bluuebunny/crossref_metadata_2025 huggingface dataset:
1423-P: The Association of the American Heart Association’s Life’s Simple 7 with Self-Reported Health, Diabetes, and Adiposity in African American Males
Authors: ABOAGYE-MENSAH EMMANUELA B. , AZAP ROSEVINE A. , ODEI JAMES B. , GRAY DARRELL M. , NOLAN TIMIYA S. , ELGAZZAR RANA , WHITE DEVEONNE L. , GREGORY JOHN H. , JOSEPH JOSHUA
Published: June 2020

Background: African American (AA) men have the highest age-adjusted all-cause mortality rate in the U.S. and a high burden of risk factors contributing to chronic diseases. The African American Male Wellness Walk (AAMWW) seeks to reduce health disparities and promote attainment of Life’s Simple 7 (LS7) among AA males. We investigated the association of six components of the American Heart Association’s LS7 metrics: blood pressure, body weight, cholesterol, physical activity, smoking, and blood glucose with self-reported health, diabetes prevalence, body fat percentage (BF%), and family history of diabetes.

Methods: Our study included 731 AA male participants from the 2017 and 2018 AAMWWs. ANOVA and Chi-square tests analyzed continuous and categorical variables, respectively. Six metrics of LS7 developed a total cardiovascular health score, categorized by the number of ideal LS7 components as 0-2, 3, 4, 5-6. Logistic and linear regression models examined the association of LS7 with outcomes adjusted for age and insurance status.

Results: Participants with 5-6 ideal metrics compared to 0-2 had 261% higher odds of a 1 category higher self-reported health (p<0.0001). Individuals with 3-6 compared to 0-2 ideal metrics had 88% lower odds of diagnosed diabetes (p<0.001). Participants with 5-6 ideal metrics had a 12.2% lower body fat percentage compared to participants with 0-2 ideal metrics (p=0.0003).

Conclusion: Attainment of LS7 metrics is associated with improved self-reported health and inversely associated with diabetes prevalence and BF% among AA men in the AAMWW. Interventions targeting LS7 ideal metrics among AA men may promote health equity.

Disclosure

E.B. Aboagye-Mensah: None. R.A. Azap: None. J.B. Odei: None. D.M. Gray: Consultant; Self; Genentech, Inc. T.S. Nolan: None. R. Elgazzar: None. D.L. White: None. J.H. Gregory: None. J. Joseph: None.
1425-P: White Blood Cell Count Predicts Cardiovascular Prognosis in Type 2 Diabetic Patients with Established Coronary Artery Disease
Authors: KAWABE ATSUHIKO , NAKATANI YUKI , ONO SHOYA , MIYASHITA YASUSHI , MATSUMURA MIHOKO , BANBA NOBUYUKI , YASU TAKANORI
Published: June 2020

Introduction and Hypothesis: White blood cell (WBC) count in healthy persons is reported to be associated with the risk of coronary artery disease (CAD) and all-cause death. The aim of our study was to determine whether WBC count predicts cardiovascular outcome, including heart failure and mortality, in consecutively registered patients with type 2 diabetes.

Methods and Results: This was a post-hoc study from the Intensive Lipid and Blood Pressure Lowering and Cardiovascular Outcome Randomized Controlled Trial in Patients with CAD and type 2 diabetes. A total of 7,608 participants (mean age 68 years, 72% men) had WBC measured at baseline and were eligible for this study. Participants were followed for a mean of 1,328 days. We used Cox proportional hazards regression model to assess the hazard ratio (HR) and 95% confidence interval (CI). Participants with WBC count in the highest quartile had an adjusted HR for all-cause death of 1.66 (95% CI, 1.33 to 2.06, Figure) compared to those in the lowest quartile (WBC <5300 cells/µL). Additionally, similar findings were observed for the risk of acute myocardial infarction and heart failure; however, no significant difference was found for stroke risk (Figure).

Conclusions: In patients with CAD and type 2 diabetes, higher WBC count may have potential as a predictor for all-cause death, myocardial infarction, and heart failure but not stroke.

Disclosure

A. Kawabe: None. Y. Nakatani: None. S. Ono: None. Y. Miyashita: None. M. Matsumura: None. N. Banba: None. T. Yasu: None.
1431-P: Risk of Venous Thromboembolism amongst Initiators of SGLT2 Inhibitors Compared with Other Glucose-Lowering Agents
Authors: GOPALAKRISHNAN CHANDRASEKAR , DESAI RISHI J. , KIM SEOYOUNG C. , PATORNO ELISABETTA
Published: June 2020

The comparative safety of frequently used second-line agents to treat type 2 diabetes (T2D) with respect to the risk of venous thromboembolism (VTE) in routine care is unknown. It has been hypothesized that the diuretic effect of SGLT2 inhibitors (SGLT2i) may have an unintended impact on VTE risk by increasing blood viscosity. Using Optum Clinformatics, a large U.S. commercial health insurance claims database, we assessed the risk of an incident hospitalization for VTE within two pair-wise 1:1 propensity score (PS)-matched cohorts of patients with T2D who initiated a SGLT2i or a comparator, i.e., a GLP-1 receptor agonist [GLP-1 RA (n=59,712 pairs)], or a DPP-4 inhibitor [DPP-4i (n=50,178 pairs)] between April 2013-March 2019. We estimated hazard ratios (HR) and 95% CI controlling for over 100 baseline characteristics including common risk factors for VTE, baseline comorbidites, medication use and healthcare utilization. SGLT2i had a similar risk of VTE compared to GLP-1 RA [HR (95% CI) = 0.99 (0.68, 1.44)] and DPP-4i [HR (95% CI) = 1.01 (0.66, 1.52)] (Table 1), with incidence rates ranging between 1.1 and 1.3 events per 1,000 person-years. Results were consistent within subgroups of age, frailty and cardiovascular disease. In a large population-based study of adult patients with T2D, SGLT2i had similar risk of VTE compared to GLP-1 RA and DPP-4i, with reassuringly low absolute rates overall.

Disclosure

C. Gopalakrishnan: None. R.J. Desai: Research Support; Self; Bayer AG, Novartis AG. S.C. Kim: Research Support; Self; AbbVie Inc., Bristol-Myers Squibb. E. Patorno: Other Relationship; Self; Boehringer Ingelheim International GmbH.

Funding

National Institute on Aging (K08AG055670)
1432-P: Association between Insulin Use and Long-Term Cardiovascular Disease Outcomes in Older Adults
Authors: VISARIA AAYUSH , DHARAMDASANI TINA , WICKRAMASINGHE KAVINDYA , LO DAVID , MALHOTRA RAJ
Published: June 2020

Introduction: Exogenous insulin therapy has been the mainstay of treatment for those with uncontrolled type 2 diabetes; however, recent literature has pointed to a lack of risk reduction for cardiovascular disease (CVD). We sought to determine the association between insulin use and major adverse cardiovascular events (MACE) among older adults with type 2 diabetes with a long-term follow-up.

Methods: A cohort of 1,084 participants >50 years with type 2 diabetes from the National Health and Nutrition Examination Survey-III (1988-1994) was followed for an average 22.4 years through 2015. Subjects were divided into two groups: 1) those using insulin therapy and 2) those using oral medications only. The primary outcome was major adverse cardiovascular events (MACE), a combination of self-reported myocardial infarction, stroke, or CVD mortality. We used multivariable logistic regression, adjusting for HbA1c, demographic, metabolic, and inflammatory factors and accounting for the survey design.

Results: Among the participants, 227 (21%) regularly used insulin. Those using insulin were of similar age, more likely to be male, have similar BMI, waist circumference, blood pressure, and lipids, have higher HbA1c (8.2% vs. 7.3%, p<0.01), and have significantly higher serum insulin levels (mean[SD]: 51.1[4.2] vs. 18.5[0.7], p<0.001). Those taking insulin had nearly twice the adjusted odds of MACE relative to those only taking oral agents (aOR [95% CI]: 1.89 [1.11, 3.24]). When assessing individual conditions, those taking insulin had significantly increased odds of stroke, but not MI or CVD mortality (aOR [95% CI]: stroke = 3.69 [1.26, 10.78], MI = 1.41 [0.75, 2.65], CVD mortality = 1.19 [0.69, 2.06]). There was no significant dose-dependent association between insulin use and MACE.

Conclusion: Long-term insulin use may be associated with increased stroke, although no dose-dependent association was present. Increased care and assessment may be warranted in patients taking insulin.

Disclosure

A. Visaria: None. T. Dharamdasani: None. K. Wickramasinghe: None. D. Lo: None. R. Malhotra: None.
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 (< 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<0.01). The diagnostic sensitivities of A1C, GA and the combined tests were: 43%, 34% and 61%, resp (P<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<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<0.0001. There was a correlation between ELF and liver enzymes: rho=0.23 for ALT, 0.34 for AST (p<0.0001). ELF negatively correlated with BMI: rho = -0.28 (p<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 < 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 <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 <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.
147-LB: The Effects of Berberine, Cinnamon, or Fenugreek Seeds on Glucose and Lipid Metabolism in Prediabetes and Diabetes: An Assessment of the Quality of the Clinical Trials
Authors: ABDI IBSA
Published: June 2020

The prevalence of diabetes is increasing. Several antidiabetic drugs are available to treat the disease, however, none has been effective in halting the progression decline in β-cell function and insulin sensitivity. Plant-derived nutraceuticals provide therapeutic potential and are widely used in integrative medicine. However, clinical trials that evaluated the efficacy of antidiabetic nutraceuticals have been inconsistent in their findings. This study assessed the quality of the clinical trials that investigated the effects of berberine, cinnamon, or fenugreek seeds on glucose and lipid metabolism. Five databases (UB Wahlstrom, PubMed, Cochrane Library, CINAHL, and Science Direct) were systematically searched for randomized controlled studies that investigated the effects of berberine, cinnamon, or fenugreek seeds on glucose and lipid metabolism in prediabetes and diabetes. Forty-three studies (11, 20, 12 on berberine, cinnamon, and fenugreek, respectively), involving 3, 459 study participants were retrieved. The studies were appraised for trial quality using the Jadad scale and the CONSORT checklist. The included berberine, cinnamon, and fenugreek studies had a Jadad score of 3.2, 3.4, and 2.4, respectively. The studies, combined, had a Jadad score of 2.98 and only 62.7% had a score ≥3. Appraisal for reporting quality showed that 33% of the trials were identified in the title or abstract as randomized. Allocation concealment, random sequence generation, and baseline demographics and clinical characteristics were reported in 35, 44 and 74% of the trials, respectively. The included studies had suboptimal methodological and reporting qualities. The studies were not efficacious enough to support their use in clinical decision making. Further RTCs with emphasis on methodological and reporting quality and comparative effectiveness need to be conducted to determine efficacious conclusions.

Disclosure

I. Abdi: None.
1470-P: Among Black New Yorkers with Type 2 Diabetes Afro-Caribbeans Are Younger and Have Lower BMI than African Americans: NYC HANES 2013/14
Authors: HORLYCK-ROMANOVSKY MARGRETHE F.
Published: June 2020

Despite type 2 diabetes (T2DM) risk differences by BMI and age among populations of African descent, current T2DM screening criteria regard all black populations as one. Few studies have had opportunity to compare T2DM point prevalence among African Americans and Afro-Caribbeans living in the United States.

Objectives: This study evaluated among African American and Afro-Caribbean New Yorkers: a) point prevalence of T2DM, b) odds of T2DM, and c) contributors to T2DM odds in either group. We used 2013/14 New York City Health and Nutrition Examination Survey (NYC HANES) data for African Americans (n=208, age 42.7±15.3y (mean±SD), BMI 29.9±7.8 kg/m2) and Afro-Caribbeans (n=111, age 48.3±14.8 years, BMI 28.6±5.7 kg/m2). T2DM was defined as self-reported diagnosis by a physician, or measured HbA1c≥6.5%, or fasting plasma glucose ≥126mg/dL. BMI was based on measured height and weight. Age, socioeconomic variables and health behaviors were self-reported. Weighted logistic regression estimated T2DM odds (aOR), adjusting for age, BMI, income, marital status, smoking, fruit and vegetable intake and physical activity.

Results: Compared to African Americans, Afro-Caribbeans had higher T2DM prevalence (20.2% vs. 15.5%). Afro-Caribbeans with T2DM were younger (age 58.8±11.2y) than African Americans with T2DM (age 61.3±15.8y), and had lower BMI of 30.1±4.4 vs. 32.8±7.6kg/m2 respectively. Odds of T2DM were not different among Afro-Caribbeans and African Americans (aOR=1.85 (95%CI 0.71, 2.40, P=0.415). In separate analyses among African Americans, BMI was associated with higher T2DM odds [aOR=1.07 (95%CI 1.01, 1.14), P=0.047]. Among Afro-Caribbeans BMI was not associated with T2DM odds [aOR=1.04 (95%CI 0.96, 1.130), P=0.37].

Conclusion: To enhance detection of T2DM among African Americans and Afro-Caribbeans future screening criteria should reflect differences in T2DM risk by BMI and age by ethnic group.

Disclosure

M.F. Horlyck-Romanovsky: None.
1481-P: Patients with Cystic Fibrosis–Related Diabetes Present with Specific Pancreatic Anomalies
Authors: ALEXANDRE-HEYMANN LAURE , PUERTO MARIE , BURGEL PIERRE-RÉGIS , LARGER ETIENNE
Published: June 2020

Cystic fibrosis related diabetes (CFRD) is found in 20 to 50% of adults with cystic fibrosis (CF). Repeated oral glucose tolerance tests are used to screen for CFRD, but are not perfect indicators and can be tiresome for patients who already undergo many medical tests. We hypothesized that pancreatic imaging may differ between patients with and without CFRD and that the patients with the more “at-risk” pancreatic morphology could be followed more closely with the aim to detect diabetes early. We performed a non-matched case-control retrospective study comparing the abdominal ultrasounds (U.S.) and computed tomography (CT) (including abdominal slices of thoracic CT) of patients with CF with or without CFRD (“CFRD patients” and “CF patients”, respectively). Forty-four CFRD patients and 58 CF patients were included. Thirty-seven percent of the U.S. results were either uninterpretable or discordant with the CT results. Therefore, only the results of the CT were eventually analyzed. Seventy-one percent of CFRD patients presented with complete pancreatic involution (CPI), versus 57% of CF patients (p = 0.0016), and 98% of CFRD patients presented with at least partial pancreatic involution. Patients with CPI presented more frequently with exocrine pancreatic insufficiency than patients with a normal CT scan (95% versus 29%, p< 0.0001). Unexpectedly, 22% of CFRD patients presented with pancreatic calcifications, versus none of the CF patients (p = 0.0003). Patients with pancreatic calcifications did not differ from patients without, except that they were less likely to be homozygous for DeltaF508 mutation (22 versus 53%, p = 0.04). CPI is more often seen in CFRD patients than in CF patients, but is still a very frequent occurrence. A more distinctive feature is the presence of pancreatic calcifications. These might be used as a warning signal to look more closely for diabetes in patients with CF, and can be searched for on abdominal slices of routinely performed thoracic CT.

Disclosure

L. Alexandre-Heymann: None. M. Puerto: Other Relationship; Self; Ipsen Biopharmaceuticals. P. Burgel: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Chiesi USA, Inc., Vertex Pharmaceuticals. Consultant; Self; GlaxoSmithKline plc., Pfizer Inc., Teva Pharmaceutical Industries Ltd., Zambon. Speaker’s Bureau; Self; Novartis AG. E. Larger: None.
1482-P: Effect of Age on Diabetes-Specific Autoantibodies in a Large Laboratory-Based Cohort
Authors: DAHL AMANDA R. , PITTOCK SIOBHAN , MCKEON ANDREW , FOSTER JESICA , MILLS JOHN
Published: June 2020

Type 1 diabetes mellitus (T1DM) can occur at any age, the presence of diabetes related autoantibodies predicts increased risk of disease and supports an autoimmune etiology for T1DM. Since 2017, Mayo Clinic Laboratories has been offering a comprehensive type 1 diabetes autoantibody evaluation (DM1Eval) which includes testing for 4 autoantibodies targeting glutamic acid decarboxylase autoantibodies (GAD), protein tyrosine phosphatase-like islet antigen 2 (IA-2), insulin (IAA), and zinc transporter 8 protein (ZnT8).

The aim of this study was to determine the frequency of individual antibodies and antibody clusters (2, 3 or 4) stratified into 4 ages groups (children 0-17, young adult 18-35, middle aged 36-55 and older >55 years).

Over a 30 month period (June 2017-Nov 2019) the DM1Eval was performed on 6,446 samples. At least 1 autoantibody was found in 3596 (56%) of all samples: 68% of children, 49% of young adults, 40% of middle aged and 41% of older adults.

In patients with at least 1 antibody positive, GAD 65 antibodies were the most common in all age groups followed by ZnT8 in those <36 years or IAA antibody in those 36 and older older (Figure). The frequencies of IA2 and ZnT8 antibodies dropped significantly with increasing age strata.

Autoantibody clusters of 3 or 4 antibodies were more frequently encountered in younger patients (41% of pediatric and 27% of young adult patients in contrast to just 12% in middle and older age groups).

Disclosure

A.R. Dahl: None. S. Pittock: None. A. McKeon: None. J. Foster: None. J. Mills: None.
1486-P: Identification of Undiagnosed Diabetes Mellitus and Associated Alternation of Predicted ASCVD Risk Using Chinese and U.S. Risk Calculators
Authors: YANG JING , ZHAO YANGLU , REN YI , LAN LIZHEN , XU LINXIN , YIN JIANHONG , XU QISHAN , LI YONGZE
Published: June 2020

Background: It is unknown how the identification of undiagnosed DM (UDM) among Chinese changes the estimation of atherosclerotic cardiovascular disease (ASCVD) risk using the Chinese and the U.S. risk calculators.

Methods: We included 1884 adults aged 30-75 free of ASCVD from 4 urban and rural communities in Shanxi Province, China. UDM was defined as newly found DM by glucose or HbA1c with no DM history or DM medication. 10-year ASCVD risk was estimated using the Prediction for ASCVD Risk in China (China-PAR) score and 2013 AHA/ACC Pooled Cohort Equation (PCE) and classified into risk categories. For those with UDM, the risk scores were calculated before and after DM diagnosis.

Results: Among 266 (14.1%) DM patients, 161 (8.5%) were UDM. Compared to those with diagnosed DM, those with UDM had milder DM and better CVD risk profiles. The mean China-PAR among non-DM, UDM (before diagnosis) and diagnosed DM were 6.0% 14.3% and 18.8% and mean PCE were 2.5%, 5.3% and 13.0%, respectively. Among those with UDM, the mean China-PAR and PCE increased to 16.7% and 9.2% after DM diagnosis (both p <0.0001); 6.2% and 34.8% were reclassified into higher risk groups according to the Chinese and U.S. guidelines (Figure).

Conclusion: Identification of UDM had greater impact on estimated ASCVD risk using PCE than China-PAR among Chinese and may change the preventive treatment by risk reclassification.

Disclosure

J. Yang: None. Y. Zhao: None. Y. Ren: None. L. Lan: None. L. Xu: None. J. Yin: None. Q. Xu: None. Y. Li: None.

Funding

Research Fund for Public Welfare, National Health, and Family Planning Commission of China (201402005)
149-OR: In Utero Exposure to Gestational Diabetes Mellitus Is Associated with Increased Food Intake and Orbital Frontal Cortex Responses to Food Cues
Authors: LUO SHAN H. , ANGELO BRENDAN C. , CHOW TING , ALVES JASMIN , BUCHANAN THOMAS A. , XIANG ANNY , PAGE KATHLEEN A.
Published: June 2020

Children exposed to gestational diabetes mellitus (GDM) in utero have an increased propensity of developing obesity. Little is known about the mechanisms underlying this propensity. Here we examine the relationship between GDM exposure and its timing on energy intake (EI) and brain reward responses to food cues in children. Participants were 142 children (39% boys; 56% GDM-exposed) aged from 7 to 11 years old. GDM status was extracted from EMR. Adiposity measurements were collected. Repeated 24-hour recalls were conducted to assess mean daily EI (kcal/day). A subset (n=89) of children completed an MRI session where they viewed food and non-food cues. %signal change in the orbital frontal cortex (OFC), insula and amygdala for food vs. non-food contrast was measure of interest. GDM exposure was modeled by: 1) yes vs. no at any time in pregnancy and 2) GDM diagnosed at <= 26 weeks (early exposed), > 26 weeks (late exposed) and unexposed. GDM exposure (vs. unexposed) was associated with greater EI (mean difference ±SE: 169 ±65, P=0.01) and OFC food cue reactivity (0.19±0.09, P=0.04). Results were strengthened after adjusting for age, sex, physical activity, SES and pre-pregnancy BMI (EI: P=0.008; OFC: P=0.024). In the adjusted models, both subgroups (early exposed(N=27): 178 ± 92, P=0.055; late exposed (N=53): 173±72, P=0.018) had greater EI than controls. Early exposed group had greater OFC food cue reactivity than controls (0.30±0.15, P=0.048) and the difference between late exposed and controls was marginally significant (0.20±0.11, P=0.07). Children exposed to GDM (vs. unexposed) had larger WHR (0.02±0.01, P=0.03), and this was driven by the difference between early exposed vs. controls (0.04±0.01, P=0.006). Exposure to GDM in utero, in particular before 26 weeks gestation, is associated with increased energy intake, enhanced OFC food cue reactivity and increased WHR. Whether these changes predict development of obesity remains to be determined.

Disclosure

S.H. Luo: None. B.C. Angelo: None. T. Chow: None. J. Alves: None. T.A. Buchanan: None. A. Xiang: None. K.A. Page: None.

Funding

National Institutes of Health (K01DK11563)
1490-P: Disparities in Deaths Due to Diabetes, Diabetes Ketoacidosis, and Diabetic Coma by Urbanization among Children, Adolescents, and Young Adults: 1999-2017, United States
Authors: SHAYDAH SHARON , IMPERATORE GIUSEPPINA , MERCADO CARLA , BULLARD KAI M. , BENOIT STEPHEN R.
Published: June 2020

Although previous studies have reported higher diabetes (DM) mortality among individuals who live in rural areas, little is known about deaths due to DM, diabetic ketoacidosis (DKA) or diabetic coma by urbanization among U.S. population under age 45 years. We used National Vital Statistics System data from 1999 to 2017 filed in all 50 states and the District of Columbia obtained from CDC Wonder (wonder.cdc.gov). DM-related deaths were based on any listed ICD-10 codes E10-E14. DKA or diabetic coma deaths were based on any listed ICD-10 codes E10-E14 with X.1 or X.0. Urbanization was classified into 5 categories based on the 2013 National Center for Health Statistics definition. Results were reported for 1999- 2007, 2008-2017 and age standardized to the 2000 U.S. population by 10-year age groups for age 5 to 44 years. For both DM-related and DKA and diabetic coma deaths, rates for large fringe metro were lower than other areas (p < 0.001). (Table) The absolute difference in DM-related deaths increased over time in all urbanization categories (p < 0.05) except in large central metro. Rates of DKA or diabetic coma death increased significantly in medium/small and non-core areas (p < 0.05), but remained stable in large central metro. (Table) Exploring underlying causes for the disparities in deaths by urbanization may lead to improved care and fewer deaths.

Disclosure

S. Shaydah: None. G. Imperatore: None. C. Mercado: None. K.M. Bullard: None. S.R. Benoit: None.