bluuebunny/crossref_metadata_2025_split huggingface dataset:
2196-P: HB-EGF Signaling Is Required for Glucose-Induced Pancreatic ß-Cell Proliferation in Rats
Authors: MAACHI HASNA , SCOTT DONALD , GHISLAIN JULIEN , POITOUT VINCENT 
Published: June 2019

Background: Glucose is a major β-cell mitogen. Despite recent progress, the underlying mechanisms remain unclear. In a rat model of nutrient excess we previously showed that nutrient-induced β-cell proliferation is blocked when either EGF receptor (EGFR) or mTOR signaling is inhibited. Parallel transcriptomic analyses identified the EGFR ligand, HB-EGF as a potential mediator of nutrient-induced β-cell proliferation.
Objective: To determine the role of HB-EGF in glucose-induced β-cell proliferation.
Methods: HB-EGF mRNA levels were assessed by real-time PCR in isolated rat islets following a 24-h exposure to 2.8 or 16.7 mM glucose. The Carbohydrate-Responsive Element-Binding Protein (ChREBP) transcription factor was down-regulated by siRNA in dispersed rat islets. For β-cell proliferation studies islets were exposed to 16.7 mM glucose or HB-EGF (100 ng/ml) in the presence of 2.8 mM glucose for 72 h. Islets were co-cultured with the EGFR inhibitor AG1478 (300 nM) or the HB-EGF inhibitor CRM197 (10 ug/ml). shRNA was used to knockdown HB-EGF in isolated islets and either cultured ex vivo or transplanted under the kidney capsule of glucose-infused rats. β-cell proliferation was assessed by immunohistochemistry for Ki67 and insulin.
Results: Glucose increased HB-EGF mRNA levels and this was prevented by ChREBP knockdown. HB-EGF potently stimulated β-cell proliferation. Inhibition of the EGFR or HB-EGF completely blocked not only the proliferative response to HB-EGF but also the response to 16.7 mM glucose. Knockdown of HB-EGF blocked the β-cell proliferative response to glucose in isolated rat islets as well as in transplanted islets.
Conclusion: HB-EGF is a potent β-cell mitogen in rat islets. Glucose increases HB-EGF gene expression via ChREBP. The proliferative response to glucose requires an intact HB-EGF - EGFR pathway. Our findings identify a novel player in the complex mechanisms controlling β-cell proliferation in response to glucose.

Disclosure
H. Maachi: None. D. Scott: None. J. Ghislain: None. V. Poitout: None.

Funding
National Institutes of Health; Fonds de recherche du Québec-Santé
2200-PUB: Interest among T1D and T2D Patients Taking Insulin in Adding a New Drug Therapy to Prevent Nocturnal Hypoglycemia
Authors: LIGGINS RICHARD , PICHE CLAUDE , RIDDELL MICHAEL , WOOD RICHARD , PANG CHRISTIANNE , LAFONTAINE MARTIN , MIDMER MICHAEL 
Published: June 2019

Hypoglycemia (HG) and fear of HG are well-known problems for people using insulin, impacting quality of life, glycemic control, and health care cost. We evaluated patient perceptions of the unmet need of HG prevention in insulin users, exploring various patient aims in managing HG (Figure 1) via a survey of 637 T1D and T2D patients. Respondents rated the importance of each aim, and their current satisfaction in meeting them with current therapy. Compared to T2D, T1D patients (and also CGM users compared to non-users) had lower satisfaction with status quo for all aims except in managing meals. T1D and T2D placed greatest importance on avoiding waking due to nocturnal hypoglycemia (NH). Avoiding waking at night and reducing anxiety due to NH were identified as areas of high unmet need (low satisfaction, high importance) in both T1D and T2D (particularly those on MDI) while managing exercise and meals were prominent needs in T1D.
Although CGM technologies are becoming the standard of care for insulin users, and are a proven tool for warning of HG, CGM users have mixed feelings about HG alerts, especially in NH. Respondents were asked about their interest (4 point “intent to use” scale) in adding a drug to their existing regimen (insulin ± CGM) that would prevent NH. There was strong interest in adjunctive use of a therapy to prevent NH from all groups, and CGM users showed the greatest interest in an adjunctive therapy.

Disclosure
R. Liggins: None. C. Piche: Board Member; Self; Zucara Therapeutics Inc. Employee; Self; Locemia Solutions. Stock/Shareholder; Self; Beta Bionics, Bigfoot Biomedical, Biolinq, Capillary Biomedical, Inc., Diasome Pharmaceuticals, Inc. M. Riddell: Advisory Panel; Self; Xeris Pharmaceuticals, Inc. Consultant; Self; Lilly Diabetes. Research Support; Self; Dexcom, Inc., Insulet Corporation, Novo Nordisk Inc., Sanofi. Speaker's Bureau; Self; Medtronic MiniMed, Inc., OmniPod. Stock/Shareholder; Self; Zucara Therapeutics Inc. R. Wood: Other Relationship; Self; Multiple companies in the diabetes field (&gt;10 companies). C. Pang: Consultant; Self; dQ&A Market Research, Inc. M. Lafontaine: Consultant; Self; Diasome Pharmaceuticals, Inc., Metronom Health Europe, Montmed, Tolerion, Inc., Zucara Therapeutics Inc. Stock/Shareholder; Self; Locemia Solutions. Other Relationship; Self; 360 Marketing Strategic Services. M. Midmer: Employee; Self; Zucara Therapeutics Inc.

Funding
The Leona M. and Harry B. Helmsley Charitable Trust
2204-PUB: Risk Factors for Hypoglycemia in Older Adults: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: ECHOUFFO TCHEUGUI JUSTIN B. , DAYA NATALIE R. , PANKOW JAMES S. , WINDHAM B. GWEN , SELVIN ELIZABETH 
Published: June 2019

Background: Older adults with type 2 diabetes are at increased risk of hypoglycemia. However, risk factors for hypoglycemia among older adults with diabetes in the general population are largely uncharacterized.
Methods: We included 845 participants with diabetes who attended the recent ARIC visit 6 (2016-2017). An episode of hypoglycemia was defined as the occurrence of one or more self-reported episode of severe low blood sugar reactions in the previous year (i.e., passing out, needing help to treat the reaction). We also examined alternative definitions using both broader (feeling of unacceptably low blood glucose) and stricter (two or more episodes of severely low blood glucose) self-reported criteria. We used logistic regression to evaluate risk factors for hypoglycemia.
Results: The mean age of participants was 79 years (SD: 4.3), 37% were black and 58% were female. There were 53 episodes of hypoglycemia reported. In the fully adjusted analyses, insulin therapy, lipid lowering medication, and dementia were significantly associated with hypoglycemia. Blacks were less likely to experience hypoglycemia. Results were similar with alternative definitions of hypoglycemia definitions.
Conclusions: The identified factors may aid personalization of diabetes management that reduces hypoglycemia risk among older adults, particularly those with dementia, in whom de-escalating therapy may be needed.

Disclosure
J.B. Echouffo Tcheugui: None. N.R. Daya: None. J.S. Pankow: None. B. Windham: None. E. Selvin: None.
221-LB: Omega-3 plus Plant Sterols Regulate Glucose and Lipid Metabolism in Impaired Glucose Regulation Individuals: A Parallel, Double-Blind Controlled and Randomized Clinical Trial
Authors: RUIRONG PAN 
Published: June 2019

The balance of lipid metabolism has been recognized as one of the significant causes of impaired glucose metabolism in T2DM, which is steadily increasing worldwide. IGR plays a vital role in the prevention and treatment of T2DM. This study focused on roles of plant sterols (PS), omega-3 fatty acids or their combination on IGR individuals, moreover, further clarifying whether there is synergistic effect of combination PS with omega-3 fatty acids on the prevention and treatment of IGR through a randomized, double-blind, placebo-controlled, 2×2 factorial design trial. 200 participants consented were randomized to receive PS and omega-3 fatty acids (n=50), PS alone (n=50), omega-3 fatty acids alone (n=50) and placebo soy bean powder plus placebo capsules (n=50) for 12 weeks. To investigate the characteristics of body composition (weight, height, waistline, BMI, body fat rate, visceral fat rating), blood pressure, glucose metabolism (FPG, FINS, HOMA-IR, HbA1c), lipid metabolism (TG, TC, HDL-C, LDL-C) and inflammatory factors (Hs-CRP, IL-6) in IGR individuals. Compared with placebo group, the combined intervention significantly decreased TG, HDL-C, FBG, HOMA-IR and HbA1c. Omega-3 fatty acids alone led to significant reductions in waistline, TG, FBG, HOMA-IR and Hs-CRP. PS alone just decreased TG and Hs-CRP. No intervention produced significant changes in body weight, BMI, blood pressure, FINS, body fat rate, visceral fat rating, TC, LDL-C and IL-6.
In conclusion, we have demonstrated for the first time that PS, omega-3 fatty acids or their combination significantly improved inflammation, insulin resistance, as well as glucose and lipid metabolism in IGR individuals. And combinative interaction has better effects than single dietary supplement.

Disclosure
P. Ruirong: None.

Funding
Affiliated Hospital of Jiangsu University
221-OR: Pancreas Transplantation from Pediatric Donors: An Opportunity to Increase Donor Pool
Authors: CONTE CATERINA , SOCCI CARLO , SECCHI ANTONIO , MAFFI PAOLA 
Published: June 2019

Background: Pancreas transplants (PTx) from pediatric donors (PDs, age &lt;18 years) might expose to greater technical difficulties and provide less insulin independence in the long-term due to smaller beta cells mass. Most available data on pancreas transplants from PDs relate to simultaneous pancreas-kidney transplants, whereas little is known on pancreas transplant alone (PTA) from PDs.
Methods: We retrospectively analyzed perioperative surgical complications and graft survival in T1D recipients of PTA or pancreas after kidney (PAK) transplant from PDs or adult donors (ADs) between Jan 2010 and May 2018. Data were collected through electronic medical record review.
Results: A total of 43 PTx recipients (35 PTA) had data available for analyses. Age at PTx was 40.0±8.3 years, T1D duration 25±10 years, 46.5% female, BMI 23±3 k/m2. Nearly half (49%) pancreas grafts were from PDs. Median donor age was 18 [IQR: 16] years (min. 2, max 45 years). Donor characteristics (age, BMI, body surface area [BSA]) significantly differed between groups (all p&lt;0.05), but recipient characteristics (age at PTx, T1D duration, BMI) were similar. Median length of stay was similar in the AD and PD groups (17.5 [8.5] vs. 14 [7.0] days, p=NS). Rates of any perioperative surgical complications (55% vs. 33%), re-laparotomy (41% vs. 19%) and explanation (36% vs. 10%) were numerically lower and early graft thrombosis was significantly lower (55% vs. 10%, p&lt;0.01) in the PD group. Median graft survival was numerically greater in the AD vs. the PD group (8.5 vs. 5.7 years, p=0.34). However, rejection rate was significantly higher in the PD group (4.5% vs. 52%, p&lt;0.01). We found no correlation between donor characteristics (age, BMI, BSA and donor/recipient BSA ratio) and graft survival.
Conclusions: PTx from PDs tended to be associated with less surgical complications vs. PTx from ADs. Graft survival was similar. Expanding selection criteria to include PDs would increase the availability of pancreas grafts and possibly improve clinical outcomes.

Disclosure
C. Conte: None. C. Socci: None. A. Secchi: None. P. Maffi: None.
2211-PUB: Hand Grip Strength Predicts Mortality Independently from Type 2 Diabetes and the Presence of Coronary Artery Disease
Authors: LARCHER BARBARA , VONBANK ALEXANDER , HEINZLE CHRISTINE , ZANOLIN-PURIN DANIELA , MADER ARTHUR , SAID ABDURAHMAN , DREXEL HEINZ , SAELY CHRISTOPH H. 
Published: June 2019

Hand grip strength (HGS) is widely used as a simple, inexpensive and non-invasive diagnostic parameter for frailty and sarcopenia. Low HGS in community-dwelling populations has been reported to predict a higher mortality risk. Whether this association is independent from the presence of type 2 diabetes (T2DM) and pre-existing coronary artery disease (CAD) is not known and is addressed in the present study. We prospectively recorded deaths over a mean follow-up time of 9.2±3.1 years in a cohort of 845 subjects in whom the baseline CAD state was determined angiographically. At baseline, HGS was higher in male than in female participants (41.5±10.3 vs. 24.0±5.06 kg; p&lt;0.001); it did not differ significantly between patients with T2DM and nondiabetic subjects. Prospectively, low HGS predicted overall mortality both in men and women, with standardized adjusted HRs of 0.90 [0.83-0.99]; p=0.035 and HR 0.65 [0,50-0,82]; p&lt;0.001 after multivariate adjustment including T2DM and the presence of CAD at baseline. We conclude that low hand grip strength predicts mortality independently from T2DM and the presence of CAD.

Disclosure
B. Larcher: None. A. Vonbank: None. C. Heinzle: None. D. Zanolin-Purin: None. A. Mader: None. A. Said: None. H. Drexel: None. C.H. Saely: None.
2214-PUB: Cytokine Profile in Patients with Type 2 Diabetes Mellitus and Evolution of ST-Elevation Acute Myocardial Infarction of Buryat Ethnic Group
Authors: BARDYMOVA TATIANA , PROTASOV KONSTANTIN , BELOCHVOSTIKOVA TATIANA , TSYRETOROVA SESEG , MISTIAKOV MAKSIM , DONIROVA OYUNA , BEREZINA MARINA 
Published: June 2019

Inflammatory processes during type 2 diabetes mellitus (T2D) and evolution of ST-elevation acute myocardial infarction (STEMI) are different in various ethnic groups. Buryats are the main northern group of Mongolians, they are a core population of Siberia.
We have examined the associations between cytokines and high sensitivity C-reactive protein (hs-CRP) in 14 patients (36% males) with T2D and STEMI of Buryat ethnic group (60 years, diabetes duration 7.9 years, A1c 8.0%); in 21 Caucasian patients (48% males) with T2D and STEMI (60 years, diabetes duration 8.0 years, A1c 7.9%); in 13 patients (77% males, 59 years) with STEMI without T2D of Buryat ethnic group and 18 Caucasian patients (72% males, 61 years) with STEMI without T2D.Buryat patients with T2D and STEMI had higher hs-CRP and lower interleukin-8 (IL-8) and interleukin-10 (IL-10) compared to Buryat patients with STEMI without T2D. Caucasian patients with T2D and STEMI had higher hs-CRP and lower tumor necrosis factor alpha (TNF-α) compared to Caucasian patients with STEMI without T2D. Buryat patients with T2D and STEMI had lower interleukin-6 (IL-6), IL-8, IL-10 and hs-CRP compared to Caucasian patients with T2D and STEMI. We have determined decreased secretion of cytokines and hs-CRP in patients with T2D and STEMI of Buryat ethnic group compared to Caucasian patients.

Disclosure
T. Bardymova: None. K. Protasov: None. T. Belochvostikova: None. S. Tsyretorova: None. M. Mistiakov: None. O. Donirova: None. M. Berezina: None.
222-LB: Islet Dysfunction and Progression of NAFLD in Diabetic Patients: Islet-Liver Cross Talk from Metal Study
Authors: WANG NINGJIAN , WANG YUYING , ZHANG WEN , CHEN YI , CHEN XIAOMAN , WANG CHIYU , LU YINGLI 
Published: June 2019

Objectives: Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in type 2 diabetes, thus crosstalk between islet cells (mainly α and β cells) and liver is suspected. We aim to investigate whether islet dysfunction (evaluated by C-peptide and glucagon) associates with NAFLD progression in Chinese type 2 diabetic adults.
Methods: 4,937 diabetic participants were enrolled from Shanghai, China in 2018. Liver steatosis was detected by ultrasound. Subjects with NAFLD were categorized into simple NAFLD and probable nonalcoholic steatohepatitis (NASH) by the presence of metabolic syndrome. NAFLD fibrosis score was used to identify patients with higher likelihood of bridging fibrosis (stage 3) or cirrhosis (stage 4). Regression analyses were used.
Results: With longer history of type 2 diabetes, individuals were prone to have lower C-peptide, relatively stable glucagon, lower prevalence of probable NASH and higher prevalence of significant fibrosis. C-peptide was positively associated with simple NAFLD and probable NASH, with the ORs of 4.55 (95% CI 3.16, 6.55) and 5.28 (95% CI 3.94, 7.09), comparing quartile 4 with quartile 1 (both P for trend &lt;0.001). Unlike C-peptide, glucagon quartiles were negatively associated with probable NASH (P for trend &lt;0.05). Moreover, 1SD increment of ln(C-peptide/glucagon) was significantly associated with progression ranging from non-NAFLD, simple NAFLD to probable NASH (OR 1.26, 95% CI 1.21, 1.32). Furthermore, 1SD increment of ln(C-peptide), but not glucagon and C-peptide/glucagon ratio, was significantly and negatively associated with fibrotic progression (OR 0.88, 95% CI 0.79, 0.98).
Conclusion: Significant associations were observed among C-peptide, glucagon, C-pepide/glucagon ratio and inflammatory and fibrotic progression of NAFLD. Further understanding the crosstalk among α and β islet cells and liver tissue may help to personalize treatment strategies of NAFLD patients with type 2 diabetes.

Disclosure
N. Wang: None. Y. Wang: None. W. Zhang: None. Y. Chen: None. X. Chen: None. C. Wang: None. Y. Lu: None.

Funding
National Natural Science Foundation of China; Science and Technology Commission of Shanghai Municipality; Commission of Health and Family Planning of Pudong District; Shanghai Municipal Commission of Health and Family Planning
2226-PUB: A Survey of Primary Care Physicians (PCPs): Knowledge of Cardiovascular Outcomes Trials and Treatment Implications
Authors: DAILEY GEORGE E. , PAK JONATHAN , SHUBROOK JAY H. 
Published: June 2019

Background: Cardiovascular outcomes trial (CVOT) results have led to changes in diabetes position statements and indications for some glucose-lowering agents. This study aimed to understand PCPs’ knowledge of CVOTs and beliefs about T2D medications for CV disease (CVD).
Methods: WebMD, LLC fielded a 23-item online survey from Sept 18-20, 2018 to 47,534 Medscape members who were randomly selected across U.S. internal medicine and family PCPs (quota=500).
Results: Overall, 503 of 702 PCPs were eligible and completed the survey. Overall, 39% of respondents were slightly/not at all familiar with the 2018 ADA treatment recommendations for those with T2D and atherosclerotic CVD (ASCVD). Many respondents did not know which CVOT showed superiority for major adverse CV events (26%) or CV mortality (31%). PCPs were most familiar with TECOS and LEADER and least familiar with EXAMINE. Also, 24-58% did not know which CVOTs showed an increased risk of AEs (e.g., amputation, genital infection, pancreatitis, retinopathy, etc.). The main challenges PCPs experienced using T2D agents with CV benefits included insurance coverage (75%), cost (73%), and formulary changes (61%). Using T2D medications with CV benefits was ranked the least important treatment priority by 33% (P&lt;.05; Figure).
Conclusions: PCPs have knowledge gaps and treatment barriers using T2D medications for patients with T2D and ASCVD.

Disclosure
G.E. Dailey: Research Support; Self; Eli Lilly and Company, Novo Nordisk Inc., Sanofi US. Speaker's Bureau; Self; Sanofi US. J. Pak: Employee; Self; Boehringer Ingelheim Pharmaceuticals, Inc. J.H. Shubrook: Advisory Panel; Self; Intarcia Therapeutics, Inc. Consultant; Self; Eli Lilly and Company, Novo Nordisk Inc.

Funding
Boehringer Ingelheim; Eli Lilly and Company
2229-PUB: Comparison of Cardiovascular (NTProBNP) and Renal Biomarkers in 280 T2DM Patients with Microalbuminuria vs. Normoalbuminuria
Authors: GUPTA VISHAL , TELI VAISHALI 
Published: June 2019

Methodology: 280 T2DM patients aged 18-75 years irrespective of their A1c, on standard glucose lowering, lipid lowering and BP lowering therapy were divided into 2 groups, group 1N (105 patients normoalbuminuria UACR &lt;30) and group 2M (175 patients microalbuminuria eUACR &gt;30). Both groups were followed-up for 2 years and assessed every 3-6 months for for renal (creatinine, eGFR, UACR) and CV (BP, BMI, Lipid profile, hs-CRP, NTProBNP) parameters. Patients with history of major surgery, coronary intervention, IHD or hospitalization in last 1 year, eGFR &lt;45, potassium &gt;5.3 were excluded. Data was analyzed using PSPP version 1.0.1 and represented as Mean (SD) and paired t-test was used, P-value of 0.01 was considered to be significant.
Results: Baseline treatment characteristics were well matched. For BP, use of ARB was 82.9% (1N) and 96.1% (2M) group, CCB was 35.2% (1N) and 61.2% in (2M) group. At Baseline SBP (2M 139.17±22.35 vs. 1N 131.91 ±14.66, p&lt;0.001), Cr (2M 1.02 ±0.29 vs. 1N 0.91 ±0.23, p&lt;0.001), UACR (2M 429.69 ±1214.86 vs. 1N 11.08 ±5.87), Non-HDL (2M 101.29 ±44.5 vs. 1N 85.83 ±30.87, p-0.001 were higher in 2M group. In both group there was a significant reduction in A1c, TC, LDL, TG, non-HDL, hsCRP. In addition, mean chol remnant 12.56 (95% CI 8.60-16.51 p &lt;0.001) and UACR 215.97 (95% CI 88.70-343.23, p-0.001) reduced significantly in 2M group. At the end of 2 years mean SBP (2M 135.9 ±17.34 vs. 1N 128.58 ±15, p&lt;0.001), potassium (2M 4.63 ±0.5 vs. 1N 4.46 ±0.44, p-0.007), UACR (2M 218.82 ±622.48) vs. 1N 11.80 ±7.54) was higher in 2M group. The NTproBNP was elevated in both groups (1N 136.57 ±202.14 vs. 2M 176.40 ±252.38, p-0.17).
Conclusion: Patients with eUACR had a significantly elevated SBP, non-HDL cholesterol, and creatinine, compared to nUACR at baseline. Despite CV risk factor optimization systolic-BP remained significantly higher in eUACR group. NTProBNP remained high in both groups although it trended to be slightly elevated in eUACR group although it was statistically NS.

Disclosure
V. Gupta: None. V. Teli: None.
2235-PUB: Detection and Validation of Hidden Driven Networks in Diabetic Microangiopathy
Authors: CHEN YANMING , LI HAICHENG , GUAN DAOGANG 
Published: June 2019

Aim: To find the molecular interact network specific for different diabetic microangiopathy complications that will direct us to research the mechanism involved in the pathological process of those complications. At present, the plentiful multiomics data of microvascular complications allow us to construct multidimentional regulator network for different microvascular complications from a integrated system perspective. In this study, we introduced hierarchical Bayesian Mode, drivenRN, to decode multi-regulation that form inner regulatory networks in different microvascular complications by combining multi-regulator and transcriptional kinetics into one single model framework, drivenRN can naturally integrate gene expression data and regulator-binding signals in order to identify the hidden driven networks and to detect the key function gene signature. Our study finds out the specific driven networks related to diabetic nephropathy, diabetic retinopathy and diabetic feet respectively. These complication specific driven networks not only offer a new kind biomarker for susceptible patients’ identification but also help us to research the pathological process of microvascular complications systematically. Then offer potential therapy targets and forewarning mechanisms for clinical practice.
Figure 1. The Specific Driven Networks for Different Microvascular Complications of Diabetes Mellitus.

Disclosure
Y. Chen: None. H. Li: None. D. Guan: None.

Funding
National Key Research and Development Program of China (2017YFA0105803); National Natural Science Foundation of China (81770826); Sun Yat-sen University (2015015); Science and Technology Plan Projects of Guangdong Province (2016A050502010); Key Special Projects of Medical and Health Collaborative Innovation of Guangzhou City (201604020016); Special Scientific Research Project of Guangzhou City (2060404)