bluuebunny/crossref_metadata_2025_split huggingface dataset:
1051-P: Improving Glycemic Outcomes in T1D Using an Automated Decision Support Recommender System: Evaluation In Silico and Compared with Physician Recommendations
Authors: TYLER NICHOLE S. , MOSQUERA-LOPEZ CLARA M. , WILSON LEAH M. , RESALAT NAVID , DODIER ROBERT , BRANIGAN DEBORAH , GABO VIRGINIA , YOUSSEF JOSEPH EL , CASTLE JESSICA R. , JACOBS PETER G. 
Published: June 2019

Most people with type 1 diabetes use multiple daily injections (MDI) therapy, yet there are limited decision support tools for this population. We designed and evaluated a K-nearest-neighbors decision support system (KNN-DSS) that utilizes continuous glucose data and Bluetooth-enabled insulin dose capture devices to detect problematic glycemic patterns and recommend insulin dosage adjustments to maximize time-in-range (70-180 mg/dL) and minimize hypoglycemia (&lt; 70 mg/dL). The KNN-DSS employs distance and class weighting, a carb ratio aggressiveness algorithm, and an expert-opinion quality-control algorithm to filter erroneous recommendations.
The KNN-DSS was evaluated both in silico and in comparison with physician recommendations. In silico virtual patients (n=30) of varying weight, total daily insulin requirement, insulin sensitivity, and compliance with care were evaluated in a 1-year study whereby they received weekly recommendations. The primary outcome measures were the % time-in-range and % time-in-hypoglycemia. The KNN-DSS was further evaluated for accuracy compared with endocrinologist recommendations collected during a 4-week, at-home clinical trial of CGM-augmented MDI therapy (N = 12, 7 female, 30.8 ± 5 years, 79.6 ± 18.9 kg), and compared using Dice similarity coefficient.
In silico, the KNN-DSS improved time-in-range from 66.8% at baseline to 81.0% (21% relative improvement, p &lt;0.005), and reduced time-in-hypoglycemia from 3.14% at baseline to 1.37% (56% relative improvement, p &lt; 0.005) after one year. Compared to endocrinologists, the KNN-DSS recommendations to real-world patients were within acceptable agreement 75% of the time, 6% contraindicated, and 19% whereby KNN-DSS gave a recommendation when the physician gave no recommendation. KNN-DSS improves glycemic outcomes in silico and exhibits acceptable agreement with physician recommendations. Future clinical studies are planned.

Disclosure
N.S. Tyler: None. C.M. Mosquera-Lopez: None. L.M. Wilson: None. N. Resalat: None. R. Dodier: None. D. Branigan: None. V. Gabo: None. J. El Youssef: None. J.R. Castle: Advisory Panel; Self; Novo Nordisk Inc., Zealand Pharma A/S. Consultant; Self; Dexcom, Inc. Research Support; Self; Dexcom, Inc., Xeris Pharmaceuticals, Inc. P.G. Jacobs: Stock/Shareholder; Self; Pacific Diabetes Technologies.

Funding
The Leona M. and Harry B. Helmsley Charitable Trust (2018PG-T1D001)
1057-P: Performance Enhancement of Fully Closed-Loop Insulin Delivery in Type 2 Diabetes by Automatized Bolusing
Authors: ORNETZEDER CLEMENS , REITERER FLORIAN , CHRISTENSEN MERETE B. , NØRGAARD KIRSTEN , DEL RE LUIGI 
Published: June 2019

Introduction: Systems for fully closed loop insulin delivery (AP) lack bolus administration at mealtimes, resulting in higher postprandial glucose excursions than hybrid APs. In order to mitigate this disadvantage an algorithm can be used for the automatic delivery of bolus insulin (BI) in case a meal is recognized from the CGM recordings. The use of a full AP with automatic BI delivery is tested in simulations against a hybrid AP with manual bolusing and a full AP without any meal boluses.
Methods: The simulation approach used for this purpose combines data from real clinical trials with mathematical models. A cohort of five insulin-treated T2D patients is used to test the feasibility of the different AP concepts.
Results: Using a full AP with automatized bolusing more patients were able to achieve their therapeutic goals (defined here as HbA1c &lt; 7%) than for the case without meal boluses (4/5 vs. 1/5). Time in hypoglycemia is at a comparably low level for both considered full AP versions (0.9±1.5% vs. 0.4±0.8%), whereas time in hyperglycemia (21.9±5.4% vs. 30.9±7.9%) and HbA1c (6.8±0.3% vs. 7.4±0.5%) is significantly reduced for the case with automatized bolusing. However, as can be expected, a hybrid AP approach with manual bolusing does result in even better glycemic outcomes.
Conclusion: Results show that automatized bolusing does indeed lead to enhanced glycemic outcomes in full AP systems.

Disclosure
C. Ornetzeder: None. F. Reiterer: None. M.B. Christensen: None. K. Nørgaard: Advisory Panel; Self; Abbott, Medtronic, Novo Nordisk A/S. Speaker's Bureau; Self; Bayer US, Medtronic, Roche Diabetes Care, Rubin Medical, Sanofi, Zealand Pharma A/S. Stock/Shareholder; Self; Novo Nordisk A/S. L. del Re: None.
1062-P: Insulin Requirement Profiles of Short-Term Continuous Subcutaneous Insulin Infusion Therapy in Chinese Patients with Type 2 Diabetic Nephropathy
Authors: LIN SHUO , ZHANG KUIXING , LI PING , FANG KE , ZENG LONGYI 
Published: June 2019

Our study aims to explore the insulin requirement profiles of short-term intensive continuous subcutaneous insulin infusion (CSII) in Chinese patients with type 2 diabetic nephropathy. CSII was applied in 68 patients with diagnosed type 2 diabetic nephropathy (using Paradigm 712, Medtronic). Daily insulin doses were titrated and recorded to achieve and maintain target glucose levels (FPG&lt;7.0mmol/L and 2hPBG&lt;10mmol/L) for 8-12 days. The patients were 60.0±13.1 years in age, 45.6% female (n=31), mean duration 11.3±7.2 years, BMI 25.0±3.3 kg/m2, mean HbA1c of 9.4±2.5%, median urinary microalbumin/creatine 78.2 mg/g (inter-quartile range 36.0-274.6 mg/g), and median creatine 72.0umol/l (inter-quartile range 53.5-110.8 umol/l). At the first day after the glycemic targets were achieved (Day1), total daily insulin dose (TDD), total basal and premeal dose were 44.3±17.5 IU (0.67±0.27 IU/kg), 19.6±9.2 IU (0.30±0.14 IU/kg) and 24.7±10.3 IU (0.37±0.15 IU/kg), respectively. At the end of CSII therapy, TDD was 43.7±18.1 IU (0.66±0.28 IU/kg). Total basal dose and total pre-meal dose were 19.2±9.0 IU (0.29±0.14 IU/kg, P&gt;0.05 compared with Day1) and 24.5±11.2 (0.37±0.17 IU/kg, P &gt; 0.05 compared with Day1), respectively. The ratio of basal insulin dose to TDD were 44%±11% at Day1 and 44%±12% at the end, respectively. The ratio of basal insulin dose to TDD at day 1 were 45%±11% and 40%±9% in subjects with eGFR &gt;60ml/min (n=48) or eGFR &lt;60ml/min (n=20), respectively (P=0.11). The ratio of basal insulin dose to TDD at day 1 were 49%±18% and 39%±12% in subjects with eGFR 60-90 ml/min or eGFR &lt;30ml/min, respectively (P=0.041). The TDD at Day1 were 45.8±12.4 IU in subjects with 40.9±26.1 IU in subjects with eGFR &gt;60ml/min or eGFR &lt;60ml/min, respectively (P&gt;0.05). These results suggested the ratio of basal insulin dose to TDD might be decreased while eGFR declined in patients with type 2 diabetic nephropathy.

Disclosure
S. Lin: None. K. Zhang: None. P. Li: None. K. Fang: None. L. Zeng: None.

Funding
Science and Technology Planning Project of Guangdong Province (2017A020215026); Medical Scientific Research Foundation of Guangdong Province (A2017314)
1072-P: Comparison of the Efficacy between a Needle-Free Insulin Injector and Conventional Insulin Pen in Glycemic Control in Insulin-treated Type 2 Diabetic Patients in China
Authors: GAO LEILI , JI LINONG , GUO LIXIN , WANG YANGANG , CHEN LIMING , WANG GUIXIA , RAN XINGWU , XU XIANGJIN , SUN ZILIN , MA ZHONGSHU , SHAN ZHONGYAN 
Published: June 2019

Background: Needle free insulin injector is designed for diabetics with needle anxiety or fear of injection pain resulting in reluctance to initiate insulin therapy when it is actually indicated. This device has faster absorption of insulin and has better glycemic control compared with conventional insulin pen. But the efficacy of glycemic control was only evaluated by postprandial blood glucose or the area under blood glucose curve.
Objective: To investigate the efficacy of needle free insulin injector by HbA1c level compared with conventional insulin pen in insulin treated type 2 diabetic patients in multicenter, prospective, randomized, open-label trial.
Methods: A total of 427 patients with HbA1c levels of ≥7.5% to ≤11% while receiving basal or premixed insulin were randomized 1:1 to needle free insulin injector group (NFII) or conventional insulin pen group (CIP). The primary efficacy endpoint was change of HbA1c leve after 16 weeks treatment. The change of 7-point blood glucose profile and the percentage of patients with HbA1c level &lt;7% were also observed.
Results: Of the 412 patients (mean age 57.92±10.03ys; BMI 28.33±2.96kg/m2; HbA1c 8.25±1.00%) who completed the study, 206 patients were insulin treated via NFII and 206 via CIP. There were no significant differences in baseline characteristics between the two groups (P&gt; 0.05). The HbA1c reduction 0.55% (95% CI: -0.71, -0.39) at week 16 in NFII group was non-inferior and statistically superior compared with that of 0.26% (95% CI: -0.42, -0.11) in CIP group. There were no differences between two groups in the percentages of patients achieving the HbA1c target (27.32% vs. 24.26%; P&gt; 0.05) or in the change of 7-point blood glucose profile at week 16.
Conclusions: The device non-inferior and statistically superior efficacy in glycemic control compared to conventional insulin pen in insulin-treated type 2 diabetic Patients in China.

Disclosure
L. Gao: None. L. Ji: Advisory Panel; Self; AstraZeneca. Consultant; Self; AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Bristol-Myers Squibb Company, Eli Lilly and Company, Merck KGaA, Merck Sharp & Dohme Corp., Novartis AG, Novo Nordisk A/S, Roche Pharma, Sanofi, Takeda Pharmaceutical Company Limited. Research Support; Self; AstraZeneca, Bristol-Myers Squibb Company, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novartis AG, Roche Pharma, Sanofi. L. Guo: None. Y. Wang: None. L. Chen: Research Support; Self; Becton, Dickinson and Company. G. Wang: None. X. Ran: None. X. Xu: None. Z. Sun: None. Z. Ma: None. Z. Shan: None.
1073-P: A Study of Flat and Circadian Insulin infusion Rates in Continuous Subcutaneous Insulin Infusion (CSII) in Adults with Type 1 Diabetes (FIRST1D)
Authors: RILSTONE SIAN K. , REDDY MONIKA , OLIVER NICK 
Published: June 2019

Background and Aims: Initiation of continuous subcutaneous insulin therapy (CSII) in people with type 1 diabetes (T1D) requires conversion of a basal insulin dose to a continuous infusion regimen. There are limited data to guide the optimal insulin profile to rapidly achieve target glucose and minimize healthcare professional input. The aim of this study was to compare circadian and flat insulin infusion rates in CSII naïve adults with T1D.
Materials and Methods: Adults with T1D who met the NICE criteria for CSII were recruited. Participants were randomized to either a circadian profile or a flat basal rate, each calculated from the total daily dose. Basal rate testing was undertaken on days 7, 14 and 28 of CSII and basal rates were adjusted according to protocol. The primary outcome was the between group difference in absolute change in insulin basal rate over 24 hours following 3 rounds of basal testing. Secondary outcomes included the number of basal rate changes and the time blocks. Data from blinded continuous glucose monitoring were also collected.
Results: Seventeen participants (mean age 33.3 (SD 8.6)) were recruited. There was no significant difference in absolute change in insulin basal rates between the two groups (p=0.85) from baseline to the end of the study. In the circadian basal group, there was significant variation in the number of changes made across the 24 one-hour blocks with the most changes early in the morning (p=0.005). In the flat basal group, there were no significant variation in the number of changes made across the time points (p=0.09).
Conclusion: Commencing CSII with a flat or circadian profile does not impact on the magnitude of basal rate insulin changes during optimization in the first 28 days. The circadian profile requires changes at specific time points, while the flat basal rate requires even optimization throughout the 24-hour period. Further development of the circadian profile early in the morning may address this.

Disclosure
S.K. Rilstone: None. M. Reddy: None. N. Oliver: Advisory Panel; Self; Roche Diabetes Care. Research Support; Self; Dexcom, Inc., Roche Diabetes Care. Speaker's Bureau; Self; Dexcom, Inc., Sanofi.

Funding
Roche
1074-P: Performance of an Artificial Pancreas System in Swine during Severe Hypo- and Hyperglycemic Provocations
Authors: DEJOURNETT JEREMY , DEJOURNETT LEON 
Published: June 2019

Introduction: Intensive care unit (ICU) patients develop stress induced insulin resistance causing hyperglycemia, large glucose variability and hypoglycemia, all of which increase mortality rates. Tight glucose control (TGC) in the ICU is challenging, and usually significantly increases the risk for treatment induced hypoglycemia. The only way to achieve safe TGC will be through use of an artificial pancreas (AP) system. Our goal with the present study was to assess the safety and performance of an AP system, composed of the EIRUS (Getinge AB) continuous glucose monitor (CGM) and novel artificial intelligence-based (AI-based) glucose control software, in a swine model using unannounced hypo- and hyperglycemia challenges.
Methods: Fourteen piglets (6 control, 8 treated) underwent sequential unannounced (to the AP system) hypoglycemic and hyperglycemic challenges with 3 U of insulin aspart and a large glucose infusion over the course of 5 hours. In the control animals an ICU physician used every 30-minute arterial blood glucose values to maintain control to a range of 4.4 - 9 mmol/L through use of 20% dextrose for hypoglycemia and insulin aspart for hyperglycemia. In the treated group the AP system attempted to maintain blood glucose control to a range of 4.4 - 6.6 mmol/L in a fully autonomous mode.
Results: Five of six control animals and none of eight treated animals experienced severe hypoglycemia (&lt; 2.22 mmol/L). The area under the curve 3.5 mmol/L was 28.9 (21.1 - 54.2) for control and 4.8 (3.1 - 5.2) for the treated animals. The percent time in range 4.4 - 6.6 mmol/L was 32.8 (32.4 - 47.1) for the control and 55.4 (52.9 - 59.4) for the treated animals. After the start of the experiment the control animals underwent 4 (3-5) human interventions to maintain control whereas the treated animals underwent none. Data are median (25-75).
Conclusions The AP system abolished severe hypoglycemia and outperformed the ICU physician both in avoiding hypoglycemic excursions and maximizing time in range.

Disclosure
J. DeJournett: Employee; Self; Ideal Medical Technologies. L. DeJournett: Stock/Shareholder; Self; Ideal Medical Technologies.
1076-P: Increased Time-in-Range (TIR) Observed after Introduction of a Connected Insulin Pen
Authors: ADOLFSSON PETER , HARTVIG NIELS V. , KAAS ANNE , NYGÅRD KNUDSEN NIKOLINE , MÅRDBY ANN-CHARLOTTE , HELLMAN JARL 
Published: June 2019

The capture and visualization of insulin injection patterns together with blood glucose data has potential to improve dialogue between patients and HCPs about dose, injection time and missed injections. This may improve glycemic control. The objective of this non-interventional study was to investigate how a connected insulin pen (NovoPen®6) influences glycemic control in patients with T1DM in a real-world setting. Patients were recruited from 12 Swedish diabetes clinics. At baseline patients received a NovoPen®6, which logs time of injection and number of insulin units. HCP visits were conducted according to clinical practice. At each visit, pen data were downloaded at the clinic to support patient-HCP dialogue. Adults with T1DM (n=94) using NovoPen®6 for basal and/or bolus and CGM were included in the analyses. The effect on TIR was based on a 14-day interval after each visit using a linear mixed-effects model. A significant increase in TIR from baseline to after ≥5 HCP visits (median time in study 6 months) of 1.9 hours/day (9.2 to 11.1 hours/day) was found (p=0.0009). Accordingly, significant reduction in time spent in hyper- and L2 hypoglycemia (-1.8 hours/day p=0.003; -0.3 hours/day p=0.005) was observed. There was no change in time in L1 hypoglycemia (p=0.181). These real-world findings in patients with T1DM highlight the potential benefit on glycemic control when accurate connected pen data contribute to patient-HCP dialogue.

Disclosure
P. Adolfsson: Advisory Panel; Self; Eli Lilly and Company, Novo Nordisk A/S, Roche Pharma. Employee; Self; Region Halland. Research Support; Self; Region Halland. N.V. Hartvig: Employee; Self; Novo Nordisk A/S. Stock/Shareholder; Self; Novo Nordisk A/S. A. Kaas: Employee; Self; Novo Nordisk A/S. Stock/Shareholder; Self; Novo Nordisk A/S. N. Nygård Knudsen: Employee; Self; Novo Nordisk A/S. A. Mårdby: Employee; Self; Novo Nordisk A/S. Stock/Shareholder; Self; Novo Nordisk A/S. J. Hellman: Advisory Panel; Self; Abbott, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi. Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Novo Nordisk A/S, Sanofi.

Funding
Novo Nordisk A/S
1081-P: Incidence of Hypoglycemia within 24 Hours of Hospital Admission in Patients Using Insulin Pumps
Authors: HALSTROM AMANDA , MOLEDINA IRAM , PERAGALLO-DITTKO VIRGINIA , ANCONA KARENA , ISLAM SHAHIDUL , ROTHBERGER GARY , KLEK STANISLAW P. 
Published: June 2019

Background: Insulin pumps have become an increasingly popular alternative to traditional forms of insulin therapy for patients with type 1 and type 2 diabetes. Despite the increasing prevalence of insulin pumps, the safety of their use in hospitalized patients has not been well studied. In this study, we aim to determine the incidence of hypoglycemia in hospitalized patients using insulin pumps within 24 hours of admission prior to any adjustments of their insulin pump settings.
Methods: This is a retrospective analysis of adult patients with diabetes (type 1 and 2) who used insulin pumps during the first 24 hours of admission to NYU Winthrop Hospital and did not make any adjustments to the pump settings during that time. Patients &lt;18 years of age, pregnant patients and those who were electively admitted for surgery were excluded from this study. Demographic data and clinical data were collected, which included the presence of steroid use, total daily dose of basal insulin, creatinine level, HbA1c level, and serum and capillary blood glucose values. Hypoglycemia was defined as blood glucose &lt;70mg/dL and severe hypoglycemia was defined as blood glucose &lt;40mg/dL.
Results: Two hundred and fifty-seven patients were included in the study. The mean age was 56 years, 152 (59%) patients were male, and 130 (55%) had type 1 diabetes. The mean hemoglobin A1c was 7.9%. A total of 2097 finger stick blood glucose values were obtained, and 1290 (62%) were &lt;180 mg/dL. There were 88 episodes of hypoglycemia (4.1% of all finger stick blood glucose values) and 2 episodes of severe hypoglycemia (0.1% of all finger stick blood glucose values).
Conclusion: Insulin pumps are safe and effective for the treatment of both type 1 and type 2 diabetes in the first 24 hours of hospital admission.

Disclosure
A. Halstrom: None. I. Moledina: None. V. Peragallo-Dittko: None. K. Ancona: None. S. Islam: None. G. Rothberger: None. S.P. Klek: None.
109-LB: Potent Weight Loss Mechanism by a Novel Long-Acting Glucagon Analog, HM15136, in Animal Models
Authors: LEE JONG SUK , KIM JUNG KUK , KIM JINYOUNG , PARK EUNJIN , LEE SANG HYUN , BAE SUNGMIN , CHOI IN YOUNG 
Published: June 2019

Clinical use of glucagon (GCG) has long been limited to the acute treatment of insulin-induced hypoglycemia. However, recent studies demonstrate that GCG also plays a central role in the regulation of lipid metabolism and body weight, suggesting its potential application in managing obesity. Consistent with this new concept, we observed that chronic treatment with the novel long-acting glucagon analog, HM15136, led to body weight loss (BWL) with minimized effects on blood glucose control (BG). To further explore the therapeutic potential of HM15136 in obesity, the present study compared the BWL effects of HM15136 with various incretin therapeutics targeting obesity, and investigated the potential BWL mechanism in vivo. In DIO mice, HM15136 showed greater BWL effects than GLP-1 agonists such as liraglutide, dulaglutide, and semaglutide. Of note, more BWL was also confirmed even under pair-feeding conditions with liraglutide, indicating appetite-independent BWL by HM15136. As to the postulated mechanism, HM15136 increased the expression of PGC-1α and UCP-1 in white adipose tissue (WAT). Consistent with these results, HM15136 enhanced the energy expenditure in DIO mice. Taken together with the reduced respiratory exchange ratio, these results suggested that HM15136 may induce WAT browning a mechanism through which energy expenditure can increase. We then evaluated a flexible dosing regimen for HM15136, and similar BWL effects were confirmed for human weekly- and monthly-mimetic dosing groups. Most interestingly, BWL achieved by HM15136, but not liraglutide, was maintained after 4 weeks without drug treatment. No abnormal changes in BG and HbA1c were observed. Based on these results, we propose that the novel long-acting glucagon analog, HM15136, could be a potential therapeutic option for the management of obesity. Human studies are needed to confirm these therapeutic benefits and to evaluate the safety of HM15136.

Disclosure
J. Lee: None. J. Kim: None. J. Kim: None. E. Park: None. S. Lee: Employee; Self; Hanmi Pharm. Co., Ltd. S. Bae: None. I. Choi: Employee; Self; Hanmi Pharm. Co., Ltd.
1093-P: The Prevalence and Clinical Characteristics of Insulin Antibody Formation in Patients with Type 2 Diabetes Treated with Insulin
Authors: ZHOU LINGLI , LUO YINGYING , CAI XIAOLING , HAN XUEYAO , JI LINONG 
Published: June 2019

Objective: To investigate the prevalence of insulin antibody (IA) formation among patients with type 2 diabetes receiving insulin therapy and their clinical characteristics.
Research Design and Methods: IA formation was evaluated using a polyethylene glycol (PEG) precipitation assay in 726 patients with type 2 diabetes (396 on insulin therapy and 330 who had never used insulin), and 87 nondiabetes controls. Risk factors for IA formation were analyzed by logistic regression.
Results: IAs were detected in 154 of the 396 type 2 diabetes patients on insulin therapy (38.9%). IA formation was independently associated with fasting insulin concentration or insulin/C-peptide ratio, IA titers and the incidence of hypoglycemia. The area under ROC curve for fasting insulin/C-peptide ratio in predicting IA formation was 0.830, indicating good diagnostic performance. The insulin/C-peptide ratio cutoff value of 9.3 uIU/ng(Figure 1)showed a sensitivity of 78% and specificity of 73% for predicting the presence of IAs.
Conclusions: Our findings suggest that IA formation should be suspected if insulin-treated diabetes patients experience frequent hypoglycemia, and that the fasting insulin/C-peptide ratio can be used to detect IA formation. Our study thus provides the foundation for developing more clinically convenient methods for identifying IAs in insulin-treated type 2 diabetes patients.

Disclosure
L. Zhou: None. Y. Luo: None. X. Cai: None. X. Han: None. L. Ji: Advisory Panel; Self; AstraZeneca. Consultant; Self; AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Bristol-Myers Squibb Company, Eli Lilly and Company, Merck KGaA, Merck Sharp & Dohme Corp., Novartis AG, Novo Nordisk A/S, Roche Pharma, Sanofi, Takeda Pharmaceutical Company Limited. Research Support; Self; AstraZeneca, Bristol-Myers Squibb Company, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novartis AG, Roche Pharma, Sanofi.