bluuebunny/crossref_metadata_2025_split huggingface dataset:
1433-P: Protective Effect of GLP-1 Receptor Agonists (GLP-1 RA) and SGLT2 Inhibitors (SGLT2i) against Adverse Cardiovascular (CV) Events in HIV and Type 2 Diabetes Mellitus (T2DM) When Compared with Metformin Alone: A National Database Study
Authors: ALABER OMAR A. , CHANDAR APOORVA K. , DAHASH BASMA A. , ZUZEK ALEONA C. , RAJPAL AMAN 
Published: June 2020

Introduction: T2DM and HIV independently confer an increased risk of CV adverse events. We aimed to evaluate the effect of newer oral antidiabetic medications (GLP-1 RA/SGLT2i) on CV outcomes in adults with HIV and T2DM.
Methods: Using a national database (IBM Explorys Solutions, IBM, Inc.), we searched for cases (HIV + T2DM patients on GLP-1 RA/SGLT2i and metformin) and controls (HIV + T2DM patients on metformin alone). We calculated comparative odds ratios (OR) and 95% confidence interval (CI) for the risk of association of GLP-1 RA/SGLT2i use and incident CV adverse events, namely myocardial infarction (MI) and acute heart failure (AHF).
Results: Out of a total of 61,917,780 patients in Explorys, 29,920 had both HIV and T2DM. Patients on GLP-1 RA or SGLT2i were significantly less likely to experience an incident adverse CV event when compared to controls (Table 1). When stratified by individual drug classes (either GLP-1 RA or SGLT2i), patients on the newer antidiabetic medications were still significantly less likely to experience an adverse CV event in comparison to metformin alone (Table 1).
Conclusion: GLP-1 RA and SGLT2i seem to confer a protective effect against major adverse CV events such as MI and AHF in patients with both HIV and T2DM.

Disclosure
O.A. Alaber: None. A.K. Chandar: None. B.A. Dahash: None. A.C. Zuzek: None. A. Rajpal: None.
1434-P: Patients with Type 2 Diabetes Present with Multiple Anomalies of the Pancreatic Arterial Tree
Authors: ALEXANDRE-HEYMANN LAURE , BARRAL MATTHIAS , DOHAN ANTHONY , LARGER ETIENNE 
Published: June 2020

Epidemiological and experimental studies suggest that cardio-vascular risk factors could foster the development of type 2 diabetes (T2D). This could partly be mediated by pancreatic atherosclerosis resulting in pancreatic ischemia. We hypothesized that patients with T2D present with more severe atherosclerosis of pancreas-bound arteries than control patients without T2D.
We performed a case-control retrospective study comparing the abdominal computed tomography of patients with T2D and of control subjects matched for gender and for age. Forty-eight patients with T2D and 48 control subjects were included. A calcification score of the splenic artery was defined (from 0: no calcification to 3: continuous linear calcifications). It was higher in patients with T2D than in control subjects (0.6 versus 0.2, p=0.02). The mean number of pancreas-bound branches among the greater pancreatic artery, the dorsal pancreatic artery and the inferior pancreatic artery (from 0 to 3) and of visible intrapancreatic arterial subdivisions (from 0 to 2) was lower in patients with T2D than in control subjects (1.1 versus 1.7, p=0.003 and 0.7 versus 1.3, p=0.0017, respectively). Post-injection enhancement of the pancreas tended to be lower in patients with T2D than in control subjects (57 versus 68 Hounsfield units, p=0.06). None of these differences correlated with the duration of diabetes. Moreover, in control subjects, the pancreas volume was higher and the pancreas density and enhancement were lower with higher BMI. This relationship was not confirmed in patients with T2D. Thus, it could be hypothesized that more powerful factors than BMI could impact pancreas volume and density in patients with T2D. Pancreatic atherosclerosis could be one of these.
Patients with T2D present with more anomalies of the pancreatic arterial tree than control subjects. These anomalies do not correlate with the duration of diabetes, which may imply an early role of pancreatic atherosclerosis in T2D natural history.

Disclosure
L. Alexandre-Heymann: None. M. Barral: None. A. Dohan: None. E. Larger: None.
1436-P: Association between Sleep Duration and Mortality among Adults with Type 2 Diabetes: A Prospective Cohort Study
Authors: CHEN XIONG , XIAO JIAN , YU WEIHUI , HU XIANG , WANG YAFENG , SHEN FEIXIA 
Published: June 2020

Objective: We aimed to address the association of sleep duration and all-cause and cause-specific mortality (CVD, cancer and other causes) in people with type 2 diabetes.
Research Design and Methods: The sample consisted of 24,212 adults with type 2 diabetes from the National Health Interview Survey (2004 to 2013). The relationship between sleep duration and mortality were investigated using Cox proportional hazards regression model.
Results: A J-shaped relationship existed between sleep duration and all-cause mortality in people with type 2 diabetes. Compared to the reference group (7 hours/day), both shorter and longer sleep duration were significantly associated with increased risk of all-cause mortality. Similar associations were also observed for mortality from CVD, cancer, kidney disease, Alzheimer’s disease, and chronic lower respiratory diseases (CLRD). Greater risks of all-cause and CVD mortality were associated with longer sleep duration in men with a younger age of onset, as well as shorter sleep duration in those with both taking insulin and diabetes pills.
Conclusions: In people with type 2 diabetes, sleeping less or more than 7 hours/day was associated with increased risk of all-cause and condition specific mortality. The association was more prominent in men with a younger age at diabetes onset and those taking diabetes pills and insulin.

Disclosure
X. Chen: None. J. Xiao: None. W. Yu: None. X. Hu: None. Y. Wang: None. F. Shen: None.

Funding
Natural Science Foundation of Zhejiang Province (LWY20H020001); China Scholarship Council (201908330235); Science and Technology Project of Wenzhou Science and Technology Bureau (Y20190125); First Affiliated Hospital of Wenzhou Medical University (FHY2019015)
144-OR: The Antirheumatic Drug Auranofin Improves the Metabolic Phenotype of Obesity
Authors: COX AARON , MASSCHELIN PETER M. , CHERNIS NATASHA , SAHA PRADIP , LIAN ZEQIN , FELIX JESSICA B. , KIM KANGHO , WU HUAIZHU , HARTIG SEAN M. 
Published: June 2020

Obesity is associated with chronic low-grade inflammation, reflecting significant alterations in the composition of immune cell populations that reside in white adipose tissue (WAT). The ensuing pro-inflammatory environment likely impinges on the metabolic functions of adipocytes and may partially explain the insulin resistance that characterizes type 2 diabetes mellitus (T2DM). We recently demonstrated ectopic expression of the microRNA miR-30a in the subcutaneous fat pad of diabetic mice coupled improved insulin sensitivity and increased energy expenditure with decreased ectopic fat deposition in the liver and reduced WAT inflammation. We subsequently pursued the notion that pharmacological inhibitors of inflammation that exhibit a gene expression profile similar to ectopic miR-30a expression in WAT should represent new drugs for insulin resistance and T2DM. To this end, we used the Broad Connectivity Map to analyze a library of small molecules that induce mRNA profiles similar to that of exogenous miR-30a expression in WAT. Through this process, we nominated the rheumatoid arthritis compound auranofin. Treatment of obese mice with auranofin improved insulin sensitivity and glucose tolerance. Auranofin treatment also normalized other obesity-associated abnormalities, including hepatic steatosis, serum insulin and leptin. Mechanistically, a combination of proteomics and immunophenotyping established auranofin likely exerts antidiabetic activities by opposing low-grade inflammation in WAT and ectopic liver fat accumulation. These studies reveal important metabolic properties of anti-inflammatory treatments that may be re-purposed as therapies for insulin resistance and T2DM.

Disclosure
A. Cox: None. P.M. Masschelin: None. N. Chernis: None. P. Saha: None. Z. Lian: None. J.B. Felix: None. K. Kim: None. H. Wu: None. S.M. Hartig: None.

Funding
American Diabetes Association (1-18-IBS-105 to S.M.H.); National Institutes of Health (R01DK114356)
1440-P: Detecting Undiagnosed Dysglycemia in Primary Care with Automated Clinical Decision Support and Patient Outreach
Authors: CHEN PATRICIA M. , HIGASHI ROBIN T. , LEE SIMON J.C. , LINGVAY ILDIKO , MENEGHINI LUIGI , OBIALO E. ELIZABETH , KASSA SENTAYEHU , HALM ETHAN , BOWEN MICHAEL E. 
Published: June 2020

Many patients at risk for T2D in clinical practice remain unscreened. Scalable, EHR-driven strategies are needed to assess glycemic risk and improve screening in health systems.
We developed and implemented an automated, EHR risk score linked to clinical decision support (CDS) to detect undiagnosed dysglycemia (PDM+T2D). The risk score (random glucose, age, race, BMI, hypertension) was linked to an Epic reporting workbench (RWB) and used by clinic nurses to bulk-order screening HbA1cs and notify patients. We deployed 2 patient outreach strategies in 2 clinics: 1) population health, inviting high-risk patients for screening with letters, regardless of scheduled appointments; 2) pre-visit labs with text notification 2 weeks before scheduled clinic appointments.
Using mixed-methods, we report patient response rates, case-finding yields, and acceptability. Over 6 months, 754 patients (mean age 55; 80% female; 49% Hispanic, 32% non-Hispanic Black; mean BMI 32) had screening tests ordered. Patient response rates were similar for the population health (N=404) and pre-visit lab (N=350) strategies (40% vs. 34%; p=0.12). Of those screened with the population health strategy (N=162), 45% had PDM and 3.7% had T2D. Of those screened with the pre-visit lab strategy (N=120), 48% had PDM and 5% had T2D. In surveys, stakeholders (N=16) reported the intervention was appealing (75%), easy to use (68%), and not time consuming (100%). One interviewee said, “It’s not a time-eating monster,” and noted, “It’s very user friendly, and the end result is something happens without me having to put a lot of labor into it⋯it can find something that changes a person’s life.”
Automated CDS for T2D screening and patient outreach is feasible in real-world primary care using existing resources. Population health and pre-visit outreach strategies had similar response rates with case yields reflecting the rates of undiagnosed PDM and T2D in the U.S. population.

Disclosure
P.M. Chen: None. R.T. Higashi: None. S.J.C. Lee: None. I. Lingvay: Consultant; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Intarcia Therapeutics, Janssen Pharmaceuticals, Inc., MannKind Corporation, Novo Nordisk A/S, Sanofi, TARGET PharmaSolutions, Valeritas, Inc. Other Relationship; Self; Novo Nordisk A/S. L. Meneghini: Advisory Panel; Self; Novo Nordisk Inc., Sanofi US. Consultant; Self; Applied Therapeutics, Sanofi US. E. Obialo: None. S. Kassa: None. E. Halm: None. M.E. Bowen: None.

Funding
National Institute of Diabetes and Digestive and Kidney Diseases (DK104065)
1441-P: Predicting Diabetes (DM) Diagnoses Dates Using the Electronic Health Record (EHR)
Authors: LENOIR KRISTIN M. , WAGENKNECHT LYNNE E. , DIVERS JASMIN , CASANOVA RAMON , LAWRENCE JEAN M. , DABELEA DANA , PIHOKER CATHERINE , SAYDAH SHARON , LIESE ANGELA D. , STANDIFORD DEBRA , WELLS BRIAN J. 
Published: June 2020

Surveillance of DM status, type, and date of diagnosis requires chart review. We previously showed that ≥ 2 international classification of diseases (ICD) DM codes predicts DM status well. This project aimed to derive an EHR-based algorithm to predict diagnosis date. Youth (&lt; 20 yrs) with potential DM evidence in 2017 (ICD DM code, elevated glucose or HbA1c, or DM medication) were identified from the inpatient and outpatient EHR data of 3 Children’s Hospitals participating in the SEARCH for Diabetes in Youth Study. Potential cases were chart reviewed to determine true DM status, DM type, and diagnosis date. Cases were restricted to those with diagnosis date and data post-2008 due to EHR limitations. We compared 2 algorithms for predicting diagnosis date: (1) first occurrence of an ICD DM code, and (2) first occurrence of any of the following: ICD DM code, elevated glucose or HbA1c, or DM medication. Among cases identified by the ICD status algorithm (n=3,678), the ICD code and multi-criteria algorithms classified diagnosis year correctly 88.9% and 88.4% of the time, respectively. Classification accuracy improved over time (Figure). Performance was poorer for type 2 than type 1. An ICD code model to predict date of diagnosis can accurately identify diagnosis date within these pediatric hospital systems. Improvement over time is likely due to increases in the amount of EHR data. Manual review of type 2 cases may be necessary.

Disclosure
K.M. Lenoir: None. L.E. Wagenknecht: None. J. Divers: None. R. Casanova: None. J.M. Lawrence: None. D. Dabelea: None. C. Pihoker: None. S. Saydah: None. A.D. Liese: None. D. Standiford: None. B.J. Wells: None.

Funding
Centers for Disease Control and Prevention (5U18DP006131-05-00)
1446-P: A1C and Glycated Albumin Combined Improves Detection of Abnormal Glucose Tolerance in Africans
Authors: SUMNER ANNE E. , HOBABAGABO ARSENE F. , SHOUP ELYSSA M. , HORMENU THOMAS , OSEI-TUTU NANA H. , DUBOSE CHRISTOPHER , MABUNDO LILIAN , CHUNG STEPHANIE T. , SACKS DAVID B. 
Published: June 2020

In nonwhite populations the prevalence of abnormal glucose tolerance (Abnl-GT) is increasing in the nonobese. However, the prevalence of Abnl-GT in African-born blacks is unknown. As BMI correlates positively with A1C and negatively with glycated albumin (GA) and fructosamine (FA), BMI may influence the diagnostic sensitivity of nonfasting markers of glycemia. Working with Africans, our goals were to determine: a) by BMI category the prevalence of Abnl-GT; and b) the diagnostic value of nonfasting markers of glycemia, individually and combined. In 416 African-born blacks living in America (male: 66%; age: 39±10 (mean±SD), range 20 to 65y, BMI: 27.7±4.5, range 18.2-42.4 kg/m2) OGTT were performed. A1C, GA and FA levels were measured. A1C, GA and FA levels were repeated 11±7 days later in 136 participants. Abnl-GT was defined by glucose: 0h ≥100 and/or 2h ≥140 mg/dL. Thresholds for A1C, GA and FA were defined by the cut-off at the upper quartile for the population (5.7%, 14.2%, 234 µM/L, resp). Analytic tools were κ-statistic, Spearman correlations and the McNemar test. In short, Abnl-GT occurred in 36% (152/416). Of the individuals with Abnl-GT, 68% (104/152) were nonobese. Reproducibility of A1C and GA were excellent (both κ≥0.8) but only moderate for FA (κ=0.6). For this reason, results focus on A1C and GA. BMI positively correlated with A1C (r= 0.18) and negatively with GA (r=-0.18) (both P&lt;0.01). The diagnostic sensitivities of A1C, GA and the combined tests were: 43%, 34% and 61%, resp (P&lt;0.01 compared to A1C alone). By test, 66 people with Abnl-GT were detected by A1C or A1C and GA; whereas 25 people were detected by GA alone. People with Abnl-GT detected by GA only had lower BMI than those detected by A1C (26.8±2.4 vs. 30.4±4, P&lt;0.01). Overall, two-thirds of African-born blacks with Abnl-GT are nonobese. As GA detects Abnl-GT in nonobese individuals not detected by A1C, using both tests could improve screening and lead to earlier intervention.

Disclosure
A.E. Sumner: None. A.F. Hobabagabo: None. E.M. Shoup: None. T. Hormenu: None. N.H. Osei-Tutu: None. C. DuBose: None. L. Mabundo: None. S.T. Chung: None. D.B. Sacks: Other Relationship; Self; Sebia, Trinity Biotech plc.
1448-P: Enhanced Liver Fibrosis (ELF) Test Can Accurately Predict Advanced Fibrosis in Patients with Type 2 Diabetes and Nonalcoholic Fatty Liver Disease (NAFLD)
Authors: YOUNOSSI ZOBAIR , FELIX SEAN , JEFFERS THOMAS , YOUNOSSI ELENA , NADER FATEMA , PHAM HUONG , AFENDY ARIAN , CABLE REBECCA , RACILA ANDREI , YOUNOSZAI ZAHRA , LAM BRIAN P. , GOLABI PEGAH , HENRY LINDA , CLEMENT STEPHEN , STEPANOVA MARIA 
Published: June 2020

Background: The ELF test (score calculated from markers of fibrosis: hyaluronic acid, procollagen III amino-terminal peptide, and tissue inhibitor of matrix metalloproteinase 1) is a non-invasive blood test used to estimate fibrosis stage in chronic liver disease. Since NAFLD patients with advanced fibrosis are at the highest risk for adverse long-term outcomes, the aim is to assess performance of ELF for identification of advanced fibrosis in patients with NAFLD.
Methods: Patients with biopsy-proven NAFLD were included. ELF scores were calculated using an ADVIA Centaur XP analyzer.
Results: There were 409 patients with NAFLD: 47 ± 12.9 years, 30% male, 70% white, 34% type 2 diabetes (T2DM), 56% hyperlipidemia, 54% hypertension, mean (SD) BMI 41.0 ± 10.0 kg/m2, ALT 48.4 ± 42.0 U/L, mean ELF score was 9.0 ± 1.3. Of the study cohort, 23% patients (N=93) had advanced fibrosis. Patients with advanced fibrosis had significantly higher ELF: 10.2 ± 1.3 vs. 8.6 ± 1.0, p&lt;0.0001. There was a correlation between ELF and liver enzymes: rho=0.23 for ALT, 0.34 for AST (p&lt;0.0001). ELF negatively correlated with BMI: rho = -0.28 (p&lt;0.0001). Across all NAFLD patients, ELF had good performance for identifying patients with advanced fibrosis: area under curve (AUC) = 0.83 (0.79 - 0.87). The performance of ELF was similar in NAFLD patients with [AUC = 0.81 (0.73 - 0.87)] and without [AUC = 0.83 (0.77 - 0.87)] T2DM. With the commonly used cut-off of ELF ≥9.8 for prediction of advanced fibrosis, observed accuracy was as follows: sensitivity 62.4% (51.7% - 72.2%), specificity 89.6% (85.6% - 92.7%) positive predictive value (PPV) 63.7% (55.1% - 71.6%), negative predictive value (NPV) 89.0% (86.1% - 91.3%). Cut-off of 11.3 returned almost perfect specificity 99.0% (97.3% - 99.8%) with a sensitivity of 22.6% (14.6% - 32.4%), PPV 87.5% (68.1% - 95.8%), NPV 81.3% (79.6% - 82.9%).
Conclusions: ELF test performs well in identifying high risk NAFLD patients with or without T2DM.

Disclosure
Z. Younossi: Consultant; Self; AbbVie Inc., Bristol-Myers Squibb, Gilead Sciences, Inc., Intercept Pharmaceuticals, Inc., Novo Nordisk Inc., Terns and Viking. S. Felix: None. T. Jeffers: None. E. Younossi: None. F. Nader: None. H. Pham: None. A. Afendy: None. R. Cable: None. A. Racila: None. Z. Younoszai: None. B.P. Lam: None. P. Golabi: None. L. Henry: None. S. Clement: None. M. Stepanova: None.
1453-P: Adaption of the ACMG/AMP Variant Interpretation Guidelines for GCK, HNF1A, HNF4A-MODY: Recommendations from the ClinGen Monogenic Diabetes Expert Panel
Authors: ZHANG HAICHEN , MALONEY KRISTIN A. , BARBETTI FABRIZIO , GREELEY SIRI ATMA W. , KETTUNEN JARNO L.T. , MIRANDA JOSÉ P. , MIRSHAHI UYENLINH L. , MOLNES JANNE , MURPHY RINKI , NAYLOR ROCHELLE N. , PAKYZ RUTH E. , PHILIPSON LOUIS H. , PRUDENTE SABRINA , TUOMI TIINAMAIJA , UDLER MIRIAM , COLCLOUGH KEVIN , JENG LINDA , POLLIN TONI I. 
Published: June 2020

Genetic testing for monogenic diabetes, essential for accurate diagnosis and appropriate treatment is underutilized. Obstacles include clinical overlap with type 1 and type 2 diabetes and difficulty distinguishing clinically significant (pathogenic/likely pathogenic; P/LP) from normal (benign/likely benign; B/LB) variation. The ClinGen Monogenic Diabetes Expert Panel (MDEP) was formed to adapt American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) variant interpretation guidelines to monogenic diabetes genes and enable depositing of expert panel variant reviews into ClinVar, a public database relating gene variants to phenotypes. MDEP includes endocrinologists, laboratory directors, genetic counselors, medical geneticists, clinical scientists and researchers from 37 academic and commercial institutions, allowing the panel to benefit from multiple expert perspectives and pooling of case-level data. Currently, MDEP is focusing on the three most commonly implicated monogenic diabetes genes: GCK, HNF1A and HNF4A. MDEP generated gene-specific modifications and/or strength adjustments to existing rules to provide guidance for the use of evidence, including molecular, phenotypic, segregation, functional, and minor allele frequency data. Our guidelines have so far been tested on 98 HNF1A variants, 15 HNF4A variants and 22 GCK variants selected from ClinVar and the literature. Fourteen of 31 variants of uncertain significance (VUS) in ClinVar were re-classified: nine to P/LP (enabling diagnosis and treatment) and five to B/LB (reducing ambiguity). Six LP variants and one LB variant from ClinVar were re-classified to VUS (stimulating further surveillance). MDEP’s work will improve accuracy, standardization and concordance of variant interpretation for monogenic diabetes and support wider implementation of precision medicine in diabetes.

Disclosure
H. Zhang: None. K.A. Maloney: None. F. Barbetti: Consultant; Self; Amring. S.W. Greeley: None. J.L.T. Kettunen: None. J.P. Miranda: None. U.L. Mirshahi: None. J. Molnes: None. R. Murphy: None. R.N. Naylor: None. R.E. Pakyz: None. L.H. Philipson: None. S. Prudente: None. T. Tuomi: None. M. Udler: None. K. Colclough: None. L. Jeng: None. T.I. Pollin: None.

Funding
National Institutes of Health (5U24HD093486, R01DK104942, P30DK020595 )
1456-P: Identifying Diabetic and Prediabetic Patients Who Require Pharmacotherapy for Nonalcoholic Steatohepatitis Using the FAST Score
Authors: AGGARWAL PANKAJ , ALKHOURI NAIM 
Published: June 2020

New pharmacologic agents to treat fatty liver in diabetics are expected to be approved in 2020 and will target those with nonalcoholic steatohepatitis (NASH) and significant fibrosis (NASH-F). The FAST (Fibroscan + AST) score was recently developed to predict the presence of (NASH-F) based on measuring controlled attenuation parameter (CAP) for steatosis, liver stiffness measurement (LSM) for fibrosis, and AST for inflammation. The aim of this study was to assess the utility of FAST score in patients with T2DM and prediabetes to identify those that require NASH pharmacotherapy.
Methods: Consecutive patients with T2DM or A1c ≥5.7% who presented for evaluation of fatty liver were included. All had Fibroscan to measure CAP and LSM + AST within 6 months. Based on published data, FAST ≥0.75 was used to rule in the presence of NASH-F and therefore as an indication for pharmacotherapy. FAST &lt; 0.40 was used to rule out NASH-F. Nominal and continuous variables were analyzed with chi-squared and 2-sided T-tests, respectively.
Results: 90 patients were identified; average age 56 (13.55) years, BMI was 35.06 (6.29) kg/m2, and 58 (64.4%) were female. A total of 11 (12.3%) patients had a FAST ≥0.75 indicating that they qualify for pharmacotherapy once available. Patients with FAST ≥0.75 were older (57.3 years vs. 47; p=0.01), had higher ALT (139.63 u/L vs. 57.06; p &lt;0.01), and triglycerides (234.87 mg/dL vs. 162.44; p =0.02). Patients with FAST ≥0.75 were not more likely to have higher A1c, hypertension, or metabolic syndrome. 34 patients (37.7%) had FAST &lt;0.4 indicating the absence of significant disease and 45 patients (50%) had FAST between 0.4 and 0.75.
Conclusion: Using a high cutoff value of 0.75, the FAST score identified 12% of patients with T2DM/prediabetes that will qualify for NASH pharmacotherapy. While 38% of patients can be stratified as low risk by using a cutoff value of 0.40, 50% of patients had intermediate FAST score values indicating the need for further workup.

Disclosure
P. Aggarwal: None. N. Alkhouri: Research Support; Self; Allergan plc.