bluuebunny/crossref_metadata_2025_split huggingface dataset:
217-LB: A Novel GPR119 Agonist, DA-1241, Improves Hepatic Inflammation and Fibrosis in ob-NASH Mice
Authors: PARK HANSU , LEE BORAM , CHAE YUNA , KIM MI-KYUNG 
Published: June 2020

GPR119 activation is known to inhibit de novo lipogenesis in hepatocytes, but it still remains elusive if and how GPR119 agonists can affect the pathogenesis of hepatic inflammation and fibrosis in NASH. Herein, we report the therapeutic potential of DA-1241 for NASH, especially for hepatic inflammation and fibrosis. DA-1241 was given to ob/ob mice with western diet for 10 weeks. Plasma and liver tissue samples were tested for biochemical and histological analyses. Human monocyte cells and primary hepatic stellate cells were used for in vitro proof-of-concept. At the end of experiment, ob/ob NASH mice distinctly exhibited increased plasma total cholesterol and hepatic lipid accumulation, but plasma glucose and triglyceride values were within normal range. After 10-weeks of treatment, DA-1241 significantly blocked the progression of hepatic inflammation and fibrosis compared to the NASH control (-39% and -64% for NAS and fibrosis score; p&lt;0.05), while MBX-2982, a GPR119 agonist under clinical development, failed to reach statistical significance at the same dose (-19.4% and -29%; p&gt;0.05). Moreover, plasma total glucagon-like peptide-1 levels were increased by DA-1241 treatment, but not by MBX-2982. Plasma ALT and AST levels were significantly lower in DA-1241-treated mice, which were much lower than those of MBX-2982-treated mice. Of note, DA-1241 were more efficacious than MBX-2982 in reducing the hepatic expression of fibrotic proteins such as type 1 collagen, α-SMA, and TIMP1, and pro-inflammatory proteins including CCL2, TNFα. To explore its underlying modes of action in vitro, THP-1 macrophages or primary hepatic stellate cells were activated by LPS or TGFβ, respectively. DA-1241 inhibited the differentiation and activation of macrophages and blocked stellate cells activation. Our findings suggest that DA-1241 has a therapeutic potential for NASH, which may be partly attributed to blocking macrophage and stellate cell activation in addition to the inhibition of lipogenesis.

Disclosure
H. Park: Employee; Self; Dong-A ST Co., Ltd. B. Lee: Employee; Self; DONG-A ST Co,Ltd. Y. Chae: Employee; Self; Dong-A ST Co., LTD. M. Kim: Employee; Self; Dong-A ST Co., Ltd.
2172-PUB: Factors Influencing Parent Emotional Functioning after Young Child’s Type 1 Diabetes Diagnosis
Authors: TULLY CARRIE , HILLIARD MARISA E. , MONAGHAN MAUREEN , WANG JICHUAN , STREISAND RANDI 
Published: June 2020

Introduction: Young child type 1 diabetes (YC-T1D) diagnosis can cause significant stress. While rates of increased depression have been documented, less is known about parent general emotional functioning (EF). This study aims to evaluate four hypothesized domains that may be related to parents’ EF: family characteristics, diabetes health characteristics, family protective factors (PF), and diabetes-specific functioning.
Method: 157 newly diagnosed YC-T1D (M age=4.43±1.67; M days post diagnosis =28.78±15.10) and their primary caregivers (72% Caucasian, 90% female) were assessed for an RCT evaluating a behavioral intervention. Medical data were extracted from the EHR. Parents completed a psychosocial battery at baseline; selected measures were identified to explore hypothesized domains associated with parents’ EF: family characteristics (Race), PF (Protective Factors Survey, Social Support), diabetes-specific functioning (Self-Efficacy for Diabetes-Parent) and parent EF (Perceived Stress Scale).
Results: Table 1 presents findings from regression analyses.
Conclusion: Preliminary findings demonstrate associations among family characteristics, PF, and diabetes-specific functioning with parent EF. Results provide initial support for a broader model, which may incorporate additional variables; future research may examine a broader model over the first year after diagnosis.

Disclosure
C. Tully: None. M.E. Hilliard: None. M. Monaghan: Research Support; Self; American Diabetes Association. J. Wang: None. R. Streisand: None.

Funding
National Institute of Diabetes and Digestive and Kidney Diseases (R01DK102561)
218-LB: Liver-Humanized Mice Reveal Similarity and Divergence in Genomic Response between Human and Mouse
Authors: JIANG CHENGFEI , CAO HAIMING 
Published: June 2020

Mouse is the most widely used preclinical animal model yet the translational rate is dismal. To understand the molecular underpinnings of the differential pathophysiology between human and mouse, we analyzed similar or discordant gene expression networks regulated by a variety of metabolic conditions under multiple complementary experimental settings, and tested these regulations in humanized mice where the confounding factors are minimized. We first analyzed human and mouse liver transcriptomes derived from conditions ranging from differentially expressed genes in fatty liver disease to genes regulated by transcriptional or posttranscriptional factors. In addition to genes that are exclusively regulated in human or mouse, we identified that a large fraction of commonly regulated genes (up to 50%) exhibit completely opposite regulation. To determine the intrinsic similarity and differences between human and mouse liver biology, we further analyze gene expression in a humanized mouse model in which human and mouse hepatocytes co-exist in the humanized liver and are exposed to identical in vivo metabolic milieu. Strikingly, divergent gene expressions in human and mouse hepatocytes are recapitulated in the humanized mice. By integrating the data of humanized mice, we are able to reveal the intrinsic consistently and oppositely regulated genes and pathways between human and mouse in each condition we analyzed. Although the regulations of these genes are largely condition dependent, the most constant consistently or oppositely regulated pathways can be identified. Furthermore, our analysis suggests that human and mouse lncRNAs might play a critical role in the differential gene regulations in human and mouse. Our work provides a foundation to understand the molecular basis for divergent metabolic responses in human and mouse liver, highlighting the importance of a human or humanized system for translational studies.

Disclosure
C. Jiang: None. H. Cao: None.
2181-PUB: The Patient Characteristics of Contour Diabetes App Users Worldwide
Authors: RICHARDSON JAMES M. , PARDO SCOTT , SHAGINIAN RIMMA 
Published: June 2020

Since 2016 more than 600,000 people have been utilizing the CONTOUR®DIABETES app (CDA) in combination with connected CONTOUR® Blood Glucose Monitoring Systems (BGMSs) worldwide. The aim of this analysis was to assess demographic data of CDA users from North America (NA) 42.6%, Europe (EU) 47.9% and Asian Pacific (APAC) region 4.5%. We examined the CDA database of patients that uploaded at least one blood glucose (BG) result during September 2019. BG results were automatically synched from a BGMS to CDA via BLE (Bluetooth Low Energy) or had the capability to enter manually in the app. All other data were self-reported and included age, gender, diabetes type, therapy mode, physical activities, carbs and location. From 625,837 users 19.9% of patients recorded at least one BG result during September 2019. In all three regions the proportion of patients above 60 years old was similar (NA 26.6%, EU 23.8%, APAC 26.5%). There were slightly fewer male users in U.S. than in EU and APAC (NA 49.3%, EU 52.6%, APAC 52.8%). The proportion of T1D and T2D users was as follows in NA: T1D 12.9%, T2D 48.6%, EU :T1D 23.2%, T2D 39.4% and APAC: T1D 15.9%, T2D 48.9%. Analysis of treatment mode demonstrated that T2D patients treated by insulin alone or in combination with other glucose lowering medications (OAM) differed from region to region (NA 28.0%, EU 38.1%, APAC 14.5%). Among them daily BG testing adherence also varied (NA 25.5%, EU 33.3%, APAC 23.9%). The daily BG testing in T1D patients was also different per region (NA 30.3%, EU 33.8%, APAC 26.3%). Around 20% of patients that registered with CDA since 2016 were actively using the app. The majority of them were T2D patients across all regions. The proportion of insulin use in this population varied by region. This analysis showed that real world BG testing frequency in T2D patients treated with insulin alone or in combination with OAM as well as in T1D patients appears lower than current recommendations. Further analysis is planned to identify the profile of patients who would mostly benefit from the use of CDA.

Disclosure
J.M. Richardson: Employee; Self; Ascensia Diabetes Care. Employee; Spouse/Partner; Ascensia Diabetes Care. S. Pardo: Employee; Self; Ascensia Diabetes Care. R. Shaginian: Employee; Self; Ascensia Diabetes Care.
2185-PUB: Once-Weekly Semaglutide 1mg vs. Empagliflozin 25mg as Add-On to Metformin Monotherapy in Patients with Type 2 Diabetes: A Meta-regression Analysis of Individual Patient Data
Authors: LINGVAY ILDIKO , CATARIG ANDREI-MIRCEA , SANDBERG ANNA , LAWSON JACK , CAPEHORN MATTHEW , JOHANSEN PIERRE , SHAW ROBERT D. , PAINE ABBY 
Published: June 2020

There are no published head-to-head trials of once-weekly semaglutide 1 mg vs. once-daily empagliflozin 25 mg in type 2 diabetes (T2D). We indirectly compared the pooled semaglutide arms in SUSTAIN 2, 3 and 8 with the empagliflozin arm in PIONEER 2 using individual patient data, for those on metformin monotherapy. Although all trials had similar inclusion criteria and duration, meta-regression analyses adjusting for effect modifiers and prognostic factors further controlled for differences in design and population. Mean baseline characteristics were similar with semaglutide and empagliflozin (age: 56 vs. 58 years, diabetes duration: 7 vs. 8 years, BMI: 33 vs. 33 kg/m2, HbA1c: 8.2% vs. 8.1%, respectively). Semaglutide reduced mean HbA1c by -1.4 vs. -0.8%-point with empagliflozin (p&lt;0.001), and body weight by -5.3 vs. -3.7 kg with empagliflozin (p&lt;0.001, Table). Sensitivity analyses, which were performed to assess robustness of these findings, supported these results. A significantly greater proportion of patients on semaglutide vs. empagliflozin also achieved HbA1c targets and clinically relevant weight-loss targets (Table). In this indirect comparison, pooled semaglutide 1 mg provided significantly greater HbA1c reduction and body weight loss compared with empagliflozin 25 mg in patients with T2D on metformin monotherapy.

Disclosure
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. A. Catarig: Employee; Self; Novo Nordisk A/S. Employee; Spouse/Partner; Novo Nordisk A/S. Stock/Shareholder; Self; Novo Nordisk A/S. A. Sandberg: None. J. Lawson: Employee; Self; Novo Nordisk A/S. M. Capehorn: Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Novo Nordisk A/S. Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Lilly Diabetes, Novartis Pharmaceuticals Corporation, Novo Nordisk A/S. Speaker’s Bureau; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Novo Nordisk A/S. P. Johansen: Employee; Self; Novo Nordisk A/S. Stock/Shareholder; Self; Novo Nordisk A/S. R.D. Shaw: Consultant; Self; Novo Nordisk A/S. A. Paine: Consultant; Self; Novo Nordisk A/S.

Funding
Novo Nordisk A/S
2193-PUB: Effect of One Month Basal Insulinization in Addition to OADs Initiation on Glycemic Parameters in Newly Diagnosed Treatment-Naïve Type 2 Diabetes Patients Presenting with Osmotic Symptoms or Glucotoxicity: A Long-Term Follow-Up Study
Authors: JAGANMOHAN BALAJI , MATHUR PRAVEER R. , DAS SAMBIT , RM MANIKANDAN , SANJOY P , MANOHAR SUDEEP P. , AHMED AFTAB , BS NARENDRA , SAI JAYAPRAKASH , MC DEEPAK , MANI AKILA , KOLUKULA VAMSI K. 
Published: June 2020

Aim: To assess the glycemic outcomes of early basal insulin therapy in newly diagnosed treatment naïve T2DM patients presenting with glucotoxicity.
Methods: A cross-sectional observational retrospective data analysis of T2DM patients visiting diabetes specialty clinic across India from January 2016 to October 2019. Patients initiated on basal insulin for one month along with oral antidiabetes drugs were included in the analysis. The demographic, clinical, and glycemic investigations data were collected from electronic medical records. Patients were followed up for at least 4 clinic visits at 3 months interval.
Results: Total 527 newly diagnosed T2DM patients were included. Males: 352 (67%) and females were 175 (33%). Mean age was 50.5 years and BMI was 27.7 kg/m2. Patients glycemic parameters at the time of initiation of insulin therapy were highly uncontrolled, their mean HbA1c, FBG, and PPBG were 10.9%, 236 mg/dL and 335 mg/dL. Among these patients, only 87 patients regularly followed up to clinic for a year. The average follow-up time period was 250 days. These patients’ glycemic parameter reduced significantly from baseline through last follow up visit. HbA1c reduced from 12.2% to 7.5%; FBG 270 mg/dL to 135mg/dL; PPBG 370 mg/dL to 181 mg/dL (p &lt;0.001). Further, there was clinically significant improvement in the lipid profile of these patients. In addition, TC 199 to 151 mg/dL; TG 222 to 161 mg/dL; low density lipoprotein 122 to 81 mg/dL were also reduced.
Conclusions: Early initiation of basal insulin therapy has shown to reduce glycemic burden and the disease progression suggesting early insulinization should be the treatment option for effective control of diabetes and long term benefits in avoiding the complications. This is even supported by international guidelines as part of an individualized approach to chronic disease management.

Disclosure
B. Jaganmohan: None. P.R. Mathur: None. S. Das: None. M. Rm: None. P. Sanjoy: None. S.P. Manohar: None. A. Ahmed: None. N. Bs: None. J. Sai: None. D. Mc: None. A. Mani: None. V.K. Kolukula: None.
2194-PUB: Structured Basal-Bolus Insulin Injection in Hospitalized Patients with Type 2 Diabetes: Tertiary Teaching Hospital Experience
Authors: MOON SUN JOON , JANG HAN NA , YANG YE SEUL , KWAK SOO HEON , JUNG HYE SEUNG , PARK KYONG SOO , CHO YOUNG MIN 
Published: June 2020

Objectives: Although the efficacy of basal-bolus insulin regimen (BBI) in type 2 diabetes (T2D) patients has been demonstrated in clinical studies, few studies have revealed changes in glycemic control following the introduction of BBI in hospital practice. This study was aimed to evaluate the effect of structured BBI in clinical practice for hospitalized patients with T2D.
Methods: We retrospectively analyzed non-critically ill T2D patients treated with insulin, who were hospitalized for glycemic control at Seoul National University Hospital (SNUH) from 2004 to 2018. The effects of BBI in T2D patients after 2007, when the current BBI protocol was introduced to SNUH, compared to that of the other types of insulin in T2D patients until 2007. Patients were propensity-score-matched in a 1:1 ratio.
Results: Among 294 BBI treated patients (age, 60.4 ± 13.8 years; male, 141 [48.0%]; HbA1c, 10.4 ± 1.9%) and 294 other insulin-treated patients (age, 59.9 ± 12.6 years; male, 148 [50.3%]; HbA1c, 10.3 ± 1.9%), mean admission pre-prandial blood glucose level were 181.0 ± 37.7 mg/dl and 200.0 ± 34.0 mg/dl, respectively (P &lt;0.05). Blood glucose target of &lt;140 mg/dl was achieved in 56.1% of patients in the BBI group and in 33.7% of those in the other insulin group on the sixth day of admission. The mean first target achievement day was 3.6 ± 1.3 days in the BBI group and 4.2 ± 1.5 days in other insulin groups, respectively (P &lt;0.05). Events of hypoglycemia (≤70 mg/dL) and severe hypoglycemia (&lt;55 mg/dL) were not different between the groups.
Conclusion: In this study of clinical practice in a tertiary hospital, structured BBI showed significantly improved glycemic control compared to other types of insulin regimens for T2D patients.

Disclosure
S. Moon: None. H. Jang: None. Y. Yang: None. S. Kwak: None. H. Jung: None. K. Park: None. Y. Cho: None.
22-LB: Incident Myocardial Infarction Is Associated with Insulin Resistance and Liver Fibrosis Scores
Authors: M ÖSER CLARA , ZAHARIA OANA P. , ROTHE MAIK , HWANG JONG-HEE , BOBROV PAVEL , BURKART VOLKER , B ÖNNER FLORIAN , JUNG CHRISTIAN , KELM MALTE , RODEN MICHAEL , SZENDROEDI JULIA 
Published: June 2020

Insulin resistance and nonalcoholic fatty liver disease associate with increased risk of cardiovascular disease and predict a worse outcome. The underlying mechanisms are yet unclear. We hypothesized that individuals who suffer from their first acute myocardial infarction (MI) already feature not only lower insulin sensitivity (M-value) and ejection fraction (EF), but also higher hepatocellular lipids (HCL) and liver fibrosis scores (MRE) than matched individuals without MI. We compared participants of the DISTEMI (DIabetes and ST-Elevation MI) Study at 6-12 weeks after MI (MI+; n=21, 81% male, 29% type 2 diabetes, age 61±8 years, BMI 26.8±2.8 kg/m2, HbA1c 5.8±1.0%) with humans without MI (MI-; n=34, 71% male, 32% type 2 diabetes, age 57±8 years, BMI 27.8±3.1 kg/m2, HbA1c 5.5±0.6%). Participants were matched by sex, age, HbA1c and body mass index. They underwent a 75-g oral glucose tolerance and hyperinsulinemic-euglycemic clamp tests. HCL, MRE, EF, infarct size and microvascular obstruction (MVO) were measured with 1H-magnetic resonance (MR) spectroscopy and imaging. MI+ had a lower whole-body insulin sensitivity (M-value: 7.3±2.0 vs. MI- 9.0±3.1 mg*kg-1*min-1, p&lt;0.05). HCL was comparable (2.9±2.8% vs. 5.7±6.7%), while MRE was higher in MI+ compared to MI- (2.5±0.4 kPa vs. 2.1±0.4 kPa, p&lt;0.05). EF was lower in MI+ than in MI- (53±16% vs. 65±7%, p&lt;0.05). In MI+, EF correlated negatively with infarct size (r=-0.91) and MVO (r=-0.82) as well as with HbA1c (r=-0.61) and fasting blood glucose (r=-0.61, all p&lt;0.05).
In conclusion, individuals with incident MI have lower insulin sensitivity, reduced ejection fraction and higher liver fibrosis scores, which relate to worse glucose metabolic control and may contribute to increased risk of heart failure after the first MI.

Disclosure
C. Möser: None. O.P. Zaharia: None. M. Rothe: None. J. Hwang: None. P. Bobrov: None. V. Burkart: None. F. Bönner: None. C. Jung: None. M. Kelm: Research Support; Self; Abbott, B. Braun Medical Inc., Philips. Other Relationship; Self; Amgen, Ancora Heart, Dai-ichi Life Insurance Company. M. Roden: Advisory Panel; Self; Servier. Board Member; Self; Poxel SA. Consultant; Self; Eli Lilly and Company, Gilead Sciences, Inc., ProSciento, TARGET PharmaSolutions. Research Support; Self; Boehringer Ingelheim International GmbH, Novartis Pharma K.K., Sanofi US. Speaker’s Bureau; Self; Novo Nordisk A/S. J. Szendroedi: None.

Funding
SFB 1116
22-OR: Increased Adverse Glycemia and Hospital-Acquired Infection following Withdrawal of the RAPIDS Early Intervention Model for Diabetes Care in Medical and Surgical Inpatients
Authors: KYI MERVYN , WANG JOANNA , WRAIGHT PAUL R. , COLMAN PETER G. , FOURLANOS SPIROS 
Published: June 2020

Background: We previously reported an early intervention model of diabetes care, whereby an inpatient diabetes team performed glycemic surveillance and provided proactive management within 24 hours of admission. In the RAPIDS cluster randomized study, early intervention decreased hyperglycemia and hospital-acquired infection (HAI) compared to usual care [Diabetes Care. 2019;42(5):832-40]. We investigated if improvements in ward glucose control and patient outcomes were sustained following the completion of proactive care intervention.
Methods: We performed a 3-month extension observational study on eight medical and surgical wards immediately following the completion of the RAPIDS study, recruiting consecutive inpatients with pre-existing diabetes or new hyperglycemia. Glycemic and clinical outcomes during the three time periods: baseline (usual care), active (proactive care), and extension (usual care) were compared.
Results: We analyzed 1518 inpatients (mean age 71y, 87% type 2 diabetes, 25% insulin-treated) and observed 8610 patient-days. In the intervention wards, during baseline, active and extension periods, patient-day mean glucose were: mean 9.4 (SD 3.3), 9.0 (2.7), and 9.4 (3.1) mmol/L (p&lt;0.001); and proportion of patient-days with mean glucose &gt;15 mmol/L were 7.3%, 3.3%, and 5.7% (p&lt;0.001). HAI rates paralleled hyperglycemia: 6.4% during baseline period, 2.4% active period (p=0.022 vs. baseline), and 5.4% extension period (p=0.056 vs. active). In the control wards there was no change in hyperglycemia or HAI rates.
Conclusion: Following withdrawal of proactive care with early intervention, hyperglycemia and HAI rates increased to baseline levels. Ongoing intervention with specialist diabetes care teams may be required to achieve sustained glycemic and clinical improvements in hospital.

Disclosure
M. Kyi: None. J. Wang: None. P.R. Wraight: None. P.G. Colman: None. S. Fourlanos: Advisory Panel; Self; Medtronic, Mylan, Sanofi. Speaker’s Bureau; Self; AstraZeneca, Novo Nordisk Inc.

Funding
Australian Diabetes Society; Sanofi; National Health and Medical Research Council of Australia (APP1093152); Royal Melbourne Hospital (GIA-030-2019, GIA-027-2016)
2201-PUB: The Combined Effect of Gender and Age on Remission Rate in Patients with Newly Diagnosed Type 2 Diabetes after Intensive Insulin Therapy
Authors: XUESI WAN , HUANG ZHIMIN , LIU LIEHUA , LI YANBING 
Published: June 2020

According to our previous study, short-term intensive insulin therapies(SIIT) can induce long-term remission from T2DM in half of the patients. It’s interesting that young male patients seem to recover better. In order to examine the combined effect of gender and age on remission of T2DM, an observation of 160 patients with newly diagnosed T2DM (n=160, 103 male, aged 50±10 ys, HbA1C 11±2.1%) after 2-week therapy were studied. Men and women differed in age with T2DM onset (47±10 ys vs. 54 ±9ys, Fig A.). The average remission time in a 5-year follow-up was 30 months for men and 21 months for women(Fig B.). But in the same age stage, the remission time was similar between male and female, as well as the improvement of HOMA-B and HOMA-IR by this therapy(Fig C., D., E.).There were no statistical gender differences in each age stage.
In conclusion, the gender differences in age of onset for T2DM affected the remission rate from T2DM after SIIT. The male often has diabetes earlier and was better to recover.

Disclosure
W. Xuesi: None. Z. Huang: None. L. Liu: None. Y. Li: None.

Funding
National Key Research and Development Program of China (2018YFC1314100)