bluuebunny/crossref_metadata_2025 huggingface dataset:
1367-P: Effect of Nationwide Reimbursement of Sensor-Augmented Pump (SAP) Therapy in a Paediatric Type 1 Diabetes (T1D) Population on HbA1c, Hypoglycaemia, and Quality of Life (QoL) According to Age Groups in the RESCUE-Paediatrics Study
Authors: DE RIDDER FRANCESCA , JACOBS SEPPE , CHARLEER SARA , GILLARD PIETER , CASTEELS KRISTINA , VAN AKEN SARA , GIES INGE , MASSA GUY , LYSY PHILIPPE A. , LOGGHE KARL , LEBRETHON MARIE-CHRISTINE , DEPOORTER SYLVIA , LEDEGANCK KRISTIEN J. , DE BLOCK CHRISTOPHE , BRINKER MARIEKE DEN ,   ON BEHALF OF THE RESCUE TRIALISTS
Published: June 2019

Background: Long-term real-life data of SAP in pediatric T1D patients are scarce.

Objectives: To assess the impact of 12 months use of SAP in a nationwide study of pediatric T1D patients on HbA1c, hypoglycemia and quality of life1 according to age.

Methods: Between 12/2014 and 02/2017, 75 children entered Belgian reimbursement system for SAP and were followed for 12 months. Study endpoints included change in HbA1c at 0-4-8-12 months; time-in-hypoglycemia (<70mg/dl) and time-in-severe-hypoglycemia (<50mg/dl) (%/day) at 0-12 months; and QoL2 at 0-12 months. Puberty was defined as age ≥11.6y in boys and ≥11.2y in girls.

Results: Seventy-three patients used SAP for 12 months. Baseline HbA1c (7.2±0.7%) decreased to 7.1±0.8% at 4 months (p=0.02), remained stable at 8 months (p=0.03) and 12 months (p=0.15). In pubertal children (n=29) baseline was 7.1±0.7%. It decreased to 6.8±0.7% at 4 months (p=0.003), increased to 7.0±0.8% at 8 months (p=0.02) and to 7.1±0.8% at 12 months (p=0.20). In prepubertal children (n=43) baseline Hb1Ac was 7.3±0.7%; and evolved towards 7.1±0.8% at 12 months (p=0.40).

In pubertal children, time-in-hypoglycemia decreased from 7.1±6.9% to 5.7±5.1% (p=0.06) the first year, while time-in-severe-hypoglycemia did not significantly change (1.0±1.7% to 1.3±2.0%). In prepubertal children, both parameters did not significantly change (5,9±5,4% to 5,6±3,4% - 0,8±1,4% to 1,1±1,4%).

In pubertal children and their parents, QoL did not significantly change. In prepubertal children, satisfaction scores improved after 12months from 67±12 to 70±9 (p=0.026).

Conclusions: One year reimbursement of SAP in pediatric T1D patients improved HbA1c in the first 8 months in all; tended to decrease hypoglycemia in pubertal children; while improving QoL in prepubertal children.

1RESCUE-NCT02601729. 2Impact, satisfaction, worry (children) and parents.

Disclosure

F. De Ridder: None. S. Jacobs: None. S. Charleer: Other Relationship; Self; Roche Diabetes Care. P. Gillard: None. K. Casteels: None. S. Van Aken: None. I. Gies: None. G. Massa: None. P.A. Lysy: None. K. Logghe: None. M. Lebrethon: None. S. Depoorter: None. K.J. Ledeganck: None. C. De Block: None. M. den Brinker: None.
1370-P: Pediatric to Adult Transition Interventions and Outcomes in Type 1 Diabetes: A Scoping Review
Authors: LUNDGRIN ERIKA L. , BLANCHETTE JULIA E. , MUCCI ANDREA
Published: June 2019

Introduction: Adolescents and young adults (AYA) transitioning from pediatric to adult T1D care struggle with glycemic control and continuity of care while experiencing psychosocial complexities. The purpose of this review was to examine associations between transition interventions and relevant outcomes.

Methods: A predefined search strategy was used to retrieve papers published in the past five years evaluating transition programs for AYA with T1D. Nine observational studies and eight controlled trials were independently reviewed by two authors, with discrepancies addressed by a third.

Results: A total of 1491 AYA with T1D aged 12-39 (mean 18.5) years were represented in 17 publications. The most frequent intervention components included a transition coordinator (7), transition education (5), a multidisciplinary appointment (4), and a virtual transition program (4). Outcomes most frequently reported included HbA1c (12), satisfaction (10), psychological well-being (7), and continuity of care (7). Associations between interventions and outcomes are presented in Table 1.

Conclusions: There is a paucity of recent RCTs evaluating T1D transition interventions. While AYA with T1D reported satisfaction with a variety of interventions, programs including a transition coordinator and multidisciplinary appointment may also positively impact HbA1c, psychological well-being, and continuity of care.

Disclosure

E.L. Lundgrin: None. J.E. Blanchette: Consultant; Self; Dexcom, Inc., Tandem Diabetes Care. A. Mucci: None.
1373-P: Variables in Depression Screening Using PHQ-9 and PROMIS in Adolescents with T1DM
Authors: NADELLA SILPA , FRITZ SOBHA P. , MUIR ANDREW B.
Published: June 2019

Background: Depression in teens with type 1 diabetes (T1DM) is associated with poor disease management. Multiple depression screening questionnaires are validated in teens with chronic disease; no ideal instrument has been identified.

Methods: Subjects aged 11 - 17 years with T1DM, completed the PROMIS and PHQ-9 on the same day (n=20), within 3 months (n=17), or within 6 months (n=11). PHQ-9 was completed by the subject and PROMIS was completed by the subject (PROMIS-Ch) and a parent (PROMIS-P). 1-way ANOVA determined statistical significance.

Results:

1. Subjects with no or mild risk of depression on PHQ-9 had a PROMIS-Ch or PROMIS-P score >1.5 SD.

2. Clinical evaluation confirmed risk for depression in 5/6 subjects with moderate/severe risk on PHQ-9. PROMIS-Ch >1.5 SD in 2/5 subjects and PROMIS-P score >2 SD in 1/5 subjects.

3. Mean PHQ-9 score of 4 subjects with documented suicidal ideation (SI) was 18.4 (±6.7). The PROMIS-Ch was >1.5 SD in 2 of 4; PROMIS-P was >1.5 SD in 1 of 4.

Conclusions: Both surveys distinguished children at moderate/severe risk of depression from those with no/mild risk. Neither PROMIS survey distinguished between children who were at mild or no risk on PHQ-9. Those with SI had mean high risk PHQ-9 score, but did not have consistently high risk PROMIS scores. When screening for depression in adolescents, PHQ-9 had a higher sensitivity when compared to PROMIS.

Disclosure

S. Nadella: None. S.P. Fritz: None. A.B. Muir: None.
1374-P: Parent Preferences for Delaying Insulin Dependence in Children at Risk of Stage III Type 1 Diabetes (T1D)
Authors: HEDRICK JOSEPH , SUTPHIN JESSIE , DISANTOSTEFANO RACHAEL L. , GALLAHER KATHLEEN , MANSFIELD CAROL
Published: June 2019

Purpose: Preference studies ascertain what is important to individuals when weighing benefits and risks of interventions. The purpose of this study was to investigate parents’ preferences for treatments to delay the onset of insulin dependence in children who will develop Stage III T1D.

Methods: A web-based discrete-choice experiment (DCE) survey measured the preferences of U.S. parents of children with T1D and without T1D. In a hypothetical scenario where their child (<18 years) would become insulin dependent in 6 months or 2 years, respondents were offered a series of choices between hypothetical treatments that would delay insulin dependence or no treatment (monitoring only). Treatments were defined by 6 attributes with varying levels (years until insulin dependence; reductions in the risks of long-term complications, diabetic ketoacidosis (DKA), and serious infection; injection site reaction; and nausea). Random parameters logit analysis evaluated the relative importance of benefits and risks. Maximum acceptable risk (MAR) was calculated.

Results: Parents of children with T1D (n=600) and parents with children without T1D (n=901) from an online consumer panel completed the survey instrument. Most parents chose an active treatment (2% always chose monitoring only for all 8 choices). For parents without a T1D child, delaying insulin dependence and reducing the risk of long-term complications and serious infection were the most important treatment attributes, while parents with a T1D child valued these 3 attributes and reducing the risk of DKA as most important. MAR of serious infection ranged from 1%-7% for an additional 2 to 4-year delay in insulin dependence.

Conclusions: When told to assume their child would develop Stage III T1D, most parents considered hypothetical treatments to delay progression. The preferences expressed over the benefits and harms in this survey provide guidance on acceptable tradeoffs for future treatments to delay insulin dependence in T1D.

Disclosure

J. Hedrick: Employee; Self; Johnson & Johnson. Employee; Spouse/Partner; PTC Therapeutics. J. Sutphin: Other Relationship; Self; Multiple Companies. R.L. DiSantostefano: Employee; Self; Janssen Research & Development. K. Gallaher: Other Relationship; Self; Multiple companies. C. Mansfield: Other Relationship; Self; Multiple companies.

Funding

Janssen Research & Development, LLC
1390-P: Maternal Plasma Ceramides Predict Preeclampsia in Women with Type 1 Diabetes
Authors: KELLY CLARE B. , HAMMAD SAMAR M. , KLEIN RICHARD L. , LOPES-VIRELLA MARIA F. , LEYVA MISTI J. , YU JEREMY , JENKINS ALICIA J. , NANKERVIS ALISON J. , HANSSEN KRISTIAN F. , GARG SATISH K. , SCARDO JAMES A. , ASTON CHRISTOPHER E. , LYONS TIMOTHY
Published: June 2019

The risk for preeclampsia (PE) is increased 4-fold in women with type 1 diabetes (T1D), in whom we previously demonstrated that elevated cholesterol-rich lipoproteins confer risk at the 1st trimester. Sphingolipids, including ceramides (Cer) and glycosphingolipids (hexosyl- (HexCer) and lactosyl-ceramides (LacCer)), are lipoprotein constituents that regulate cell signaling. We propose that these bio-active lipids could be modulators of PE risk.

In a prospective T1D pregnancy cohort (studied at 12, 22, 32 weeks’ gestation), we used liquid chromatography/electrospray ionization-tandem mass spectrometry to determine plasma levels of 12 species of Cer, HexCer, and LacCer in 23 women with T1DM who did vs. 24 who did not develop PE, and in 19 normotensive nondiabetic pregnant women. All were free of microalbuminuria and hypertension at enrolment; all visits preceded clinical PE onset.

Results: Plasma levels of C22-Cer (1st and 3rd study visits); C26:1-Cer (1st and 2nd visits); C26-Cer (1st visit); C18-Cer and C18:1-Cer (2nd visit) were significantly higher in women with T1DM who did vs. did not develop PE. C22-Cer and C26-Cer were significantly lower in T1DM vs. non-T1DM (1st visit). There were no overall PE- or diabetes-related differences in any HexCer- or LacCer species. Longitudinally, most Cer and HexCer species increased throughout pregnancy in all groups (except C14- and C18-Cer; and C14 and C26-HexCer). C16-LacCer increased, while C22:1-, C26-, and C26:1-LacCer decreased as pregnancy advanced, independent of PE status. Independent of LDL-C, total Cer increased throughout pregnancy in all groups.

Conclusions: Maternal Cer species may serve as early biomarkers for PE in women with T1DM. T1DM was associated with lower levels of two Cer species. Like cholesterol-rich lipoproteins, Cer, HexCer and some LacCer species increase as pregnancy advances in all groups, but other LacCer species decrease: the significance of these findings requires further study.

Disclosure

C.B. Kelly: None. S.M. Hammad: None. R.L. Klein: None. M.F. Lopes-Virella: None. M.J. Leyva: None. J. Yu: None. A.J. Jenkins: Advisory Panel; Self; Abbott, Australian Diabetes Society, Medtronic. Research Support; Self; Abbott, GlySens Incorporated, Medtronic, Mylan. Speaker's Bureau; Self; Eli Lilly and Company, Novo Nordisk Inc. A.J. Nankervis: None. K.F. Hanssen: None. S.K. Garg: Advisory Panel; Self; Eli Lilly and Company, Roche Pharma, Sanofi-Aventis, Zealand Pharma A/S. Research Support; Self; Eli Lilly and Company, WebMD. J.A. Scardo: None. C.E. Aston: None. T. Lyons: None.

Funding

JDRF; Novo Nordisk; National Institutes of Health
1394-P: The Role of the Unfolded Protein Response in High Glucose-Induced mESC Pluripotency and Impaired Differentiation
Authors: SUN WINNY , YANG PENGHUA , YE FEI , YANG PEIXIN
Published: June 2019

Maternal diabetes is associated with various risks during pregnancy, including structural birth defects. Gene dysregulation and reduced progenitor cell formation and differentiation are two major mechanisms that are implicated in diabetic embryopathy. Our lab has previously shown that E14 mouse embryonic stem cells (mESCs) grown in high glucose conditions have delayed differentiation to both neurons and cardiomyocytes. However, treatment of 4-PBA (4-phenylbutyrate), a chemical chaperone used as an endoplasmic reticulum (ER) stress inhibitor, rescued this delay of differentiation to neurons. On the other hand, high glucose increased mESC pluripotency and activated the unfolded protein response (UPR) in undifferentiated conditions, specifically the protein kinase RNA-like endoplasmic reticulum kinase (PERK) pathway. To determine the role of the UPR in enhanced mESC pluripotency by high glucose, E14 mESCs grown in high glucose were treated with or without 4-PBA for 8 days. Untreated E14 mESCs grew in dome-shaped colonies with defined edges, while 4-PBA-treated cells grew in flat colonies with cells emerging out of the colonies, indicative of a more differentiated state. Microarray analysis showed that 4-PBA-treated cells had upregulated expression of primed state markers and downregulated expression of pluripotency markers, compared to untreated cells. Our results suggest that inhibition of the UPR through ER stress inhibition abolishes the stimulatory effect of high glucose on mESC pluripotency, leading to a shift from native state to a more differentiated ESC stage.

Disclosure

W. Sun: None. P. Yang: None. F. Ye: None. P. Yang: None.

Funding

National Institutes of Health
1397-P: A Pregnancy Lifestyle Intervention Improves Metabolic Profile of Women and Infants by Reducing Gestational Weight Gain (GWG): The GLOW Randomized Controlled Trial
Authors: FERRARA ASSIAMIRA , HEDDERSON MONIQUE M. , BROWN SUSAN D. , TSAI AI-LIN , FENG JUANRAN , ZHU YEYI , GALARCE MAREN N.R. , MARCOVINA SANTICA M. , QUESENBERRY CHARLES
Published: June 2019

Among pregnant women with overweight or obesity, intensive interventions have reduced GWG but had only small effects on metabolic profile. In the Gestational weight gain and Optimal Wellness (GLOW) randomized controlled trial, we randomized pregnant women with overweight or obesity to a lifestyle intervention (n=199) or standard care (n=195) to evaluate the intervention’s efficacy in reducing GWG and improving metabolic biomarkers during pregnancy and in cord blood. Women in the intervention, vs. those in standard care, had significantly lower weekly rate of GWG from 10 to 32 weeks’ gestation (mean [SD], mean condition difference [95% CI]: 0.31 [0.18] vs. 0.42 [0.16], -0.11 [-0.15 to -0.08] kg/week) and lower total GWG (10.2 [5.6] vs. 12.4 [5.3], -2.2 [-3.3 to -1.1] kg). The intervention significantly reduced women’s fasting insulin, HOMA-IR and leptin from 10 to 32 weeks’ gestation and cord blood C-peptide, and yielded a borderline significant reduction of cord blood leptin (Table). The intervention’s effect on each biomarker was partially mediated by GWG, with the proportion of mediation effects ranging from 50 to 90% (all p-values <.02). Reducing GWG via lifestyle intervention resulted in improved metabolic profile of women and their infants.

Disclosure

A. Ferrara: None. M.M. Hedderson: None. S.D. Brown: None. A. Tsai: None. J. Feng: None. Y. Zhu: None. M.N. Galarce: None. S.M. Marcovina: None. C. Quesenberry: None.

Funding

National Institutes of Health (NICHDR01HD073572, NIDDKP30DK092924)
14-LB: Somatostatin Receptor 2 Antagonism Enhances Plasma Glucagon Levels during Insulin-Induced Hypoglycemia in a Rodent Model of Type 2 Diabetes Mellitus
Authors: NEJAD-MANSOURI MEHRAN , ZAREE BAVANI PARINAZ , AIKEN JULIAN , DSOUZA NINOSCHKA C. , HOFFMAN EMILY G. , LIGGINS RICHARD , RIDDELL MICHAEL
Published: June 2019

Somatostatin Receptor 2 antagonists (SSTR2a) increase glucagon counter-regulation to hypoglycemia in various rodent models of type-1 diabetes mellitus. Here we investigated the efficacy of SSTR2a in improving glucagon counter-regulation in a rat model of type-2 diabetes mellitus (T2DM). For this, male Sprague Dawley rats (n=18) were given a high fat diet for 3 weeks, followed by low-dose streptozotocin exposure (35 mg/kg, IP) to induce T2DM. Rats were then divided into SSTR2a treatment (PRL-2903, 10 mg/kg) or vehicle (n=9 for each) 1-hour before insulin-induced hypoglycemia (3 IU/kg NovoRapid). This process was repeated 1 week later in a cross-over design, with the data pooled over SSTR2a and vehicle treatments. A group of normal-chow-fed rats (n=3) served as nondiabetic controls. Mean blood glucose levels were higher at 20, 30, 40, and 50 minutes post insulin administration in the T2DM rats treated with PRL-2903, as compared to vehicle (p ≤ 0.05). The number of T2DM rats that developed biochemical hypoglycemia (blood glucose ≤ 3.5 mmol/L) tended to be less with PRL-2903 (5/18) vs. vehicle (9/18). Compared with vehicle treatment, PRL-2903 promoted higher plasma glucagon counter-regulation, as indicated by area under curve (AUC) analysis (p < 0.05). Thus, SSTR2a treatment improves the attenuated glucagon response to hypoglycemia in T2DM rats.

Disclosure

M. Nejad-Mansouri: None. P. Zaree Bavani: None. J. Aiken: None. N.C. DSouza: None. E.G. Hoffman: None. R. Liggins: None. M. Riddell: Advisory Panel; Self; Xeris Pharmaceuticals, Inc. Research Support; Self; Dexcom, Inc. Speaker’s Bureau; Self; Insulet Corporation, Medtronic MiniMed, Inc. Stock/Shareholder; Self; Zucara Therapeutics Inc.

Funding

National Research Council Canada; Zucara Therapeutics
140-LB: NGM313, a Novel Activator of b-Klotho/FGFR1c, Improves Insulin Resistance and Reduces Hepatic Fat in Obese, Nondiabetic Subjects
Authors: DEPAOLI ALEX , PHUNG VAN , BASHIR MUSTAFA R. , MORROW LINDA , BEYSEN CARINE , YAN ANDREW , LING LEI , BAXTER BRYAN , LUSKEY KENNETH L. , OLEFSKY JERROLD M.
Published: June 2019

Background: NGM313 is a humanized monoclonal antibody activator of β-klotho/FGFR1c that has been shown to reduce HOMA-IR in obese subjects. This study compared the effects of a single dose of NGM313 vs. daily pioglitazone (PIO) on insulin sensitivity, liver fat content (LFC) and lipids in insulin resistant, obese subjects with increased liver fat.

Methods: 25 subjects were randomized 2:1 to either a single dose of NGM313 240 mg SC (n=17) or PIO 45 mg PO QD (n=8) for 36 days. Whole-body insulin sensitivity was determined by a two-step hyperinsulinemic, euglycemic clamp and LFC by magnetic resonance imaging-proton density fat fraction (MRI-PDFF).

Results: (Table 1) A single dose of NGM313 significantly increased glucose disposal rate and was comparable to PIO. Suppression of endogenous glucose production was enhanced by both NGM313 and PIO. Significant reductions in LFC, HbA1c, serum triglycerides and LDL-C, and an increase in HDL-C, were observed with NGM313. NGM313 produced a greater reduction in LFC vs. PIO at day 23. The safety and tolerability profile was favorable for both drugs.

Conclusion: NGM313 is a potent insulin sensitizer, comparable to PIO. In addition, NGM313 is highly effective in reducing LFC in subjects with increased liver fat. As such, NGM313 has significant potential to be an effective treatment for nonalcoholic steatohepatitis and type 2 diabetes.

Disclosure

A. DePaoli: Employee; Self; NGM Biopharmaceuticals. V. Phung: Employee; Self; NGM Biopharmaceuticals. Stock/Shareholder; Self; NGM Biopharmaceuticals. M.R. Bashir: Consultant; Self; RadMD. Research Support; Self; Madrigal Pharmaceuticals, Metacrine Inc, NGM Biopharmaceuticals, Pinnacle Clinical Research, ProSciento, Siemens Corporation. L. Morrow: Employee; Spouse/Partner; Eli Lilly and Company. Employee; Self; ProSciento. C. Beysen: None. A. Yan: None. L. Ling: Employee; Self; NGM Biopharmaceuticals. Stock/Shareholder; Self; NGM Biopharmaceuticals. B. Baxter: Employee; Self; NGM Biopharmaceuticals. K.L. Luskey: Consultant; Self; NGM Biopharmaceuticals. J.M. Olefsky: None.
1403-P: Functional Data Analysis Reveals Differences in Temporal Glucose Profiles Associated with Large for Gestational Age: A Secondary Analysis of the CONCEPTT Study
Authors: SCOTT ELEANOR M. , MURPHY HELEN R. , FEIG DENICE , LAW GRAHAM
Published: June 2019

Background: Continuous glucose monitoring (CGM) provides far greater detail about fetal exposure to maternal glucose across the 24 hour day, but recommended summary statistics give no dynamic information about the glucose profile across 24 hours.

Aim: To examine whether differences in temporal glucose control occur in women with type 1 diabetes who develop large for gestational age infants (LGA).

Research Design and Methods: CGM data was available from 200 pregnant women (100 CGM intervention; 100 controls) in the CONCEPTT study, at baseline, 24 and 34 weeks gestation. All women were being treated to tight glycemic targets (mean HbA1c 6.4% at 34 weeks gestation). Functional data analysis (FDA) was applied to determine differences in temporal glucose profiles. LGA was defined as birth weight ≥90th percentile adjusted for infant sex, gestational age, maternal BMI, ethnicity and parity.

Results: 122/200 women had a LGA infant (61%). FDA revealed that those women who gave birth to a LGA infant ran a significantly higher glucose (by 9-14mg/dL; 0.5-0.8 mmol/l) for 16.5 hours of the day compared to those women who did not have a LGA infant (see fig).

Conclusion: Women who go on to have LGA infants have significantly higher fetal exposure to glucose across the 24 hour day, despite being treated to tight glucose targets.

Disclosure

E.M. Scott: Advisory Panel; Self; Abbott. Speaker's Bureau; Self; Abbott, Eli Lilly and Company. H.R. Murphy: Advisory Panel; Self; Medtronic MiniMed, Inc. D. Feig: Advisory Panel; Self; Medtronic. Speaker's Bureau; Self; Medtronic. G. Law: None.

Funding

JDRF; Canadian Clinical Trials Network; National Institute for Health Research
1407-P: Laboratory Glycemic Markers vs. Continuous Glucose Monitoring (CGM) for Prediction of Neonatal Outcomes in Type 1 Diabetes Pregnancy—An Ancillary Study of the CONCEPTT Trial
Authors: MEEK CLAIRE L. , TUNDIDOR DIANA , MURPHY HELEN R. , YAMAMOTO JENNIFER M. , SCOTT ELEANOR M. , MA DONGDONG , HALPERIN JOSE , FEIG DENICE , CORCOY ROSA
Published: June 2019

Type 1 diabetes (T1D) in pregnancy is associated with increased neonatal morbidity, which improves with optimal glycemic control.

Aim: To compare lab and CGM glucose summary measures as predictors of neonatal outcomes in T1D pregnancy.

Methods: 225 CONCEPTT participants had 6-day CGM and blood analysis of glycemic markers in 1st trimester, 24 and 34 weeks (Average glucose; % time in target 63-140 mg/dl, coefficient of variation (CV)); HbA1c; glycated CD59 (gCD59); 1,5-anhydroglucitol (1,5AG); glycated albumin). Outcomes: large for gestational age (LGA), neonatal hypoglycemia (NH) and neonatal intensive care unit (NICU) admission. Statistics: Unadjusted logistic regression.

Results: All glucose summary measures excluding CV predicted neonatal outcomes (Table). Glycemic control at all timepoints from 1st trimester was important for LGA, but emerged later for NH (24 and 34 weeks) and NICU (mainly 24 weeks). Both CGM time in target and average glucose and lab markers HbA1c, 1,5AG and gCD59 predicted all three outcomes studied. Time in target was the best CGM predictor. The best lab predictors were HbA1c, 1,5AG and gCD59. HbA1c was the strongest predictor of LGA and NH, but only predicted NICU admission late in pregnancy.

Conclusions: In women with T1D, both CGM and lab glucose summary measures can predict neonatal outcomes from 1st trimester.

Disclosure

C.L. Meek: None. D. Tundidor: None. H.R. Murphy: Advisory Panel; Self; Medtronic MiniMed, Inc. J.M. Yamamoto: None. E.M. Scott: Advisory Panel; Self; Abbott. Speaker's Bureau; Self; Abbott, Eli Lilly and Company. D. Ma: None. J. Halperin: Stock/Shareholder; Self; Mellitus, LLC. D. Feig: Advisory Panel; Self; Medtronic. Speaker's Bureau; Self; Medtronic. R. Corcoy: None.

Funding

JDRF; Canadian Clinical Trials Network; National Institute for Health Research; European Foundation for the Study of Diabetes/Sanofi; Diabetes UK (17/0005712 to C.L.M.); Asahi Kasei Pharma Corporation; GlycoMark, Inc.
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 < 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<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 >92, >180, and >163 mg/dl at 0, 1 and 2h, respectively. At 1 and 2h, mean AGS-CBG vs. Glucola-CBG was 107 vs. 126 (p<.0001) and 89 vs. 113 mg/dl (p<.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 >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<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<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, <70 and >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 >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, <70 and >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.)