bluuebunny/crossref_metadata_2025_split huggingface dataset:
1410-P: Genetics of TG/HDL-C Ratio and Its Change over Time in Nondiabetic Subjects
Authors: AN PING , LU YANLI , THYAGARAJAN BHARAT , KUIPERS ALLISON L. , ANEMA JASON A. , MILJKOVIC IVA , DAW EDWARD W. , PROVINCE MICHAEL 
Published: June 2020

TG/HDL-C ratio (THR) represents a single inherited surrogate predictor of hyperinsulinemia or insulin resistance that is associated with frank development of T2D, premature aging processes and increased mortality. To identify gene variants for THR and its change over time (THRGC), we conducted GWAS among subjects of European ancestry who had complete data from two exams collected ∼7 years apart from the LLFS (n = 3091), a study with familial clustering of exceptional longevity in the U.S. and Denmark. We sought replication in the FamHS (n = 3108, ∼7 years apart between two visits). Subjects with T2D or using medications for dyslipidemia were excluded from this analysis. THRGC was derived using growth curve modeling. Each phenotype was adjusted for age, sex, PCs and familial membership, and then log-transformed to approximate normality. EPACTS with make-kin and emmax options for familial clustering assuming additive genetic effects was used. P&lt;5e-8 was used to declare genome-wide significance. Heritability estimates reached 38% for THR and 46% for THRGC in the LLFS. GWAS identified two significant loci for THR (LPL-rs328, stop gain, coding sequence variant, MAF=0.11, p=8e-9, replication p=4e-9; BUD13-ZNF259-APOA5-rs2072560, intron variant, MAF=0.07, p=2e-8, replication p=8e-14) and one locus for THRGC (LPL-rs78458743, ∼20 kb downstream, MAF=0.1, p=4e-8, replication p=0.01). The LPL gene encodes lipoprotein lipase that hydrolyzes chylomicrons and VLDL-C. Additionally, linkage scan identified a significant (Lods&gt;3) locus on 3q28 (Lods=4.1) for THRGC in the LLFS. Further query of sequence elements under the linkage peak is underway.
In conclusion, this first GWAS of THR identified the LPL gene (including a functional variant rs328) and the BUD13-ZNF259-APOA5 gene cluster for THR variation. The new findings highlight the importance of the LPL and APOA5 gene regulation of THR in subjects without diabetes selected for exceptional survival and healthy aging.

Disclosure
P. An: None. Y. Lu: None. B. Thyagarajan: None. A.L. Kuipers: None. J.A. Anema: None. I. Miljkovic: None. E.W. Daw: None. M. Province: None.

Funding
National Institute on Aging (U01AG023712, U01AG023744, U01AG023746, U01AG023749, U01AG023755)
1414-P: Characteristics Associated with Sulfonylureas and Basal Insulin Use following Metformin in Older Adults
Authors: DECARLO KRISTEN E. , O’BRIEN MATTHEW , LISS DAVID T. , KANG RAYMOND , COOPER ANDREW J. , CHERUPALLY MANISHA , PARKER EMILY D. , AIKMAN CASSANDRA , ACKERMANN RONALD T. , WALLIA AMISHA 
Published: June 2020

Sulfonylureas (SFU) and basal insulin (BI) are to be used with caution in older adults due to safety risk (eg hypoglycemia). Using 2013-2017 data from a national insurer, we studied 84,720 Medicare Advantage adults ≥ 65 years (yrs) who started one of six antidiabetic medication (ADM) classes after metformin monotherapy. Outcomes were new start of SFU (vs. GLP-1 receptor agonists [GLP-1], SGLT2 inhibitors [SGLT2], thiazolidinediones [TZD], DPP-4 inhibitors [DPP-4]); or BI (vs. GLP-1, SGLT2, TZD, DPP-4). Multivariable logistic regression models examined associations between prescriber and patient characteristics (demographics, cognitive impairment [none, mild and severe], and diabetes related complications [diabetes complications severity index, DSCI score]). Most older adults received SFU followed by DPP-4, while few received GLP-1 and SGLT2 (SFU N=45,734 [54%], DPP-4 N=15,790 [19%], BI N=12,165 [14%], GLP-1 N=3,298 [4%], SGLT2 N=3,365 [4%], and TZD N=4,368 [5%]). Older subcategories of adults were increasingly more likely to receive SFU than those 65-67 yrs (70-74 yrs, OR1.08, 1.04-1.12; 75-79 yrs OR1.2, 1.13-1.25; ≥80 yrs OR1.35, 1.27-1.42). No differences in SFU use were seen in those with cognitive impairment and minority groups. For those receiving BI, females (vs. male OR 1.10, 1.05-1.15) and blacks (vs. whites OR1.26, 1.17-1.15) were more likely to receive BI. Those with severe cognitive impairment (vs. none OR1.98, 1.75-2.24) and high DSCI score (3+) (vs. 0 OR1.40, 1.31-1.50) were more likely to receive BI. Older subcategories of adults were less likely to receive insulin than 65-67 yrs of age (68-70 yrs, OR0.83, 0.77-0.89; 70-74 yrs, OR0.85, 0.80-0.90; 75-79 yrs OR0.93, 0.87-0.99). Older subcategories of adults were increasingly more likely to receive SFU; younger, cognitively impaired and those with diabetes complications were more likely to receive basal BI. Further research is needed to elucidate factors underlying differences in SFU and BI prescribing patterns.

Disclosure
K.E. DeCarlo: None. M. O’Brien: Research Support; Self; UnitedHealth Group. D.T. Liss: None. R. Kang: Research Support; Self; UnitedHealth Group. A.J. Cooper: None. M. Cherupally: None. E.D. Parker: None. C. Aikman: None. R.T. Ackermann: Research Support; Self; National Institute of Diabetes and Digestive and Kidney Diseases, UnitedHealth Group. A. Wallia: Research Support; Self; Eli Lilly and Company, Novo Nordisk Inc., UnitedHealth Group.

Funding
UnitedHealth Group (SP0036847)
1418-P: Increased Risk of Incident Heart Failure and All-Cause Mortality in Insulin-Resistant People with Type 2 Diabetes in the United Kingdom Prospective Diabetes Study (UKPDS)
Authors: WAMIL MALGORZATA , COLEMAN RUTH L. , ADLER AMANDA , MCMURRAY JOHN J. , HOLMAN RURY R. 
Published: June 2020

Background and Aims: Insulin resistance (IR) is a possible mediator for development of heart failure (HF). We examined prospectively whether IR in people with newly-diagnosed type 2 diabetes (T2D) increased their risk of a composite endpoint of incident HF or all-cause mortality (ACM) (as death is a competing risk).
Methods: UKPDS participants with Homeostasis Model Assessment v2 Insulin Resistance (HOMA2_IR) values (derived from paired fasting plasma glucose and insulin measures) were used in multivariable Cox model and Kaplan Meier survival curves to evaluate a possible association between HOMA2_IR and HF/ACM or HF alone, adjusting for potential confounders (variables with a univariate association (P&lt;0.1) and a multivariable P value &lt;0.05 were retained in the full model).
Results: Of 5102 UKPDS participants, 4344 had the data required. They were mean (SD) age 52.5 (8.7) years, HbA1c 7.2 (1.8) %, body mass index 28.8 (5.5) kg/m2, with median (IQR) HOMA2_IR 1.6 (1.1-2.2). Over median 16.4 years the composite endpoint occurred in 1974 (45.4%) participants (235 HF, 1897 death first events) with a 27% greater risk for those with HOMA2_IR ≥1.6 (compared with &lt;1.6), and a 55% greater risk for HF (Table).
Conclusion: Insulin resistant patients with newly-diagnosed T2D were more likely to develop HF or die than those who were more insulin sensitive.

Disclosure
M. Wamil: None. R.L. Coleman: None. A. Adler: None. J.J. McMurray: Other Relationship; Self; AbbVie Inc., Alnylam Pharmaceuticals, Amgen, AstraZeneca, Bayer Healthcare Pharmaceuticals Inc., Bristol-Myers Squibb, Cardurion, GlaxoSmithKline plc., Novartis Pharmaceuticals Corporation, Theracos, Inc. R.R. Holman: Advisory Panel; Self; Merck Sharp & Dohme Corp., Novartis AG, Novo Nordisk A/S. Research Support; Self; AstraZeneca, Bayer AG, Merck Sharp & Dohme Corp.

Funding
Oxfordshire Health Services Research Committee (1239)
1419-P: Lower Medium and Total HDL Particle Concentrations May Contribute to CVD Risk in Type 1 Diabetes
Authors: COSTACOU TINA , VAISAR TOMAS , JU JINGHUI , BORNFELDT KARIN , ORCHARD TREVOR J. , HEINECKE JAY 
Published: June 2020

Although it has long been proposed that HDL is dysfunctional in type 1 diabetes (T1D), this hypothesis has not been formally tested in large cohorts using validated functional and biochemical HDL metrics. We therefore determined whether HDL particle concentration (HDL-P) and function differed between 187 middle-aged adults with childhood-onset T1D (mean age 51 years, T1D duration 43 years, 53% women) and 200 individuals with normal glucose tolerance (NGT) of similar age and sex distribution. HDL-P was assessed by calibrated ion mobility analysis. HDL function, i.e., serum HDL cholesterol efflux capacity, was quantified in J774 cells using a validated assay. Separate stepwise linear regression models were constructed for each HDL metric, allowing for T1D status and potential confounding factors, including HDL cholesterol (HDL-C). The presence of significant effect modification by sex was evaluated. After adjustment, the concentrations of total (T-HDL-P; β=-0.44, p=0.09) and medium-sized (M-HDL-P; β=-0.84, p&lt;0.0001) HDL particles were lower in the T1D compared with the NGT group. In contrast, T1D status was not significantly associated with small (S-HDL-P) and large-sized (L-HDL-P) HDL-P. A significant sex by T1D status interaction term was observed for M-HDL-P (p=0.03), indicating that women had higher M-HDL-P only in NGT; M-HDL-P did not differ by sex in T1D. Moreover, a marginally significant sex by T1D status interaction was observed for L-HDL (p=0.08), suggesting that women had higher L-HDL-P only in T1D. Unexpectedly, serum HDL cholesterol efflux capacity was higher in the T1D compared with the NGT group (β=0.29, p&lt;0.0001).
In conclusion, lower levels of T-HDL-P and M-HDL-P in T1D may explain in part the higher cardiovascular risk in T1D, as these metrics were recently shown to be associated with protection from vascular complications. The lack of a difference in M-HDL-P by sex in T1D may contribute to the loss of cardioprotection associated with female sex.

Disclosure
T. Costacou: None. T. Vaisar: Consultant; Self; AstraZeneca. J. Ju: None. K. Bornfeldt: None. T.J. Orchard: None. J. Heinecke: None.

Funding
National Institutes of Health (HL130153, DK34818)
142-LB: Very Low Dose SGLT2 Inhibition Is as Effective as Angiotensin II Receptor Blockage for Cardiac and Renal Fibrosis in High Salt 5/6 Nephrectomized Rats
Authors: ZENG SHUFEI , HASAN AHMED A. , DELIC DENIS , XIONG YINGQUAN , CHU CHANG , YIN LIANGHONG , FRANKENREITER SANDRA , KRÄMER BERNHARD , KLEIN THOMAS , HOCHER BERTHOLD 
Published: June 2020

SGLT2 inhibition has beneficial effects on cardiovascular and renal endpoints but the lowest effective dose is unknown. Effects of the SGLT2 inhibitor, empagliflozin (EMPA) were evaluated in nondiabetic, 5/6 nephrectomy (5/6 Nx) rats. Rats were treated for 8 weeks: Sham + normal diet + placebo (PBO); 5/6Nx + 2% high salt diet (HSD) + PBO; 5/6Nx + HSD + EMPA 1.2 mg/kg/day); 5/6Nx + HSD + telmisartan (5 mg/kg/day); 5/6Nx + HSD + linagliptin (3 mg/kg/day). EMPA increased urinary glucose excretion at dosages eight times lower than currently used low doses. 5/6Nx HSD rats treated with EMPA showed significantly (-29.95/-25.00 mmHg, p&lt;0.001) lower blood pressure (BP) and significantly reduced renal (-33.67%; p&lt;0.05) and cardiac (- 34.85%; p&lt;0.05) fibrosis vs. PBO. Effects of EMPA on BP and renal and cardiac fibrosis were comparable to telmisartan (BP: -31.89/-24.24 mmHg, p&lt;0.001; renal fibrosis -43.96%; p&lt;0.01; cardiac fibrosis: -36.37%; p&lt;0.01) and effects on fibrosis were comparable to linagliptin (renal fibrosis -41.54%; p&lt;0.05; cardiac fibrosis: -50.01%; p&lt;0.001). Many genes were differentially regulated among groups, e.g., transferrin receptor (Trfc), A-kinase anchor protein 1 (Akap1) and mitogen-activated protein kinase 9 (Mapk9) were affected by EMPA and telmisartan while Caspase 1 (Casp1) gene expression was altered by EMPA only in the heart. In the kidney, both EMPA and linagliptin led to differential regulation of pleckstrin homology domain-containing family A member 1 (Plekha1), while only EMPA resulted in differential expression of prostaglandin E synthase (Ptges) and G protein-coupled receptor, class C, group 5, member A (Gprc5a) gene expression. Very low dose EMPA was almost as effective as standard dosages of telmisartan or linagliptin in counteracting BP increase and cardiac and renal fibrosis. The underlying mechanism involves regulation of genes involved in cardiac and renal fibrosis.

Disclosure
S. Zeng: None. A.A. Hasan: Research Support; Self; Boehringer Ingelheim International GmbH. D. Delic: None. Y. Xiong: None. C. Chu: None. L. Yin: None. S. Frankenreiter: Employee; Self; Boehringer Ingelheim Pharma GmbH & Co. KG. Other Relationship; Self; Evotec International GmbH. B. Krämer: Advisory Panel; Self; Boehringer Ingelheim International GmbH. T. Klein: Employee; Self; Boehringer Ingelheim International GmbH. B. Hocher: Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc.

Funding
Boehringer Ingelheim & Eli Lilly and Company Diabetes Alliance
1420-P: Trends in Cardiovascular and Economic Outcomes of Patients Hospitalized for Stroke and Diabetes in the U.S.: Data from the National Inpatient Sample (2005-2014)
Authors: TABBALAT AYA , DARGHAM SOHA R. , ELSHAZLY MOHAMED B. , KHALIL CHARBEL ABI 
Published: June 2020

Background: As the prevalence of diabetes is increasing worldwide, our aim is to assess the recent cardiovascular and economic trend in outcomes of patients with stroke and diabetes in the U.S.
Methods: Data from the National Inpatient Sample was analyzed between 2005 to 2014. We studied: In-hospital mortality, length of stay (LoS) and overall hospital charges in patients hospitalized for stroke, &gt;18 years of age and known to have diabetes.
Results: The prevalence of diabetes gradually increased from 28.2% to 35.5% in all patients hospitalized for stroke (p trend&lt;0.001) between 2005 and 2014. In those patients with diabetes, mean (SD) age slightly decreased from 70 (13) years to 69 (13) years (p trend &lt;0.001). Interestingly, hospitalization for stroke increased from 17.4 to 20.0/100 000 U.S. adults (p trend &lt;0.001). However, in-hospital age-adjusted mortality decreased from 4.64% to 3.73% (p trend &lt;0.001). Age-adjusted mortality of hemorrhagic strokes - which represent only a small proportion of all strokes- decreased from 28.1% to 23.1%, that of ischemic strokes decreased from 3.23% to 2.48% (p trend &lt;0.01 for both) whereas that of TIA was almost stable and lower than 0.2%. As expected, total charges of hospital stay almost doubled as they went up from 15,970 to 31,018 USD/stay (adjusted for inflation). Nevertheless, median (IQR) LoS slightly decreased from 4 (2-6) to 3 (2-6) days (p trend &lt;0.05).
Conclusion: Our preliminary data show that the prevalence of diabetes in patients hospitalized for stroke is gradually increasing. Moreover, hospitalization for stroke is also increasing. Nevertheless, in-hospital mortality is on a descending slope, which comes at a price of an almost 2-fold increase in hospital charges from 2005 to 2014.

Disclosure
A. Tabbalat: None. S.R. Dargham: None. M.B. Elshazly: Stock/Shareholder; Self; Ember Medical. C. Abi Khalil: None.
1424-P: Generalizability of Glucagon-Like Peptide-1 Receptor Agonist Cardiovascular Outcome Trials to the Type 2 Diabetes Population in China
Authors: CAI XIAOLING , ZHANG LIN , WU HAIYA , HUO LI , MA XIAO , CAO HAIJUN , JI LINONG 
Published: June 2020

Introduction: A number of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have been evaluated in cardiovascular outcome trials (CVOTs). In this study, we aim to examine the generalizability of results from GLP-1 RAs CVOTs among Chinese type 2 diabetes (T2D) population.
Methods: Patients enrolled or eligible for inclusion in four GLP-1RAs CVOTs (EXSCEL, LEADER, REWIND and SUSTAIN-6) were examined in reference to 3B (Blood Glucose, Blood Pressure and Blood Lipid) population, a nationally representative population of T2D patients in China (n=25,411). We descriptively compared key baseline characteristics of the populations in each trial to those in 3B population. We also estimated the proportions of patients in 3B population who would have met the six key inclusion and exclusion (I/E) criteria (age, HbA1c, BMI, eGFR, CVD history and antidiabetic medication) in each trial.
Results: The REWIND population most closely matched 3B population in sex, diabetes duration, HbA1c, DBP, LDL, CVD history and prior MI. The EXSCEL most matched in age, BMI and SBP, while the SUSTAIN-6 most matched in eGFR (Table 1). Based on I/E criteria, 31.10% of the 3B population were eligible for enrolment in REWIND, versus 15.04% in SUSTAIN-6, 12.97% in LEADER, and 11.30% in EXSCEL.
Conclusions: Among the four CVOTs, REWIND has the most generalizable eligibility to the Chinese T2D population.

Disclosure
X. Cai: None. L. Zhang: Employee; Self; Eli Lilly and Company. H. Wu: None. L. Huo: Employee; Self; Eli Lilly and Company. X. Ma: None. H. Cao: None. L. Ji: None.
1426-P: Utilization of Glucose-Lowering Drugs in Patients with T2DM and Established CVD in the U.S.
Authors: GANZ MICHAEL L. , USTYUGOVA ANASTASIA V. , SAWALHI-LECKENBY NICOLA , SOUZA SABRINA DE , GAO RAN , HOMSY DIANA , GUNNARSSON ERIK , ZHANG LU , DESAI NIHAR 
Published: June 2020

Background: People with T2DM have increased risks of CV morbidity and mortality. Glucagon-like peptide-1 receptor agonists (GLP-1 RA) and sodium-glucose cotransporter-2 inhibitors (SGLT2i) have been shown to reduce risks of CV events, but the degree to which they are used in clinical practice remains unknown. Our objectives were to describe glucose-lowering drug utilization in U.S. patients with T2DM and established CVD (eCVD) in 2014-18.
Methods: Annual drug use by adults (≥ 18 years) with T2DM and eCVD (during the same 12-months) was determined from the MarketScan claims database.
Results: We identified 345,340 (2014) to 227,418 (half year 2018) patients with T2DM and eCVD; hypertension and ischemic heart disease were the most prevalent eCVDs. About 55-60% of patients used any type of glucose lowering drug. Although the use of GLP-1 RA and SGLT2i increased 6.2 and 9.5 percentage points respectively across 2014-18, the use of dipeptidyl peptidase-4 inhibitors (DPP-4i) decreased by 3.7 points and use of other glucose lowering drugs decreased by 10.8 points. Patients who used GLP-1 RA and SGLT2i were 8 years younger than users of DPP-4i or other glucose lowering drugs. SGLT2i users had the lowest prevalence of chronic heart failure and chronic kidney disease.
Conclusion: Despite recent increases, GLP 1-RA and SGLT2i are significantly underused among patients with T2DM and eCVD in the MarketScan claims database.

Disclosure
M.L. Ganz: None. A.V. Ustyugova: Employee; Self; Boehringer Ingelheim International GmbH. N. Sawalhi-Leckenby: None. S. de Souza: None. R. Gao: None. D. Homsy: None. E. Gunnarsson: None. L. Zhang: None. N. Desai: None.
1427-P: Higher Prevalence of Heart Failure and Length of Stay in Hospitalized Type 2 Diabetics with Atrial Fibrillation
Authors: ALKHAYRU ALI , TAPPUNI BASSMAN , KASEER BELAL , BRANDT DOMINIQUE M. , GHAZI FREIDOON , WINNER MARSHALL W. , SHEMISA KAMAL 
Published: June 2020

Background: Cardiovascular (CV) disease is a major cause of morbidity in patients with type 2 diabetes mellitus (DM2). DM2 patients often experience Atrial Fibrillation (AF) with aggravated CV morbidity and mortality. We investigated the clinical risk factors in patients with DM2 hospitalized with AF with rapid ventricular response (RVR).
Methods: A retrospective study was conducted using a community hospital EMR database from 2013-2018. Adults with admission codes for AF with RVR were included in the study, and were stratified based on the presence or absence of DM2. Patient characteristics, and clinical outcomes were compared.
Results: Among 1643 patients with AF with RVR, 501 (30.5%) had DM2. Median (IQR) age for DM2 patients compared to controls was 72(64, 79) vs. 73(62, 83), P=0.12, 54.5% vs. 54.6% were female P=0.98, had coronary artery disease [39.5% vs. 25.3% (P&lt;.0001)], heart failure (HF) [68.5% vs. 51.8 % (P&lt;.0001)], hypertension [88% vs. 67.7% (P&lt; 0.0001)]. length of stay (LOS), 3(2,6) days vs. 2(1,4) days, (P&lt;.0001)] LOS was higher for DM2 patients with HF with 4(2,6) vs. 3(2,5) (p &lt;.0001).
Conclusion: Among patients hospitalized for AF with RVR, DM2 patients had a higher prevalence of cardiovascular disease and longer LOS. A higher prevalence of HF may be a contributing factor to longer LOS. Understanding the risk of HF in patients with DM2 and AF is needed to address clinical outcomes in the future.

Disclosure
A. Alkhayru: None. B. Tappuni: None. B. Kaseer: None. D.M. Brandt: None. F. Ghazi: Speaker’s Bureau; Self; AstraZeneca K.K., Boston Scientific, Janssen Pharmaceuticals, Inc. M.W. Winner: None. K. Shemisa: Speaker’s Bureau; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Pfizer Inc.
143-OR: All-Cause Mortality over 16 Years in Look AHEAD
Authors: WING RENA R. , CLARK JEANNE , GREGG EDWARD W. , KRITCHEVSKY STEPHEN B. , LEWIS CORA E. , PI-SUNYER XAVIER , REBOUSSIN DAVID M. , WADDEN THOMAS A. , WAGENKNECHT LYNNE E. , YANOVSKI SUSAN Z. ,   THE LOOK AHEAD GROUP
Published: June 2020

Whether intentional weight loss reduces mortality in overweight/obese individuals with diabetes is unclear. Look AHEAD, a randomized trial of intensive lifestyle intervention (ILI) and diabetes support and education (DSE) (control) in 5145 individuals with overweight/obesity and type 2 diabetes, is ideal for examining this due to large sample, extended follow-up, excellent retention, and sustained difference in weight loss (y1: 8.6% ILI; 0.7% DSE; y10: 6.1% ILI; 3.9% DSE). After 10 years of intervention, participants had 6-month calls and biennial visits. The primary outcome for the current phase is all-cause mortality from randomization to 16 years. Data were analyzed with proportional hazards regression stratified by clinical site; significance was based on the likelihood ratio. All-cause mortality was 9% lower in ILI compared to DSE, not a statistically significant difference (Fig 1). Deaths by arm were: ILI 496/2570 and DSE 530/2575. Interactions of treatment with prespecified subgroups (sex, CVD history, age) were not significant. In post-hoc analyses, ILI participants who lost &gt;10% at 1year had an 18% reduced risk (HR=.82, CI 0.68,0.97) and ILI participants who gained or lost &lt;2% had a 29% higher risk (HR=1.29, CI 1.01,1.67) relative to all DSE. The difference in mortality between ILI and DSE was not statistically significant. Post-hoc analyses suggest an association between magnitude of weight change and all-cause mortality in ILI.

Disclosure
R.R. Wing: None. J. Clark: None. E.W. Gregg: None. S.B. Kritchevsky: None. C.E. Lewis: None. D.M. Reboussin: None. T.A. Wadden: Board Member; Self; Novo Nordisk Inc., Weight Watchers International, Inc. L.E. Wagenknecht: None. S.Z. Yanovski: None.

Funding
National Institutes of Health