bluuebunny/crossref_metadata_2025_split huggingface dataset:
1438-P: The Novel Extracellular Matrix Hormone Endotrophin, a Fragment of Collagen Type VI, Is Associated with Diabetes and Is a Risk Factor for Mortality in Elderly Women
Authors: MØLLER ALEXANDRA , RASMUSSEN DANIEL G.K. , KARSDAL MORTEN A. , CHRISTIANSEN CLAUS , STAUNSTRUP LINE M. , BAGER CECILIE L. 
Published: June 2020

As a result of the aging population and obesity, diabetes is a major, increasing public health issue approaching global epidemic proportions. It is well known that patients with diabetes have higher levels of inflammation and that the underlying pathology contributes to blood vessel damage resulting in cardiovascular complications. Recently it was suggested that a fragment of collagen type VI (COL VI), released during deposition, is in fact a novel hormone (endotrophin; ETP), suggesting the extracellular matrix (ECM) to be involved in the regulation of type 2 diabetes. In this study, we investigated the association of ETP (measured by the PRO-C6 ELISA) with diabetes and mortality in a large prospective cohort.
From 1999-2001, 5855 postmenopausal women with a mean±SD age of 71±6.5 were included in the Prospective Epidemiological Risk Factor study, and visits were planned according to a pre-defined protocol. The diagnoses for diabetes and mortality were extracted from the Danish Health Registries. We measured ETP in serum of 5608 women at baseline (samples collected from 1999-2001). ETP levels were measured in 2016. ETP levels were significantly elevated in women who died (p&lt;0.0001). Additionally, we found that ETP levels were higher in women diagnosed with diabetes prior to baseline visit (n=206) compared to women diagnosed with diabetes after baseline (n=515, p=0.017), that ETP were higher in women with diabetes prior to baseline compared to healthy women (p&lt;0.0001), and a trend of higher levels of ETP in women diagnosed with diabetes after baseline compared to healthy women (p=0.10).
In conclusion, we demonstrate that the hormone ETP, a biomarker also reflecting COL VI deposition, was increased in serum of postmenopausal women with diabetes compared to healthy women. In addition, we show that ETP was associated with mortality, suggesting that turnover of the ECM is very important in metabolic disorders.

Disclosure
A. Møller: None. D.G.K. Rasmussen: Employee; Self; Nordic Bioscience. M.A. Karsdal: Stock/Shareholder; Self; Nordic Bioscience. C. Christiansen: None. L.M. Staunstrup: None. C.L. Bager: None.

Funding
Danish Research Foundation
1444-P: Discordance between Insulin and C-Peptide Is Associated with Liver Function and Ethnicity
Authors: PERKINS CHARLOTTE , CAMPBELL ERIN , CISTOLA DAVID P. 
Published: June 2020

Introduction and Hypothesis: Insulin and c-peptide are co-secreted in a 1:1 ratio, but cleared from the blood by different mechanisms. Insulin is cleared by the liver (t1/2 ∼ 4 min), while c-peptide is cleared by the kidney (t1/2∼ 40 min). Thus, differences between steady-state serum insulin and c-peptide may reflect subject-to-subject variation in liver and/or kidney clearance rates.
Specific Aim: In lieu of direct measures of clearance, the aim was to examine the association of insulin/c-peptide residuals with markers of liver and kidney function. Associations were analyzed using cross-sectional data from the 1999-2000 U.S. National Health and Nutrition Examination Survey.
Methods: The inclusion criterion was age ≥ 12, and the exclusion criteria were diabetes, pregnancy, fasting &lt; 8 h, serum creatinine &gt; 2, or missing insulin or c-peptide values, yielding 2,417 subjects. Insulin residuals were calculated as the difference between observed Ln insulin and the predicted value from the regression line for Ln insulin vs. Ln c-peptide.
Results: Insulin residuals were positively correlated with insulin levels (r=0.55, p&lt;0.0001). After adjusting for serum creatinine (kidney function), the association of insulin residuals with other markers was assessed using multiple linear regression. Positive associations were observed with ALT, LDH, CRP and urinary NTx/creatinine, as well as Hispanic ethnicity. Negative associations were observed with age, male gender, white and black race, total serum protein and bilirubin.
Conclusion: Insulin residuals, adjusted for creatinine, are associated with markers of liver dysfunction, inflammation, bone resorption and race/ethnicity. The hepatic clearance rate of insulin is known to be affected by some of these factors. Higher insulin residuals presumably reflect slower hepatic insulin clearance, which promotes hyperinsulinemia. Insulin residuals could be a simple surrogate for assessing differences in insulin clearance. Further studies are warranted.

Disclosure
C. Perkins: None. E. Campbell: None. D.P. Cistola: None.

Funding
National Institutes of Health (R21HL143030)
145-OR: GLP-1 Analogue Effects on Neural Responses to High-Fructose Corn Syrup and Eating Behavior in Obesity
Authors: JOSEPH KELLY , LEVENTHAL JESSICA , HWANG SEUNGJU , KNIGHT MARI-LYNET , SEO DONGJU , LACADIE CHERYL , VAN NAME MICHELLE A. , CAPRIO SONIA , SHERR JENNIFER , TAMBORLANE WILLIAM V. , SINHA RAJITA , JASTREBOFF ANIA M. 
Published: June 2020

GLP-1 analogues (GLP-1a) may change sweet food preferences but the neural mechanisms are not fully understood. We studied the effect of GLP-1a on neural responses to drinking high fructose corn syrup (HFCS) using fMRI in 5 lean (LN, BMI 21kg/m2, mean age 21, A1c 5.3%) and 7 obese (OB, BMI 38, age 26, A1c 5.5%) subjects. The OB group had a second fMRI after 3-mos treatment with liraglutide 3.0 mg daily. Food intake was evaluated by dietary recall. At baseline, OB group had increased cerebral blood flow (CBF) in regions implicated in reward/motivation (putamen) and taste perception (insula) vs. LN (p=.05). However, the OB group’s responses to HFCS changed markedly after 3-mos GLP-1a treatment. As shown in the Figure, CBF in OB group increased in regions related to impulse control (anterior cingulate cortex/ventromedial prefrontal cortex), taste perception (insula), and thalamus. It is also noteworthy that CBF did not increase in the reward/motivation region (putamen) during liraglutide treatment. Changes in neural responses to HFCS intake during GLP-1a treatment were accompanied by a 1080 kcal/d decrease in food intake (p&lt;.006), as well as a &gt;50% decrease in daily sugar intake. These preliminary data suggest decreased food and sugar intake induced by GLP-1a may be related to neural mechanisms that promote impulse control while simultaneously suppressing dysregulated reward responses following sugar intake.

Disclosure
K. Joseph: None. J. Leventhal: None. S. Hwang: None. M. Knight: None. D. Seo: None. C. Lacadie: None. M.A. Van Name: None. S. Caprio: None. J. Sherr: Advisory Panel; Self; Bigfoot Biomedical, Cecelia Health. Consultant; Self; Eli Lilly and Company, Lexicon Pharmaceuticals, Inc., Medtronic, Sanofi, T1D Exchange. W.V. Tamborlane: Consultant; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Medtronic, Novo Nordisk Inc., Sanofi US. Other Relationship; Self; Eisai Inc., MannKind Corporation. R. Sinha: None. A.M. Jastreboff: Consultant; Self; Novo Nordisk Inc., Rhythm Pharmaceuticals.

Funding
American Diabetes Association (1-18-JDF-003 to A.M.J.)
1454-P: Identifying Maturity-Onset Diabetes of the Young in Electronic Health Records
Authors: SULIEMAN LINA , RAMIREZ ANDREA 
Published: June 2020

Maturity onset diabetes of the young (MODY) is a rare cause of diabetes. Most clinical information required to diagnose MODY is difficult to extract from Electronic Health Records (EHR) due to the lack of specific billing code and diagnoses found only in clinical notes. Natural language processing (NLP) can be used to extract information from clinical text and assign labels. In this study, we designed NLP algorithms to scan clinical notes, characterize structured information, and confirmed classification with chart review to develop a reusable process to identify MODY patients in EHR.A de-identified version of the EHR from a large academic medical center was used. We built NLP algorithms to identify notes that mention MODY or MODY 14 genes. We further characterized the relevant mention with context labels), then reviewed charts to confirm MODY cases. We implemented published electronic phenotype algorithms for type 1 diabetes (T1D) and type 2 diabetes (T2D) to identify alternative diagnoses and characterize overlap. Finally, we extracted structured clinical features related to diabetes including frequency of billing codes, outpatient diabetes prescriptions, and laboratory values (A1C, c-peptide, antibody).The total number of notes identified with NLP was 6240 belonging to 959 unique subjects. The notes including negation, affirmation, possible, and family FH were 799, 3407, 1408, and 372 and subjects were 122, 354, and 181, respectively. The MODY count confirmed with review was 354.In MODY cohort, 66% of MODY subjects had T1D codes, 59% had T2D codes, 45% had both T1D and T2D codes, and 20% had no diabetes codes. The number of subjects identified using published algorithms that overlapped the MODY cohort was 26 subjects for T2D and 6 subjects for T1D. On average, MODY subjects had more T1D codes compared to T2D diabetes (59.8 vs. 35.3). The mean A1C of MODY subjects was 7.7 which was lower than for algorithm defined T1D, 8.2. They received lower insulin treatment compared to non-insulin treatment, on average.

Disclosure
L. Sulieman: None. A. Ramirez: None.
1461-P: Liver Fibrosis Is Common in Patients with Type 2 Diabetes Mellitus (T2DM) and Nonalcoholic Fatty Liver Disease (NAFLD)
Authors: LOMONACO ROMINA , FANOUS NADA , KALAVALAPALLI SRILAXMI , TEJERA LAZARO J. , MCCAULEY ALLISON , GODINEZ EDDISON , MANSOUR LYDIA , SHRESTHA SULAV , MARTE JONATHAN S. , FAKHRY JONATHAN , WANG HANNAH , BARB DIANA , BRIL FERNANDO , CUSI KENNETH 
Published: June 2020

In 2019, the ADA recommended screening for NASH and liver fibrosis in patients with T2DM and steatosis or elevated ALT. However, the true prevalence of liver fibrosis in unselected patients with T2DM in the United States remains unknown. To this end, we screened patients with T2DM attending either internal medicine (IM), family medicine (FM) or endocrinology (E) clinics unaware of having NAFLD. Screening for fibrosis (1º outcome) was done by vibration-controlled transient elastography (VCTE) and steatosis by controlled attenuation parameter (CAP) (2º outcome). We also measured diagnostic panels of fibrosis (APRI and FIB-4). A liver biopsy was done based on pre-established imaging/panel parameters if suggestive of significant fibrosis (F≥2). A total of 527 patients (IM: 112; FM: 255; E: 160) were recruited (age 60±12; 55% females; 58% non-Hispanic whites, 29% AA, 4% Asian; BMI 33±6 Kg/m2; A1c 7.5±1.7%; AST 22±10 U/L; ALT 24±17 U/L). Only 10% of patients had an ALT &gt;40 IU/L. The prevalence of NAFLD by CAP (≥280 dB/m) was 66% with only 14% having an ALT &gt;40 IU/L. The prevalence of fibrosis was 23% (kPa ≥7.0). In 74% of patients with liver fibrosis AST/ALT were &lt;40 IU/L. Diagnostic panels (APRI, FIB-4) were normal in ∼50% of patients and in the “indeterminate zone” in 36%, highlighting the value of combining them with imaging when screening. Steatosis was similar across E, IM and FM clinics, but F2-3 fibrosis was more common in E than in IM and FM clinics (30 vs. 16 and 21%, respectively; both p&lt;0.05). BMI correlated strongly with steatosis (r = 0.43) and with fibrosis (r = 0.25; both p&lt;0.001), but glycemic control (A1c) did not correlate with either.
In conclusion, NAFLD requires greater awareness among clinicians as there is a high prevalence of undiagnosed liver steatosis and fibrosis in patients with T2DM. An approach based on ALT alone is inadequate, but a combination of diagnostic panels plus imaging is promising and deserves further exploration.

Disclosure
R. Lomonaco: None. N. Fanous: None. S. Kalavalapalli: None. L.J. Tejera: None. A. McCauley: None. E. Godinez: None. L. Mansour: None. S. Shrestha: None. J.S. Marte: None. J. Fakhry: None. H. Wang: None. D. Barb: None. F. Bril: None. K. Cusi: Consultant; Self; Allergan plc., AstraZeneca, Bristol-Myers Squibb, Genentech, Inc., Gilead Sciences, Inc., Merck & Co., Inc. Research Support; Self; Cirius Therapeutics, Echosens, Eli Lilly and Company, Inventiva Pharma, Janssen Pharmaceuticals, Inc., Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., Poxel SA, Zydus Pharmaceuticals, Inc.

Funding
Echosens
1467-P: Retinal Vascular Biomarkers in Diabetic Peripheral Neuropathy
Authors: BURGE MARK R. , SOLIZ PETER , BENSON JEREMY , JOSHI VINAYAK 
Published: June 2020

Purpose: Studies have shown that individuals with retinal blood vessel abnormalities often present with other biomarkers associated with diabetic peripheral neuropathy (DPN). Existing software requires extensive manual intervention to measure structures in the retinal vasculature (e.g., arterial caliber, artery/vein ratios, fractals, etc.) for the purpose of studying the relationship of these structures to DPN. The goal of this study was to demonstrate an artificial intelligence (AI) software system for determining DPN risk based on retinal vascular abnormalities. Our approach circumvented the need to explicitly measure vessel characteristics by using AI as applied to a state-of-the-art methodology known as “convolutional neural networks” (CNN) to characterize the retinal vascular structures. CNNs have been demonstrated to be effective in a number of medical applications. This study is the first time CNNs have been used to extract retinal vascular features for DPN risk assessment.
Methods: From a database of 25,000 cases previously labeled as healthy (controls), unaffected diabetes (DM), or DPN, we have identified 331 cases that fit the requirements for this study. Controls (N=103) had monofilament and vibration tests to confirm normal peripheral nerve function. DM patients (N=163) were classified based on their medical records and monofilament and vibration tests. DPN patients (N=65) were confirmed by clinical examination and their medical record. With these cases, an AI classifier was trained to identify individuals with DPN biomarkers based on spatial features extracted from the retinal abnormalities.
Results: 80% of cohort data were used for training and 20% was used for testing. The resulting AI tool demonstrated 95% specificity and 78% sensitivity when using the clinical exam as the reference standard.
Conclusions: AI-based CNN analysis of retinal vascular features show promise for identifying subjects with DPN and reduced human manipulation and measurement of tedious vessel geometries.

Disclosure
M.R. Burge: None. P. Soliz: None. J. Benson: None. V. Joshi: None.

Funding
National Institutes of Health (DK104578)
1474-P: Association between Low Birth Weight and ß-Cell Function in Adults without Diabetes from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil)
Authors: BRANDA JULIA I. , PITITTO BIANCA ALMEIDA , BENSENOR ISABELA M. , LOTUFO PAULO A. , GOUVEA F.G. VIVOLO SANDRA ROBERTA 
Published: June 2020

Based on the fetal origins of diseases hypothesis, adverse intrauterine environment - reflected by low birth weight (LBW) - has been linked to insulin resistance and type 2 diabetes later in life. Whether β cell function reduction could be detected even in middle-aged adults is less investigated. We examined the association of LBW with β cell function and insulin sensitivity. This is a cross-sectional analysis of 2634 ELSA-Brasil participants aged between 34 and 59 years. Exclusion criteria were diabetes, glomerular filtration rate &lt;60 ml/min/m2, thyroid dysfunction, liver disease, BMI &lt;18.5 kg/m2 and macrosomia. Participants were stratified according to LBW defined as &lt;2.5 kg and their clinical data were compared. HOMA-IR, HOMA-β, HOMA-adiponectin, TyG index and QUICKI were calculated. Associations of LBW with β cell function and insulin sensitivity indexes were tested using multiple linear regression including adjustments suggested by Directed Acyclic Graphs. The sample (47.0±6.3 years) was composed of 58% of women and 9% had LBW. Subjects with LBW had lower mean body weight at age 20 but similar current BMI than the normal weight born ones. In average, cardiometabolic risk profile as well as indexes of β cell function and insulin sensitivity were within normal ranges. Lower median HOMA-β values in the subset with LBW did not differ statistically from normal birth weight ones. In regression analysis, log-transformed HOMA-β - but not with the other indexes - was associated with LBW (p=0.016) independent of sex, skin color, prematurity and family history of diabetes. The association between HOMA-β and LBW suggests that decrease in insulin secretion may occur in healthy middle-aged adults. Our data are coherent with a relatively reduced β cell mass in low weight born subjects that could contribute to the risk of glucose metabolism disturbances.

Disclosure
J.I. Branda: None. B. Almeida Pititto: None. I.M. Bensenor: None. P.A. Lotufo: None. S.F.G. Vivolo: None.

Funding
Fundação de Amparo à Pesquisa do Estado de São Paulo - FAPESP; Coordenação de Aperfeiçoamento de Pessoal de Nível Superior-Brasil (CAPES); CNPq - National Research Council
1479-P: Regional Variations in Chronic Kidney Disease Prevalence among Patients with or without Type 2 Diabetes (RADAR) in the U.S.
Authors: FENG XUE , FAREJ RYAN , XIA FANG , GAISER ANDREW S. , KONG SHELDON , ELLIOTT JAY , LINDEMANN STEFANIE , SINGH RAKESH 
Published: June 2020

Introduction: Type 2 diabetes (T2D) represents the leading cause of Chronic Kidney Disease (CKD) worldwide. While variation in T2D prevalence in the U.S. is well established, regional variation in the prevalence of CKD in patients with or without (w/o) T2D is less well characterized and may inform targeted implementation of risk-reducing interventions.
Objective: We explored regional variations in the prevalence of CKD in patients with or w/o T2D in the U.S.
Method: Data from January 1, 2013 through December 31, 2017 from an employer-based claims database (MarketScan) was used for this analysis. Continuously enrolled patients aged ≥18 years diagnosed with CKD with or w/o T2D were identified using International Classification of Disease diagnosis codes. We estimated overall CKD, CKD+T2D, and CKD w/o T2D prevalence for each year from 2013 to 2017. Geo-mapping was used to visualize the prevalence of CKD. Univariate and differential local indicators for spatial analyses (LISA) were performed to describe the geographic differences of CKD prevalence.
Results: The overall prevalence of CKD doubled from 1.50% in 2013 to 3.11% in 2017. Within the CKD population, 46.3% had T2D in 2017. The prevalence of CKD+T2D increased from 0.70% in 2013 to 1.44% in 2017. From 2013 to 2017, low-low clusters from univariate LISA were consistently observed in the Northwest regions (e.g., MT, WY) (P&lt;0.05), indicating the consistently low prevalence of CKD in these areas. High-high clusters from differential LISA, which implied the clusters of increasing CKD prevalence, were found in the Southeast regions (e.g., FL, MS) (P&lt;0.05).
Conclusion: This study provides real-world evidence of regional variations in CKD prevalence in the U.S. Additionally, this study identified lower CKD prevalence than previously cited in the literature, which may indicate major under-coding in the employer-based claims database. Further characterization of CKD patients with or w/o T2D could help understand these variations.

Disclosure
X. Feng: None. R. Farej: Employee; Self; Bayer U.S. F. Xia: None. A.S. Gaiser: None. S. Kong: None. J. Elliott: None. S. Lindemann: None. R. Singh: None.
148-LB: Timely Administration of Rapid-Acting Insulin in Hospitalized Children with Diabetes: A Quality Improvement Project
Authors: ENG LIANE , DUHAME DANIELLE , UNDERLAND LISA 
Published: June 2020

Background: The preferred management of insulin-dependent diabetes (IDDM) for pediatric patients includes rapid-acting insulin analogs administered at mealtimes in conjunction with carbohydrate counting. Hospitalized children with IDDM are dependent on hospital personnel to administer rapid-acting insulin, which should occur within 15-30 minutes of the onset of eating. Delays in insulin administration can result in hyperglycemia, poor patient satisfaction, and inappropriate insulin regimen adjustments. At the Children’s Hospital at Montefiore (CHAM), we found that rapid-acting insulin is administered within 15 minutes of glucose check at breakfast time in only 18% of patients, and within 30 minutes of glucose check in only 40% of patients.
Methods: We formed a multi-disciplinary team and used process mapping to identify barriers to timely insulin administration and implement interventions. We studied the time to rapid-acting insulin administration at breakfast for children with IDDM admitted to the 6th floor of CHAM from November 2018 to present before and after PDSA cycles, which have included nurse and resident education in carbohydrate counting, standardization of diabetes menus to include carbohydrate content, and standardization of communication method between nurses and residents.
Results: As of December 2019, median time from blood sugar check to rapid-acting insulin administration at breakfast improved from 32.5 minutes at baseline to 26 minutes. The percentage of children with IDDM who receive rapid-acting insulin within 15 minutes of blood sugar check has not changed, but the percentage of children who receive rapid-acting insulin within 30 minutes of blood sugar check improved from 40% at baseline to 60%.
Conclusions: Timely administration of rapid-acting insulin to hospitalized children with IDDM is a complex process involving coordination of care by multiple providers, and can be improved upon with a multidisciplinary team approach.

Disclosure
L. Eng: None. D. Duhame: None. L. Underland: None.