bluuebunny/crossref_metadata_2025_split huggingface dataset:
141-OR: Regulation of Mitochondrial Dynamics in Brown Adipocytes by the Endoplasmic Reticulum-Associated Degradation
Authors: ZHOU ZHANGSEN , TORRES MAURICIO , QI LING 
Published: June 2019

Recent studies have implicated the endoplasmic reticulum (ER) in organelle crosstalk including mitochondria; however, the underlying molecular mechanism and physiological significance remain largely unclear. Here we show that the Sel1L-Hrd1 protein complex of the most conserved ER-associated protein degradation (ERAD) in brown adipocytes is essential for cold-induced thermogenesis in part by managing mitochondrial dynamics. While largely indistinguishable from their wild type littermates, adipocyte or brown adipocyte-specific Sel1L-deficient mice are cold sensitive. Mechanistically, we found that mitochondria in Sel1L-deficient brown adipocytes are dysfunctional with a large portion of them being enlarged and becoming irregularly shaped, i.e., “megamitochondria,” as a result of attenuated fission. Moreover, Sel1L deficiency in cold-stimulated brown adipocytes alters ER-mitochondrial contact and consequently, mitochondria grow around ER tubules leading to the formation of unique intramitochondrial tubule(s). Lastly, brown adipocyte-specific Hrd1-deficient mice exhibit similar phenotypes in terms of cold sensitivity, mitochondrial morphology and dynamics, but not Ire1a- and β-adrenergic receptors-deficient mice. We conclude that Sel1L-Hrd1 ERAD in brown adipocytes is intimately involved in the regulation of mitochondrial dynamics in thermogenesis and provides exciting novel insights into the emerging field of organelle crosstalk.

Disclosure
Z. Zhou: None. M. Torres: None. L. Qi: None.

Funding
American Diabetes Association (1-19-PDF-093 to Z.Z.); National Institutes of Health
1413-P: Nutrient and Fuel-Mediated Teratogenesis in Fetal Growth and Body Composition
Authors: DESHMUKH MADHURA K. , BHALERAO ABOLI A. , RAUT DEEPA A. , MEMANE NILAM S. , KAMAT RAJASHREE , BHAT DATTATRAY , DAMLE HEMANT , WAGLE SONALI S. , YAJNIK CHITTARANJAN S. 
Published: June 2019

Background: Maternal nutrition during pregnancy is a strong determinant of fetal size, body composition and future health. A few studies have measured detailed neonatal anthropometry and body composition. We studied the association between maternal pregnancy measurements and neonatal size and body composition in GDM and NGT pregnancies.
Methods: Mothers from antenatal clinics were tested with 75gm OGTT (IADPSG criteria). Maternal demographic, anthropometric, and nutritional (vit B12, folate, homocysteine) and metabolic (glucose, insulin, lipids) measurements were obtained. Detailed neonatal anthropometry and body composition (DXA) were measured. We studied maternal predictors of neonatal size and composition by adjusting for socio economic status (SES), gestation at delivery and sex of baby.
Results: We studied 398 pregnancies (234 NGT, 164 GDM). GDM mothers were older, more affluent, obese, and had higher triglycerides but lower HDL and total cholesterol concentrations compared to NGT mothers. Neonates of GDM mothers were heavier and more adipose (skinfolds, DXA body fat%) but 25% were SGA (INTERGROWTH). In addition to the conventional predictors (maternal size, adiposity and weight gain), we found novel associations of neonatal size (birthweight and length) with maternal folate (direct) and homocysteine (inverse) and of neonatal adiposity with maternal glucose and insulin resistance (direct), and HDL cholesterol and disposition index (inverse).
Conclusion: Our results highlight a role for maternal micronutrient nutrition, fuels and insulin resistance in influencing neonatal size and body composition. These findings expand the concept of ‘fuel mediated teratogenesis’ (Freinkel, 1980) to ‘dual teratogenesis’ (Yajnik, 2009) and offer additional opportunities to improve fetal growth and body composition. Increasing dietary methyl donors may be useful in addition to controlling maternal insulin resistance may reduce fetal adiposity.

Disclosure
M.K. Deshmukh: None. A.A. Bhalerao: None. D.A. Raut: None. N.S. Memane: None. R. Kamat: None. D. Bhat: None. H. Damle: None. S.S. Wagle: None. C.S. Yajnik: None.
1419-P: Pregravid Metabolic Syndrome and Risk of Adverse Outcomes in Pregnancy: A Preconception Cohort Study
Authors: RETNAKARAN RAVI , WEN SHI WU , TAN HONGZHUAN , YE CHANG , SHEN MINXUE , SMITH GRAEME N. , WALKER MARK C. 
Published: June 2019

Women with a history of adverse outcomes in pregnancy (including pre-term birth, delivery of a small-for-gestational-age (SGA) infant, preeclampsia, and gestational diabetes (GDM)) have a higher prevalence of metabolic syndrome (MetS) and cardiovascular disease, as compared to their peers. However, it is not known if MetS precedes the index pregnancy in women who develop these outcomes. Thus, we sought to evaluate the impact of pre-gravid MetS on the risk of adverse outcomes in pregnancy. In this prospective pre-conception cohort study, 1183 newly-married women underwent systematic assessment of cardiovascular risk factors (anthropometry, blood pressure, lipids, glucose) and then were followed across a subsequent pregnancy for the outcomes of interest. The women were stratified into two groups based on the presence (n=49) or absence (n=1134) of pre-gravid MetS (harmonized definition). The groups did not differ in length of gestation (p=0.31) or infant birthweight (p=0.21). Of note, women with pre-gravid MetS were more likely to have a Caesarean delivery (61.4% vs. 38.6%, p=0.003). However, there were no differences between the groups in the incidence of pre-term delivery, SGA, LGA, preeclampsia or GDM (Table).
In conclusion, the increased lifetime risk of MetS observed in women with a history of these adverse pregnancy outcomes does not necessarily manifest prior to their pregnancy.

Disclosure
R. Retnakaran: Consultant; Self; Eli Lilly and Company, Novo Nordisk Inc., Sanofi. Research Support; Self; Boehringer Ingelheim International GmbH, Novo Nordisk Inc. S. Wen: None. H. Tan: None. C. Ye: None. M. Shen: None. G.N. Smith: None. M.C. Walker: None.

Funding
Canadian Institutes of Health Research
1430-P: Time Trends in Pregnancy-Related Outcomes among U.S. Women with Type 1 Diabetes Mellitus, 2004-2017
Authors: HELMAN SARIT , JAMES-TODD TAMARRA , BELLAVIA ANDREA , MCELRATH THOMAS , BROWN FLORENCE M. 
Published: June 2019

Objective: To examine a knowledge gap in U.S pregnant women with type 1 diabetes mellitus for time trends in maternal characteristics (i.e., maternal body mass index (BMI), nephropathy and gestational weight gain); treatment (i.e., glycemic control, insulin pumps and continuous glucose monitors (CGMs) use); and delivery outcomes (i.e., gestational age at delivery, birth weight and mode of delivery).
Research Design and Methods: We extracted clinical data from the medical records of 755 pregnant women seeking care at the Joslin and Beth Israel Deaconess Medical Center Diabetes in Pregnancy Program. Eligible women were 18 years old, had a singleton pregnancy, had clinically diagnosed type 1 diabetes mellitus and delivered from 2004-2017. We calculated means for continuous variables; proportions for categorical variables. We calculated P-values for trend over time. P- values &lt; 0.05 were considered statistically significant.
Results: Between 2004 and 2017 the use of insulin pumps and CGMs increased from 38% to 71%, and 0% to 39%, respectively (p&lt;0.0001). Despite these changes in treatment, HbA1c in each trimester was unchanged across the analysis period. The rates of nephropathy decreased from 4.6% to 0.4% (p=0.004). Excessive gestational weight gain increased (p=0.03). Gestation length also increased (p=0.008), as well as the rates of vaginal deliveries (p=0.007). Birth weight also appeared to increase over time marginally (p=0.06). However, the rates of macrosomia and large for gestational age (LGA) neonates, did not change.
Conclusion: Changes in treatment and guidelines may have improved specific pregnancy outcomes (i.e., gestation length and mode of delivery). However, other outcomes may need more attention, including excessive gestational weight gain, macrosomia, and LGA.

Disclosure
S. Helman: None. T. James-Todd: None. A. Bellavia: None. T. McElrath: None. F.M. Brown: None.
1432-P: Local Glucose Source for Gestational Diabetes Screening in Resource-Limited Settings
Authors: RONCIERE LEANNE , CORIOLAN BIDJINIE-STEFFY , DESTINE RODNEY , BELANGER-BISHINGA CLEMENT , MALHAME ISABELLE , VON OETTINGEN JULIA E. ,   DYAMAN STUDY GROUP
Published: June 2019

Background: In resource-limited settings, screening for gestational diabetes (GDM) is not routine. Standard commercial glucose preparations are often not available.
Objectives: To test a locally accessible, cheaper alternative glucose source (AGS) for GDM screening in Haiti.
Methods: Double cross-over trial of 138 pregnant women 24-28 weeks gestational age. Two one-step 75g oral glucose tolerance tests (oGTT) with capillary blood glucose (CBG) obtained at 0, 1 and 2h were performed 3-5 days apart with the standard glucose drink Glucola and with AGS. Each participant served as her own control. Logistic and linear regression were used to assess AGS-CBG as a predictor of GDM and of Glucola-CBG, respectively. Tolerance of AGS was surveyed.
Results: Fourteen women (10%) had GDM, and 5, 2, and 7 were diagnosed based on Glucola-CBG of &gt;92, &gt;180, and &gt;163 mg/dl at 0, 1 and 2h, respectively. At 1 and 2h, mean AGS-CBG vs. Glucola-CBG was 107 vs. 126 (p&lt;.0001) and 89 vs. 113 mg/dl (p&lt;.0001), respectively, and they were positively correlated (r=0.65 and r=0.68, p≤0001). The 1h AGS-CBG had an area under the curve of 0.82 (p=0.0002) to predict GDM. A cut-off of ≥120 mg/dl had a sensitivity, specificity, positive and negative predictive value of 100%, 78%, 25% and 100% to predict GDM not diagnosed by a fasting CBG.
Conclusion: Using a fasting CBG of &gt;92 mg/dL and a 1h post-AGS CBG of ≥120 mg/dL, AGS can determine the need for a Glucola-based oGTT, avoiding 3 out of 4 Glucola based tests. Women prefer AGS over Glucola.

Disclosure
L. Ronciere: None. B. Coriolan: None. R. Destine: None. C. Belanger-Bishinga: None. I. Malhame: None. J.E. von Oettingen: None.

Funding
McGill University
1438-P: Antidiabetic Medication and Risk of Dementia in Patients with Type 2 Diabetes
Authors: WIUM-ANDERSEN IDA , OSLER MERETE , BALSLEV JØRGENSEN MARTIN , RUNGBY JØRGEN , WIUM-ANDERSEN MARIE 
Published: June 2019

Background: Diabetes is a risk factor for dementia, but whether antidiabetic medication decreases the risk is unclear. We examined the association between antidiabetic medication and dementia.
Methods: We performed a nested case-control study within a cohort of all 176,250 patients registered with type 2 diabetes in the Danish National Diabetes Register between 1995-2012. This population was followed for dementia diagnosis or anti-dementia medication use until May 2018. Using risk-set sampling, each dementia case (n=11,619) was matched on follow-up time and calendar year of dementia with four controls randomly selected among cohort members without dementia (n=46,476). Ever use and mean daily defined dose of antidiabetic medication was categorized in types (insulin, metformin, sulfonylurea and glinides combined, glitazone, dipeptidyl peptidase 4 (DPP-4) inhibitors, glucagon-like peptide 1 (GLP-1) analogs, sodium-glucose transport protein 2 (SGLT2) inhibitors and acarbose). Conditional logistic regression models were fitted to calculate odds ratios (ORs) for dementia associated with antidiabetic medication use, adjusting for potential confounders.
Results: Use of metformin, DPP-4 inhibitors, GLP-1 analogs, and SGLT2 inhibitors were associated with lower odds of dementia after multiple adjustments (ORs of 0.90 (95% confidence interval (CI) 0.86-0.96), 0.80 (95% CI 0.73-0.88), 0.53 (95% CI 0.38-0.74), and 0.53 (95% CI 0.38-0.74), respectively), with a gradual decrease in odds of dementia for each increase in daily defined dose. Analyses of the most frequent treatment regimens did not show any synergistic effects of combined treatment.
Conclusion: Use of metformin, DPP-4 inhibitors, GLP-1 analogs and SGLT2 inhibitors were associated with lower risk of dementia in patients with type 2 diabetes. If confirmed in future studies these antidiabetics should be considered in interventions to prevent dementia.

Disclosure
I. Wium-Andersen: None. M. Osler: None. M. Jørgensen: None. J. Rungby: None. M. Wium-Andersen: None.

Funding
Jaschafonden; Lundbeck Foundation; Danish Medical Association; Danish Diabetes Association; M.D. Gerhard Linds Grant; Lundbeck Foundation/Novo Nordisk Foundation; Family Hede Nielsen Foundation; Holger Rabitz and Wife Doris Mary, born Phillip’s Memorial Foundation
1443-P: The Association between Hepatic Steatosis and Skeletal Muscle Mass Index in Korean Patients with Type 2 Diabetes
Authors: SEO DA HEA , JUNG MIHYE , AHN SEONG HEE , HONG SEONGBIN , NAM MOON-SUK , LEE YONG-HO , CHOI YOUNGJU , HUH BYOUNG WOOK , HUH KAP BUM , KIM SO HUN 
Published: June 2019

Background and Aims: Recent epidemiological studies have suggested the association between sarcopenia and nonalcoholic fatty liver disease (NAFLD) in the general population. However, the association between skeletal muscle mass and hepatic steatosis in patients with type 2 diabetes mellitus (T2DM) has not been well studied. Therefore, we investigated the association between skeletal muscle index (SMI) and hepatic steatosis in patients with T2DM.
Methods: In this cross-sectional study, a total of 5,394 patients (2,718 men and 2,676 women) with T2DM were recruited from the outpatient clinic of Huh’s Diabetes Center from 2003 to 2016. Those patients who had a history of viral or other liver diseases or had alcohol consumption ≥140 g/week were excluded from the study. Skeletal muscle mass was estimated from bioimpedance analysis measurements and skeletal muscle mass index (SMI, %) was defined as skeletal muscle mass (kg)/total body weight (kg) × 100. NAFLD was defined as the presence of hepatic steatosis on ultrasonography.
Results: Thirty-six percent of men and 38% of women had NAFLD. Those with NAFLD had higher body mass index (BMI), waist circumference (WC), HbA1c, total cholesterol, triglyceride and blood pressure and lower HDL-cholesterol. SMI was lower in those with NAFLD (44.7 ± 8.1 vs. 45.7 ± 8.6%, p&lt;0.001 in men and 37.6 ± 8.3 vs. 38.7 ± 8.9%, p=0.002 in women). Lower SMI tertiles were independently associated with higher prevalence of NAFLD (Ptrend&lt;0.001). Odds ratio for NAFLD was 1.72 (95% confidence interval [CI] 1.25-2.37; p = 0.001) in patients with lowest SMI tertile compared with highest tertile after adjusting for possible confounding factors.
Conclusion: Low skeletal muscle mass is independently associated with NAFLD in patients with T2DM. These findings suggest that sarcopenia is a risk factor for NAFLD in patients with T2DM.

Disclosure
D. Seo: None. M. Jung: None. S. Ahn: None. S. Hong: None. M. Nam: None. Y. Lee: None. Y. Choi: None. B. Huh: None. K. Huh: None. S. Kim: None.

Funding
National Research Foundation of Korea (2017R1D-1A1B03034581)
1453-P: Glycemic Profiles and Insulin Use in 2,313 Medicare-Eligible Older Adults with Diabetes Using the Omnipod Insulin Management System with Cloud-Based Data Management
Authors: LAYNE JENNIFER E. , HE JIALUN , JANTZ JAY , ZHENG YIBIN , BENJAMIN ERIC , LY TRANG T. 
Published: June 2019

Increased access and reimbursement for insulin pumps is critically important for older adults. Recently the Centers for Medicare and Medicaid Services (CMS) issued guidance that the tubeless Omnipod® Insulin Management System (Insulet Corp., Acton, MA) is eligible for coverage under the Medicare Part D (prescription drug) program. This observational study is the first report of glycemic profiles and insulin use in a large cohort of adults aged ≥65 years with diabetes using the Omnipod System and integrated BG meter (Abbott Diabetes Care Inc, Alameda, CA) with a data management system (Glooko, Mountain View, CA). Data uploaded from the pump system to the data management system from January 2015 through September 2018 were matched via device serial number to a second database of self-reported demographic data and de-identified. BG data and insulin use patterns from ≥3 mo of system use per patient were analyzed. Glycemic outcomes included mean glucose, estimated A1C and percent time in range 70-180, &lt;70 and &gt;180 mg/dL. Patients (n=2,313) were mean age 69.7 y (range 65-96 y), 53% female, 23% T1D, 12% T2D, 1% other and 64% not reported. Three percent used CGM for &gt;50% of overall time of system use. Mean glucose was 168±32 mg/dL with an estimated A1C of 7.5%. Percentage time in range 70-180, &lt;70 and &gt;180 mg/dL was 56.8±16.5, 5.3±4.8 and 38.0±17.2, respectively. The total daily insulin was 43.5±22.1 U/d delivered as 55% basal/45% bolus. There was an average of 4.3±1.9 bolus deliveries per day and the average bolus amount was 4.8±3.2 U. These real-world data of a large cohort of Medicare-eligible older adults with diabetes suggest that use of a tubeless insulin pump was associated with glycemic profiles that compare favorably to large national registry data including the T1D Exchange. These results also highlight the importance of access and choice of insulin delivery technology for older adults with diabetes to optimize treatment outcomes.

Disclosure
J.E. Layne: Employee; Self; Insulet Corporation. J. He: Employee; Self; Insulet Corporation. J. Jantz: Employee; Self; Insulet Corporation. Employee; Spouse/Partner; Insulet Corporation. Y. Zheng: Employee; Self; Insulet Corporation. Stock/Shareholder; Self; Insulet Corporation. E. Benjamin: Employee; Self; Insulet Corporation. T.T. Ly: Employee; Self; Insulet Corporation.

Funding
Insulet Corporation
1457-P: Residential Segregation, Hemoglobin A1c, and Risk of Cardiovascular (CVD) Events: The Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study
Authors: CUMMINGS DOYLE M. , PATIL SHIVAJIRAO P. , LONG D. LEANN , CARSON APRIL P. , CHERRINGTON ANDREA , SAFFORD MONIKA , JUDD SUZANNE , HOWARD VIRGINIA J. , HOWARD GEORGE 
Published: June 2019

Higher A1c has been associated with an increased risk of CVD but the role of social determinants of health is poorly described. We examined the association of A1c with incident CVD and whether this varied by residential segregation. This case-cohort study included 2,273 participants from a stratified random sample at baseline (2003-2007) and 1,927 participants with incident CVD, both free of CVD at baseline (mean age 65.7 ± 10.6; 48% African American; 52% female; 17.7% with diabetes). During a median follow-up of 7.7 years., there were 171 strokes and 195 CHD events adjudicated among those with diabetes; 504 strokes and 494 CHD events adjudicated among those without diabetes. Cox proportional hazards models were used to examine the association between higher baseline A1c and time to incident CVD. Models sequentially adjusted for demographics, risk factors (BP, cholesterol, smoking, BMI), individual socioeconomic status (education; income), and tract-level residential segregation indices derived from census data (dissimilarity index, interaction index, isolation index). Additional models included two-way interactions of A1c with each residential segregation index. Higher A1c was associated with an increased risk of CVD [HR = 1.20 (95% CI: 1.06-1.37) per 1 unit increase in A1c] among those with diabetes in the fully adjusted model. However, there was no association among those without diabetes [HR = 0.94 (95% CI: 0.77-1.16)]. Two-way interactions with A1c were significant (p for interaction) for each residential segregation index for those with diabetes: dissimilarity index (p=0.01), interaction index (p=0.04), and isolation index (p=0.02). However, only the A1c and interaction index was significant among those without diabetes. Residential segregation may impact the relationship of higher A1c with risk for incident CVD; this association may be stronger among diabetic individuals with greater residential segregation.

Disclosure
D.M. Cummings: None. S.P. Patil: Research Support; Self; Novo Nordisk Inc. D. Long: None. A.P. Carson: Research Support; Self; Amgen Inc. A. Cherrington: None. M. Safford: None. S. Judd: None. V.J. Howard: None. G. Howard: None.

Funding
National Institutes of Health
1461-P: Cardiac Troponin T and Troponin I and Incident Diabetes in the General Population: Generation Scotland Scottish Family Health Study
Authors: WELSH PAUL , PREISS DAVID , CAMPBELL ARCHIE , PORTEOUS DAVID J. , MILLS NICHOLAS L. , SATTAR NAVEED 
Published: June 2019

Background: Recent data demonstrate that cardiac troponin T (cTnT) and I (cTnI) have different associations with cardiovascular risk factors and outcomes. Although limited data have reported associations of troponins with incident type 2 diabetes, no large study has directly compared cTnT and cTnI.
Methods: High-sensitivity cTnT and cTnI were measured in serum from 18,775 individuals without baseline diabetes in the Generation Scotland Scottish Family Health Study. Median follow-up was 6.6 years (IQR 5.8-8.0). Each troponin was split into three groups (low; cTnT ≤3ng/L (n=8932) cTnI ≤1.8ng/L (n=9172), intermediate; cTnT 3-5.8ng/L (n=5024) cTnI 1.9-3.0ng/L (n=4879), high; cTnT ≥5.9ng/L (n=4819) cTnI ≥3.1ng/L (n=4724)), so that the proportion within each grouping was similar for each troponin. Associations of troponin with incident diabetes (490 cases from national electronic health records) was determined using Cox models, including adjustment for age, sex, BMI, lipids, systolic blood pressure, smoking, socioeconomic deprivation, rheumatoid arthritis, glucose, baseline CVD and medication use.
Results: After adjustment for age and sex only, cTnI was strongly associated with risk of diabetes (HR 1.73 for high compared to low; 95% CI 1.36-2.21) whereas for cTnT the association was slightly weaker (HR 1.35 for high compared to low; 95% CI 1.05-1.73). On further adjustment for additional risk factors, the association for cTnI attenuated to the null (HR 1.31; 95% CI 1.01-1.71), whereas the association for cTnT became slightly stronger (HR 1.44; 95% CI 1.11-1.88). High levels of both cTnT and cTnI increased risk further (HR 1.63; 95% CI 1.17-2.28). Exclusion of 740 participants with baseline CVD did not materially affect the results.
Conclusions: These results demonstrate a consistent association of subclinical myocardial injury, as measured by both cTnI and cTnT, with risk of future diabetes independent of common risk factors.

Disclosure
P. Welsh: Research Support; Self; AstraZeneca, Boehringer Ingelheim International GmbH. D. Preiss: Other Relationship; Self; Boehringer Ingelheim International GmbH. A. Campbell: None. D.J. Porteous: None. N.L. Mills: Speaker's Bureau; Self; Abbott Laboratories, Siemens Corporation. N. Sattar: Advisory Panel; Self; Amgen Inc., AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Novo Nordisk A/S. Consultant; Self; NAPP Pharmaceuticals Limited. Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc. Speaker's Bureau; Self; Amgen Inc., Eli Lilly and Company, Mitsubishi Tanabe Pharma Corporation, Novo Nordisk A/S, Roche Diagnostics France, Sanofi.

Funding
Chief Scientist Office of the Scottish Government Health Directorates (ASM/14/1, CZD/16/6); Scottish Funding Council (HR03006); Medical Research Council UK; Butler British Heart Foundation (FS/16/14/32023 to N.L.M.)