bluuebunny/crossref_metadata_2025_split huggingface dataset:
1429-P: A Review of Prepregnancy Care and Pregnancy Outcomes in Pregestational Diabetes—Are Prior Improvements in Pregnancy Preparation and Outcomes Maintained for Women with Pregestational Diabetes?
Authors: NEWMAN CHRISTINE , CARMODY LOUISE , EGAN AOIFE M. , OWENS LISA A. , DUNNE FIDELMA 
Published: June 2019

Women with pre-existing diabetes (T1DM/T2DM) face increased risk in pregnancy. Optimising glycaemic control, folic acid use and smoking cessation are all advised to improve outcomes. Maintaining these goals can be difficult. We retrospectively analysed data from sites across our Atlantic DIP network from 2015-17 and compared outcomes to data 2010-14 to see if prior improvements were maintained. Data was collected on pre-pregnancy care (PPC), glycaemic targets and neonatal outcomes. In total 98 women attended; 76 (78%)/22 (22%) with T1DM and T2DM respectively. Booking maternal BMI reduced but a fall in PPC attendance lead to lower folic acid use, greater teratogenic medication use and static smoking rates. Trimester 1 HbA1C was suboptimal in T1DM but patients subsequently reached target. HbA1C improved throughout pregnancy for T2DM and was at target (Table 1). Between the two time periods outcomes were unchanged for miscarriage, shoulder dystocia, NICU admission, macrosomia, LGA, SGA and birth weight. We recorded no stillbirths or congenital malformations. Improvements occurred in prematurity (&lt;003C34w) and neonatal hypoglycaemia.
It is reassuring to record maintenance/improvement in neonatal outcomes but ongoing education on the importance of PPC and novel ways to reach patients are required.

Disclosure
C. Newman: Speaker's Bureau; Self; Sanofi. L. Carmody: None. A.M. Egan: None. L.A. Owens: None. F. Dunne: None.
1431-P: Intuitive Eating in Pregnancy Is Associated with BMI, Fasting Glucose, and A1c at One-Year Postpartum in Women with GDM: A Cohort Study
Authors: QUANSAH DAN YEDU , GROSS JUSTINE , GILBERT LEAH , HORSCH ANTJE , PUDER JARDENA J. 
Published: June 2019

In women with GDM, there is a need to investigate novel lifestyle approaches to reduce the risk of future diabetes. Intuitive eating (IE) is an adaptive eating behavior where individuals accurately interpret and adhere to instinctive feedback regarding the required amount and timing of food. We evaluated the associations between IE during and after pregnancy with BMI, fasting glucose and A1c at 1-year postpartum (PP) in 117 women with GDM and in high-risk GDM subgroups with PP prediabetes or overweight/obesity. Women with GDM who consented and completed the “Eating for Physical rather than Emotional Reasons (EPR)” and “Reliance on Hunger and Satiety cues (RHSC)” subscales of the validated Intuitive Eating Scale-2 questionnaire during the first GDM clinic visit at 24-32 weeks of gestation and at 1-year PP were included. Participants mean age was 33.21±5.37 years, weight and BMI before pregnancy and at 1-year PP were 69.46±13.99kg, 25.82±4.69kg/m2 and 72.79±16.22kg, 27.06±5.54kg/m2 respectively, and the prevalence of prediabetes at 1-year PP was 46.2%. EPR at the first GDM visit predicted lower BMI (β=-0.219, p=0.017) and fasting glucose (β=-0.229, p=0.014) at 1-year PP, while associations were not significant for RHSC. At 1-year PP, EPR and RHSC were inversely associated with BMI (β=-0.243 to -0.337, both p≤ 0.012), whereas EPR was inversely associated with A1c and fasting glucose (β=-0.216 to -0.222, both p=0.018). In the subgroup of women with prediabetes, EPR and RHSC at the first GDM visit predicted lower fasting glucose at 1-year PP, while in the overweight/obese subgroup this was only significant for EPR (all p≤0.02). At 1-year PP however, both EPR and RHSC were inversely associated with BMI in women with prediabetes and with fasting glucose in overweight/obese women (all p≤0.03). No associations were found in low-risk GDM subgroups. Higher adherence to IE could represent a novel approach for PP BMI and glycemic control in women with previous GDM.

Disclosure
D.Y. Quansah: None. J. Gross: None. L. Gilbert: None. A. Horsch: None. J.J. Puder: None.

Funding
Swiss National Science Foundation; Lausanne Integrative Metabolism and Nutrition Alliance
144-OR: Ultra Rapid Lispro (URLi) Improves Postprandial Glucose (PPG) Control vs. Humalog (Lispro) in T1D: PRONTO-T1D Study
Authors: KLAFF LESLIE J. , CAO DACHUANG , DELLVA MARY A. , TOBIAN JANET , MIURA JUNNOSUKE , DAHL DOMINIK , BUE-VALLESKEY JULIANA M. 
Published: June 2019

URLi is a novel prandial insulin lispro formulation developed to more closely match physiological insulin secretion. This phase 3, 26-week trial evaluated the efficacy and safety of URLi vs. lispro in 1222 adults with T1D. The primary endpoint was A1C change from baseline after 26 weeks of treatment, with multiplicity adjusted objectives for PPG excursions (PPGE) after test meal. After an 8-week lead-in to optimize basal insulin glargine or degludec, patients were randomized to double-blind URLi (n=451) or lispro (n=442) given at the start of the meal, or open-label URLi (n=329) given 20 minutes after the meal (URLi +20).
A1C was reduced for URLi and lispro and non-inferiority (NI) was shown: estimated treatment difference (ETD) -0.08 [-0.16; 0.00] p=0.06 (Figure). NI for URLi +20 vs. lispro was also shown: ETD +0.13 [0.04; 0.22] p=0.003. URLi was superior to lispro in controlling 1- and 2-h PPGE during the test meal (Figure).
No significant differences were seen between URLi vs. lispro in rate or incidence of severe hypoglycemia; overall daily or postprandial hypoglycemia (&lt;54 mg/dL) ≤4 h after meals, but URLi had a 37% lower hypoglycemia rate in the period &gt;4 h, (p=0.013). Overall, the incidence of treatment-emergent adverse events was similar between groups.
URLi was efficacious with a similar safety profile to lispro and, when given at start of the meal, provided superior PPG control vs. lispro.

Disclosure
L.J. Klaff: Research Support; Self; Abbott, Ascensia Diabetes Care, Cnoga Medical, Gan & Lee Pharmaceuticals, Lilly Diabetes, Medtronic MiniMed, Inc., Novo Nordisk Inc., REMD Biotherapeutics, Sanofi, Senseonics, Xeris Pharmaceuticals, Inc., Zealand Pharma A/S. D. Cao: Employee; Self; Eli Lilly and Company. M.A. Dellva: Employee; Self; Eli Lilly and Company. J. Tobian: Employee; Self; Eli Lilly and Company. J. Miura: None. D. Dahl: None. J.M. Bue-Valleskey: Employee; Self; Eli Lilly and Company.

Funding
Eli Lilly and Company
1440-P: Does HbA1c Impact Survival in the Newly Diagnosed Elderly Aged 75 Years and Over?
Authors: MCGILL MARGARET , MOLYNEAUX LYNDA M. , CONSTANTINO MARIA I. , TWIGG STEPHEN M. , MIDDLETON TIMOTHY , WU TED , WONG JENCIA 
Published: June 2019

Clinical practice guidelines recommend screening for diabetes after the age of 45 years, but without an upper age limit. An ageing population has resulted in increasing numbers of older people being diagnosed. Previous reports indicate a J-shaped relationship between HbA1c and mortality in older populations with largely longstanding diabetes. However, whether these mortality relationships hold true in the newly diagnosed elderly remains uncertain, as do appropriate glycaemic targets. We aimed to study the relationship between HbA1c and mortality in newly diagnosed elderly aged ≥ 75 years. Records from the RPA Diabetes Clinical Database from 1988 to 2015, linked with the Australian National Death Index to establish all cause, IHD and cancer mortality outcomes were examined. 376 subjects were studied; median diabetes duration at first visit was 0.8 years (IQR 0.2-2.4), with mean age at diagnosis 78.7±3.1 years, 48% male and 53% Angloceltic. Data were stratified by updated HbA1c% NGSP Units categories (&lt; 6; 6.1-7.0; 7.1-8.0; 8.1-9.0 and &gt;9) with a median of 1.8±1.5 measures. Over a median observation period of 6.0 (IQR 2.8-10.4) years there were 237 deaths (17% from cancer, 38.9% from IHD). Using Kaplan-Meier survival analysis for all-cause mortality, no differences in survival between the HbA1c categories were seen (logrank p=0.8). Cox regression was used to examine the relationship between all-cause mortality and updated HbA1c categories after accounting for age or duration at first visit, gender and ethnicity. No significant differences nor observable trends in RR were seen using the HbA1c 6.1-7% group as reference. Prior albuminuria, stroke history and lipid status also had no impact on this relationship. Examination of IHD and cancer-related deaths similarly showed no relationship with HbA1c in this population. Whilst current guidelines recommend a general HbA1c target of 7% to 8% in the elderly we did not demonstrate a survival benefit for any HbA1c level in these newly diagnosed over 75 years of age.

Disclosure
M. McGill: None. L.M. Molyneaux: None. M.I. Constantino: None. S.M. Twigg: Advisory Panel; Self; Abbott, Boehringer Ingelheim Pharmaceuticals, Inc., Novo Nordisk Inc., Sanofi-Aventis. Board Member; Self; AstraZeneca. Research Support; Self; Abbott. Speaker's Bureau; Self; Abbott, AstraZeneca, Merck Sharp & Dohme Corp., Novo Nordisk Inc., Sanofi-Aventis. T. Middleton: Other Relationship; Self; AstraZeneca. T. Wu: Advisory Panel; Self; Boehringer Ingelheim International GmbH, Eli Lilly and Company, Novo Nordisk A/S, Sanofi. Speaker's Bureau; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi. J. Wong: Advisory Panel; Self; Sanofi. Speaker's Bureau; Self; AstraZeneca, Lilly Diabetes.
1441-P: Correlation of Serum Osteocalcin Levels and Relative Skeletal Muscle Index and Hyperglycaemia in a Cohort of Middle-Aged and Elderly Individuals
Authors: XU YITING , MA XIAOJING , SHEN YUN , GU CHENGCHENG , TANG JUNLING , BAO YUQIAN 
Published: June 2019

Aims: Osteocalcin is involved in energy metabolism and is sufficient to prevent age-related muscle loss. The aim of the present study was to investigate the association of serum osteocalcin levels with muscle mass and the role of metabolic factors in this association.
Methods: A total of 1742 middle-aged and elderly subjects (median age: 61.2 years; interquartile range: 56.9-65.3 years) were enrolled from Shanghai communities, including 775 men and 967 postmenopausal women. Serum osteocalcin levels were measured by an electrochemical immunoluminescence assay. An automatic bioelectric impedance analyser (BIA) was used to measure body compositions. Relative skeletal muscle index (SMI) was calculated using the BIA equation from Janssen et al.
Results: SMI was significantly higher in men than in postmenopausal women (37.30% [35.14%-39.63%] versus 27.72% [25.99%-29.66%], P &lt; 0.001). Increasing SMI was associated with decreases in the frequency of overweight/obesity, central obesity, dyslipidaemia, elevated blood pressure, and hyperglycaemia (all P &lt; 0.001). Serum osteocalcin levels were positively correlated with SMI in both men and women, regardless of treatment as a categorical or continuous variable (all P &lt; 0.001). However, after accounting for confounding variables, the relationship remained only in men with hyperglycaemia (standardized β = 0.068, P = 0.024). Among men with isolated impaired glucose tolerance, the odds ratio of increased SMI was 2.861 in the fourth osteocalcin quartile compared with the lowest (P = 0.046). Multiple stepwise regression revealed that each standard deviation (SD) increase of serum osteocalcin levels resulted in an increase of 0.131 SD in SMI (P = 0.024).
Conclusion: In men with hyperglycaemia, especially in those with isolated impaired glucose tolerance, serum osteocalcin levels were positively correlated to SMI. However, no association was detected in postmenopausal women.

Disclosure
Y. Xu: None. X. Ma: None. Y. Shen: None. C. Gu: None. J. Tang: None. Y. Bao: None.
1449-P: Longitudinal Changes in Sex Hormone Binding Globulin (SHBG) and Risk of Diabetes: The Study of Women's Health Across the Nation (SWAN)
Authors: HEDDERSON MONIQUE M. , LEE CATHERINE , CAPRA ANGELA , LEE JENNIFER , CHANG PO-YIN , GOLD ELLEN , WAETJEN ELAINE , HABEL LAUREL A. , EL KHOUDARY SAMAR R. 
Published: June 2019

Low circulating levels of sex hormone-binding globulin (SHBG), a putative marker of androgenicity, have been associated with poor glucose control in studies conducted primarily among post-menopausal women. However, the relation of long-term changes in endogenous SHBG to risk of type 2 diabetes (T2DM) in women during and after the menopause transition is unclear. We aimed to assess the longitudinal associations between SHBG levels and risk of developing T2DM among such women. We included 3,060 participants in the Study of Women’s Health Across the Nation (SWAN) who were free of diabetes at baseline. SWAN is a longitudinal cohort study with up to 17 years of follow-up. SHBG levels were measured at 13 visits. Participants reported diagnosed diabetes status at all visits, and fasting glucose was measured at 8 follow-up visits. T2DM was defined based on self-report or fasting glucose levels. Women averaged 46 (SD=3) years of age at baseline. 311 women developed T2DM during follow-up. We used complementary log-log-based discrete time survival models anchored at baseline to estimate associations of longitudinal SHBG with incident T2DM. A 5-unit (nM) increase in time-varying SHBG was associated with a hazard ratio (HR) of 0.86 (95% CI 0.82, 0.90), for T2DM, after controlling for race-ethnicity, age, cycle day of blood draw, site, time-varying body mass index (BMI), testosterone, and baseline SHBG level. After adjusting for covariates, women in the lowest ((-92.0 - -1.1 nM/year) vs. highest quartile (0.7 - 42.1 nM/year) for time-invariant average rate of change per year in SHBG levels) had a HR of 5.18 (95% CI: 3.55,7.56). No association was observed for other quartiles in rate of change of SHBG with developing T2DM. Women with low levels of SHBG and/or decreases in SHBG levels were at increased risk to develop T2DM. Clinicians should be aware that declining levels of SHBG in mid-life women is strongly associated with developing T2DM, independent known T2DM risk factors.

Disclosure
M.M. Hedderson: None. C. Lee: None. A. Capra: None. J. Lee: None. P. Chang: None. E. Gold: None. E. Waetjen: None. L.A. Habel: None. S.R. El Khoudary: None.

Funding
National Institutes of Health
145-LB: Phase 1/2 Safety and Proof of Biological Activity Study of AT-001, an Aldose Reductase Inhibitor in Development for Diabetic Cardiomyopathy
Authors: SHENDELMAN SHOSHANA , PERFETTI RICCARDO 
Published: June 2019

Hyperactivation of the polyol pathway (PP) contributes to development of diabetic complications. Aldose reductase (AR) is the rate-controlling enzyme in PP that catalyzes NADPH-dependent reduction of glucose to sorbitol. In hyperglycemic and ischemic conditions, PP activation causes intracellular sorbitol accumulation leading to osmotic stress, cell death and diabetic complications. We developed AT-001 based on further characterization of AR and structural changes within the active site of AR following enzymatic activation to design molecular AR inhibitors with enhanced specificity, affinity and selectivity compared with previous AR inhibitors that failed to inhibit redox-activated AR and were associated with off-target effects and/or lack of efficacy. AT-001 safety, pharmacokinetics (PK) and efficacy were assessed in a phase 1/2 study comprised of single oral ascending doses (SAD, n=8 per group) of 5, 10, 20 and 40 mg/kg once daily (QD) and multiple doses (MAD) of placebo (Pbo) or AT-001 5, 20, 40 mg/kg QD or 20 mg/kg twice daily (BID) for 7 d. Subjects with type 2 diabetes, age 18-75 and HbA1c 5.0-8.5% were allocated to each dose cohort (n=8 AT-001, n=2 Pbo). AT-001 was well-tolerated with no drug-related AEs or changes in liver or renal function up to the highest dose tested. Mean half-life (T1/2) and time of maximum concentration (Tmax) ranged from 1.7-3h and 1.75-3h, respectively in both SAD and day 1 MAD with no accumulation at day 7. AR inhibition was confirmed by significant dose-dependent reductions in whole blood sorbitol in SAD and MAD up to approximately -50% change from baseline in SAD and days 1 and 7 of MAD vs. a -3% change in Pbo (p&lt;0.05 for all doses vs. Pbo). Maximum inhibition occurred between 2-4 h. Conclusions: greater selectivity and affinity of AT-001 for AR may endow acceptable safety. These findings support further investigation of the therapeutic potential of AT-001 in subjects with diabetes complications.

Disclosure
S. Shendelman: Stock/Shareholder; Self; Applied Therapeutics Inc. Other Relationship; Self; Applied Therapeutics Inc. R. Perfetti: Employee; Self; Applied Therapeutics Inc., Sanofi. Stock/Shareholder; Self; Applied Therapeutics Inc., Sanofi.
1451-P: The Association of Metformin with Mortality in Frail Older Veterans with Diabetes
Authors: MILYANI RANEEM , APARICIO-UGARRIZA RAQUEL , GUERRA JULIANA FERRI , SALGUERO DOUGLAS , MOHAMMED YAQUB NADEEM , VALENCIA WILLY , FLOREZ HERMES , RUIZ JORGE G. 
Published: June 2019

Diabetes (DM) is associated with an accelerated aging that promotes frailty, a state of vulnerability to stressors resulting in higher morbidity, mortality and healthcare utilization. Data from the UKPDS showed that metformin may lead to lower risk of overall mortality in middle aged adults with type 2 DM (T2D) but the evidence is less clear in frail older adults. The aim of this study was to determine whether metformin is associated with reduced mortality in frail older Veterans. This is a retrospective cohort study of 393 Veterans 65 years and older with DM, who were identified as frail through calculation of a 44-item frailty index (FI≥.21) on January 2016-August 2017 and followed until October 2018. The FI was constructed as a proportion of all potential variables (demographics, comorbidities, medications, laboratory tests, and ADLs) at the time of the screening. At the end of follow-up, we aggregated data on mortality of those Veterans with frailty and compared those who were taking metformin (n=164, 41.7%) versus those who were not taking that medication (n=229, 58.3%). After adjusting for age, race, ethnicity, BMI, DM complications, level of glycemic control, use of insulin or sulfonylureas and comorbidities, the association of metformin with mortality was determined using a multivariate Cox regression model. Patients were 56.3% white, 76.9% non-Hispanic, 98.7% male, mean age was 73.14 (SD=7.31) years. Over a median follow-up period of 593 days (IQR=179), 62 deaths occurred (n=15, in those taking metformin vs. n=47 in those not taking it). After adjusting for covariates, frail Veterans taking metformin had a lower risk for mortality, adjusted hazard ratio (HR) .466 (95% CI: .255-.849), p=.013 than those not taking the drug. These results suggest that metformin may reduce all-cause mortality in frail older adults with diabetes. Further studies may be needed to assess the impact of metformin on quality of life and potential benefits on specific morbidity and mortality in this high-risk population.

Disclosure
R. Milyani: None. R. Aparicio-Ugarriza: None. J. Ferri Guerra: None. D. Salguero: None. Y. Mohammed: None. W. Valencia: None. H. Florez: None. J.G. Ruiz: None.

Funding
Miami VA Healthcare System Geriatric Research Education and Clinical Center
1455-P: Evaluating Opportunities for Deprescribing in the Elderly and Extreme Elderly with Diabetes
Authors: SHARP SABRINA A. , OVERLAND JANE , MCGILL MARGARET , MOLYNEAUX LYNDA M. , WU TED , TWIGG STEPHEN M. , WONG JENCIA 
Published: June 2019

Individualised approaches to diabetes management are essential so that an optimal balance is realised between the risk and benefits of treatment. In the elderly (E, 75-84 years) and extreme elderly (EE, ≥ 85 years) treatment adjustment is the cornerstone of management, in order to provide medicines that deliver efficacy, and to de-prescribe agents to limit iatrogenic adverse effects. To assess the opportunity to de-prescribe and better target prescribing, we performed a retrospective audit of 1,806 patients (E, n=1,649; EE, n=157). Data are presented as E and EE respectively. The majority had T2DM (99.1%), with long duration (median, IQR 13.9, 7.4-21.7; 17.5, 10.3-25.1 years); and were overweight (mean ± SD BMI 28.7 ± 5.4; 27.0 ± 4.5 kg/m2). Over 50% used polypharmacy for glycaemic control; 37.9% and 40.8% used insulin +/- tablets. 39.4% of E and 33.3% of EE achieved an HbA1c of &lt;7.0%, with HbA1c 7.5 ±1.4% and 7.8 ± 1.6% (mean± SD NGSP units). Over half (55.8%) of the EE group with an HbA1c &lt;7.0% were treated with insulin and/or sulphonyureas, whereas only 38.2% of E were treated with these agents (p=0.01). While reported severe hypoglycaemia was uncommon (1.5% E and 2.8% EE), 35% of EE patients using insulin and/or sulphonyureas experienced hypoglycaemia. Metformin had appropriately been ceased in all but 7 of the 63 patients with an eGFR &lt; 30 ml/min/1.73m2. While lipid profiles were favourable (HDL: 1.3 ± 0.4 mmol/L; LDL: 2.3 ± 0.9 mmol/L, Trig: 1.5, IQR: 1.1-2.1 mmol/L and HDL: 1.3 ± 0.3 mmol/L; LDL: 2.3 ± 1.0 mmol/L, Trig: 1.5, IQR: 1.0-2.1 mmol/L), lipid lowering therapy was used less frequently in EE (51.0%) versus E (62.6%) (p=0.004). Only 1 in 2 patients with known macrovascular disease were on anti-platelet treatment. This data demonstrates the potential over treatment of glycaemia in the EE specifically in hypoglycaemia inducing agents, highlighting the need to consider de-prescribing. Conversely, under-utilisation of evidence-based medication to address macrovascular risk is also evident.

Disclosure
S.A. Sharp: None. J. Overland: None. M. McGill: None. L.M. Molyneaux: None. T. Wu: Advisory Panel; Self; Boehringer Ingelheim International GmbH, Eli Lilly and Company, Novo Nordisk A/S, Sanofi. Speaker's Bureau; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi. S.M. Twigg: Advisory Panel; Self; Abbott, Boehringer Ingelheim Pharmaceuticals, Inc., Novo Nordisk Inc., Sanofi-Aventis. Board Member; Self; AstraZeneca. Research Support; Self; Abbott. Speaker's Bureau; Self; Abbott, AstraZeneca, Merck Sharp & Dohme Corp., Novo Nordisk Inc., Sanofi-Aventis. J. Wong: Advisory Panel; Self; Sanofi. Speaker's Bureau; Self; AstraZeneca, Lilly Diabetes.