ml extra-virgin olive oil and a handful of nuts (mainly pistachios).
Results: GDMw had higher HbA1c levels, fastinG insulin and HOMA-IR at 24-28 gestational weeks as compared with NGT. At 36-38 gestational weeks these values became similar. Insulin therapy was necessary in 26.6% of GDMw. Rates of macrosomia, large-for-gestational-age, pregnancy-induced hypertensive disorders, prematurity and c-sections were similar between groups. Crude RR analysis showed that GDMw had a higher risk of insufficient weight gain [2.37(1.64-3.30), P=.001], urinary tract infection [1.69(1.20-2.38), P=.005], small-for-gestational age newborns [2.05(1.29-3.24), P=.009] and neonate ICU admission [3.42(1.45-8.04), P=.006].
Conclusions: Using a Mediterranean-diet-based MNT in GDMw helps to achieve a near-normoglycemia, making most pregnancy outcomes similar to women with NGT. The higher rates of small-for-gestational-age and insufficient weight gain require further analysis.

Disclosure
A. Duran: None. C. Assaf-Balut: None. N. Garcia de la Torre: None. M. Fuentes: None. E. Bordiu: None. L. Del Valle: None. A.M. Barabash: None. M. Cuesta: None. M.A. Rubio: None. A.L. Calle: None.