bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diet Choices at 3 and 12 Months for Women and Their Partners after Recent Gestational Diabetes (GDM)—Results of the Families Defeating Diabetes (FDD) Study
Authors: VEZINA ANICK , MCMANUS RUTH M. , DONOVAN LOIS E. , MILLER DAVID B. , GIROUX ISABELLE T. 
Published: June 2018

Objectives: FDD was a 12 month, multi-centre, Canadian, randomized study translating diabetes-protective messages after GDM. Male partner participation was encouraged. We compared paternal vs. maternal food choices for interventional (INT) and control (CON) participants before and after FDD.
Methods: INT maternal and paternal participants received information promoting high fibre/low fat foods; portion control; healthy restaurant choices via postpartum seminar, access to branded FDD website and twice-monthly email contact. CON maternal subjects received a postpartum healthy living handout. One-day food records at 3 and 12 months were analyzed for fast food intake (FF) and Canada’s Food Guide (CFG) servings.
Results: 15 INT and 16 CON maternal/paternal pairs provided food records at 3 and 12 months. Considering INT and CON cohorts together: paternal and maternal grain products, milk/alternatives and meat/alternatives consumption met CFG guidelines at 3 and 12 months. Paternal and maternal vegetables and fruit (V and F) intakes were similar but lower than recommended (paternal: goal 8-10 servings/day; baseline 3.8±2.2; 12 months 4.6±2.9; maternal: goal 7-8 servings/day; baseline 4.1±2.8; 12 months 5.4±3.2). Paternal FF intake was higher than maternal at baseline: (0.41±0.61 vs. 0.12±0.34; p=0.03) but not at 12 months (0.44±0.62 vs. 0.34±0.40, p=0.6). Paternal and maternal V and F intakes were modestly correlated by 12 months (r=0.35, p=0.05).
Conclusions: Notable paternal and maternal postpartum diet choices were: servings of V and F did not meet CFG recommendations at 3 and 12 months for men or women; paternal FF intake was higher than maternal soon after delivery, but not at 12 months as maternal servings increased; paternal and maternal V and F intakes were correlated at 12 months postpartum. Therefore, it may be helpful to target both paternal and maternal food choices when promoting healthy living after GDM.

Disclosure
A. Vezina: None. R.M. McManus: None. L.E. Donovan: None. D.B. Miller: None. I.T. Giroux: None.
GDM—Impact of BMI in Maternal Bioquimical-Metabolic Variables and Its Association with Macrosomia
Authors: ARGERICH MARIA INES , DAVID RAUL ALEJANDRO , BOCCHINI ANDREA 
Published: June 2018

Maternal Overweight/obesity increases risk of GDM and macrosomia
Objectives: Compare pregestational BMI. Frequency of macrosomia. Correlationship between BMI first trimester fasting glycemia (1stTFG&gt;92) fasting glycemia OGTT (FGOGTT), glycemia 120 minutes OGTT (2HPG), maternal weight gain during pregnancy (MWG) and macrosomía
Research Design Methods: Analysis of 120 GDM medical records using ALAD diagnostic criteria. BMI categories were compared in Groups A ≥30 vs. ≤24.9 B 25-29.9 vs. ≤24.9 C ≥30 vs. 25-29.9 Variables: maternal age (MA), 1stTFG&gt;92; FGOGTT, 2HPG, birth weight (BW), HbA1c, maternal triglyceridemia on last trimester (MTAG) maternal weight gain (MWG) SPSS V22.
Results: BMI ≥30 N:39 BMI 25-29.9 N:42 BMI≤24.9 N:33 Mean HBA1C for all groups 5%. Table 1 comparison groups. Macrosomía N:13 (N:5 BMI 25-29.9 N:8 BMI ≥30 N:0 BMI group ≤24.9) p0.026. Correlation of macrosomia and FG1stT&gt; 92 FGOGTT 2HPG MWG ≥ 7KG in BMI ≥30 is p0.046 p0.017 p0.096 P0.0001 respectively. Correlation between macrosomia and FG1stT&gt; 92 FGOGTT 2HPG MWG ≥ 11KG in BMI 25-29.9 is p0.0001 P0.011 p0.012 p0.001 respectively
Discussion: Pregestational BMI excessive MWG 1stTFG and higher levels of MTAG in BMI ≥30 increases risk of macrosomia. 1stTFG&gt; 92 should considered as an independent risk factor for GD/macrosomia in overweight/obese pregancys. In BMI ≥25 consider lower thresholds of FG for GDM diagnostic criteria to prevent macrosomia.

Disclosure
M. Argerich: None. R. David: None. A. Bocchini: None.
Glycemic Variability during Pregnancy in T1D on CSII
Authors: DADLANI VIKASH , O'MALLEY GRENYE , KULINA GEORGIA , KUMARI KANCHAN , DESJARDINS DONNA , XIE YAN YAN S. , MCCRADY-SPITZER SHELLY K. , THAPA PRABIN , CASTORINO KRISTIN , PINSKER JORDAN E. , DASSAU EYAL , LEVY CAROL J. , KUDVA YOGISH C. 
Published: June 2018

Artificial pancreas (AP) technology is achieving tight and safer glycemic control (GC) in non-pregnant T1D populations but has been insufficiently tested in pregnant T1D patients. We evaluated glucose variability (GV) in pregnant women with T1D on Continuous subcutaneous insulin infusion (CSII) during each trimester to facilitate design of future studies. Data from 17 pregnant women with T1D, age 29 ± 4 years, DOD 17.8 ± 6 years, gestational age at delivery 38.6 ±1 weeks and fetal weight 3525± 524 gms are presented. GV at initial visit and at least 2 weeks per trimester (6-8, 10-12, 21-23, 26-28, 32-34, and 36-38) and maternal/fetal outcomes were analyzed. GV indices are shown in the Table. Mean HbA1c 7.2 ± 1.3% at baseline decreased to 6.6 ± 1.2%, 5.8 ± 0.8% and 6.0 ±0.7% during 1st, 2nd and 3rd trimester respectively. Mean BMI during 1st trimester was 27.7 ± 7.3 kg/m2 and increased to 29 ± 7.7 kg/m2and 31.7 ± 7 kg/m2 during 2nd and 3rd trimesters respectively. 8 subjects had C-section, 7 preeclampsia; 3 excessive blood loss during delivery, and 1 preterm labor, polyhydramnios and maternal infection. Additionally, 4 infants were admitted to intensive care, 4 developed hypoglycemia, one was born with malformation and one with macrosomia. GV and maternal/fetal morbidity continue to be unacceptably high during pregnancy in T1D with current technologies stressing the urgent need for AP development and testing in this context.

Disclosure
V. Dadlani: None. G. O'Malley: None. G. Kulina: None. K. Kumari: None. D. Desjardins: None. Y.S. Xie: None. S.K. McCrady-Spitzer: None. P. Thapa: None. K. Castorino: None. J.E. Pinsker: Research Support; Self; Insulet Corporation, Dexcom, Inc., Tandem Diabetes Care, Inc. E. Dassau: Consultant; Self; Insulet Corporation. Research Support; Self; Insulet Corporation. Consultant; Self; Animas Corporation. Research Support; Self; Dexcom, Inc.. Speaker's Bureau; Self; Roche Diabetes Care Health and Digital Solutions. Research Support; Self; Roche Diabetes Care Health and Digital Solutions, Xeris Pharmaceuticals, Inc.. Consultant; Self; Eli Lilly and Company. Research Support; Self; Tandem Diabetes Care, Inc.. Other Relationship; Self; ModAGC. Research Support; Self; LifeScan, Inc., DreaMed Diabetes, Ltd. C.J. Levy: Advisory Panel; Self; Medtronic MiniMed, Inc.. Research Support; Self; Lexicon Pharmaceuticals, Inc., Dexcom, Inc.. Y.C. Kudva: None.
d-ROMs and BAP as Potential Predictive Factors for New-Onset Diabetes
Authors: OKAHATA SUMIE , SAKAMOTO KENTARO , MITSUMATSU TAKAKO , YANO MASAO , ISHIZAKA YUKO , YAMAKADO MINORU , SHIBA TERUO 
Published: June 2018

Background: Increased oxidative stress plays a role in the progression of atherosclerosis. Yet only few reports in NOD.
Method: Derivatives of reactive oxygen metabolites(d-ROMs) and biological antioxidant potential (BAP) were measured in 859 subjects undergoing general health screenings in both 2011 and 2015. 779 individuals (mean age 60.6, 562 men) were screened for NOD by the following criteria in 2015: (1) confirmed diagnosis of DM, or treatment with antidiabetic agent(s) between 2011 and 2015, (2) FPG≧126mg/dl or 2hPG≧200 mg/dl in 75gOGTT and HbA1c≧6.5%.
Results: Among 779 subjects, 70 were newly screened as DM in 2015. As for data in 2011 FPG (105/97), HbA1c (6.1/5.7), dROM (367/325U.CARR), and CRP (0.34/0.13mg/dl) were significantly higher in NOD population in 2015 than the rest, whereas BAP (2437/2527μmol/L) and BAP/d-ROM(6.86/8.0) significantly lower. In univariate regression analysis by data in 2011, HbA1c was correlated with d-ROMs positively and B/R negatively. By multivariate logistic regression analysis with B/R, BMI, SBP (mmHg), LDL (mg/dl), CRP(mg/dl), and eGFR (ml/min/1.73m2) as explanatory variables, NOD was associated with FBS, HbA1c positively, and B/R negatively.
Discussion and Conclusion: In addition to the conventional risk factors, indices for oxidative stress, B/R derived from d-ROMs and BAP exhibited significant predictive values for NOD by the composite criteria in 2015. Several reports have pointed out the involvement of oxidative stress in micro- and macrovascular complications. Only bilirubin, a powerful antioxidant, has been proven to show preventive value against NOD. Oxidative stress would be positioned as novel indicators for diabetes risk and target for prevention of NOD.

Disclosure
S. Okahata: None. K. Sakamoto: None. T. Mitsumatsu: None. M. Yano: None. Y. Ishizaka: None. M. Yamakado: None. T. Shiba: Speaker's Bureau; Self; Shionogi & Co., Ltd., Pfizer Inc., Merck Sharp & Dohme Corp., Kowa Company, Ltd., Daiichi Sankyo Company, Limited.
Identification and Characterization of a Novel Insulin Sensitizer to Treat Diabetes and Nonalcoholic Steatohepatitis
Authors: CHEN YANA , CHAMBERS KARI , MCDONALD WILLIAM , FINCK BRIAN N. , MCCOMMIS KYLE S. 
Published: June 2018

Thiazolidinediones (TZDs) enhance insulin sensitivity and have efficacy for treating nonalcoholic steatohepatitis (NASH). However, the use of TZDs, like rosiglitazone and pioglitazone, has been curtailed by significant side effects mediated via the peroxisome proliferator-activated receptor γ (PPARγ). We conducted a screen to identify compounds with insulin-sensitizing effects that did not contain a thiazolidinedione ring and act independently of PPARγ. A lead candidate, MSDC-5514, was selected for further study due to its ability to induce uncoupling protein 1 expression in brown adipocyte precursors and an inability to bind and activate PPARγ even at high concentrations. We gavaged diet-induced obese (DIO) mice with 30 mg/kg/day MSDC-5514 for six days. MSDC-5514 treatment did not affect body weight, but completely normalized glucose tolerance in insulin-resistant DIO mice. DIO mice exhibited elevated plasma insulin, free fatty acid, and triglyceride concentrations compared to lean mice, all of which were corrected by MSDC-5514 treatment. Liver diacylglycerol and triglyceride content, which were markedly increased in DIO mice compared to lean controls, were significantly decreased by MSDC-5514. The resolution of hepatic steatosis may be due to increased fatty acid oxidation since the expression of several genes encoding fatty acid oxidation enzymes was significantly elevated in livers from MSDC-5514 treated mice and directly by treatment of hepatocytes with MSDC-5514 in culture. Markers of liver injury and NASH, including plasma ALT and liver expression of markers of inflammation, stellate cell activation, and fibrosis were also attenuated by MSDC-5514 treatment. Although the molecular target of MSDC-5514 remains unclear, chemical-genetic screens are ongoing to identify the mechanism of action.
In conclusion, these data suggest that MSDC-5514 may be a new PPARγ-independent insulin sensitizer with efficacy for treating diabetes and NASH.

Disclosure
Y. Chen: None. K. Chambers: None. W. McDonald: Stock/Shareholder; Self; Metabolic Solutions Development Company, LLC. B.N. Finck: Board Member; Self; Cirius Therapeutics. K.S. McCommis: None.
Screening for Diabetes Mellitus and Gestational Diabetes in a Resource-Poor Setting—Implementing a Selective Protocol
Authors: CABRERA KEVIN A. , PENDI ARIF , LASHKARI NASSIM , EL-TOBGY ERIC , LABROT BEN B. 
Published: June 2018

Background: Screening for diabetes mellitus and gestational diabetes in resource-poor settings requires efficiency. To make the best use of resources, we proposed a selective diabetes screening protocol for patients in rural Panama as a cost-effective solution for diabetes screening in resource-limited settings. We proposed to screen adults aged 35 years or above and pregnant women of all ages.
Methods: Patients that attended a three-day clinic in Bocas del Toro, Panama established by the non-for-profit organization Floating Doctors were screened for non-fasting blood glucose levels. The proposed selective diabetes screening protocol was applied to determine whether it identified patients that were diabetic or prediabetic. Criteria for diabetes and prediabetes were based on existing American Diabetes Association guidelines: patients with a non-fasting blood glucose concentration of ≥200 mg/dl were considered diabetic and patients with a non-fasting blood glucose concentration of ≥140 mg/dl but &lt; 200 mg/dl were considered prediabetic.
Results: Of 84 patients that attended clinic, 2 were diabetic (2.3%) and 55 were prediabetic (65.5%). The sub-group of 41 patients (48.8%) met the selective screening protocol criteria of being at or above the age of 35 years and/or pregnant. This group included 2 patients that screened positive for diabetes (4.9%) and consisted of 16 patients with prediabetes (39.0%). The group excluded by the proposed protocol (51.2%) consisted of no patients with diabetes and 17 with prediabetes (39.5%).
Conclusion: The proposed selective diabetes screening protocol effectively identified all patients with diabetes but only about half the patients with prediabetes, suggesting this protocol may have utility in diagnosing diabetes for treatment purposes. However, because a significant number of prediabetic individuals were excluded, other strategies are necessary for preventative efforts.

Disclosure
K.A. Cabrera: None. A. Pendi: None. N. Lashkari: None. E. El-Tobgy: None. B.B. LaBrot: None.
Characterization of Patients with Type 2 Diabetes (T2D) Who Discontinue DPP-4is following Insulin Initiation
Authors: FERNANDES GAIL , IGLAY KRISTY , LIU ZHIWEN , RAVI SHANKAR R. , GANTZ IRA , RAJPATHAK SWAPNIL 
Published: June 2018

While discontinuation of oral drugs, such as DPP-4i, at the time of insulin initiation is not uncommon, the characteristics associated with this discontinuation are not well understood. We conducted a retrospective database study using the Optum claims data to describe the prevalence of and factors associated with discontinuation of DPP-4i among patients on dual therapy of metformin and DPP-4i after initiating insulin. Our study included adult T2D patients on this dual therapy who initiated insulin (index) from Jan 2006-Sep 2015. 3,388 T2D patients met the study criteria; mean age: 62 years, 55% male, and 61% and 88% reported micro- and macrovascular complications, respectively. 32% (n=1086) of the study population discontinued DPP-4i therapy within 12 months after insulin initiation, with 1075 patients discontinuing in the first 3 months. Median time to discontinuation was 25 days (IQR 13-31 days). Available patient characteristics between continuers vs. discontinuers are described in TABLE. Data available from claims showed that patients who discontinue had higher out of pocket costs and higher proportion of renal and liver disease. Limitation of this study is lack of information on A1C and other clinical variables such as BMI. A Cox regression model will be employed to further investigate if these factors are predictive of discontinuation.

Disclosure
G. Fernandes: Employee; Self; Merck & Co., Inc.. Employee; Spouse/Partner; Janssen Research & Development. Stock/Shareholder; Self; Merck & Co., Inc.. Stock/Shareholder; Spouse/Partner; Janssen Research & Development. K. Iglay: Employee; Self; Merck & Co., Inc.. Stock/Shareholder; Self; Merck & Co., Inc. Z. Liu: Employee; Self; Merck & Co., Inc. R. Shankar: Employee; Self; Merck & Co., Inc.. Employee; Spouse/Partner; NGM Biopharmaceuticals. I. Gantz: Employee; Self; Merck Sharp & Dohme Corp. S. Rajpathak: Employee; Self; Merck & Co., Inc..
Metabolomic Profiling of Nonproteinogenic Amino Acids in Patients with Type 2 Diabetes and Hypertension
Authors: CIOBANU DANA M. , BALA CORNELIA G. , ROMAN GABRIELA 
Published: June 2018

Introduction: Identifying the amino acid signature of increased blood pressure might help us understand hypertension pathophysiology. We aimed to investigate the relationship of non-proteinogenic amino acids with ambulatory blood pressure mean and variability in type 2 diabetes patients.
Methods: Serum non-proteinogenic amino acids’ profiling was performed by high performance liquid chromatography coupled with mass spectroscopy analysis. Blood pressure variability was calculated as standard deviation of mean systolic and diastolic blood pressure evaluated over 24-hour ambulatory monitoring.
Results: The study population consisted of type 2 diabetes hypertensive patients (n=80), 58% women, aged 59.8±7.7 years old with diabetes duration 9.0±8.7 years. Serum non-proteinogenic amino acids levels (nmol/mL) were: gamma-aminobutyric acid 0.2±0.1, aminoisobutyric acid 22.6±7.9, beta-aminoisobutyric acid 1.2±0.7, 4-hydroxyproline 12.2±9.9, 3-methylhistidine 4.7±2.8, alpha-aminoadipic acid 1.0±0.5, sarcosine 11.3±5.6. In linear regression analysis, aminoisobutyric acid was significantly associated with 24-hour systolic blood pressure variability (r=0.23; p=0.044), sarcosine was significantly associated with nighttime systolic blood pressure variability (r=0.27; p=0.017), while beta-aminoisobutyric acid was significantly associated with mean daytime (r=-0.25; p=0.024) and 24-hour (r=-0.24; p=0.032) diastolic blood pressure.
Conclusion: Serum metabolomes aminoisobutyric acid and sarcosine directly associated with ambulatory systolic blood pressure variability, while beta-aminoisobutyric acid inversely associated with mean diastolic blood pressure. Our results indicate changes in serum non-proteinogenic amino acids as consequences of increased blood pressure that should be further evaluated in connection to cardiovascular disease, particularly in the presence of type 2 diabetes.

Disclosure
D.M. Ciobanu: Other Relationship; Self; Sanofi, AstraZeneca, Merck Sharp & Dohme Corp., Eli Lilly and Company, Merck KGaA. C.G. Bala: Consultant; Self; Sanofi, AstraZeneca. G. Roman: None.
Metabolic Inflexibility Revisited—Muscle Substrate Oxidation Is Mechanistically Dissociated from Muscle Insulin Resistance in Rats
Authors: SONG JOONGYU D. , PERRY RACHEL J. , MUNK ALEXANDER , ZHANG YE , ZHANG DONGYAN , SHULMAN GERALD I. 
Published: June 2018

The Metabolic Inflexibility Hypothesis and Randle Hypothesis posit that alterations in muscle glucose and fat oxidation are key factors in the pathogenesis of obesity (lipid)-associated skeletal muscle insulin resistance. In order to test these hypotheses we used a stable isotope tracer ([U-13C]glucose) to measure the ratio of pyruvate dehydrogenase flux and citrate synthase flux (VPDH/VCS), a highly tissue-specific index for the proportional contribution of glucose oxidation to total mitochondrial oxidation in vivo. We found that insulin resistant rats fed a high fat diet (HFD) for 4 weeks did not have altered substrate (VPDH/VCS) oxidation in soleus muscle in the fasting state (5.8%±2.5% vs. 2.6%±1.0%). Hyperinsulinemic-euglycemic clamps increased relative glucose oxidation in both normal and insulin resistant rats, although this increase was blunted in insulin resistant rats (51.6±4.9% vs. 33.3±4.5%, p&lt;0.05), which could be mostly attributed to an impairment in insulin-stimulated muscle glucose transport flux (124.4±18.7 vs. 69.3±11.3 nmol/(g•minute), p&lt;0.05). Additionally, we found that an acute infusion of lipid during a clamp in normal rats significantly reduced relative glucose oxidation in soleus muscle (49.0±3.6% vs. 26.7±2.7%, p&lt;0.001) without any effects on insulin-stimulated peripheral glucose metabolism (27.2±1.4 vs. 24.3±1.5 mg/(kg•minute), NS) or muscle glucose transport (143.8±22.4 vs. 138.1±18.3 nmol/(g•minute), NS).
Conclusion: These data show that basal substrate preference in muscle is not altered in insulin resistant rats and that acute modulation of substrate oxidation in normal rats does not affect muscle insulin sensitivity, therefore challenging the Metabolic Inflexibility Hypothesis and Randle Hypothesis in the pathogenesis of lipid-induced muscle insulin resistance.

Disclosure
J.D. Song: None. R.J. Perry: None. A. Munk: None. Y. Zhang: None. D. Zhang: None. G.I. Shulman: Advisory Panel; Self; AstraZeneca, Janssen Research & Development, Merck & Co., Inc., Novo Nordisk Inc.. Research Support; Self; Gilead Sciences, Inc..
MALAT1 and HOTAIR—Key Epigenetic Regulators in Diabetic Retinopathy
Authors: BISWAS SAUMIK , THOMAS ANU A. , FENG BIAO , CHEN SHALI , AREF-ESHGHI ERFAN , GONDER JOHN , SADIKOVIC BEKIM , CHAKRABARTI SUBRATA 
Published: June 2018

Introduction: With the increasing incidence of diabetic retinopathy (DR), the need for novel and specific therapy is essential. Genomic studies have identified several long non-coding RNAs (lncRNAs). However, majority of lncRNAs have not been characterized in DR. We examined the roles of lncRNAs MALAT1 and HOTAIR in DR.
Methods: Human retinal endothelial cells (HRECs) were cultured in 5 mM/L (NG) or in 25 mM/L (HG) glucose. RNA expressions of MALAT1, HOTAIR, and inflammatory and angiogenic cytokines were tested. HRECs were similarly examined following siRNA-mediated MALAT1 or HOTAIR knockdown, or treatment with histone (DZNep) and DNA methylation (52019-aza-dC) blockers. DNA methylation patterns and RNA-protein interactions were analyzed. Retinal tissues from Malat1 knockout (KO) and wild type (WT) mice with or without diabetes were examined. We further assessed MALAT1 a’nd HOTAIR in human diabetic and nondiabetic vitreous.
Results: HG caused upregulations of MALAT1, HOTAIR, IL-6, TNF-α, and VEGF-A transcripts in HRECs. HG increased binding of EZH2 (a PRC2 component) with MALAT1 and HOTAIR and evoked unique DNA methylation patterns in the MALAT1 and HOTAIR CpG regions. DZNep, 5-aza-dC and knockdown of MALAT1 or HOTAIR reduced mRNA expressions of IL-6, TNF-α, and VEGF-A. Similarly, diabetes-induced elevations of these inflammatory and angiogenic cytokines in the retina were prevented in the Malat1 KO mice. Furthermore, MALAT1 and HOTAIR levels were elevated in the diabetic vitreous.
Conclusions: Our findings allude to the importance of lncRNAs in influencing DR through epigenetic mediators. Understanding the role of lncRNAs may allow the development of better-targeted therapies in DR.

Disclosure
S. Biswas: None. A.A. Thomas: None. B. Feng: None. S. Chen: None. E. Aref-Eshghi: None. J. Gonder: None. B. Sadikovic: None. S. Chakrabarti: None.