bluuebunny/crossref_metadata_2025_split huggingface dataset:
1482-P: Low-Density Lipoprotein Cholesterol (LDL-C) Management in Patients with Atherosclerotic Cardiovascular Diseases (ASCVD) and Preexisting Diabetes in Alberta, Canada
Authors: CHEN GUANMIN , FARRIS MEGAN S. , COWLING TARA , TAI MING-HUI , PINTO LIONEL , COLGAN STEPHEN , ROGOZA RAINA , ANDERSON TODD J. 
Published: June 2019

Background: Lipid-lowering therapy (LLT) reduces the risk of CV events, however, limited real-world data exist on the management of LDL-C in patients with ASCVD and pre-existing diabetes in Canada. Our study describes the clinical characteristics and LDL-C management of patients with ASCVD and diabetes using health system data in Alberta.
Methods: A retrospective study was conducted linking multiple health system datasets to examine clinical characteristics and LDL-C levels in those receiving LLT (e.g., statins) after the first LDL-C test. Patients with ASCVD were identified using ICD diagnostic codes between 2011-2015. Similarly, diabetes status was assessed in the year prior to ASCVD diagnosis. LDL-C was assessed at the first (index) and second (follow-up) tests during the study period. LDL-C levels were evaluated based on a threshold of 2.0 mmol/L, as per the 2016 Canadian blood cholesterol management guidelines.
Results: Among 144,607 patients with ASCVD and a prescription for LLT (mean age=66.3; 66% male), 27,540 (19.0%) patients were identified with diabetes. Patients with diabetes were more likely to have stroke, myocardial infarction, or peripheral arterial disease. Congestive heart failure and hypertension were found in 26.8% and 87.8% of patients with diabetes compared to 12.5% and 71.5% in those without, respectively. Of the patients with diabetes who had an index and follow-up LDL-C test (n=18,214), 35.0% (n=6,380) did not achieve the guideline specified LDL-C threshold at index. At follow-up (mean=238.9 days after index), 49.0% (n=3,129) of those who did not achieve threshold at index failed to meet the threshold.
Conclusions: Nearly half of patients above the LDL-C threshold at the index test did not achieve threshold at the follow-up test, despite receiving LLT. Multifaceted interventions may be required to improve cholesterol management of patients with ASCVD and diabetes in Alberta.

Disclosure
G. Chen: Consultant; Self; Medlior Health Outcomes Research Ltd. M.S. Farris: Employee; Self; Medlior Health Outcomes Research Ltd. T. Cowling: Stock/Shareholder; Self; Medlior Health Outcomes Research Ltd. M. Tai: Employee; Self; Amgen Inc. L. Pinto: Employee; Self; Amgen Inc. S. Colgan: Employee; Self; Amgen Inc. R. Rogoza: Employee; Self; Amgen Inc. Stock/Shareholder; Self; Amgen Inc. T.J. Anderson: None.
1485-P: Defining a Hierarchy of Mortality Risk in Metabolic Syndrome
Authors: VISARIA AAYUSH , AMOROSA LOUIS F. 
Published: June 2019

Purpose: ATP III defined metabolic syndrome (MetS) as at least three of five criteria (waist circumference [WC], elevated fasting glucose [FG], low HDL [HDL], high triglycerides [TG], elevated blood pressure [BP]). We developed a novel score to account for the differing all-cause mortality hazards of individual criteria and to better reflect the increased mortality with increasing number of criteria.
Methods: A population of 2,392 non-pregnant individuals &gt;20 years with data on demographics, MetS criteria, smoking status, and mortality were included in this secondary analysis of NHANES III (1988-1994). Outcomes included all-cause mortality as of Dec. 31st, 2011. Cox hazard models were run adjusting for potential confounders and accounting for the complex survey design. Hazard weights for each criterion were developed using univariate Cox models and summed for an overall score.
Results: There were 991 deaths from all causes among the 2,393 individuals over 250-months. Among those with MetS, increasing number of criteria coincided with increasing mortality hazards compared to those with 0 criteria (3: aHR=1.47, 95% CI [1.18, 1.83]; 4: aHR=1.77 [1.42, 2.21]; 5: aHR=2.39 [1.89, 3.02]). In our model individual criterion mortality hazards were rounded and assigned as points. The sum of the points of the criteria formed a weighted score. From highest to lowest hazard, the criteria hierarchy was BP (5 points), FG (3), WC (2), TG (1), and HDL (1) for a total possible score of 12 points. Scores 6 points and above had similar or higher hazard to those with traditional MetS when compared to normals (Score of 6: aHR= 1.50 [1.20, 1.88] vs. MetS: aHR: 1.29 [1.17, 1.42]). Increasing points corresponded to increasing mortality hazard; those with 10-12 points had nearly double the hazard as normals (aHR= 2.07 [1.54, 2.79]).
Conclusion: The developed weighted score is a more comprehensive ranking which assesses aggregate mortality hazard and may better assess all-cause mortality hazard in U.S. adults than current MetS diagnostic criteria.

Disclosure
A. Visaria: None. L.F. Amorosa: None.
1491-P: Increase in HbA1c at Time of Diagnosis Upon Change to New Diagnostic Criteria in Denmark
Authors: CARSTENSEN BENDIX , RØNN PERNILLE F. , JØRGENSEN MARIT E. 
Published: June 2019

Introduction: In 2011 the diagnostic criteria for diabetes in Denmark was changed from an oral glucose tolerance test (OGTT) to HbA1c. Several studies have shown that the OGTT identifies diabetes at a lower HbA1c level than the current threshold. Several countries have seen a decreasing type 2 diabetes incidence after 2011, possibly related to new diagnostic criteria. It is therefore conceivable that the HbA1c level at the time of diagnosis should be increasing after 2011. We investigated the level of HbA1c in newly diagnosed type2 diabetes patients in Denmark in the period 2010-16, to test this conjecture.
Methods: We obtained HbA1c measurements from the national laboratory database which contains person-identifiable laboratory measurements on all Danish citizens. These were linked to a national register on all type 2 diabetes patients, which was based on national health care registers. We chose the HbA1c measurement closest to the date of diabetes, but only in a window from 3 months before to 1 month after diagnosis.
Results: Information on HbA1c was available for 98,010 out of 132,534 persons with type 2 diabetes registered in the period 2010-16 incl. The overall level of HbA1c was stable in the period 2010-13, but from 2013 we saw weak increase in the median HbA1c at diagnosis, most pronounced for men (48 to 56 mmol/mol) compared to women (47 to 52 mmol/mol). But the 90th percentile of HbA1c increased in the period 2013-16 for men from 78 to 101 and for women from 65 to 88 mmol/mol, while percentiles of HbA1c below the median were stable.
Conclusion: HbA1c at diagnosis increased in the period 2013-16, presumably because the diagnosis is made at a more advanced state when using HbA1c as criterion as compared to OGTT. In the same period the incidence rates of type 2 diabetes was increasing to 2011, then declining till 2015 and after that increased again. Future studies will show whether changes in HbA1c levels influences the prevalence, incidence and mortality of persons included as diabetes patients in the register.

Disclosure
B. Carstensen: Consultant; Self; Leo Pharma. Speaker's Bureau; Self; Novo Nordisk A/S. Stock/Shareholder; Self; Novo Nordisk Inc. P.F. Rønn: Research Support; Self; Amgen AB. Stock/Shareholder; Spouse/Partner; Novo Nordisk A/S. M.E. Jørgensen: Research Support; Self; Amgen Inc., AstraZeneca, Danish Diabetes Association, Sanofi-Aventis. Stock/Shareholder; Self; Novo Nordisk A/S.
1494-P: Glycated Albumin May Be an Effective Alternative to A1C in the Presence of Hemoglobin C Trait
Authors: BRIKER SARA M. , HORLYCK-ROMANOVSKY MARGRETHE F. , MUGENI REGINE , ADUWO JESSICA Y. , DUBOSE CHRISTOPHER , SUMNER ANNE E. 
Published: June 2019

Hemoglobin C (HbC) trait is a heterozygous hemoglobinopathy common in West Africa. Due to interference with the HPLC assay, heterozygous hemoglobinopathies such as HbC trait may lead to readings for A1C which are artefactually low. Therefore, the value of A1C as a diagnostic test may be compromised. Glycated albumin (GA) may be an effective alternate to A1C because it is a nonfasting measure of glycemia which is not impacted by Hb variants. No study has focused on HbC trait and evaluated the ability of A1C and GA to detect glucose tolerance status. Our goals were to evaluate the diagnostic efficacy of A1C and GA in the detection of dysglycemia in the 4% (13/366) of African-born blacks enrolled in the Africans in America Study who had HbC trait documented by hemoglobin electrophoresis. OGTT was performed in the 13 participants (age 37±7y (mean±SD), BMI 26.9±3.4 kg/m2). Glucose tolerance status was defined by the OGTT. The ability of A1C≥5.7% and GA≥14.2% to diagnose dysglycemia was evaluated. Both A1C≥5.7% and GA≥14.2% represent the upper quartile cut-off for their distribution in the Africans in America cohort. Mean A1C was 4.8±0.7%, range 3.1- 5.6%. Mean GA was 13.9±1.3%, range 11.9 - 15.4%. Thirty-nine % (5/13) of the participants had prediabetes and 8% (1/13) had diabetes. However, A1C was &lt;5.7% in all participants. Therefore, for A1C sensitivity and specificity were 0% and 100% resp. In contrast, for GA the sensitivity and specificity were 83% and 71%, resp. Although the number of individuals with HbC trait in our cohort was small, our findings suggest that GA may be an important screening test to be used in populations with a high prevalence of HbC trait.

Disclosure
S.M. Briker: None. M.F. Horlyck-Romanovsky: None. R. Mugeni: None. J.Y. Aduwo: None. C. DuBose: None. A.E. Sumner: None.
150-OR: BioChaperone Pramlintide Insulin (BCPramIns), a New Co-Formulation of Pramlintide (PRAM) and Human Insulin (INS), Improves Postprandial Blood Glucose (BG) vs. Both Separate Injections of PRAM+INS and Insulin Lispro (LIS) in Subjects with T1D
Authors: MEIFFREN GRÉGORY , SEROUSSI CYRIL , RANSON AYMERIC , CHARVET RICHARD , GAUDIER MARTIN , ANDERSEN GRIT , ZIJLSTRA ERIC , DEVRIES J. HANS , HEISE TIM , SOULA RÉMI , SOULA OLIVIER 
Published: June 2019

BCPramIns is developed to leverage the beneficial effects of PRAM on post-prandial BG control in a convenient co-formulation with INS. This double-blind, randomized cross-over study investigated pharmacodynamics, pharmacokinetics and safety of BCPramIns in 24 subjects with T1DM [mean±SD age 41±10 years; BMI 25±2.3 kg/m²; HbA1c 7.2±0.6%] who received fixed doses of 7.5 IU INS and 45 µg PRAM either as a single injection of BCPramIns or separate injections (PRAM+INS) before a mixed meal tolerance test in comparison to 7.5 U insulin lispro (LIS) with BCPramIns, BG excursions in the first 2 hours post-meal were reduced by 97% (p&lt;0.0001) and 82% (NS) compared to LIS and PRAM+INS, respectively (Table). Time to maximum BG was prolonged by BCPramIns compared to LIS and slightly delayed compared to PRAM+INS, (5.00h vs. 3.00h and 4.25h respectively, Table). Insulin exposure was similar between BCPramIns and PRAM+INS (AUCINS_0-6h 87 vs. 86 mU*h/L), indicating no impairment in insulin absorption with BCPramIns. Six adverse events occurred with BCPramIns, 4 with PRAM+INS and 3 with LIS. Hypoglycemia during dosing visit days were balanced between the three treatment groups (4-3-3).
In conclusion, BCPramIns was well tolerated and improved postprandial BG versus LIS.

Disclosure
G. Meiffren: Employee; Self; ADOCIA. Stock/Shareholder; Self; ADOCIA. C. Seroussi: Employee; Self; ADOCIA. Stock/Shareholder; Self; ADOCIA. A. Ranson: Employee; Self; ADOCIA. Stock/Shareholder; Self; ADOCIA. R. Charvet: None. M. Gaudier: Employee; Self; ADOCIA. Stock/Shareholder; Self; ADOCIA. G. Andersen: None. E. Zijlstra: Speaker's Bureau; Self; Novo Nordisk A/S. J. DeVries: Advisory Panel; Self; Novo Nordisk A/S. Employee; Self; Profil Institute for Metabolic Research. Research Support; Self; Medtronic. Speaker's Bureau; Self; Novo Nordisk A/S. T. Heise: Advisory Panel; Self; Mylan. Research Support; Self; ADOCIA, Boehringer Ingelheim International GmbH, Dance Biopharm Holdings Inc., Eli Lilly and Company, Gan & Lee Pharmaceuticals, Johnson & Johnson, MedImmune, Mylan, Nordic Bioscience, Novo Nordisk A/S, Pfizer Inc., Poxel, Saniona, Sanofi, Wockhardt, Zealand Pharma A/S. Speaker's Bureau; Self; Eli Lilly and Company, Novo Nordisk A/S. R. Soula: Board Member; Self; Cellnovo. Employee; Self; ADOCIA. O. Soula: Board Member; Self; ADOCIA. Employee; Spouse/Partner; ADOCIA. Employee; Self; ADOCIA. Stock/Shareholder; Spouse/Partner; ADOCIA. Stock/Shareholder; Self; ADOCIA.
1505-P: Plasma Glucose Level at 1h Post 75g OGTT Is the Best Predictor of the Development of Glucose Intolerance in Subjects with Normal Glucose Tolerance—The Toon Health Study
Authors: TAKAKADO MISAKI , TAKATA YASUNORI , HADATE TOSHIMI , MATSUSHITA YUMI , KAWAMURA RYOICHI , MARUYAMA KOUTATSU , SAITO ISAO , OSAWA HARUHIKO 
Published: June 2019

Background: Although glucose intolerance (GI) is diagnosed by fasting and 2h plasma glucose (PG) levels during a 75g OGTT, the upper limit of 1h PG level remains to be undefined in subjects with NGT. Previous report focusing on changes from NGT + IGT to diabetes has reported that 1h PG with ≥155 mg/dl is the risk for future diabetes in the world. However, IGT is well known as a risk factor for cardiovascular disease, few studies have focused on changes from NGT to GI. We therefore conducted a 5-year prospective study intended for NGT subjects to clarify the best predictor of the development of GI.
Methods: To diagnose GI, we performed a 75gOGTT. We enrolled 1383 NGT subjects from The Toon Health Study. Finally, we analyzed 981 individuals with NGT who had a repeat health checkup. To investigate valuable predictive factors of progression of GI, we performed ROC curve analyses and compared fasting PG, 1h post OGTT, 2h post OGTT, and HbA1c.
Results: ROC curve analyses revealed that 1h post OGTT was the best predictor of the development of GI in NGT (sensitivity 66%, specificity 74%, at a cutoff value of 149 mg/dl). In NGT with 1h PG&gt;149mg/dl, odd ratio for the development of GI was 4.7 (95% CI: 3.25-6.80) compared to the reference after adjustment for age, sex, and BMI (p&lt;0.0001).
Conclusions: PG level at 1h post 75g OGTT was the best predictor of the development of GI in NGT.

Disclosure
M. Takakado: None. Y. Takata: None. T. Hadate: None. Y. Matsushita: None. R. Kawamura: None. K. Maruyama: None. I. Saito: None. H. Osawa: None.
1517-P: A Longitudinal Study of a Panel of Adipokines and Gestational Diabetes Risk
Authors: FRANCIS ELLEN C. , LI MENGYING , HINKLE STEFANIE , CHEN JINBO , CHEN LIWEI , ZHANG CUILIN 
Published: June 2019

Prospective studies with measurement of a comprehensive panel of adipokines in early pregnancy and gestational diabetes (GDM) risk are sparse, and studies of adipokines for prediction of GDM are limited. We investigated a panel of adipokines in relation to GDM risk. In a nested case-control study within the NICHD Fetal Growth Studies-Singleton cohort (2009-2013), we identified 107 GDM cases and selected 214 controls matched on age, race/ethnicity, and gestational week (GW) at blood draw. Plasma Leptin, Soluble Leptin Receptor (sOB-R), Free Leptin, Chemerin, Fatty Acid Binding Protein 4 (FABP4), Retinol Binding Protein 4, Adiponectin, Omentin1, and Vaspin were measured prior to GDM at GWs 10-14, 15-26. Adjusting for maternal age, GW of blood collection, nulliparity, and family history of diabetes, conditional logistic analysis was performed to estimate adjusted odds ratios (aOR) for associations of adipokines with GDM. Receiver-operating-characteristic (ROC) curves assessed the predictive value of adipokines for GDM diagnosis. Leptin, Free Leptin, Chemerin, and FABP4 concentrations were significantly higher. Adiponectin, and sOB-R were significantly lower among cases than controls. At GW 10-14, Adiponectin, and sOB-R were significantly and inversely related to GDM risk. For example, across increasing quartiles of sOB-R the aOR were 1.00 (ref), 0.37 (0.19, 0.74), 0.28 (0.13, 0.59), and 0.24 (0.11, 0.52) (Ptrend≤.0001). In contrast, Leptin, Free Leptin, Chemerin, and FABP4 were significantly and positively associated with GDM risk. In general, associations of adipokines with GDM were stronger at GW 15-26. In addition, at GW 15-26, sOB-R significantly improved GDM prediction over conventional risk factors (age, GW, race, nulliparity, family history of diabetes, prepregnancy BMI) and glucose (P = 0.02). A panel of adipokines may be implicated in the pathogenesis of GDM with significant associations and incremental predictive value detected in early pregnancy before GDM is usually screened for.

Disclosure
E.C. Francis: None. M. Li: None. S. Hinkle: None. J. Chen: None. L. Chen: None. C. Zhang: None.

Funding
National Institutes of Health
152-LB: Sodium-Glucose Cotransporter Inhibitor Impairs Adhesion of Cancer Cells by Increasing Shedding and Dephosphorylation of Discoid Domain Receptor
Authors: OKADA JUNICHI , OKADA SHUICHI , YAMADA MASANOBU 
Published: June 2019

Dapagliflozin, a selective inhibitor of the sodium/glucose cotransporter 2 (SGLT2), is used clinically to reduce circulating glucose levels in patients with type 2 diabetes mellitus by blocking the reabsorption of glucose from the kidney. Dapagliflozin is metabolized and inactivated by UDP glucuronosyltransferase 1 family, Polypeptidase A9 (UGT1A9). Dapagliflozin treatment of HCT116 cells that express SGLT2 but not UGT1A9 display loss of cell adhesion whereas HepG2 cells that express both UGT1A9 and SGLT2 are resistant to dapagliflozin. Knockdown of UGT1A9 in HepG2 cells increased dapagliflozin sensitivity whereas overexpression of UTG1A9 in HCT116 cells protect against dapagliflozin-dependent loss of cell adhesion. Dapagliflozin treatment had no effect on the cellular interaction with fibronectin, vitronectin, or laminin but induced a loss of interaction with collagen I and IV. In parallel, dapagliflozin treatment reduced the protein levels of the discoidin domain receptor 1 (DDR1) concomitant with Y792 dephosphorylation and appearance of cleaved DDR1. Concomitant with these observations, dapagliflozin increased sheddase and tyrosine phosphatase activities. Physiologically, dapagliflozin reduced tumor burden of HCT116 cells in chick chorioallantoic membrane assays. Taken together, these data present a new potential role for dapagliflozin therapy as an anti-cancer reagent in tumor cells that express SGLT2 but not UGT1A9.

Disclosure
J. Okada: None. S. Okada: None. M. Yamada: None.
1522-P: Serum Mac-2 Binding Protein Glycosylation Isomer Level and the Risk of Type 2 Diabetes in a Japanese Community: The Hisayama Study
Authors: HIGASHIOKA MAYU , HIRAKAWA YOICHIRO , YOSHINARI MASAHITO , HONDA TAKANORI , SAKATA SATOKO , SHIBATA MAO , YOSHIDA DAIGO , HATA JUN , KITAZONO TAKANARI , OSAWA HARUHIKO , NINOMIYA TOSHIHARU 
Published: June 2019

Background: Serum Mac-2 binding protein glycosylation isomer (M2BPGi) is a novel biomarker of chronic liver disease including liver fibrosis. Chronic liver disease has been acknowledged to cause glucose intolerance. However, few studies have addressed the association between serum M2BPGi levels and the risk of type 2 diabetes (T2D).
Methods: A total of 2,143 participants aged 40-79 years without diabetes were followed-up for a median of 7.0 years. Serum M2BPGi levels were measured at baseline and were categorized into quartiles: ≤ 0.40; 0.41-0.55; 0.56-0.75; and ≥0.76 (cut-off index). A Cox’s proportional hazards model was used to estimate hazard ratios (HRs) and their 95% CIs for the incident T2D with the adjustment for confounders-namely age, sex, family history of diabetes, systolic blood pressure, use of antihypertensive agents, serum total and HDL cholesterol, serum triglyceride, use of lipid-modifying agents, BMI, smoking, drinking, regular exercise, and fasting plasma glucose. The impact of serum M2BPGi levels on the predictive ability of incident T2D was evaluated with Harrell’s C statistics, continuous net reclassification improvement (cNRI), and integrated discrimination improvement (IDI).
Results: During follow-up periods, 219 subjects developed T2D. The multivariable-adjusted HR (95% CI) of developing T2D increased significantly with higher serum M2BPGi levels (p for trend=0.03), being 1.00 (reference) in Q1, 1.38 (0.89-2.15) in Q2, 1.51 (0.95-2.39) in Q3, 1.70 (1.07-2.70) in Q4. The predictive ability of incident T2D was improved by adding serum M2BPGi level to the model comprising aforementioned confounders: Harrell’s c-statistics from 0.787 to 0.795 (p=0.03), cNRI 0.19 (p=0.03), and IDI 0.004 (p=0.07).
Conclusion: Our findings suggest that higher serum M2BPGi level was a significant risk factor for T2D in the general Japanese population. Measuring serum M2BPGi level may be effective to detect the high-risk population of T2D.

Disclosure
M. Higashioka: None. Y. Hirakawa: None. M. Yoshinari: None. T. Honda: None. S. Sakata: None. M. Shibata: None. D. Yoshida: None. J. Hata: None. T. Kitazono: None. H. Osawa: None. T. Ninomiya: Research Support; Self; Asahi Kasei Corporation, Denka Company Limited, DeSC Healthcare, Inc, Mochida Pharmaceutical Co., Ltd., Suntory Beverage & Food Limited, Sysmex Corporation.
1526-P: Delayed Heart Rate Recovery after Exercise as a Risk Factor of Incident Metabolic Syndrome: A Retrospective Cohort Study
Authors: YU TAE YANG , JIN SANG-MAN , HUR KYU YEON , BAE JI CHEOL , JEE JAEHWAN , KIM JAE HYEON , LEE MOON-KYU 
Published: June 2019

Background: There have been several cross-sectional studies reporting that delayed heart rate recovery (HRR) after exercise is associated with the development of the metabolic syndrome (MetS). However, there have been few longitudinal studies. We evaluated the longitudinal association of delayed HRR following a graded exercise treadmill test (GTX) with the incident MetS including metabolic parameters as adjusting factors.
Methods: A retrospective longitudinal cohort study of participants without MetS, diabetes or cardiovascular diseases has been designed. HRR was calculated as peak heart rate minus heart rate after a 1-minute rest (HRR 1), heart rate after a 2-minute rest (HRR 2), and heart rate after a 3-minute rest (HRR 3). To investigate the association between HRR and incident MetS, multivariate Cox proportional hazards analysis was performed.
Results: During 9,683 person-years of follow-up between 2006 and 2012, there were 676 (31.2%) incident cases of the MetS. After adjustment for age, sex, smoking status, baseline heart rate, peak heart rate, peak oxygen uptake, hs-CRP, waist circumference, systolic blood pressure, TG, LDL-C, HDL-C, fasting plasma glucose, HOMA-IR, and HbA1c, the hazard ratios (HR) [95% confidence interval (CI)] of incident MetS comparing the first and second tertiles to the third tertile of HRR 3 were 1.492 (1.146-1.943) and 1.277 (1.004-1.624) (P for trend = 0.003). As a continuous variable, after full adjustments, the HR (95% CI) of incident MetS associated with each 1-second decrease in HRR3 was 1.015 (1.005 -1.026) (P = 0.004).
Conclusion: Delayed HRR 3 after exercise could predict incident MetS, even after adjusting for metabolic parameters. However, HRR 1 and HRR 2 have not shown the statistic significance.

Disclosure
T. Yu: None. S. Jin: None. K. Hur: None. J. Bae: None. J. Jee: None. J. Kim: None. M. Lee: None.