bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of mixture velocity for given equivalence ratio on flame development in Swiss roll combustor
Authors: Mane Deshmukh Sagar , Arunagiri Krishnamoorthy , Bhojwani Virendra
Published: June 2019

Small-scale power generation using heat energy from hydrocarbon fuels is a proven technology. In this study, we analyzed 2-D flame development in meso-scale Swiss roll combustor. A mixture of 60% butane and 40% propane was used (0.25?0.55 L per minute). During all the analyses, equivalence ratio (1.1) was kept constant by adjusting air quantity against fuel quantity. The effect of increase in the mixture velocity on the development of flame shapes/patterns was monitored. We found different patterns of flame, e. g., planar, concave, and conical, with the increase in mixture velocity. Increase in combustion chamber temperature was also noted. No flashback was observed and blowout was observed with very high mixture velocity. Combustion chamber temperatures were found to be increasing with the increase in mixture velocity at the same equivalence ratio. Elongation of the flame was observed because of the increased flow velocity. Heat re-circulation to the reactants enhances flame characteristics.
Experimental investigation on packed bed cool storage system for supply-demand management in building air-conditioning system suitable for micro thermal grid
Authors: Narayanasamy Rajamani , Vellaichamy Pandiyarajan , Sharma Mangat , Ramalingam Velraj
Published: June 2019

In most of the developed nation, the increase in percentage share of renewable power in the total power generation causes major concerns over the integration of these renewable power with the grid resulting grid instability. Energy storage is a new frontier technology which is considered as the ultimate solution in developing micro-smart grid with distributed renewable power generation. Most of the hot countries like India spend nearly 24% of the electricity generated on air-conditioning and food preservation. Under such scenario, among the various types of storage systems, the cool thermal storage plays a vital role to promote renewable power in an economical way. Considering the importance in the present renewable energy scenario, in the present work, an experimental investigation was performed on a packed bed cool storage system integrated with a chiller system which has major advantages in central air-conditioning system for demand management strategies. The storage system consists of encapsulated spherical balls filled with a mixture of distilled water and pseudomonas (nucleating agent) as phase change material and a mixture of distilled water and mono-ethylene glycol as heat transfer fluid. The essential parameters such as reduction in subcooling, instantaneous, and cumulative heat transfer during the charging process are presented for the efficient operation.
Transition towards a sustainable heating and cooling sector - case study of southeast European countries
Authors: Rutz Dominik , Worm Jakob , Doczekal Christian , Kazagic Anes , Duic Neven , Markovska Natasa , Batas-Bjelic Ilija , Sunko Rok , Tresnjo Dino , Merzic Ajla , Doracic Borna , Gjorgievski Vladimir , Janssen Rainer , Redzic Elma , Zweiler Richard , Puksec Tomislav , Sunko Blaz , Rajakovic Nikola
Published: June 2019

Many traditional heating systems which are based on fossils face challenges such as lack of investment or unfavorable price regulations, low technical performance, environmental impacts and negative consumer perceptions. The CoolHeating project which is, funded by the EU?s Horizon 2020 programme and presented in this paper promotes the implementation of small modular renewable heating and cooling grids for communities in South-Eastern Europe. Core project activities bincluded measures to stimulate the interest of communities and citizens to set-up renewable district heating systems in five target communities in Slovenia, Croatia, Bosnia and Herzegovina, Serbia, and North Macedonia up to the investment stage. Single criteria and multi-criteria assessment approaches, considering economic, environmental and social indicators of the targeted projects, have been applied in this work in order to investigate opportunities for the sustainable transition of the heating and cooling sectors of the target communities of Southeast Europe. Both approaches confirm the feasibilities of the transition from traditional to renewable energy-based heating systems for each target community in the countries of South-Eastern Europe. After simulation and replication of the results, the sustainability analysis indicatively shows that the transitions from traditional fossil-based, poor-maintained, and difficult-to-manage heating systems towards renewable district heating and cooling systems in Southeast Europe are sustainable solutions. Having in mind the modularity of such systems, those solutions can be replicated in other Southeast European cities and other countries.
1003-P: Clinical Response (HbA1c ≥1% and/or Body Weight ≥5% Reduction) to Semaglutide by Baseline HbA1c and Body Weight in the SUSTAIN Program
Authors: ARODA VANITA R. , LARSEN JULIE F. , ØSTOFT SIGNE HARRING , REA ROSANGELA R. , SUGIMOTO DANNY , ZIEGLER UWE , VILSBØLL TINA
Published: June 2019

The SUSTAIN clinical development program assessed semaglutide once weekly, a glucagon-like peptide-1 (GLP-1) analog, across the continuum of type 2 diabetes (T2D) care, including in drug-naïve subjects and those on a background of oral antidiabetic drugs and/or insulin. Semaglutide demonstrated superior reductions in HbA1c and body weight (BW) vs. placebo and comparators (sitagliptin, exenatide extended release, insulin glargine, dulaglutide). This post hoc analysis assessed the proportion of semaglutide-treated subjects achieving clinically relevant responses (composite endpoint: ≥1% HbA1c reduction and ≥5% BW loss; individual components: ≥1% HbA1c or ≥5% BW loss) by baseline HbA1c and BW across SUSTAIN 1-5 and 7. A consistently high proportion of semaglutide-treated subjects achieved clinically relevant responses (composite, 42.0%; ≥1% HbA1c reduction, 76.6%; ≥5% BW loss, 49.9%), regardless of baseline HbA1c and BW (Figure). Baseline HbA1c and BW did not affect the likelihood of achieving the composite and ≥5% BW endpoints. A ≥1% HbA1c reduction was significantly more likely to be achieved with higher baseline HbA1c (143% increased odds per 1% unit higher baseline HbA1c;p<0.0001). Semaglutide provides meaningful reductions in HbA1c and BW across a range of HbA1c and BW. Individuals with poorly controlled HbA1c were more likely to achieve a ≥1% HbA1c reduction.

Disclosure

V.R. Aroda: Consultant; Self; ADOCIA, AstraZeneca, Becton, Dickinson and Company, Novo Nordisk Inc., Sanofi, Zafgen, Inc. Employee; Spouse/Partner; Merck & Co., Inc. Research Support; Self; AstraZeneca, Calibra Medical, Eisai Inc., Janssen Research & Development, Novo Nordisk Inc., Sanofi, Theracos, Inc. J.F. Larsen: Employee; Self; Novo Nordisk A/S. S.H. Østoft: Employee; Self; Novo Nordisk A/S. R.R. Rea: Other Relationship; Self; Amgen Inc., AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Novo Nordisk A/S, Sanofi. D. Sugimoto: Research Support; Self; Gan & Lee Pharmaceuticals, Novo Nordisk A/S, Sanofi. U. Ziegler: Employee; Self; KOEHLER eClinical GmbH, Freiburg im Breisgau, Germany. T. Vilsbøll: None.

Funding

Novo Nordisk A/S
101-OR: Identification of Warm Sensitive Neurons in the Hypothalamic Preoptic Area as Powerful Regulators of Glucose Homeostasis
Authors: DEEM JENNIFER D. , OGIMOTO KAYOKO , NELSON JARRELL , PHAN BAO ANH N. , VELASCO KEVIN R. , DAMIAN VINCENT , KNIGHT ZACHARY , SCHWARTZ MICHAEL W. , MORTON GREGORY J.
Published: June 2019

Inhibition of warm sensitive neurons (WSNs) in the hypothalamic preoptic area (POA) has been suggested to play a key role in the thermogenic response to cold exposure. As this response is enabled by a marked increase of insulin sensitivity in thermogenic tissues, we hypothesized that 1) WSN inhibition mediates metabolic as well as thermogenic responses to cold, and therefore, 2) WSN activation has the opposite effects. To test this hypothesis, we utilized DREADD technology to activate or inhibit a recently identified subpopulation of POA WSNs defined by their expression of the neuropeptide, Pacap, using the drug clozapine-N-oxide (CNO). We report that, pharmacogenetic activation of this POA WSN population found significant reductions in energy expenditure (Sal vs. CNO: 0.32±0.10 vs. 0.21±0.02 kcal/hr; p<0.05) and, as previously reported, core temperature (Tc) (Sal vs. CNO: 35.4±0.1 vs. 30.4±0.1C; p=0.0001). Further, the response to pharmacogenetic activation was quite long-lived (∼2-3 days) and was accompanied by severe glucose intolerance both 1h and 24h following a single injection of CNO relative to vehicle (glucose AUC: 3610±1216 for Sal vs. 23985±2742 for 1h CNO; 28459±2411 for 24h CNO au; p<0.05 vs. saline), an effect that occurred despite a compensatory increase of glucose-induced insulin secretion at the 24h (but not the 1h) time point (p<0.05 vs. Sal). Thus, activation of POA Pacap+ WSNs is sufficient to reduce thermogenesis and impair glucose tolerance. Conversely, we found that inhibition of POA Pacap+ neurons in chow-fed mice led to a modest but significant increase in Tc (Sal vs. CNO: 35.4±0.1 vs. 35.9±0.1C; p=0.01) and whereas glucose tolerance was not improved in these animals, it was improved by POA Pacap+ neuron inhibition in mice with diet-induced obesity (glucose AUC: 9630±571 for Sal vs. 7517±628 for CNO au; p<0.05). We conclude that POA Pacap+ neurons constitute a subset of WSNs with profound and previously unrecognized effects on glucose homeostasis.

Disclosure

J.D. Deem: None. K. Ogimoto: None. J. Nelson: None. B.N. Phan: None. K.R. Velasco: None. V. Damian: None. Z. Knight: None. M.W. Schwartz: Consultant; Self; Novo Nordisk A/S. Research Support; Self; Novo Nordisk A/S. G.J. Morton: None.

Funding

University of Washington Diabetes Research Center
1010-P: Effects of MEDI0382, an Oxyntomodulin-Like Peptide with Targeted GLP-1/Glucagon Receptor Activity, on Amino Acids, Ketones, and Free Fatty Acids
Authors: PARKER VICTORIA E. , ROBERTSON DARREN , WANG TAO , HORNIGOLD DAVID C. , POSCH MAXIMILIAN G. , PLUM-MOERSCHEL LEONA , MEIER JURIS J. , SCHLICHTHAAR HEIKE , KLAUS BEATE M. , JERMUTUS LUTZ , AMBERY PHILIP , HIRSHBERG BOAZ
Published: June 2019

Background: MEDI0382 is an oxyntomodulin-like peptide with targeted GLP-1/glucagon receptor activity under development for type 2 diabetes mellitus (T2DM). GLP-1 has been shown to promote glucose-dependent insulin release, delay gastric emptying, and suppress appetite. Glucagon has similar effects on appetite and gastric emptying and enhances energy expenditure by upregulating energy-expensive processes such as gluconeogenesis and fatty acid oxidation.

Methods: This exploratory component of a phase 2a study measured fasting amino acid, β-hydroxybutyrate, and free fatty acid levels in overweight or obese T2DM patients randomized to once-daily SC MEDI0382 (n = 26) or placebo (n = 13) for 49 days. Doses were up-titrated weekly from 50 to 300 µg; measurements were taken at baseline and after 49 days of dosing.

Results: A significant decrease from baseline to day 49 with MEDI0382 vs. placebo in alanine was observed (-0.5 vs. 0.4 mg/dL; P = 0.017). Numerical reductions in other amino acid levels, including glutamate, cystine, valine, lysine, and tyrosine, were also seen. There were no clinically or statistically significant changes from baseline to day 49 between treatment groups in β-hydroxybutyrate or free fatty acid levels.

Conclusion: Despite the known effects of glucagon on fatty acid oxidation, MEDI0382 had no effect on ketogenesis or free fatty acids. Although the reason for this is unclear, enhanced insulin secretion may have counter-regulated this effect. MEDI0382 did promote reductions in key glucogenic amino acids, and this reduction could be related to increased gluconeogenesis and therefore glucagon receptor engagement. Similar patterns of amino acid reduction have been observed after bariatric surgery and have been attributed to excess circulating glucagon. We postulate that upregulation of an energy-consuming process such as gluconeogenesis could contribute to significant weight loss in subjects dosed with MEDI0382.

Disclosure

V.E. Parker: Employee; Self; MedImmune. Stock/Shareholder; Self; AstraZeneca. D. Robertson: Employee; Self; AstraZeneca. Employee; Spouse/Partner; GlaxoSmithKline plc. Stock/Shareholder; Self; AstraZeneca. T. Wang: Employee; Self; MedImmune. D.C. Hornigold: Employee; Self; AstraZeneca. Stock/Shareholder; Self; AstraZeneca. M.G. Posch: None. L. Plum-Moerschel: None. J.J. Meier: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi. H. Schlichthaar: None. B.M. Klaus: None. L. Jermutus: Employee; Self; AstraZeneca. Stock/Shareholder; Self; AstraZeneca. P. Ambery: Employee; Self; AstraZeneca. B. Hirshberg: Employee; Self; AstraZeneca.

Funding

AstraZeneca
1011-P: Therapeutic Potential of Novel Combination of a Long-Acting Glucagon Analog (HM15136) and Antidiabetic Drugs for the Treatment of Obesity
Authors: PARK YOUNG JIN , LEE JONG SUK , KIM JUNG KUK , KIM DAEJIN , KIM YOUNG HOON , IN YOUNG CHOI
Published: June 2019

The obesity epidemic represents a major challenge for public health. However, existing anti-obesity drugs have limited efficacy because they only suppress appetite, emphasizing the development of next generation therapeutic option. Recently, we showed that prolonged glucagon (GCG) receptor activation with HM15136, a long-acting GCG analog, could provide potent body weight loss (BWL) in obese animal models. Considering the stimulatory effect of GCG on glucose production, transient blood glucose (BG) elevation might be important when utilizing HM15136 as a novel anti-obesity drug. Antidiabetic drugs such as metformin, and DPP-4 inhibitor have been widely used for T2DM patients. Considering their safety profile and treatment adherence in addition to BG lowering nature, we hypothesized that combination of antidiabetic drugs might minimize the transient BG elevation by HM15136 and confer additional BWL. To investigate this hypothesis, the present study evaluated the combination effect of HM15136 and antidiabetic medication on BG and BW in vivo. In normal mice, HM15136-induced BG increase was effectively reversed by concomitant treatment of metformin, sitagliptin, or empagliflozin. To further confirm, DIO mice were chronically administered with HM15136 and/or antidiabetic drugs, and normal BG control was continuously maintained in COMBO groups. These results indicate that when combined, antidiabetic drugs could effectively counteract the transient BG elevation by HM15136. As to the BWL efficacy, combination of HM15136 either with metformin, sitagliptin, or empagliflozin provided additional BWL (-18% to -31% by metformin COMBO; -35% to -47% by sitagliptin COMBO; -35% to -40% by empagliflozin COMBO), highlighting the therapeutic benefit of this novel combination.

In conclusion, our results demonstrate the prolonged GCG receptor stimulation with antidiabetic medication as a novel therapeutic option for obesity treatment.

Disclosure

Y. Park: None. J. Lee: None. J. Kim: None. D. Kim: None. Y. Kim: None. I. Choi: Employee; Self; Hanmi Pharm. Co., Ltd.
1012-P: The Factors Influencing the Changes of Adipocytokines in Patients with Newly Diagnosed T2DM Treated with Exenatide
Authors: DENG HONG RONG , XU WEN , YANG XUBIN , ZENG LONGYI , YAO BIN , WENG JIANPING
Published: June 2019

Background: Previous studies found that adipocytokines could be altered by exenatide in patients with newly diagnosed T2DM. Whether the changes of the metabolic indices induced by exenatide have impacts on adipocytokines is still unclear. Thus, this study aimed to investigate the factors influencing the changes of leptin and adiponectin, two important adipocytokines in the pathogenesis of T2DM, in patients with newly diagnosed T2DM treated with exenatide.

Methods: In this multicenter prospective study, drug-naive patients with newly diagnosed T2DM were treated with exenatide for 48 weeks. The anthropometric data, HbA1c, β-cell function, insulin resistance, leptin, and adiponectin were assessed at baseline and at the end of the study.

Results: One hundred and ten patients completed the study. HbA1c, HOMA-IR and acute insulin response were improved significantly (P<0.001). Body weight and body mass index (BMI) were significantly reduced (P<0.001). Adiponectin significantly increased [5613(3353∼8352) to 7774 (4350∼12207) ng/ml, median(interquartile), P<0.001], while leptin non-significantly increased [3308(1528∼5138) to 3395(1480∼5076) pg/ml, P=0.401]. The change of leptin [∆leptin: 160 (-486∼1226) pg/ml] was significantly correlated with the change of BMI and weight [∆BMI: -1.1(-2.0∼-0.4) kg/m2, r= 0.4, P=0.02; ∆weight: -3.0 (-5.7∼-1.0) kg, r=0.3, P=0.03, respectively]. ∆adiponectin was correlated with the change of HOMA-B (r= -0.4, P=0.04), but not with ∆BMI or ∆weight. Multiple linear regression using the anthropometric data or laboratory indices as independent variables and ∆leptin and ∆adiponectin as dependent variables showed that ∆leptin was independently associated with ∆weight (B= 380.8, 95% CI: 34.3∼ 727.3, P=0.032) after adjusting for the change of HbA1c, while ∆adiponectin was not.

Conclusions: The change of leptin might be influenced by the weight loss but not the hypoglycemic effect induced by exenatide in newly diagnosed T2DM.

Disclosure

H.R. Deng: None. W. Xu: None. X. Yang: None. L. Zeng: None. B. Yao: None. J. Weng: None.

Funding

National Natural Science Foundation of China (81770821 to W.X.)
1022-P: Quantitative and Qualitative Effect of Dulaglutide in Type 2 Diabetes Patients Under Treatment with Liraglutide
Authors: SOTIROPOULOS ALEXIOS , KOUTSOVASILIS ANASTASIOS , ANTONIOU ANASTASIA , BOUSBOULAS STAVROS , PEPPAS THEODOROS
Published: June 2019

Background: Liraglutide and dulaglutide are long-acting GLP-1 receptor agonists. Dulaglutide is used once a week, while liraglutide once a day.

Aim: The aim of the study was to investigate dulaglutide’s quantitative and qualitative effect in patients, who used to take liraglutide independently of their glycemic control.

Material and Methods: 124 patients in liraglutide treatment were included in the study and switched to dulaglutide. Patients were taking the same medication before study for at least 6 months. The switch to dulaglutide was made on patients with HbA1c < 7% (Group A) and on patients with HbA1c > 7% (Group B). Parameters of glycemic control (HbA1c, Fasting Blood Glucose -FBG) and cardiovascular risk factors were recorded, while treatment satisfaction was evaluated with the Diabetes Treatment Satisfaction Questionnaire (DTSQ). Follow-up period was 24±2 weeks.

Results: Patients’ age was 57.65±7.43 years. A reduction of HbA1c was noticed on both groups. Group B’s HbA1c was reduced on the 3 and 6 month monitoring compared to the baseline (7.78±0.93 vs. 7.26±1.09 vs. 7.05±0.93, p= 0.001) and so was Group A’s on the same monitoring times (6.52±0.82 vs. 6.33±0.96 vs. 6.05±0.77, p=0.014). Body weight was also reduced on Group B (112.26 ±18.15 vs. 109.76±22.67 vs. 106.86±19.78, p=0.048), while Group A did not show any statistically significant difference (98.39±18.15 vs. 95.54±21.18 vs. 94.76±20.66, p=0.155). No change on blood pressure was noticed on Group A (p= 0.435) and Group B (p= 0.631). Treatment satisfaction was improved as evaluated via DTSQ on both Group A (p = 0.038) and Group B (p= 0.022) with a greater improvement in Group B.

Conclusions: Switching patients from liraglutide 1.2mg to dulaglutide 1.5mg leads to a significant reduction of HbA1c even in patients with HbA1c < 7% and to an improvement of the body weight in patients who have not achieved glycemic control. Patients under treatment with dulaglutide are more satisfied with their regimen.

Disclosure

A. Sotiropoulos: None. A. Koutsovasilis: None. A. Antoniou: None. S. Bousboulas: None. T. Peppas: None.
1030-P: Effect of MEDI0382 on the Pharmacodynamics and Pharmacokinetics of Warfarin or Esmolol in Healthy Volunteers
Authors: COLEMAN HUGH A. , PETRONE MARCELLA , PETROHOY THERESA M. , YANG YE , SANFORD LINDSAY J. , HANSEN LARS , FLOR ARMANDO
Published: June 2019

MEDI0382 is an oxyntomodulin-like peptide with targeted GLP-1 and glucagon receptor activity under development for T2DM treatment. Patients with T2DM have a high risk for cardiovascular disease. In an open-label, crossover, phase 1 study (NCT03347968), we evaluated the effect of MEDI0382 (SC; titrated up to 300 µg for 25 days) on the pharmacodynamics (PD) and PK of warfarin (PO; 25 mg on day [d] 2 [warfarin alone] and d 27 [warfarin + MEDI0382]) and PD of esmolol (IV; 200 µg/kg/min for 90 min on d 1 [esmolol alone] and d 26 [esmolol + MEDI0382]) in healthy volunteers (N = 22). Coprimary endpoints were prothrombin time (PT) maximum international normalized ratio (INRmax) and INRAUC of warfarin with MEDI0382, and change in heart rate from rest to after a 9-minute treadmill test (Bruce Protocol) with esmolol and MEDI0382. The coprimary endpoints were analyzed using paired t-tests. INRmax and INRAUC values were log transformed for analysis. MEDI0382 had no effect on PT INRmax, INRAUC (Table), or the PK profile of warfarin. Similar changes in heart rate with the treadmill test were observed with esmolol alone or with esmolol and MEDI0382 (Table). MEDI0382 resulted in an increased incidence of nausea and vomiting. There were no serious or severe adverse events. These results support co-administration of MEDI0382 and warfarin or esmolol and do not suggest safety concerns.

Disclosure

H.A. Coleman: None. M. Petrone: Employee; Self; MedImmune. T.M. Petrohoy: None. Y. Yang: Employee; Self; MedImmune. L.J. Sanford: None. L. Hansen: Employee; Self; AstraZeneca, MedImmune. Stock/Shareholder; Self; Bristol-Myers Squibb Company, Novo Nordisk A/S. A. Flor: Employee; Self; AstraZeneca.
1031-P: Impact of the Cardioprotective Effects of GLP-1 Agonists in the Management of Diabetes
Authors: MAHAPATRA SHAYAN S. , MILLA-MATUTE CRISTIAN , VILLABONA CARMEN V. , CARABALLO LUIS
Published: June 2019

Introduction: Cardiovascular disease is the principal cause of mortality in the diabetic population. Diabetic-cardiomyopathy increases the risk of heart failure in diabetics independently of coronary artery disease. It is characterized by ventricular dilation, myocardial fibrosis and steatosis. ELIXA, LEADER and SUSTAIN-6 trials have shown decrease in adverse cardiac events with a particular GLP-1 agonist. The aim of this study is to analyze if GLP-1 agonist improves ventricular diastolic function after 6 months of therapy.

Methods: Under IRB approval, a retrospective chart review was performed on 107 patients. (EG). Experimental group of (53) patients received GLP-1agonist and (CG)Control group (54)patients that did not receive GLP-1agonists. Inclusion criteria were DM2, age 40-60 years, 6-months GLP-1 therapy and at least 1 baseline echocardiogram. Statistical analysis were performed for data evaluation.

Results: From the population studied, female was the most prevalent gender with 58.8%(63), the mean-age was 57±6.7y/o, and the most common ethnicity Caucasian 67.2%(72). The most prevalent GLP-1 used were; Liraglutide(26.5%), Exenatide(11.2%), Dulaglutide(6.8%) and Albiglutide(1.1%). When comparing echocardiogram parameters, we found; the ejection fraction in the EG was 58±12% at baseline vs. 57±8% at six-month, Lateral-Mitral E/e’ ratio 10.3±3.8 vs. 11.35±5.2, Septal-Mitral E/e’ 13.4±5.4 vs. 14.3±6.3 and Mitral E/a’ 1.1±0.5 vs. 1.07±0.5. When analyzing the (CG) echocardiogram parameters, we found that the Ejection fraction at baseline was 60±8% vs. 58±9% at six months, Lateral-Mitral E/e’ 11.15±5.4 vs. 11.84±5.5, Septal-Mitral E/e’ 14.5±7.2 vs. 15.73±6.6, and Mitral E/a’ 0.98±0.46 vs. 1.09±0.8. No statistically significant difference was found.

Conclusions: This analysis was unable to show that GLP-1 agonists improve diastolic function at the time frame studied. Studies with larger sample and longer follow-up should be performed for better understand these findings.

Disclosure

S.S. Mahapatra: None. C. Milla-Matute: None. C.V. Villabona: None. L. Caraballo: None.
1036-P: Closed-Loop Glucose Control System for In-Hospital Use: Extended Control Trials
Authors: HASHEMI NASSEH , VALK TIMOTHY , HOULIND KIM , EJSKJAER NIELS
Published: June 2019

Background: Optimal in-hospital glucose control is a requirement for reducing mortality, morbidity and duration of admission. Present glucose concentrations in critical care are characterized by marked variability and episodes of hypoglycemia due to inadequate sensing and treatment technologies. We have previously shown (ADA 2016), that a prototype closed loop system (Admetsys™) infusing insulin/dextrose is capable of controlling blood glucose.

Aim: The aim of this study was to assess the ability of the Admetsys™ Insulin Based Infusion Systems (IBIS) (totally closed loop system) to lower, stabilize and maintain desired glucose levels and to avoid episodes of hypoglycemia for an extended period of time of up to 24 hours in patients “during admission to hospital.”

Methodology: 12 people with diabetes (ten with type 1 diabetes, two with type 2 diabetes) ranging from 26-49 years of age were admitted to our clinical research unit. The duration of the study was up to 24 hours, and at beginning of the study blood glucose levels were betwee 150 and 300 mg/dl. Through a three-way connector the Admetsys™ IBIS was connected to insulin and glucose/dextrose pumps and linked to an intravenous automated glucose sensor (VIA Glucoscout), which sent the data to the treatment system. A saline solution was infused to insure vein patency. The therapeutic target range was set to 80-125 mg/dl.

Results: Results from all twelve subjects were collected and analyzed. Mean time to reach the normoglycemic target range (80-125 mg/dl) was 2.36 hours. When target range was achieved the mean blood glucose level was 107.0 mg/dl (SD 8.6 mg/dl). No incidence of hypoglycemia (<70 mg/dl) occurred during the course of the trial.

Conclusion: The Admetsys™ IBIS system proved accurate, safe and reliable in this study. However, further studies in greater patient populations are needed to validate the full performance of this closed loop system designed for hospital use.

Disclosure

N. Hashemi: None. T. Valk: Other Relationship; Self; Admetsys. K. Houlind: None. N. Ejskjaer: None.
1040-P: Evaluation of a Medtronic Enhanced Hybrid Closed-Loop (e-HCL) System during Unannounced Meals of Medium Size
Authors: ROY ANIRBAN , GROSMAN BENYAMIN , PARIKH NEHA , WU DI , LINTEREUR LOUIS J. , KURTZ NATALIE , KAUFMAN FRANCINE R.
Published: June 2019

Background: Forgetting a premeal bolus can lead to hyperglycemia in patients with type 1 diabetes (T1D). A prototype e-HCL system was designed to automatically deliver basal insulin and correction boluses based on sensor glucose (SG) values. The effect of the system on hyperglycemia due to unannounced medium-sized meals was assessed.

Methods: Twelve subjects with T1D aged 15-25 years (median 17 years) underwent a 1-week hotel phase of e-HCL Auto Mode use, followed by a 3-week unsupervised at-home phase of use. On the third day of the hotel phase, a ∼40gm-carbohydrate (carb) dinner was consumed without a premeal bolus. Five hours of postprandial data were analyzed and compared to data captured after 40gm-carb meals eaten during the at-home phase, but accompanied by a premeal bolus.

Results: Meals without a premeal bolus resulted in postprandial SG levels statistically similar to those observed for meals accompanied by a premeal bolus (Table).

Conclusion: These data suggest that e-HCL can handle unannounced medium-sized meals to a similar extent as meals of equal size accompanied by premeal boluses. This may improve overall glycemic control of patients who underestimate or frequently forget to administer premeal boluses.

Disclosure

A. Roy: Employee; Self; Medtronic MiniMed, Inc. B. Grosman: Employee; Self; Medtronic. N. Parikh: None. D. Wu: None. L.J. Lintereur: Employee; Self; Medtronic MiniMed, Inc. N. Kurtz: Employee; Self; Medtronic MiniMed, Inc. F.R. Kaufman: Employee; Self; Medtronic.
1042-P: Real-World Treatment Patterns and Glycemic Profiles of 1,217 Adults with Type 2 Diabetes Using the Omnipod® Insulin Management System with Cloud-Based Data Management
Authors: LAYNE JENNIFER E. , JANTZ JAY , HE JIALUN , ZHENG YIBIN , BENJAMIN ERIC , LY TRANG T.
Published: June 2019

Continuous subcutaneous insulin infusion may help optimize therapy in patients with type 2 diabetes, however, there is little real-world data on pump use in this population. This observational study characterized treatment patterns and glycemic profiles of a large cohort of adults with type 2 diabetes using a tubeless insulin pump (Omnipod® Insulin Management System, Acton, MA) with integrated blood glucose (BG) meter (Abbott Diabetes Care Inc., Alameda, CA) and data management system (Glooko, Mountain View, CA). From January 2015 through September 2018, usage data from the pump system were uploaded to the data management system and matched via device serial number to a second database of self-reported demographic data and de-identified. BG and insulin data from ≥3 mo of system use per patient were analyzed. Glycemic outcomes included mean glucose, estimated A1C and percent time in range 70-180, <70 and > 180 mg/dL. Patients (n=1,217) were age (mean±SD) 56.8±10.8y, 50% female and 58% used a tubeless insulin pump for ≥1 y. Glycemic profile included BG 174±39 mg/dL, estimated A1C 7.7%, time in range 70-180, <70 and >180 mg/dL: 57.8%±20.1, 3.2%±3.9, 39.0%±20.6, respectively. The total daily insulin was 58.3±26.5 U/d delivered as 60% basal/40% bolus with an average of 3.4±1.7 bolus deliveries per day and mean bolus amount of 7.0±3.9 U. CGM was used by 5.5% of the cohort for >50% of overall time of system use. These real-world data characterizing a large cohort of adults with type 2 diabetes provide insight to self-management patterns and glycemic profiles indicating that use of tubeless insulin pump was associated with glycemic control that exceeds U.S. National Healthcare Effectiveness Data and Information Set (HEDIS) standards for adequate diabetes control.

Disclosure

J.E. Layne: Employee; Self; Insulet Corporation. J. Jantz: Employee; Self; Insulet Corporation. Employee; Spouse/Partner; Insulet Corporation. J. He: Employee; Self; Insulet Corporation. Y. Zheng: Employee; Self; Insulet Corporation. Stock/Shareholder; Self; Insulet Corporation. E. Benjamin: Employee; Self; Insulet Corporation. T.T. Ly: Employee; Self; Insulet Corporation.

Funding

Insulet Corporation
105-LB: Does HbA1c Accurately Predict Time-in-Range?
Authors: DIXON RONALD F. , MILLER DAVID P. , MAJITHIA AMIT , LEE AMY ARMENTO , ROBERTSON SCOTT , GERMANOS MARY JO , ZISSER HOWARD
Published: June 2019

Background: Onduo’s Virtual Diabetes Clinic (VDC) incorporates a continuous glucose monitor (CGM), telemedicine, and a coaching app into the management of patients with type 2 diabetes (T2D). A recent meta-analysis of studies involving CGMs (Vigersky & McMahon 2019) showed HbA1c and time in range (%TIR) are strongly correlated.

Methods: All patients in the program with CGM usage in the 45 days prior to a follow-up HbA1c were analyzed. Mean HbA1c and %TIR were added to the previously published meta-analysis plot where each study or cohort is represented by a single dot. Additionally, a regression model was fit on the patient-level data.

Results: Patient-level results from the VDC confirm the two metrics are strongly correlated (r=.-78). At the population-level, a mean %TIR of 84% in 194 VDC patients with mean HbA1c of 7.0% is 18% higher than predicted from the meta-analysis regression line. Cohorts associated with the 3 T2D studies in the meta-analysis were the 3 with the highest %TIR versus predicted, and 1 study with mixed type 1/2 was also higher than predicted.

Conclusions: Our findings add support to the strong correlation observed between TIR and A1c overall, and suggest potentially distinct calibrations in T1D vs. T2D populations. Additional CGM data in T2D will clarify if separate prediction formulae are necessary.

Disclosure

R.F. Dixon: Employee; Self; Onduo LLC. D.P. Miller: Employee; Self; Verily Life Sciences LLC. Stock/Shareholder; Self; Verily Life Sciences LLC. A. Majithia: Consultant; Self; Onduo LLC. A. Armento Lee: Employee; Self; Verily Life Sciences LLC. S. Robertson: Employee; Self; Verily Life Sciences LLC. M. Germanos: None. H. Zisser: Employee; Self; Verily Life Sciences LLC. Stock/Shareholder; Self; Verily Life Sciences LLC.
1056-P: Characterization of Multi-timescale Biological Rhythms in Individuals with Type 1 Diabetes
Authors: LEWIS DANA M. , GRANT AZURE D.
Published: June 2019

Background: Longitudinal biological rhythms in glucose and insulin outputs have not been mapped in individuals with T1D. Physiologically based, within-individual predictions of ultradian (UR), circadian (CR) or longer timescale changes in glucose and insulin are not currently possible, in part due to a lack of understanding of population heterogeneity. This is the first longitudinal analysis of biological rhythms in T1D, compared to non-T1D individuals.

Methods: Frequency decomposition using the continuous morlet wavelet transformation were created to assess change in rhythmic composition of normalized blood glucose data from 5 non-T1D individuals, and anonymized, retrospective CGM data from 19 T1D individuals using a DIY closed loop APS in the OpenAPS Data Commons.

Results: T1D individuals showed a wide range of rhythmic power at the circadian and long-period ultradian timescales compared to individuals without T1D. There is not much UR power lower than 6-hour periodicity, likely due to insulin DIA effects.

Conclusion: Such analysis of biological rhythms should be further studied across a broader T1D population, including both APS and non-users, and knowledge of the rhythms could be used for improving personalization and prediction capabilities of APS.

Disclosure

D.M. Lewis: Consultant; Self; Diabeloop SA, Roche Diabetes Care. A.D. Grant: None.
106-LB: Correlation between CGM-Derived Mean Glycemia and Measured Hemoglobin A1c in the Real World
Authors: ANGELLOTTI EDITH , MUPPAVARAPU SANGEETHA , SIEGEL RICHARD , PITTAS ANASTASSIOS G.
Published: June 2019

Objective: Continuous glucose monitoring (CGM) has emerged as a key component of diabetes care but there are issues with data synthesis and application. A published regression equation converts CGM-derived mean glycemia into an estimate of laboratory-measured HbA1c, termed glucose management indicator (GMI). How the GMI formula defers by CGM device is not known. We compared the GMI derived from published formula vs. GMI derived from FreeStyle Libre specific regression equation.

Research Design and Methods: We conducted an observational study using EHR data from a single academic endocrinology practice (Tufts Medical Center, Boston, MA). We included data from patients with diabetes and a minimum of 10-days of sensor data collected with FreeStyle Libre Pro or Personal, immediately prior to measurement of HbA1c. We plotted HbA1c and Libre average glucose and derived a Libre specific regression equation. We compared the GMI derived from the published formula (GMIp) with the Libre-specific GMI (GMIL).

Results: Data were available from 59 patients (age 62 [range 22-90], 36% women, BMI 29 Kg/m2; 80% had type 2 diabetes; 70% had diabetes ≥10 years disease; HbA1c 8.1% (range 4.8-13.7). The mean number of days with CGM data was 28 (range 10-90). The Libre specific regression equation formula was GMI (%) = 5.04 + 0.0173*(mean glucose in mg/dL)]. Mean GMIp was 8.1% (SD 0.9) and mean GMIL was 7.6% (SD 1.3)(p=0.004).

Conclusion: The GMI derived from a device-specific regression equation differs from the published GMI. The development of a device specific GMI may be warranted.

Disclosure

E. Angellotti: None. S. Muppavarapu: None. R. Siegel: None. A.G. Pittas: None.
1066-P: Improvement in Time-in-Range (TIR) with Real-Life Use of Hybrid Closed-Loop System in Patients with Type 1 Diabetes (T1D)
Authors: AKTURK HALIS K. , GIORDANO DOMINIQUE A. , JOSEPH HAL , GARG SATISH K. , SNELL-BERGEON JANET K.
Published: June 2019

Newer metrics like TIR are gaining momentum for measurement of glycemic control. The Medtronic 670G is the first commercial hybrid closed-loop (HCL) system for the management of T1D. We conducted a single-center retrospective chart review to compare continuous glucose monitor (CGM) metrics before and after initiation of 670G system in patients with T1D. Of 408 adult T1D patients who initiated 670G system during the study period, 139 patients were using an insulin pump with CGM for at least 3 months before the initiation of 670G system and had 6 months follow-up. Mean baseline age was 41±12, (60% women) with HbA1c of 7.6±0.9%. We analyzed the change in CGM data: % TIR (70-180 mg/dl), time-below-range (<70 mg/dl) and time-above-ranges (>180 mg/dl and >250 mg/dl) at 3 and 6 months of 670G system use. Use of 670G system significantly increased TIR (p<0.0001) and decreased time-below-range (p<0.0001) and time-above-range (p<0.0001) at 3 and 6 months compared to baseline (Figure). The mean percent time in auto-mode was 71% and 73% at 3 months and 6 months respectively. We conclude that HCL use in real-life significantly improves TIR and decreases hypo- and hyperglycemia.

Disclosure

H.K. Akturk: Advisory Panel; Self; Sanofi. Research Support; Self; Eli Lilly and Company, MannKind Corporation, REMD Biotherapeutics. Speaker's Bureau; Self; MannKind Corporation. D.A. Giordano: None. H. Joseph: None. S.K. Garg: Advisory Panel; Self; Eli Lilly and Company, Roche Pharma, Sanofi-Aventis, Zealand Pharma A/S. Research Support; Self; Eli Lilly and Company, WebMD. J.K. Snell-Bergeon: None.
107-OR: Profiling of Human Pancreatic Islets by Single Cell Transcriptomics Reveals α- and ß-Cell Subpopulations
Authors: SHRESTHA SHRISTI , SAUNDERS DIANE C. , WALKER JOHN T. , HALIYUR RACHANA , POFFENBERGER GREG , ARAMANDLA RADHIKA , JONES ANGELA , PRASAD NRIPESH , LEVY SHAWN E. , POWERS ALVIN C. , BRISSOVA MARCELA
Published: June 2019

Single cell RNA-sequencing (scRNA-seq) approaches are continuously improving at the point of data collection and analysis to simultaneously profile all cell types within islet microorgans to better understand heterogeneity and phenotype-function relationships and how these change with aging and disease. To better understand the advantages and limitations of scRNA-seq, we used the ChromiumTMplatform to profile human islets with a robust insulin and glucagon secretion by perifusion (5 nondiabetic donors, ages 14-66 years) and compared these results to scRNA-seq analysis of purified α and β cells. In context of the same donor (n=2), purified α and β cells (using NTPDase3 marker) showed high correlation (r=0.99) with the Seurat-identified α and β subsets originating from dispersed whole islets. Based on the analysis of a very large pool of single cells (79,881 cells; 2316 genes/cell), the Seurat-guided analysis identified cell types that segregated into eight different clusters (17% β, 66% α, 4% δ, 4% ductal, 4% mesenchymal, 2% acinar, 2% endothelial, and 1% immune). Interstingly, in this large single cell context, we did not identify the four β cell subsets previously reported on the basis of alternative cell surface markers, but found a β cell cluster with highly expressed ER stress-associated genes and an α cell cluster with higher cell cycle regulation marker expression. We concurrently investigated expression of functionally important MAFA and MAFB genes, which are expressed only in a fraction of β cells by histological analysis, and found that PERK-mediated UPR transcripts were enriched in the MAFB-expressing β cells, while the MAFA-expressing β cells differentially expressed genes associated with β cell function. Overall, our study indicates high fidelity of α and β cell clustering in dispersed and sorted islet cells and points to a different pattern of β cell heterogeneity when β cells are purified using NTPDase3 expression compared to other cell surface markers.

Disclosure

S. Shrestha: None. D.C. Saunders: None. J.T. Walker: None. R. Haliyur: None. G. Poffenberger: None. R. Aramandla: None. A. Jones: None. N. Prasad: None. S.E. Levy: None. A.C. Powers: None. M. Brissova: None.
1075-P: Safety and Efficacy of Medtronic MiniMed 670G Hybrid Closed-Loop System in the Diabetes Camp Setting: Comparison of Auto Mode (AM) vs. Manual Mode (MM)
Authors: CHAN SOPHIA H. , CHANG ERICA W. , TANG JONATHAN K. , SCHMELTZ LOWELL
Published: June 2019

Introduction: The Medtronic MiniMed 670G insulin pump is the first FDA approved commercial hybrid closed-loop system for pediatric patients with type 1 diabetes (T1D). Clinical trials have shown that the pump’s Auto Mode system effectively maintains blood glucose (BG) levels in target ranges for longer periods of time. Campers may have different insulin requirements than they are accustomed to at home due to the different foods and activity levels at camp. In this retrospective quality review, Medtronic MiniMed 670G pump data from campers attending 2018 ADA Camp MIDICHA were analyzed to investigate the safety and efficacy of campers in AM vs. MM.

Methods: We analyzed de-identified data from 34 campers (mean age 13.1 years [range 8-17]). There were 18 MM and 16 AM campers. BG levels, grams of carbohydrates consumed, and amount of insulin administered were recorded at every meal, evening snack, 12AM, and 2AM. The number of hypoglycemic events (<70 mg/dL), hyperglycemic events (>250 mg/dL), and events within the target BG range (70-250 mg/dL) were also noted.

Results: Our results showed improved glycemic control for campers in AM at breakfast (AM 166.56 mg/dL, MM 182.50 mg/dL), lunch (AM 156.08 mg/dL, MM 167.67 mg/dL), dinner (AM 191.83 mg/dL, MM 194.22 mg/dL), and evening snack (AM 164.13 mg/dL, MM 179.19 mg/dL). Average daily BG was lower for AM (AM 162.12 mg/dL, MM 173.54 mg/dL). The number of hypoglycemic events was 37 for AM and 38 for MM. The number of hyperglycemic events was 62 for AM and 80 for MM.

Discussion: Compared to MM, using the AM system allowed for a higher percentage of BG in the target range and decreased incidences of hypoglycemic and hyperglycemic events. This suggests that the AM system in the Medtronic MiniMed 670G insulin pump can safely and effectively maintain target BG levels for children with T1D in camp settings.

Disclosure

S.H. Chan: None. E.W. Chang: None. J.K. Tang: None. L. Schmeltz: Advisory Panel; Self; Sanofi. Speaker's Bureau; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Dexcom, Inc., Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk Inc.
108-LB: Sustained Glucagon Effect on Blood Glucose and Improvements of Insulin Resistance Mediated by a Novel Long-Acting Glucagon Analog, HM15136, in Animal Models
Authors: CHOI JAEHYUK , LEE SEON MYEONG , KIM JUNG KUK , LEE JONGSOO , KIM YOUNG HOON , CHOI IN YOUNG
Published: June 2019

HM15136 is a novel long-acting glucagon (GCG) analog conjugated with human IgG FC fragment via a short PEG linker. Previously, HM15136 treatment led to body weight loss (BWL) in obese animal models while showing transient effect on blood glucose (BG). Insulin resistance (IR) can lead to imbalances in BG homeostasis in obesity, representing a key risk factor for T2DM. Considering the potential benefit of BWL in IR improvement, HM15136 could be a novel therapeutic option for obesity treatment. To assess this concept, the present study evaluated the effect of HM15136 on BG as well as BW, and investigated the mechanism leading to IR improvement in vitro and in vivo. In DIO rats, 4 weeks treatment of HM15136 led to remarkable BWL (-17 ∼ -42% vs. Veh). BG monitoring showed that an initial BG elevation was rapidly normalized and maintained normal thereafter, with no HbA1c increase (3.4 and 3.7% for Veh and HM15136). Similar results were also observed in DIO mice, showing no abnormal glycemic control by HM15136. Interestingly, BWL effect were correlated with free-fatty acid (FFA) and HOMA-IR reduction. In vitro studies in 3T3-L1 adipocytes further confirmed the deteriorating effect of FFA on insulin signaling. These results suggested that improvements in the lipotoxic milieu explains, at least in part, the IR improvement seen with HM15136. To further explore additional mechanism, inflammatory markers and adipokines affecting insulin signaling were evaluated. HM15136 not only inhibited F4/80 expression, but also increased FGF-21 and adiponectin expression in white adipose tissue and 3T3-L1 adipocytes. Our results demonstrated that BWL under by HM15136 therapy is accompanied by the reduction of 1) lipotoxicity, 2) inflammatory biomarkers, and the expression of 3) insulin-sensitizing adipokines, eventually leading to IR reversal and normal BG maintenance. Human studies are needed to confirm whether these findings will translate into humans.

Disclosure

J. Choi: None. S. Lee: None. J. Kim: None. J. Lee: None. Y. Kim: None. I. Choi: Employee; Self; Hanmi Pharm. Co., Ltd.
108-OR: Inhibition of SerpinB13 Stimulates Beta-Cell Development via Notch Signaling Pathway
Authors: KRYVALAP YURY , HENDRICKSON COLE , CZYZYK JAN
Published: June 2019

Methods for repopulating the pancreas with new insulin-producing cells have strong potential for therapy in diabetes. Recently, we have found that inhibition of serpinB13 - a protease inhibitor of cathepsin L (catL) - with mAb in mouse embryos leads to a robust increase in the number of pancreatic Ngn3+ progenitor cells, significant expansion of islet mass, and improved resistance to severe diabetes in adulthood. To unveil the molecular mechanism of the augmented Ngn3+ cell response following inhibition of serpinB13 during gestation, we focused on the Notch communication system - a critical signaling pathway for pancreatic development. We found that serpinB13 is expressed and secreted by epithelial cells in murine embryonic pancreases. Moreover, in vivo and in vitro inhibition of serpinB13 during embryogenesis caused protease-dependent cleavage of the extracellular domain of Notch1 receptor in the pancreas (p<0.0001). This partial loss of the extracellular Notch was followed by decreased translocation to the nucleus of active Notch intracellular domain (aNICD), a fragment of Notch that is critical for restraining endocrine cell development. Finally, embryonic pancreases of mice with genetic deficiency of catL had significantly fewer Ngn3+ cells compared with wild type controls. Together, our data point to a novel function of serpinB13 in maintaining Notch receptor-mediated repression of pancreatic endocrine progenitors. Consequently, the perturbation of this effect of serpinB13 enables protease activity to partially dismantle Notch signaling, thereby allowing for more efficient development of Ngn3+ progenitors cells and a subsequent increase in islet mass.

Disclosure

Y. Kryvalap: None. C. Hendrickson: None. J. Czyzyk: None.

Funding

American Diabetes Association (1-17-ICTS-083 to J.C.)