bluuebunny/crossref_metadata_2025 huggingface dataset:
Modeling of intermittent convective drying of walnuts in single layer and its influence on deep bed drying simulation
Authors: Doder Djordjije , Djakovic Damir
Published: June 2019

This research concerns the convective intermittent drying of in-shell walnuts, as well as the comparison between intermittent and continuous regimes. The collected data from the continuous drying experiment served as the basis for the modeling of intermittent drying, where the kinetic semi-theoretical model was implemented. Mathematical model for the intermittent drying precedes the computer simulation and experimental procedure for a single layer. As the validity of the proposed model is confirmed, deep fixed bed drying simulation was included as well. Intermittent drying regimes with shorter tempering periods gave better results compared to the longer ones. Deep bed simulations showed that a fixed bed of walnuts should not be bigger than 15-20 cm.
100-LB: Blood Glucose Forecasting with Extended Prediction Horizon
Authors: COLBURN DAVID , ROUDSARI VIRA BEHNAM , GANDICA RACHELLE , SIA SAMUEL
Published: June 2019

Accurate forecast of blood glucose levels could predict the onset of hypo- or hyperglycemic events and provide actionable information to patients, thereby improving glycemic variability and time in range, two important metrics for managing diabetes and assessing clinical outcomes. Current commercial continuous glucose monitors (CGMs) offer glucose trend prediction, but these predictions are often inaccurate. We hypothesize that the limited performance and utility of these predictive algorithms is likely due to using only glucose as the explanatory variable. By accounting for additional relevant features, we aim to build an algorithm that accurately predicts glucose levels with a prediction horizon of 1 hour. We conducted a pilot study in which blood glucose levels, meal and insulin logs, and activity-related parameters, like heart rate and steps, were collected from 5 individuals over a period of 2 weeks. This data was used to develop algorithms for glucose level prediction based on a number of models, including: long short-term memory (LSTM) recurrent neural network (RNN), Gaussian Process (GP), Lag Method and Clockwork RNN. The predictions using the LSTM model yielded the best performance. With the inclusion of additional features, the RMSE for a 1 hour prediction horizon using the LSTM RNN was 8.71 ± 3.98 mg/dL. However, work must still be done to improve performance and determine the importance of each feature.

Disclosure

D. Colburn: None. V. Behnam Roudsari: None. R. Gandica: None. S. Sia: None.
1001-P: Effects of Efpeglenatide on Body Weight, BMI, and Waist Circumference in Patients With Obesity Without Diabetes Stratified by Baseline Characteristics: A Subanalysis of BALANCE 205
Authors: PRATLEY RICHARD E. , JACOB STEPHAN , KANG JAHOON , TRAUTMANN MICHAEL E. , HOMPESCH MARCUS , HAN OAKPIL , STEWART JOHN A. , OGBAA IKE , SORLI CHRISTOPHER H. , YOON KUN-HO
Published: June 2019

Once-weekly (QW) subcutaneous efpeglenatide (efpeg) is a long-acting GLP-1 RA being developed to improve glycemic control in patients with T2D. In the BALANCE 205 study (NCT02075281) in patients with obesity (median BMI 34.9 [28.1−57.7] kg/m2) without diabetes, all doses of efpeg (4 or 6 mg QW; 6 or 8 mg once every 2 weeks [Q2W]) significantly reduced body weight (BW) from baseline (BL) to Week 21 vs. placebo (PBO, p<0.0001; primary endpoint). In this exploratory subgroup analysis, the effects of efpeg (in each treatment arm or pooled data) on BW, BMI, and waist circumference (WC) from BL to Week 21 vs. PBO were investigated in patients stratified by BMI, WC, and age (< or ≥ median BL values). All efpeg groups were associated with significant reductions in BW and BMI from BL vs. PBO across all subgroups (Table). Efpeg also led to significant reductions in WC vs. PBO across subgroups apart from lower doses of efpeg in subgroups with BMI and WC ≥ median (4 mg QW and 6 mg Q2W), and age ≥ median (4 mg QW). The observed adverse events mirrored those known for GLP-1 RAs.

In conclusion, all doses of efpeg led to consistent, significant reductions in BW and BMI in patients with obesity without diabetes in all subpopulations tested; results were consistent with those of the overall BALANCE population.

Disclosure

R.E. Pratley: Consultant; Self; Sanofi US. Other Relationship; Self; AstraZeneca, Eli Lilly and Company, GlaxoSmithKline plc., Janssen Global Services, LLC., Janssen Research & Development, Lexicon Pharmaceuticals, Inc., Ligand Pharmaceuticals, Inc., Merck Sharp & Dohme Corp., Mundipharma, Novo Nordisk Inc., Pfizer Inc., Sanofi, Takeda Development Center Americas, Inc. S. Jacob: Advisory Panel; Self; AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Novo Nordisk A/S. Speaker's Bureau; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Lilly Diabetes, Novartis AG, Novo Nordisk A/S, Roche Diabetes Care, Sanofi. J. Kang: Employee; Self; Hanmi Pharm. Co., Ltd. M.E. Trautmann: Consultant; Self; CeQur Corporation, Hanmi Pharm. Co., Ltd., Intarcia Therapeutics, Inc., Oramed Pharmaceuticals, ProSciento, Servier. Stock/Shareholder; Self; Lilly Diabetes. M. Hompesch: Stock/Shareholder; Self; ProSciento. O. Han: None. J.A. Stewart: Employee; Self; Sanofi. Stock/Shareholder; Self; Sanofi. I. Ogbaa: Stock/Shareholder; Self; Lexicon Pharmaceuticals, Inc. Other Relationship; Self; Sanofi. C.H. Sorli: Employee; Self; Sanofi. K. Yoon: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Merck Sharp & Dohme Corp., Novo Nordisk Inc. Speaker's Bureau; Self; Takeda Pharmaceutical Company Limited.

Funding

Hanmi Pharmaceutical, Co., Ltd.; Sanofi
1006-P: Real-World Effectiveness of Semaglutide in Early Users from a U.S. Commercially Insured (CI) and Medicare Advantage (MA) Population
Authors: VISARIA JAY , DANG-TAN TAM , PETRARO PAUL V. , NEPAL BAL K. , WILLEY VINCENT
Published: June 2019

Background: With semaglutide’s FDA approval in Dec 2017, this study sought to provide real-world evidence on its effectiveness in a cohort of early users.

Methods: Claims and lab result data from a broad national U.S. CI and MA population were used to identify T2DM patients who initiated semaglutide between 12/1/17 - 6/30/18 (first claim date set as index). Of these, patients who had ≥12-month pre-index health plan eligibility as well as ≥1 HbA1c result within both ≤3 months pre- and ≥3 months post-index were selected. Changes in HbA1c were assessed in all patients, GLP-1 naïve patients and GLP-1 naïve patients with a pre-index HbA1c >9%.

Results:Of 107 individuals with T2DM initiating semaglutide, 48.6% were female with median age of 52 years. HbA1c was significantly reduced in all patients (-1.3%), GLP-1 naïve patients (-2.0%) and HbA1c >9% GLP-1 naïve patients (-2.9%) (all p<0.001, Figure 1). Attainment of HbA1c <7% increased from pre- to post-index: 22.4 - 46.7% (all), 11.8 - 49.0% (GLP-1 naïve) and 0 - 32.0% (pre-index HbA1c >9% GLP-1 naïve) (all p<0.001).

Conclusions: Semaglutide initiation was associated with a significant reduction in HbA1c and increase in HbA1c goal attainment in real-world practice in this preliminary T2DM cohort. Ongoing research will include a broader group of semaglutide users as well as allow for longer post-initiation follow-up to fully assess its effect.

Disclosure

J. Visaria: Employee; Self; HealthCore. T. Dang-Tan: Employee; Self; Novo Nordisk Inc. P.V. Petraro: Employee; Self; Novo Nordisk Inc. B.K. Nepal: None. V. Willey: Employee; Self; HealthCore.

Funding

Novo Nordisk
1009-P: The Dual GIP and GLP-1 Receptor Agonist Tirzepatide Regulates Lipid and Carbohydrate Metabolism through GIPR in Adipose Tissue
Authors: SAMMS RICARDO JUSTIN , CHRISTE MICHAEL E. , RUAN XIAOPING , MOYERS JULIE , REGMI AJIT , ROELL WILLIAM C.
Published: June 2019

Tirzepatide (TZP), a GIP receptor and GLP-1 receptor (GIPR/GLP-1R) dual agonist, has demonstrated profound effects on glycemic control and bodyweight lowering in T2D subjects. However, the mechanism of action for the dual agonism of TZP is incompletely understood. Adipose expresses GIPR but not GLP-1R and therefore presents a key target tissue to investigate TZP biology. Using differentiated human adipocytes, we explored TZP regulation of lipid and carbohydrate metabolism. TZP demonstrated significant modulation of lipid accumulation, efflux, and oxidation. Similar to insulin, TZP increased expression and secretion of active LPL. While it had no effect on its own, TZP dose dependently suppressed insulin stimulated de novo lipogenesis in [14C]glucose and [14C]acetate incorporation assays. Insulin and TZP counter-regulated lipolysis characterized by insulin suppression and TZP stimulation of glycerol release. Uncoupled oxygen consumption was increased by TZP and subsequently reduced by CPT1 inhibition (etomoxir) demonstrating regulation of fatty acid oxidation. In adipose glycemic control, TZP exhibited both direct and insulin-dependent regulation of glucose transport. TZP at low dose (10pM) provided indirect (insulin sensitizing) effects while higher doses (10 nM) directly stimulated [14C]glucose uptake in adipocytes. While acute GIP infusion in a rat hyperinsulinemic/euglycemic clamp demonstrated no change in total body glucose infusion rate (GIR), chronic treatment (two week) with TZP or GIPR agonist increased GIR and adipose tissue [14C]glucose accumulation. This suggests both tissue-specific and whole-body insulin sensitization through GIPR agonism. Taken together, this data demonstrates GIPR specific activity of TZP in regulating adipose function. These findings and ongoing pathway integration studies will provide clues to the metabolic benefit of TZP GIPR/GLP-1R dual agonism compared with GLP-1R agonism alone.

Disclosure

R.J. Samms: Employee; Self; Eli Lilly and Company. M.E. Christe: Employee; Self; Eli Lilly and Company. X. Ruan: Employee; Self; Eli Lilly and Company. J. Moyers: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company. A. Regmi: Employee; Self; Eli Lilly and Company. W.C. Roell: Employee; Self; Eli Lilly and Company.
1019-P: Glucagon-Like Peptide-1 Receptor Agonists Predominantly Reduce Body Fat Mass in Patients with Type 2 Diabetes
Authors: FUJITA YUKI , KUBOTA SODAI , KUWATA HITOSHI , YABE DAISUKE , HAMAMOTO YOSHIYUKI , SEINO YUTAKA
Published: June 2019

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) helps obese patients with type 2 diabetes (T2DM) lose weight. Because few studies have researched their effectiveness on body composition, this study aimed to investigate the effect of GLP-1 RA on body fat mass (BFM) and skeletal muscle mass (SMM) in patients with T2DM.

In this retrospective study, we reviewed the database of our clinic and identified patients who had been prescribed GLP-1 RAs between 2010-2017. Patients who were either switched from insulin, had used any drugs that affect blood glucose levels (except metformin and sulfonylurea), or who had clinically significant disease were excluded. Both baseline and 12-month body compositions were assessed via the BIA device (Inbody S10 or S20). Body weight (BW), body mass index (BMI), and HbA1c were also measured. Data were analyzed using the paired t-test, with values shown as mean±SD.

A total of 205 patients were identified and 45 were included in the final analysis; 25 were non-insulin users and 20 were insulin users. After 12-month treatment, HbA1c, BW, and BMI were significantly reduced in both groups (Table 1). Interestingly, while BFM was significantly decreased, no differences in fat free mass or SMM were noted.

In conclusion, GLP-1 RA treatment leads to weight loss by predominantly reducing body fat mass in patients with T2DM regardless of being treated or not treated with insulin.

Disclosure

Y. Fujita: None. S. Kubota: None. H. Kuwata: Research Support; Self; Eli Lilly and Company. D. Yabe: Advisory Panel; Self; Abbott. Research Support; Self; Astellas Pharma Inc. Speaker's Bureau; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo Company, Limited, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd., Sanofi K.K., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited. Y. Hamamoto: Speaker's Bureau; Self; Novo Nordisk A/S. Y. Seino: Research Support; Self; Arkray, Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited, Terumo Medical Corporation.
103-OR: Central α-Klotho Suppresses Food Intake and Improves Glucose Regulation in Mouse Models of Metabolic Disease
Authors: LANDRY TAYLOR , LI PEIXIN , BUNNER WYATT P. , RAO ZHIJIAN , HUANG HU
Published: June 2019

Background/Aims: α-Klotho is a circulating factor with well-documented anti-aging properties; however, the central role of α-Klotho in metabolism remains largely unexplored. We aimed to investigate the potential role of central α-klotho as a novel regulator of energy balance and glucose homeostasis.

Methods: Central administration of α-klotho was performed by using intracerebroventricular (ICV) injection for seven days in diet-induced obesity (DIO) and streptozotocin-injected (STZ) mice. hrNPY-GFP reporter mice were utilized for electrophysiology and immunofluorescent staining experiments to investigate the effects of α-klotho on NPY/AgRP neurons. To determine the mechanism/s of hypothalamic α-klotho, we used GT1-7 immortal hypothalamic cells in vitro along with ICV administration of fibroblast growth factor receptor 1 (FGFR1) antagonist in vivo.

Results: Central α-klotho administration decreased food intake and improved glucose profiles in DIO and STZ mice. Liver lipid content and gluconeogenic gene expression were also reduced. Electrophysiology and immunofluorescent staining revealed AgRP/NPY neurons exhibit hyperpolarization and reduced firing rate in response to α-klotho treatment. These effects are, at least partially, due to increased magnitude of mIPSC’s. In vitro, α-klotho blunted serum-starvation-induced AgRP gene expression and increased phosphorylation of ERK44/42, AKTser473, and Foxo1ser256. These downstream effects were abolished by pretreatment with inhibitors of either FGFR1 or PI3kinase. Furthermore, α-klotho-mediated suppression of food intake, but not glucose levels, was blunted in response to inhibition of FGFR1 signaling.

Conclusion: These results indicate a prominent role of hypothalamic α-klotho-FGFR1-PI3K signaling in regulation of NPY/AgRP neuron activity, energy balance, and glucose homeostasis, thus providing new insight into the pathophysiology of metabolic disease.

Disclosure

T. Landry: None. P. Li: None. W.P. Bunner: None. Z. Rao: None. H. Huang: None.

Funding

East Carolina University
1034-P: Liraglutide and Dapagliflozin Induce an Increase in Plasma GLP-1 and GLP-2 Concentrations
Authors: GHANIM HUSAM , GREEN KELLY , DANDONA PARESH
Published: June 2019

Since liraglutide suppresses plasma glucagon concentrations and dapagliflozin increases glucagon concentrations, although both improve glycemia in patients with type 1 diabetes, we have now investigated whether they alter the concentrations of the two other products of the proglucagon gene, GLP-1 and GLP-2. Thirty patients with type 1 diabetes, treated with liraglutide for 26 weeks were randomized into receiving dapagliflozin 10 mg daily (n=20) or placebo (n=10) for 12 weeks. Fasting blood samples were obtained prior to liraglutide treatment, at the onset of dapagliflozin treatment and at the end of dapagliflozin treatment. At the end of 26 weeks liraglutide treatment and then 12 weeks of dapagliflozin therapy, mean HbA1c fell by 0.31±0.19% (NS) and 0.66±0.22% (p=0.0004), respectively. There was a significant increase in the plasma concentrations of GLP-1 (by 89±24%, from 30.4±5.1pM to 48.6±8.2pM, P=0.001) but not GLP-2 after 26 weeks of liraglutide treatment with a fall in glucagon levels. Dapagliflozin treatment induced a further significant increase in plasma GLP-1 (by 72±24%, from 48.6±8.2pM to 70.8±9.2pM, P=0.001) and caused an increase in GLP-2 concentrations (by 48±18%, from 2.01±0.42ng/ml to 2.97±0.51pM, P=0.01) along with an increase in glucagon concentrations. We conclude that while liraglutide suppresses glucagon, it induces an increase in GLP-1 concentrations. In addition, dapagliflozin increases both GLP-1 and GLP-2 concentrations while also increasing glucagon.

Disclosure

H. Ghanim: None. K. Green: None. P. Dandona: Advisory Panel; Self; AbbVie Inc., AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Intarcia Therapeutics, Inc., Merck & Co., Inc., Novo Nordisk Inc., Sanofi. Research Support; Self; AbbVie Inc., AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk Inc., Sanofi.
1043-P: Glycemic Profiles and Treatment Patterns: Real-World Data from 8,020 Adults with Type 1 Diabetes Using the Omnipod® Insulin Management System with Cloud-Based Data Management
Authors: LAYNE JENNIFER E. , HE JIALUN , JANTZ JAY , ZHENG YIBIN , BENJAMIN ERIC , LY TRANG T.
Published: June 2019

While clinical trials have demonstrated significant benefits of insulin pump therapy for type 1 diabetes, there is increasing recognition of the importance of real-world population data to better understand the impact of diabetes technology on treatment outcomes. This study retrospectively analyzed data from a large cohort of adults with type 1 diabetes using the Omnipod® Insulin Management System (Insulet Corp., Acton, MA) with an integrated BG meter (Abbott Diabetes Care Inc., Alameda, CA) and data management system (Glooko, Mountain View, CA) to characterize glycemic profiles, insulin use and treatment patterns. From January 2015 through September 2018, pump system data 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. Adults ≥18 y with type 1 diabetes (n=8,020) were age (mean±SD) 40.8±15.3y, 60% female, 61% used a tubeless insulin pump for ≥1 y and 13% used CGM for >50% of overall time of system use. Glycemic profiles included mean glucose 177±39 mg/dL, estimated A1C 7.8%, percent time in target range 70-180 mg/dL, hypoglycemia <70 mg/dL and hyperglycemia >180 mg/dL: 50.2±17.3, 5.9±5.0, and 43.9±18.3, respectively. The total daily insulin was 43.4±18.7 U/d which was delivered as 54% basal and 46% bolus. There were an average of 4.7±2.2 bolus deliveries per day and the average bolus amount was 4.5±2.8 U. These real-world glycemic profiles in adults with type 1 diabetes using the Omnipod® System support the use of diabetes technology in the management of type 1 diabetes. These data indicate that use of a tubeless insulin pump is associated with outcomes that compare favorably to large national registries including the T1D Exchange.

Disclosure

J.E. Layne: Employee; Self; Insulet Corporation. J. He: Employee; Self; Insulet Corporation. J. Jantz: Employee; Self; Insulet Corporation. Employee; Spouse/Partner; 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
1045-P: Efficacy and Safety of a 24-Hour Wearable Insulin Delivery Device for Basal-Bolus Therapy in Older Adults
Authors: ZEIDAN TRISHA , NIKKEL CARLA C. , DZIENGELEWSKI ELIZABETH A.
Published: June 2019

Basal-bolus insulin therapy in older patients is challenging due to the complexities of multiple daily injections and the higher risk of adverse consequences associated with hypoglycemia in this population. The purpose of this analysis was to evaluate the clinical outcomes and prevalence of hypoglycemia in patients 65 years of age or older when delivering basal-bolus therapy with a wearable insulin delivery device (V-Go). A retrospective analysis of electronic medical records in 54 patients with T2DM evaluated change in A1C, weight, insulin total daily dose (TDD) and prevalence of hypoglycemia. Baseline mean ± SD characteristics were age 71 ± 4 years (range 65 to 83), A1C 9.5 ± 1.6%, weight 99 ± 20 kg and TDD 64 ± 41 u/day (range 10 to 224) with 81% of patients prescribed insulin and 83% prescribed concomitant anti-hyperglycemic agents. Baseline hypoglycemia documented in 36% of patients. After a mean duration of 5 months of V-Go use, mean ± SD decreases in A1C (-1.5 ± 1.8%; p<0.0001) and TDD (-9 ± 35 u/day; p=0.107) were observed. Change in weight +0.65 kg; p<0.208. Prevalence of overall and severe hypoglycemia was markedly decreased with V-Go. As people with T2DM age, it may become necessary to simplify complex insulin regimens due to a decline in self-management ability while being mindful of risk factors. In this analysis, use of V-Go in an older population proved safe and efficacious.

Disclosure

T. Zeidan: Advisory Panel; Self; Corcept Therapeutics. Research Support; Self; Valeritas, Inc. Speaker's Bureau; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Lilly Diabetes, Valeritas, Inc. C.C. Nikkel: Employee; Self; Valeritas, Inc. Stock/Shareholder; Self; Valeritas, Inc. E.A. Dziengelewski: Employee; Self; Valeritas, Inc. Stock/Shareholder; Self; Valeritas, Inc.
1052-P: Time-in-Target Glucose Range and the Glucose Management Indicator during Real-World MiniMed™ 670G System Use
Authors: GOPALAKRISHNAN SHWETA , CORDERO TONI L. , SADEGHZADEH MAHTA , STONE MICHAEL , AGRAWAL PRATIK
Published: June 2019

Continuous glucose monitoring data can be reviewed, analyzed, and ultimately leveraged for diabetes treatment decision making. The Glucose Management Indicator (GMI) which determines an average A1C level based on mean continuous glucose monitoring data (Bergenstal RM, et al. 2018;41:2275-2280) was evaluated alongside time in target glucose range (TIR) during MiniMed™ 670G system use by over 3,000 real-world individuals living with diabetes. MiniMed™ 670G system data from individuals with T1D aged 14-22 years (n=291) and >22 years (n= 3174) were voluntarily uploaded from 3/17/2017 to 12/17/2018, de-identified, and analyzed if captured over the course of ≥365 days. The percentage of time in Auto Mode, TIR (70-180 mg/dL [3.9-10.0 mmol/L]) and time spent in hypoglycemia (<54 mg/dL [3.0 mmol/L]) were assessed alongside the GMI (3.31 + 0.02392 x [mean glucose in mg/dL]), 7-10 days after starting SmartGuard™ Auto Mode use. Over the analysis period, the median (min-max) of Auto Mode use was 77% (70.0-85.5%) in the >22 years cohort, and 62% (50.4-75.0%) in the younger cohort. In both cohorts, the mean TIR was above 70.0% and the time spent at <54 mg/dL stayed below 1.0% (<14min). The GMI for the older and younger cohorts was on an average 6.9% and 7.3% respectively, which is under 7.0% and 7.5%, meeting ADA recommended A1C targets for adult and pediatric age groups with diabetes, respectively. These findings indicate maintained glycemic control with concomitant Auto Mode usage and TIR, without increasing hypoglycemia, in real-world settings for individuals living with T1D and using the MiniMed™ 670G system.

Disclosure

S. Gopalakrishnan: Employee; Self; Medtronic. T.L. Cordero: Employee; Self; Medtronic. M. Sadeghzadeh: Employee; Self; Medtronic. M. Stone: None. P. Agrawal: Employee; Self; Medtronic MiniMed, Inc. Stock/Shareholder; Self; Medtronic.
1061-P: Effect of the Omnipod® Insulin Management System on Glycemic Control in Adults with Type 1 Diabetes Previously Treated with MDI or CSII
Authors: MEHTA SANJEEV N. , KRUGER DAVIDA F. , BODE BRUCE W. , LAYNE JENNIFER E. , DUMAIS BONNIE , GALLAGHER JACK R. , LY TRANG T.
Published: June 2019

This multi-site, retrospective study evaluated the effect of treatment with a tubeless insulin pump (Omnipod Insulin Management System, Insulet Corp., Acton, MA) on glycemic control in adults with type 1 diabetes (n=166) compared to prior treatment with multiple daily injections (MDI) (63%) or continuous subcutaneous insulin infusion (CSII) (37%). The primary outcome was change in A1C from baseline to 12 months post-Omnipodinitiation. Secondary outcomes included change in A1C at 3- and 6-months, and change in A1C stratified by baseline A1C and prior treatment with MDI or other CSII. Baseline characteristics were mean±SD: age 44±14 y, diabetes duration 24±14 y, 57% female, A1C 8.1±1.5%. The decrease in A1C at 12 months post-Omnipod therapy was -0.2±1.2% (8.1±1.5% vs. 7.9±1.3%; p=0.01) compared to prior treatment. A decrease in A1C was observed at 3- and 6-mo: -0.3±1.2% (n=95; p=0.005) and -0.3±1.1% (n=87; p=0.04), respectively. The within group reduction in A1C at 12 months for prior MDI use was -0.35% (8.1±1.5% vs. 7.8±1.2%; p=0.008) vs. -0.03% (8.0±1.4% vs. 8.0±1.5%; p=0.761) for CSII. The proportion of patients grouped by A1C category is shown in the Figure.

In conclusion, long-term use of the Omnipod System was associated with significant improvement in A1C in adults with type 1 diabetes, most notably in those with A1C ≥9.0% and those previously treated with MDI.

Disclosure

S.N. Mehta: None. D.F. Kruger: Advisory Panel; Self; Abbott, Boehringer Ingelheim Pharmaceuticals, Inc., Insulet Corporation. Consultant; Self; CeQur Corporation, Hygieia. Speaker's Bureau; Self; AstraZeneca, Dexcom, Inc., Eli Lilly and Company. Stock/Shareholder; Self; Dexcom, Inc. Other Relationship; Self; Novo Nordisk Inc. B.W. Bode: Consultant; Self; ADOCIA, Lexicon Pharmaceuticals, Inc., Novo Nordisk Inc. Research Support; Self; Becton, Dickinson and Company, Dexcom, Inc., Diasome Pharmaceuticals, Inc., Eli Lilly and Company, Eyenuk Inc., Insulet Corporation, National Institutes of Health, Novo Nordisk Inc., Sanofi Research & Development, Senseonics, Xeris Pharmaceuticals, Inc. Speaker's Bureau; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc., Novo Nordisk Inc., Sanofi US, Senseonics. Stock/Shareholder; Self; AgaMatrix, Glytec, LLC. J.E. Layne: Employee; Self; Insulet Corporation. B. Dumais: None. J.R. Gallagher: None. T.T. Ly: Employee; Self; Insulet Corporation.

Funding

Insulet Corporation
1068-P: A Prospective, Multicenter, Randomized, Open-Label, Parallel-Group Clinical Trial Comparing the Safety Profile of a Needle-Free Insulin Injector with Conventional Insulin Pen Injections in Chinese Patients with Type 2 Diabetes Mellitus
Authors: CHEN LIMING , JI LINONG , WANG YANGANG , MA ZHONGSHU , RAN XINGWU , SUN ZILIN , XU XIANGJIN , WANG GUIXIA , GUO LIXIN , SHAN ZHONGYAN
Published: June 2019

Background: Needle-free insulin delivery has been shown to accelerate the absorption and the action of insulin, and to be well tolerated.

Objective: To determine the safety profile of a needle-free injector with that of conventional insulin pen injections in patients with T2DM.

Methods: A total of 427 patients with T2DM were enrolled in a multicenter, prospective, randomized, open-label clinical trial, and were randomized 1:1 to receive basal or premixed insulin via a needle-free injector or via conventional insulin pen injections. Adverse events occurring during the study were recorded in the 2 groups, and the incidences of hypoglycemia and injection site reactions were compared.

Result: The adverse events rates in the needle-free injector and insulin pen groups were 5.31% and 3.35%, respectively, but no statistically significant difference between the 2 groups (P = 0.3468). Rates of hypoglycemia (25.60% vs. 18.18%, respectively; P = 0.0671), and local injection-site reactions (bleeding/ecchymosis and redness) were also similar in the 2 groups. However, the incidence of skin scratches was decreased significantly in the needle-free injector group (15.53% vs. 23.92%; P = 0.0319). There was no new indurations observed in needle-free injector group compared 4.00% in the conventional insulin pen group (P = 0.006). Patients in the needle-free injector group also showed lower overall VAS pain scores than those in the conventional insulin pen group (mean scores, 1.11 ± 1.21 vs. 1.98 ± 1.99; P < 0.0001).

Conclusion: Administration of insulin by a needle-free injector could provide a better safety profile than insulin pen injections, by reducing skin scratches, indurations, and pain.

Disclosure

L. Chen: Research Support; Self; Becton, Dickinson and Company. 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. Y. Wang: None. Z. Ma: None. X. Ran: None. Z. Sun: None. X. Xu: None. G. Wang: None. L. Guo: None. Z. Shan: None.
1082-P: Pediatric Basal Rate Assessment of CSII System Using a Newly Developed Kalman-Filter Based Measurement Method
Authors: GIRARDOT SYLVAIN , MOUSIN FLAVIEN , HARDY SÉBASTIEN , RIVELINE JEAN-PIERRE
Published: June 2019

Introduction: Insulin pump is nowadays one of the trendiest treatment for type 1 diabetes and is about to become one artificial pancreas (AP) major component.

Insulin pump accuracy and performances are essentials and have not been so much studied so far, especially for smallest basal rate used for pediatric treatment and gold-standard assessment method also appears limited.

Method: A leading edge assessment method based on a double measurement - direct mass flow meter and a time-stamped micro-gravimetric bench test - combined with a Kalman bayesian-based mathematical filter has been elaborated here and is proven to measure insulin pump delivering accuracy at the lowest limit of flow rate with a much better accuracy compared with previous methods.

Its advantages and performances are illustrated while assessing the delivery precision of an already-marketed insulin pump at several flow rate. Mean absolute relative dispersion (MARD) is used to indicate overall errors for each 15-minutes error dose of a 8-hours experiments.

Results: The new proposed methodology offers a double reading - volume and flow rate - within a much more timewise precise measurement (0.03Hz to 10Hz): direct instantaneous basal rate is displayed for the first time. Measurement accuracy is also considerably improved: pediatric basal rate is read with a 1.2%error instead of 15.3% error before. Accuracy is shown to be different regarding the flowrate value:Pump#1(2UI/h): MARD = 12.7%, Pump#1(0.5UI/h): MARD = 20.4%Pump#1(0.1UI/h): MARD = 65.7%

Conclusion: This innovative method to assess insulin pump administration highlights an imprecision of insulin delivery, especially for lowest basal rate as used in pediatric. Error identification might increase clinical impact and feed AP control algorithm while anticipating delivering errors.

Disclosure

S. Girardot: Employee; Self; Air Liquide. F. Mousin: Employee; Self; Air Liquide. S. Hardy: Employee; Self; Air Liquide. J. Riveline: Board Member; Self; Abbott, Lilly Diabetes, Novo Nordisk Inc. Consultant; Self; Novo Nordisk Inc. Research Support; Self; Air Liquide, Amgen Inc. Speaker's Bureau; Self; Abbott, Lilly Diabetes, Sanofi.
1083-P: Comparison of Hyperglycemia Management Protocols in the ICU: Standard Protocol vs. Electronic Glycemic Management System
Authors: UMPIERREZ GUILLERMO E. , MESSLER JORDAN
Published: June 2019

A variety of continuous insulin infusion (CII) algorithms are available to improve and maintain glycemic control in the ICU. In December of 2016, our institution, a community based academic hospital of 900 beds, acquired an electronic glycemic management system (eGMS, GlucommanderTM) for the management of ICU patients with hyperglycemia. We present our experience and compared glycemic control between patients managed with eGMS and standard care between December 2016 and December 2018. The standard care group included patients who were not on eGMS with at least 2 blood glucose readings >180 mg/dl during their ICU stay.

The primary endpoint was a proportion of blood glucose (BG) readings between 70-180 mg/dl. Secondary outcomes included rates of hyperglycemia > 250 mg/dl, as well as rates of hypoglycemia < 70 mg/dl, < 54 mg/dl and <40 mg/dl, and patient-day rates for hypoglycemia.

Among a total of 2897 ICU patients, 1971(68%) were treated with standard care and 926(32%) with eGMS. eGMS resulted in improved glycemic control with lower rates of hypoglycemia, Table.

Conclusion: Treatment with eGMS significantly lowered the incidence of hypoglycemia and severe hyperglycemia compared to standard care in the ICU. eGMS is a safe and effective way to manage hyperglycemia in the ICU of an academic medical center.

Disclosure

G.E. Umpierrez: Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc. Research Support; Self; AstraZeneca, Merck & Co., Inc., Novo Nordisk Inc., Sanofi US. J. Messler: Employee; Self; Glytec, LLC.
1088-P: A PK/PD and Metabolic Head-to-Head Comparison of Clinical Doses of Insulin Glargine U300 and Degludec in Type 1 Diabetes
Authors: LUCIDI PAOLA , PORCELLATI FRANCESCA , CANDELORO PAOLA , CIOLI PATRIZIA , PASCUCCI CHIARA , BOLLI GEREMIA B. , FANELLI CARMINE
Published: June 2019

Aim: to compare head-to-head pharmacokinetics (PK), pharmacodynamics (PD), glucose fluxes and lipid metabolism of clinical doses of insulin glargine U300 (Gla-300) and degludec U100 (IDeg) in real life in T1DM.

Methods: 22 subjects [(11M, age 44±12, T1DM for 26±12 years, BMI 22.5±3.2 kg/m2, A1C 7.1±0.6% (53.4±7.1 mmol/mol)] on Gla-100, naïve to Gla-300 and IDeg, were studied (24h euglycemic clamp) with individual doses of Gla-300 and IDeg (dosing at 20.0h) after 3 months of optimal titration of basal-bolus insulin (random crossover).

Results (at present in 14 of the 22 subjects, PD only, data in progress): preclamp A1C was similar with Gla-300 vs. IDeg. Individual basal insulin dose was greater with Gla-300 vs. IDeg (0.35±0.09 vs. 0.27±0.06 U/kg, p<0.01). Average PG (0-24h) was euglycemic on both occasions (p=NS). Area under curve of glucose infused [AUC-GIR(0-24h)] was equivalent for the two insulins (ratio 1.03, 90% C.I. 0.9, 1.22) (Figure). Within-day PD variability tended to be lower with Gla-300 vs. IDegl (CV 51% vs. 59%, p<0.051).

Conclusions. In T1DM, PD of clinical doses of Gla-300 are equivalent to IDeg with a trend for lower within-day variability.

Disclosure

P. Lucidi: Other Relationship; Self; Abbott, Novo Nordisk A/S. F. Porcellati: Board Member; Self; AstraZeneca, Eli Lilly and Company, Sanofi. Consultant; Self; Medtronic. P. Candeloro: None. P. Cioli: None. C. Pascucci: None. G.B. Bolli: Advisory Panel; Self; Sanofi. Research Support; Self; A. Menarini Diagnostics, Medtronic. C. Fanelli: Advisory Panel; Self; Sanofi. Other Relationship; Self; Menarini Group.
1105-P: Impact of Switching from Twice-Daily Basal Insulin (BI) to Once-Daily Insulin Glargine 300 U/mL (Gla-300) in Patients with Type 1 Diabetes (T1DM): Phase 4 Optimize Study
Authors: MATHIEU CHANTAL , STELLA PETER , BRUHWYLER JACQUES , ALEXANDRE KATHY C.
Published: June 2019

The 28-week, prospective, multicenter, open-label OPTIMIZE study, conducted in Belgium (presented at ADA 2018) and Canada, evaluated treatment optimization with once-daily (OD) Gla-300 in combination with a prandial insulin analog in adults with T1DM previously uncontrolled (HbA1c 8-10%) on twice-daily (BID) BI as part of basal-bolus therapy.

The intent-to-treat and safety populations comprised 94 patients (53.2% women; 51.1% from Belgium); mean (SD) age 49.4 (13.1) years and BMI 27.8 (4.7) kg/m². Prior to the study, 45.7% received insulin glargine 100 U/mL and 52.1% insulin detemir. There was a statistically significant reduction in HbA1c from baseline to month 6 (p<0.0001; Table). A statistically significant increase in BI dose (p=0.032) was observed, but there were no significant changes in prandial insulin dose. Hypoglycemic event rates did not significantly change (Table). Statistically significant improvements were seen in the Diabetes Treatment Satisfaction Questionnaire total and perceived hyperglycemia scores, and patient satisfaction score for number of injections (p<0.0001).

In this clinically challenging population, better overall treatment satisfaction and improvement in HbA1c, without increase in the rate of hypoglycemia, was achieved on switching from BID to OD Gla-300 plus prandial insulin.

Disclosure

C. Mathieu: Advisory Panel; Self; Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk A/S, Roche Diabetes Care, Sanofi. Speaker's Bureau; Self; AstraZeneca, Novartis AG, Novo Nordisk A/S, Sanofi. P. Stella: Employee; Self; Sanofi. Stock/Shareholder; Self; Sanofi. J. Bruhwyler: Other Relationship; Self; Sanofi. K.C. Alexandre: Employee; Self; Sanofi. Stock/Shareholder; Self; Sanofi.

Funding

Sanofi (EudraCT 2015-001186-46)
1118-P: Effect of Patiromer in Patients 75 Years or Older with Diabetic Kidney Disease and Hyperkalemia Receiving a RAAS Inhibitor
Authors: BAKRIS GEORGE L. , WOODS STEVEN D. , ALVAREZ PAULA J. , FOGLI JEANENE , ARTHUR SUSAN , MAYO MARTHA R. , KUMAR RAJEEV
Published: June 2019

Background: Patiromer (PAT) is a sodium-free, non-absorbed potassium (K+) binder approved for the treatment of hyperkalemia (HK). HK is common in older patients (pts) with cardiorenal comorbidities and often limits the use of guideline recommended renin-angiotensin-aldosterone system inhibitor (RAASi) medications. We previously reported the design and results for AMETHYST-DN, a phase 2 multicenter, open-label, 52 week randomized clinical trial in a large cohort of adult pts (n=306; 30-80 years of age).

Methods: Here we report the results in a subgroup ≥75 years of age with type 2 DM, chronic kidney disease (CKD) (eGFR 15 to <60 mL/min/1.73 m2), hypertension and serum (s) K+ >5.0 mEq/L (n=60). All pts received a RAASi before and during the study treatment and PAT was titrated to maintain sK+ in the normal range.

Results: Two days after the first dose, mean sK+ was reduced to 4.89 mEq/L from a baseline (BL) mean of 5.19 mEq/L (p<0.001). The least square mean reduction in sK+ from BL to week 4 was -0.65 mEq/L (p<0.001) and -0.61 mEq/L (p<0.001) at 52 weeks (end of treatment). The % of pts with sK+ in the normal range (3.8-5.0 mEq/L) between weeks 12-52 ranged from 88-98%. At the end of treatment, 92% of pts had sK+ in the normal range. The most common GI-related adverse event (AE) was constipation observed in 2 pts (3.3%). Serum magnesium levels of <1.2 mg/dL were seen in 3 pts (5%). Hypokalemia (sK+ <3.5 mEq/L) did not occur in this older population. Serious AEs were reported for 9 pts (15%); none attributed to PAT by investigator. Study limitations include a lack of blinding, a lack of comparator, and a lack of diversity.

Conclusions: In this subgroup of pts ≥75 years with diabetic CKD receiving a RAASi medication, PAT reduced and maintained control of sK+ for up to 1 year. PAT was well tolerated over 52 weeks with no serious AEs attributed to its use. These results suggest that PAT may facilitate the use of RAASi medications in older pts likely to benefit from their cardiorenal protective effects.

Disclosure

G.L. Bakris: Consultant; Self; Merck & Co., Inc., Novo Nordisk Inc., Relypsa, Inc. Research Support; Self; Bayer AG, Janssen Pharmaceuticals, Inc. S.D. Woods: Employee; Self; Relypsa, Inc. P.J. Alvarez: Employee; Self; Relypsa, Inc. J. Fogli: Employee; Self; Relypsa, Inc. S. Arthur: Employee; Self; Relypsa, Inc. M.R. Mayo: Employee; Self; Relypsa, Inc. R. Kumar: None.

Funding

Relypsa, Inc.
1140-P: Efficacy and Safety of Evogliptin in Patients with Type 2 Diabetes: A Multicenter, Active-Controlled, Randomized Study with Open Label Extension (EVERGREEN Study)
Authors: LIM SOO , KIM GYURI , KWON HYUK-SANG , PARK IE BYUNG , AHN KYU JEUNG , PARK CHEOL-YOUNG , KWON SU KYOUNG , KIM HYE SOON , PARK SEOK WON , KIM SIN GON , MOON MIN KYONG , KIM EUNSOOK , CHUNG CHOON H. , WON KYU CHANG , PARK KANG SEO , KIM MIKYUNG , CHUNG DONG JIN , LEE CHANG BEOM , KIM TAE HO , LEE MOON-KYU
Published: June 2019

Background and Aims: Evogliptin is a new dipeptidyl peptidase-4 (DPP-4) inhibitor. We investigated the efficacy and safety of Evogliptin compared with linagliptin in patients with type 2 diabetes (T2D).

Materials and Methods: A total of 207 untreated patients with T2D (mean age, 56.1±10.4 years; body mass index, 26.1±3.4 kg/m2) who had HbA1c 7.0-10.0%, prior to the screening were randomized 1:1 for 5 mg Evogliptin (n=102) or 5 mg linagliptin (n=105) once daily for 12 weeks. The primary efficacy endpoint was the change from baseline HbA1c at week 12. The secondary endpoint included the change in mean amplitude of glycemic excursion (MAGE) assessed by 72-hour continuous glucose monitoring. In the extended study for another 12 weeks, open-label treatment with Evogliptin 5 mg qd was conducted in both groups; Evogliptin/Evogliptin group (n=95) and Linagliptin/Evogliptin group (n=92).

Results: After 12 weeks of treatment, the mean changes in HbA1c of Evogliptin group and linagliptin group were −0.85% and −0.75%, respectively; the between-group difference was -0.10% (95% confidence interval, −0.32-0.11%), demonstrating non-inferiority, meeting the pre-specified margin of 0.40%. The changes in MAGE were −24.6 mg/dL in the Evogliptin group and −16.7 mg/dL in the linagliptin group, which were significantly lower compared with baseline values in both groups. In the Evogliptin/Evogliptin group at week 24, the mean changes from baseline in HbA1c was −0.94%, achieving HbA1c <7.0% in 80.2% of patients. The incidence and types of adverse events including hypoglycemic events, were comparable between the two groups for 24 weeks.

Conclusion: In this study, once-daily evoglipitin 5 mg treatment significantly decreased HbA1c levels by 0.94% at week 24 and improved glycemic variability without any serious adverse events in Korean patients with T2D (ClinicalTrials.gov Identifier: NCT02974504).

Disclosure

S. Lim: None. G. Kim: None. H. Kwon: None. I. Park: None. K. Ahn: None. C. Park: None. S. Kwon: None. H. Kim: None. S. Park: None. S. Kim: None. M. Moon: None. E. Kim: None. C.H. Chung: None. K. Won: None. K. Park: None. M. Kim: None. D. Chung: None. C. Lee: None. T. Kim: None. M. Lee: None.
1147-P: Effect of Short-Term Ciclosporin A Treatment on Insulin Secretion in Patients with Adult-Onset Autoimmune Diabetes: An Open-Label, Single-Arm, Pilot Study in China
Authors: ZHANG LEI , WANG JUN , WANG NA , YANG YUXIU , YIN XIAOYAN , DONG YANHU
Published: June 2019

Adult-onset autoimmune diabetes, defined as having latent autoimmune diabetes in adults (LADA), is characterized by a less intensive autoimmune process, in which a lymphocytic infiltration of the exocrine pancreas is involved. Immunosuppressive agents may have potential therapeutic benefit. This is a pilot study examining the therapeutic effects of oral administration of ciclosporin A on insulin secretion in patients with LADA. The study was an open label, single arm, pilot trial. A total of 12 patients (8 men and 4 women with mean age of 40.2 years old) diagnosed with LADA were prospectively evaluated. All patients underwent insulin treatment at least for 3 months without any oral anti-hyperglycemic agent. Serum C-peptide concentrations were measured at baseline and after ciclosporin A intervention. We also evaluated clinical parameters including total bilirubin (TBIL), direct bilirubin (DBIL), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and creatinine (Cre) before and after ciclosporin A treatment. The primary outcome of the study was the change in serum C-peptide concentrations. A total of 12 patients completed the study. No patient was withdrawn. Serum fasting C-peptide concentrations significantly increased from 0.10 ng/ml up to 0.32 ng/ml, following treatment with ciclosporin A (50mg/day) for 4 weeks (P<0.001). After 4-week ciclosporin A intervention, there was no significant difference on TBIL (14.33 vs. 13.70 umol/L, P=0.59), DBIL(4.31 vs. 4.63 umol/L, P=0.48), AST(16.83 vs. 18.50 U/L, p=0.09), ALT(17.17 vs. 18.16 U/L, p=0.35), or Cre (67.17 vs. 66.01 umol/L, P=0.25) compared with the corresponding baseline levels. This pilot study demonstrates the potential therapeutic effects of oral administration of ciclosporin A for patients with LADA. No significant adverse effects of the drug were observed. Larger, controlled studies are needed to verify the results.

Disclosure

L. Zhang: None. J. Wang: None. N. Wang: None. Y. Yang: None. X. Yin: None. Y. Dong: None.
1151-P: Dorzagliatin Differentiates from Early Generation of Glucokinase Activators: An Enzyme Kinetics Study
Authors: CHEN LI , SHAN YONGQIANG , JIN XIAOWEI , LV XIAOBING
Published: June 2019

Over the last two decades, many glucokinase activators (GKAs) advanced into clinical studies but failed to achieve proof of concept as antidiabetics until the most recent success of Dorzagliatin (a.k.a. HMS5552). Desirable pharmacokinetic (PK) and pharmacodynamic (PD) properties of Dorzagliatin in human subjects offer clear advantage over many GKAs previously in clinical trial. Dorzagliatin benefits also from its desirable enzyme kinetic properties that improve GK’s glucose sensor function and restore glucose homeostasis. Herein we report our recent results on 5 GKAs which all advanced into Phase II clinical studies, some suffered hypoglycemia and others lacked durable efficacy in T2D patients. We evaluated key parameters in GK activation that include α, β and nH in nonessential-mixed type enzyme kinetics equation, as well as the changes under various glucose and drug concentrations. Here β represents the change in Vmax and associates with the ability of GKA to restore GK’s glucose sensor function. Partial GKAs such as AZD1656 and PF-04937319 showed β<1 and were less effective in blood glucose control. In contrast, Piragliatin and Dorzagliatin showed β value of 1.74 and 1.40 respectively, both demonstrated sustained and significant HbA1c reduction. Changes of nH result in alteration of GK’s glucose dependence and the degree of changes in nH is dependent on GKA concentration. Significant changes in nH by MK-0941 (nH = 1.21 at 10 μM GKA vs. 1.86 without GKA) correlate with its hypoglycemia risk in T2D subjects as shown in clinical trials. Our results strongly indicate that % change in nH at 10 uM GKA shall not go beyond 20% compared with drug free state. Lastly, α values for 5 GKAs all seem to fall in the range of 0.005 to 0.016, thus not appear to correlate with the behavior in clinical trials. The current study provides valuable insight to elucidate some key properties contributing to successful development of a GKA that repairs the glucose sensor function and remodels homeostasis.

Disclosure

L. Chen: Employee; Self; Hua Medicine. Y. Shan: None. X. Jin: None. X. Lv: None.