bluuebunny/crossref_metadata_2025_split huggingface dataset:
2175-PUB: Feasibility and Preliminary Effectiveness of Continuous Glucose Monitoring for Diabetes Prevention
Authors: FORTMANN ADDIE L. , BASTIAN ALESSANDRA , BAGSIC SAMANTHA R.S. , LOUPASI IOANNA , LUU KIMBERLY , HOTTINGER AMIRY R. , BARRY KIMBERLY A. , RUIZ MONICA , WALKER CHRIS , PHILIS-TSIMIKAS ATHENA 
Published: June 2020

Continuous Glucose Monitors (CGM) automatically capture interstitial glucose levels every 5 minutes, 24 hours/day, allowing users to view their glucose levels in real-time and make informed decisions about how to manage diet, exercise, and medications. While CGMs are a central component in the glucose management of type 1 diabetes and insulin-dependent type 2 diabetes, less is known about the potential value of CGMs for diabetes prevention. The original Diabetes Prevention Program (DPP) demonstrated that 5-7% weight loss - an outcome reliant upon healthful eating and exercise - was more effective than medication in preventing or delaying the onset of T2D; however, subsequent DPP translations have not consistently achieved the same weight loss outcomes. CGM may represent a way to reinforce and incentivize hard-to-make health behavior changes in real-time that are crucial to the more distal (and often elusive) weight loss outcome. This small (n=7) feasibility pilot examined the preliminary effectiveness and acceptability of integrating CGM in a DPP at Scripps Health, a large, non-profit, private insurance-based health system in San Diego, CA. Following a brief introduction to the CGM and target glucose ranges, DPP participants self-inserted and wore the CGM for 2 weeks. Mean time-in-range (70-140 mg/dL) improved from 70.4% to 76.4%, and time &gt; 140 mg/dL decreased from 29.4% to 23.1% during this period. Individual change in time-in-range ranged from -9.7% to + 38.8% (M ∆ = +6.0%). Participants reported high satisfaction with the CGM, but expressed a desire for more education on blood glucose management. Given these findings, a longer-term, randomized controlled trial is planned to investigate whether a CGM-enhanced DPP leads to greater weight loss than DPP alone. This research will also further our understanding of the potential benefit of improved glycemic control for diabetes prevention even among the subset of cases who do not ultimately achieve the targeted weight loss goal.

Disclosure
A.L. Fortmann: None. A. Bastian: None. S.R.S. Bagsic: None. I. Loupasi: None. K. Luu: None. A.R. Hottinger: None. K.A. Barry: None. M. Ruiz: None. C. Walker: None. A. Philis-Tsimikas: Advisory Panel; Self; Lilly Diabetes, Medtronic, Novo Nordisk A/S, Sanofi. Employee; Spouse/Partner; Ionis Pharmaceuticals, Inc. Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Dexcom, Inc., Lilly Diabetes, Medtronic, Novo Nordisk A/S, Sanofi.

Funding
Confidence Foundation; Dexcom, Inc.
2183-PUB: Standard Deviation Calculated from the 7-Point SMBG Glucose Profiles Is a Good Index of Glycemic Variability Reflecting MAGE Obtained from CGMS
Authors: LIU ZHIGU , LIN BEISI , XU WEN , GONG LI , YANG XUBIN , YAO BIN 
Published: June 2020

Objective: Mean amplitude of glucose excursion (MAGE) obtained from the CGMS is considered a gold standard of glycemic variability (GV). However, the implications of CGMS in routine clinical practice are limited due to its high cost and complexity. This study thus designed to explore whether the GV indices calculated from the more common measurement SMBG can be used to reflect MAGE in T2D patients.
Methods: T2D patients simultaneously underwent a 48-h to 72-h CGM and fingertip blood glucose self-monitoring were included. The GV indices calculated from the 7-point SMBG data (pre- and post- breakfast, lunch and dinner and prior to bedtime) were the means of the following indices during CGM period: the standard deviation (SD) of the 7-point glucose profiles, the largest amplitude of glycemic excursions (LAGE, the difference between the daily maximum and minimum glycemic values) and the mean postprandial glucose excursion (MPPGE, the mean value of the differences between each postprandial and preprandial blood glucose).
Results: Seventy-eight T2D patients (43.6% male, median age: 62 years, median BMI: 23.83 kg/m2) were included. The mean MAGE, SD, LAGE and MPPGE were 4.11, 2.03, 5.66, 2.57mmol/L, respectively. SD, LAGE and MPPGE were significantly correlative with MAGE (r= 0.625, 0.488 and 0.599, respectively; all P&lt;0.05). In the linear regression analysis, significant relationships were shown between MAGE and SD, LAGE and MPPGE (R2=0.391, 0.359, 0.238, respectively; all P&lt;0.001). The area under the ROC curve for SD (0.809, 95% CI: 0.712-0.906, P&lt;0.05) was superior to that for LAGE (0.793, 95% CI: 0.692-0.894, P&lt;0.05) and MPPGE (0.704, 95% CI: 0.588-0.820, P&lt;0.05) in reflecting MAGE.
Conclusions: The GV indices calculated from the SMBG data including SD, LAGE and MPPGE are positively correlated with MAGE obtained from CGM. Among these indices, SD of the 7-point SMBG glucose profiles seems to be a better GV index to reflect MAGE.

Disclosure
Z. Liu: None. B. Lin: None. W. Xu: None. L. Gong: None. X. Yang: None. B. Yao: None.

Funding
National Key Research and Development Program of China (2016YFC1304801)
2188-PUB: Efficacy and Safety in Chinese T2D Patients Discontinued from OAM to Once-Weekly Dulaglutide Monotherapy
Authors: LI YANBING , ZHANG BIN , LIU SIYING 
Published: June 2020

Background and Objective: GLP-1RAs including dulaglutide (DU) are recommended as 1st injectable therapy in T2D patients after oral antihyperglycemic medicine (OAM) failure. Efficacy and safety of DU have been studied when adding on OAMs, but not in Chinese population discontinued from OAM. This is the first post-hoc analysis to evaluate the efficacy and safety of DU in Chinese T2D patients discontinued from OAM and started with once weekly DU.
Methods: A total of 292 Chinese patients who discontinued from OAM monotherapy in AWARD-CHN1 study (NCT01644500) were included in this post-hoc analysis as modified intent-to-treat (mITT) population.
Results: Overall, the mITT population had mean age of 55.0 years, with 5.5 years’ mean duration of T2D at baseline. Previous OAM treatment included metformin, acarbose, sulfonylureas, and meglitinides. Table 1 summarized the efficacy and safety outcomes at Week 26. DU 1.5 mg was superior to glimepiride for HbA1c and body weight reduction. Greater improvement in beta cell function was observed for both DU groups, along with fewer hypoglycemia events. The most common adverse events for DU were gastrointestinal in nature, including diarrhea, abdominal distension, vomiting and nausea.
Conclusion: DU is effective and safe for Chinese T2D patients discontinued from OAM and can further improve glucose control and protect beta cell function compared to glimepiride.

Disclosure
Y. Li: None. B. Zhang: Employee; Self; Eli Lilly and Company. S. Liu: Employee; Self; Eli Lilly and Company.
2190-PUB: A Pragmatic Study of Basal and Mid-Mixture Insulins as Insulin Starters in Chinese Patients with T2DM
Authors: CHEN LULU , CHEN HONG , DU LIYING , LOU YING , JI LINONG 
Published: June 2020

This study aimed to compare the effectiveness and safety of basal insulin (BI) and mid-mixture insulin (MMI) in a real-world setting. Chinese patients with T2DM uncontrolled on oral antihyperglycemic medications (OAMs) were randomized 1:1 to receive add-on BI (QD) or MMI (BID) for 48 weeks (wks). Insulin titration and OAM dose adjustment were based on clinical practice. Compared to BI, MMI led to numerically greater decrease in HbA1c from baseline to wk 24 and statistically greater decrease in HbA1c at wk 48. Fasting blood glucose (FBG) in both groups further decreased from wk 24 to wk 48, and BI caused greater decrease at wk 48 compared to MMI. Both groups had similar decreases in postprandial glucose. Also, significant intergroup difference in OAM use change was detected (p &lt;0.0001) with more patients increasing OAM use in BI group and decreasing OAM use in MMI group. Noticeably, both groups had very limited insulin titration. Body weight increased subtly in both groups. Total hypoglycemia incidence was higher in MMI group through 48 wks, but both groups had low and similar nocturnal hypoglycemia incidence and no severe hypoglycemia. Both BI and MMI could significantly improve glycemic control in Chinese T2DM patients with OAM adjustment and limited insulin titration without major safety issues. Compared to BI, MMI showed larger improvement on glycemic control in relatively long period of treatment.

Disclosure
L. Chen: Consultant; Self; AstraZeneca, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk A/S. H. Chen: Employee; Self; Eli Lilly and Company. L. Du: Employee; Self; Eli Lilly and Company. Y. Lou: Employee; Self; Eli Lilly and Company. L. Ji: None.
2195-PUB: Use of U500 Insulin in External Pump for Insulin-Resistant Diabetic Patients: A French Experience
Authors: OUALIT YOUSSEF , PÂRIS DOMINIQUE , KESSLER LAURENCE , BAHOUGNE THIBAULT , JEANDIDIER NATHALIE , MEYER LAURENT 
Published: June 2020

Use of large insulin doses is more frequent in diabetes due to an increase in the prevalence of severe obesity worlwide. Insulin-associated treatments such as metformin or GLP-1 receptor agonists (GLP-1RA) can help and use of insulin concentrated at 500 IU/ml (U500) has been associated with an improve in glycemic control in previous studies including severe insulin resistant patients. We report our experience of U500 in subjects with high HbA1c despite insulin pump therapy (CSII) combined or not with metformin and/or GLP-1RA. Eighteen T2D and 3 T1D were studied (13M and 8F), age: 59.5 ± 9.6 years, diabetes duration : 18.8 ± 9.8 years. Eight subjects used metformin and 7 used GLP-1RA (5 used metformin and GLP-1RA). Treatment with U500 was carried out during a 5-day hospitalization. Metformin and/or GLP-1RA were continued or not during the follow-up according to the decision of the patient’s diabetologist. Mean duration of follow-up was 9 months. A decrease in HbA1c was found (initial vs. final) : 9.4 ± 1.2% vs. 8.5 ± 1.3% (p =0.05). No change was found for weight : 123.9 ± 26.4 kg vs. 121.0 ± 30.3 kg (NS), BMI : 41.5 ± 7.2 kg/m2 vs. 40.2 ± 7.3kg/m2 (NS), daily total insulin needs (U100 equivalent) : 198.4 ± 70.5 IU vs. 228 ± 121 IU (NS), basal needs : 81.8 ± 29.2 IU vs. 87 ± 36 IU (NS) and prandial needs : 116.5 ± 61.3 IU vs. 143 ± 110 IU (NS). No changes were found for lipidic parameters as total cholesterol (TC) : 1.85 ± 1.10 g/l vs. 1.80 ± 0.92 g/l (NS), HDL-C : 0.36 ± 0.08 g/l vs. 0.31 ± 0.06 g/l (NS), LDL-C : 0.83 ± 0.32 g/l vs. 0.71 ± 0.30 g/l (NS) and TG : 3.98 ± 7.56 g/l vs. 3.4 ± 5.3 g/l (NS). No change in use of metformine and/or GLP-1RA and no side effect were found during the follow-up.
Conclusion: In our practice, use of U500 in insulin-resistant patients treated with CSII is well tolerated and is associated with a decrease in HbA1c despite no change in weight or daily insulin needs. Evolution of glycemic variability (including TIR and hypoglycemias) using continuous glucose monitoring is currently being analyzed.

Disclosure
Y. Oualit: None. D. Pâris: Board Member; Self; Novo Nordisk Inc. Consultant; Self; Eli Lilly and Company, Sanofi-Aventis. L. Kessler: Consultant; Self; Lilly Diabetes, Medtronic, Novartis Pharma K.K., Novo Nordisk A/S, Vertex Pharmaceuticals. T. Bahougne: None. N. Jeandidier: Consultant; Self; Sanofi-Aventis. Research Support; Self; Lilly Diabetes. L. Meyer: Board Member; Self; Abbott, Lilly Diabetes, Novo Nordisk A/S.
220-OR: Plasma Adrenomedullin and Allelic Variation in the ADM Gene and Risk for Lower Extremity Amputation in People with Type 2 Diabetes
Authors: POTIER LOUIS , ROUSSEL RONAN , SAULNIER PIERRE-JEAN , FUMERON FRÉDÉRIC , MOHAMMEDI KAMEL , VELHO GILBERTO 
Published: June 2020

Patients with diabetes have an increased risk for lower limb amputation (LLA) but biomarker to assess risk of LLA is lacking. Adrenomedullin (ADM), a vasodilator peptide, has been shown to be associated with cardiovascular and renal risk in diabetes. The aim of this study is to assess the association between plasma MR-proADM (a surrogate of ADM), allelic variation in the ADM gene and the risk for LLA in cohorts of patients with type 2 diabetes. We studied 4532 participants of the DIABHYCAR and SURDIAGENE cohorts (men 70%, mean age 66, mean duration of diabetes 13 years, A1c 8,0%). MR-proADM was measured by immunofluorescence. Five SNPs were chosen in the haplotype block containing the ADM gene (chr11p15.4): rs4399321, rs11042725, rs7944706, rs2957692 and rs2957717. The mean follow-up was 5.3 years. Incidence of LLA by tertiles of MR-proADM (T1, T2, T3) was 1.0% (T1), 1.9% (T2) et 4.7% (T3) (p&lt;0,001). In a Cox multivariable analysis model (adjusted for cohort, age, sex, diabetes duration, hypertension, A1c, cholesterol, history of peripheral arterial disease and glomerular filtration rate eGFR), HR for LLA was 4.21 (2.18-8.66; p&lt;0.001) for T3 vs. T1, 2.46 (1.50-4.12; p=0.003) for T3 vs. T2 and 1.82 (1.25-2.67; p=0.002) for 1 unit of log [ADM]. All SNPs were significantly associated with baseline plasma ADM. Four were significantly associated with LLA: HR adjusted for sex, age, duration of diabetes, A1c, eGFR and cohort: 1.40 (1.046 - 1.84; p=0.02) for the G-allele of rs4399321 in a codominant model; 1.71 (1.13 - 2.54; p=0.01) for the AA vs. CX genotype of rs11042725; 1.61 (1.09 - 2.35; p=0.02, for the GG vs. AX genotype of rs7944706; 1.37 (1.06 - 1.77; p=0.04) for the G-allele of rs2957692 in a codominant model. We observed an association of plasma ADM with LLA and of allelic variations in the AMP locus with plasma ADM and with LLA in a large population of people with type 2 diabetes. This pattern of mendelian randomisation supports the causality of the association of plasma ADM with LLA.

Disclosure
L. Potier: Consultant; Self; Eli Lilly and Company, Novo Nordisk A/S, Sanofi. R. Roussel: Advisory Panel; Self; Abbott, AstraZeneca, Diabnext, Eli Lilly and Company, Merck & Co., Inc., Mundipharma International, Novo Nordisk A/S, Sanofi-Aventis. P. Saulnier: None. F. Fumeron: None. K. Mohammedi: None. G. Velho: None.
223-LB: Dissecting the BPA-Induced Disruptions in Liver–Gut Microbiota Interactions and Metabolic Health
Authors: DIAMANTE GRACIEL , CELY INGRID C. , LANG JENNIFER , BLINE ABIGAIL , ZAMORA ZACARY O. , SINGH MAYA , LUSIS ALDONS , YANG XIA 
Published: June 2020

Bisphenol A (BPA) is an industrial plasticizer widely found in consumer products such as plastic bottles and canned foods. Human and murine studies have shown strong associations between prenatal exposures to endocrine disruptors such as BPA during early development and the prevalence of various diseases including cardiovascular diseases, type 2 diabetes, and obesity. Previous studies have found that the liver tissue is a sensitive BPA target site, and BPA alters the microbial diversity in exposed mice. To understand whether and how the gut microbiome mediates the effects of BPA on liver gene expression to influence metabolic phenotypes, we conducted a multi-dimensional systems biology study. We treated pregnant C57BL/6 mice with a low dose of BPA at 5ug/kg/day during gestation and evaluated metabolic phenotypes, fecal microbial composition and liver transcriptome of both male and female offspring. Prenatal exposure to low dose BPA significantly not only affected liver genes involved in oxidative phosphorylation, PPAR signaling and fatty acid metabolism, but also affected the gut microbial composition in an age-dependent manner, with the most pronounced effect observed at week 20. Bacteria belonging to the S24-7 and Lachnospiraceae families were correlated to offspring body weight and differentially expressed liver genes such as Fabp1, Acadl and Dgat1. This study provides insights into the relationship between gut bacteria and host liver genes that could contribute to metabolic disease risks upon BPA exposure. Future studies will test whether the gut microbiota identified in this study play a direct causal role on the host genomic and phenotypic responses using fecal transplant and bacteria colonization experiments.

Disclosure
G. Diamante: None. I.C. Cely: None. J. Lang: None. A. Bline: None. Z.O. Zamora: None. M. Singh: None. A. Lusis: None. X. Yang: None.

Funding
American Diabetes Association (1-19-PDF-007-R to G.D.)
2232-PUB: Reasons for Treatment Discontinuation in Type 2 Diabetes (T2D): Results from an Online Patient Survey in the UK and U.S.
Authors: DE CLIMENS AUDE ROBOREL , PAIN EMILIE , BOSS ANDERS H. , SHAUNIK ALKA 
Published: June 2020

T2D is a chronic condition that requires long-term treatment to achieve and maintain glycemic control. However, up to 50% of people with T2D discontinue treatment by 1 year. To better understand why this occurs, an online questionnaire was presented to people with T2D in the UK (n=72) and U.S. (n=89) on the PatientLive® platform of Carenity, a global online patient community. For those who discontinued at least one of their T2D treatments within the last 6 months, open-ended questions aimed to assess the reasons why, how it could have been prevented, and what would have improved the experience with the discontinued treatment. Thematic qualitative analysis was performed on respondents’ answers to these open-ended questions. Overall, oral antidiabetics were the most commonly discontinued treatment type (93/161), followed by insulin (40/161) and other injectable antidiabetics (13/161). The most common reasons for treatment discontinuation were side effects (57/161), mostly gastrointestinal side effects and weight gain. Drug efficacy issues were the second most reported reason (42/161). In the U.S., cost of treatment played an important role (14/89). For the respondents, key factors to prevent discontinuation would have been an improved care pathway (45/161) and more efficacious treatments with fewer side effects (41/161). In the U.S., a lower price was also noted as an improvement factor (12/89). More information about T2D and associated treatments (56/161), help on how to manage T2D (24/161), and better informing of doctors of patients’ needs (12/161) would have been helpful for many respondents in both the UK and U.S. Notably, however, many respondents confirmed that they were sufficiently informed (64/161). These results emphasize the need for focused education and improved communication to enhance patient experience and prevent treatment discontinuation, and highlight the importance of therapies with attributes preferred by people with T2D that better fit their needs.

Disclosure
A. Roborel de Climens: Employee; Self; Sanofi. E. Pain: Consultant; Self; Sanofi. A.H. Boss: Employee; Self; Sanofi. Stock/Shareholder; Self; Novo Nordisk Inc., Sanofi. A. Shaunik: None.

Funding
Sanofi
2234-PUB: The Impact of a Community Paramedicine Program on Diabetes Outcomes and Health Care Utilization
Authors: EICKEN MEREDITH , LEE DEBBY , EWING JOSEPH A. , BUTLER JOHN N. , LUTZ MARTIN E. , SNOW JENNIFER Z. , HIPP CANDICE , THOMAS DARIN T. , HEAD CHARLES P. , HUDSON-DOBBS ROGER S. , GREEN VINCENT E. , WEBER SANDRA L. 
Published: June 2020

Background: As of 2017, South Carolina ranked 5th highest in the U.S. for percentage of adults with diabetes, which has negative health and cost implications. The innovative community paramedicine program (CPP) aims to improve management of patients with chronic diseases and high utilization of the Emergency Department (ED), by providing in-home disease management, education, and care/community resource connection by paramedics. The impact of CPs has not been extensively studied in diabetes.
Objective: To assess impact of CPP participation on health outcomes and healthcare utilization for patients with diabetes.
Methods: Retrospective analysis of CPP participants diagnosed pre-enrollment with diabetes. Demographics and variables reported as percentages, and differences between A1c values pre/post CPP tested using Student’s t-test. Healthcare cost and utilization data was extracted from EMR using SAP BusinessObjects and analyzed with Qlik.
Results: From 2015-2019, 64 people with diabetes enrolled. Participants were primarily insured by Medicare (48.4%) and/or Medicaid (35.9%) or uninsured (32.8%). Comparing pre and post-enrollment average values, participants in CPP for &gt;180 days (d) demonstrated a clinically significant improvement in A1c, although this did not reach statistical significance (181-270d: 10.04+/-1.33 to 8.51+/-1.35, p=0.159; 271-365d: 10.83+/-2.95 to 7.65+/-2.39,p=0.098; 365+d: 9.31+/-2.58 to 7.76 +/-1.45, p=0.23). Participants also showed increased rates of screening for microvascular complications. To date, the utilization analysis for the 52 CPP graduates who participated &gt;14d suggests decrease in average cost of care and ED visits per person comparing 6 months prior and up to 6 months post CPP enrollment ($16,514 vs. $4,717; 2.77 vs. 0.73 ED visits).
Conclusions: The CPP demonstrated improvement in disease control and reduced costs/ED visits for patients with diabetes. This is a promising care delivery innovation that merits further research.

Disclosure
M. Eicken: None. D. Lee: None. J.A. Ewing: None. J.N. Butler: None. M.E. Lutz: None. J.Z. Snow: None. C. Hipp: None. D.T. Thomas: None. C.P. Head: None. R.S. Hudson-Dobbs: None. V.E. Green: None. S.L. Weber: None.
225-LB: A High-Throughput CRISPR-Activation Screen Defines Human LncRNA Metabolic Regulators
Authors: MA YONGHE , CAO HAIMING 
Published: June 2020

In the past decade, long noncoding RNAs (lncRNAs) have emerged as important regulators of cellular and systemic metabolism. Deciphering the physiological functions of lncRNA by gain- or loss-of-function analyses in key metabolic organs, such as the liver, is essential to understand their disease relevance. Conventional transgenic or knockout approaches, however, have limitations in defining lncRNA function as lncRNAs transgenically expressed from ectopic genomic loci could be non-functional and partial deletion of lncRNAs. Domain negative Cas9 (dCas9) coupled with transcriptional activators can trigger endogenous lncRNA expression by targeting guide RNA (gRNA) to transcription start sites of lncRNAs, thus increasing their transcription efficiency and targeting multiple different lncRNA isoforms simultaneously. Adenovirus vector is the most commonly used tool for specifically targeting liver-enriched genes both in vitro and in animal models. A CRISPR-activation (CRISPR-a) adenovirus system thus constitutes a powerful means to active liver lncRNAs transcriptionally. In this study, we established a CRISPR-a adenovirus platform by transferring CRISPR-a units into the adenovirus vector, and our system allows one digestion-ligation step to construct the gRNA adenovirus vector seamlessly. Efficacy and versatility of this pipeline has been confirmed by the successful construction of a CRISPR-a adenovirus library containing 96 gRNAs targeting 20 liver-enriched, metabolic sensitive lncRNAs, which shows high CRISPR activation efficiency after primary human hepatocytes infection. Moreover, the expression levels of several lncRNA target genes predicted by co-relation analysis are significantly changed. This method thus provides a fast and efficient way to activate the endogenous liver lncRNAs and simplifies the procedure of lncRNA functional screening using CRISPR-a adenovirus system, which can be scaled up to a genome level to quickly define lncRNA metabolic regulators.

Disclosure
Y. Ma: None. H. Cao: None.