bluuebunny/crossref_metadata_2025_split huggingface dataset:
750-P: Novel Approach for Development of Oral GLP-1 Receptor Agonist with Superior Bioavailability and Antidiabetic Efficacy
Authors: JI PARK EUN , JEON OK-CHEOL , PARK JONG-SUNG , CHOI JIYOUNG , SHIN JAEHEE , LIM SUNGMOOK , PARK SOOBONG , LEE SEULKI 
Published: May 2022

While glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are highly effective at lowering HbA1c, currently available GLP-1 RA delivery options are suboptimal; SC administrations hinder patient adherence and oral administrations have lower bioavailability due to enzymatic instability and insufficient gastrointestinal absorption. A novel approach to deliver GLP-1 RAs with superior bioavailability and better patient adherence would further improve the antidiabetes efficacy of GLP-1 RAs. Hence, this study assesses an oral formulation facilitating intestinal absorption of DD02S, a new GLP-1RA. Biological activities, gastrointestinal stabilities and Caco-2 permeability study of DD02S were performed in vitro. The in vivo efficacy of the oral formulation was evaluated by intraduodenal injection in rats. DD02S was formulated as enteric coated tablets and orally administered in dogs. Pharmacological efficacy was demonstrated by repeated dosing in db/db mice. DD02S was designed to introduce a ligand and fatty acid to facilitate cellular uptake via intestinal transporters, increase enzyme stability, and enable reversible plasma protein binding without loss of potency. The oral formulation enhanced the intestinal stability as well as permeation via trans and paracellular routes. The increased intestinal absorption was confirmed by intraduodenal injection in rats. Following the oral administration of the enteric coated tablets to dogs, the mean bioavailability ranged from 5.0-10.1% with variability of 78-117% and pharmacokinetic parameters were suitable for once daily oral dosing. In the antidiabetes efficacy study of DD02S, significant reduction of HbA1c was observed in a dose-dependent manner. This study demonstrates the potential antidiabetes efficacy of DD02S with once daily oral dosing. Our novel approach for oral delivery is promising to development of other oral peptide therapeutics.

Disclosure
E.Park: Employee; D&D Pharmatech. O.Jeon: Employee; D&D Pharmatech. J.Park: Employee; D&D Pharmatech. J.Choi: Employee; D&D Pharmatech. J.Shin: Employee; D&D Pharmatech. S.Lim: Board Member; D&D pharmatech. S.Park: Board Member; D&D Pharmatech. S.Lee: Board Member; D&D Pharmatech.
754-P: Antifibrotic Potential of a Novel Long-Acting Glucagon/GIP/GLP-1 Triple Agonist (HM15211) in Preclinical Models of IPF
Authors: LEE SEON MYEONG , KIM JEONG A. , LEE JONG SUK , KIM JUNG KUK , BAN YOUNG-HWAN , LEE JONGSOO , BAE SUNGMIN , KIM DAEJIN , LEE SANG HYUN , CHOI IN YOUNG 
Published: May 2022

Idiopathic pulmonary fibrosis (IPF) is an irreversible and progressive pulmonary disorder in which scarring of lung tissue eventually leads to death. A large of studies have demonstrated that the core mechanisms in fibrosis across various organs are similar. Previously, excellent preclinical efficacy of HM15211, a novel long-acting Glucagon/GIP/GLP-1 triple agonist, on liver fibrosis was confirmed (the major distribution tissues of HM152were liver and lung) . These findings prompted us to hypothesize that HM152might be also a promising drug candidate for IPF. Its effect on pulmonary function and mortality was evaluated in bleomycin (BLM) -induced mouse model of lung fibrosis. BLM was instilled intratracheally to assess the therapeutic benefits of HM152over pirfenidone (PIRF) and nintedanib (NINT) (FDA-approved drugs for IPF) . Briefly, HM152was administered 7 days post BLM instillation, and then saturation of peripheral oxygen (SpO2) and survival rate were monitored until day 14 and day 21, respectively. 1.5 U/kg BLM mice showed markedly impaired lung function at day 7 as indicated by SpO2 (84.0 vs. 95.6% for normal) , which was further exacerbated until day 14 (77.1% vs. 96.0% for normal) . Interestingly, while PIRF (81.9%) and NINT (81.3%) prevent additional lung function impairment without any reversal effects, HM152treatment significantly restored impaired lung function (91.5%) at day 14. In addition, at 21 days after 2.5 U/kg BLM treatment, substantial decline in survival rate (17%) was effectively inhibited by HM15211, NINT, and PIRF. Notably, HM152 (61%) showed more improved survival rate than NINT (33%) , and PIRF (28%) , suggesting potential superiority of HM152over current IPF drugs.
In conclusion, HM152may be a novel therapeutic potential for pulmonary fibrosis over current standard of care for IPF. Further evidences from the mechanistic studies will shed light on a direct inhibitory effect of HM152on pulmonary fibrosis.

Disclosure
S.Lee: None. I.Choi: None. J.A.Kim: None. J.Lee: None. J.Kim: None. Y.Ban: None. J.Lee: None. S.Bae: None. D.Kim: None. S.Lee: n/a.
755-P: Liraglutide plus Basal Insulin Combination Therapy in Japanese Old-Aged People with Type 2 Diabetes: Peak Age at 70s
Authors: KASHIMA KOJI , SHIMIZU HIROYUKI , YAMADA MASANOBU 
Published: May 2022

Objective: In management type 2 diabetes (T2D) , it is required to pursue the A1C &lt;7% Target avoiding hypoglycemia, especially in increased old aged population in Japan. We examined the effectiveness of liraglutide (Lira) and insulin degludec (IDeg) combination therapy in 134 Japanese persons with T2D.
Methods: Hospitalized persons who started this combination therapy since year 2014 were recruited. Changes of HbA1c and basal Insulin doses were evaluated for 4.5 years after discharge. Glycemic variability (GV) was evaluated by ADRR in person who did SMBG. Since preserved β-cell function might influence the management, effectiveness was also compared by duration of T2D ≤ 5-year (SHORT; n=53) or &gt; 5-year (LONG; n=81) . Persons in SHORT were with shorter duration of T2D than LONG (0.67±1.5 vs. 18.7±9.3 years: p&lt;0.0001) , higher C-peptide Index (1.50±0.76 vs. 0.97±0.66: p&lt;0.001) .
Results: 1) Mean HbA1c in total had maintained ≤7.1% from 3rd to 54th month. But mean HbA1C in SHORT was remarkably improved, and had maintained ≤6.6% from 3th until 54th month with extremely lower ADRR score ∼5. 2) At hospitalization, maximum IDeg dose was 15.5±9.2 (6∼46) (SHORT) vs. 14.0±7.6 (4∼40) U/day (LONG) , because of higher HbA1C (12.3±2.3% vs. 10.3±2.4%: p&lt;0.0001) at the baseline. But insulin requirement rapidly decreased in SHORT. On titration, IDeg was titrated not to reach BG &lt;80mg/dL. IDeg could be quitted in ∼75% vs.∼15% at 24th month, respectively. On 3rd month in insulin user, IDeg dose decreased to 7.5±4.1U/day vs. 9.6±5.6U/day, despite lower Lira dose in SHORT with 0.66±0.15mg/day vs. in LONG 0.72±0.23mg/day. 3) Distribution of peak age in total was 70s, and the CKD rate was the more pronounced at 57% (25/44) . Although SHORT group were younger (60.8±11.7 vs. 70.8±11.0 years old: p&lt;0.01) , they already had CKD in 32.1%.
Conclusion: Lira based therapy is useful for attaining HbA1c Target with simple insulin titration, longer durability, and for pursuing reno-protection in whole generation with CKD.

Disclosure
K.Kashima: None. H.Shimizu: None. M.Yamada: None.
756-P: The Effect of Semaglutide on Alanine Aminotransferase (ALT) Levels: Results from the Association of British Clinical Diabetologists (ABCD) Audit
Authors: CRABTREE THOMAS S.J. , SENNIK DEVESH K. , BICKERTON ALEX , BARNES DENNIS , SIVAPPRIYAN SIVA , ADAMSON KAREN , PHILLIPS SUZANNE M. , EVANS ALISON , LARSEN NIELS , PANESAR AVINASH , CULL MELISSA L. , GALLEN IAN W. , IDRIS ISKANDAR R. , RYDER ROBERT E. 
Published: May 2022

Obesity and type 2 diabetes are important drivers for the development of nonalcoholic fatty liver disease (NAFLD) . Glucagon-like peptide-1 receptor agonists (GLP1RAs) are efficacious for these conditions, but their potential as treatments for NAFLD remains unclear. As serum ALT concentration is routinely measured in clinical care, we evaluated the impact of the GLP1RA, semaglutide, on ALT in those at risk of NAFLD.
Methods: Data submitted to the ABCD semaglutide audit (launched in 2019) were analysed. Change in ALT from baseline was assessed and corrected for change in covariates and concomitant medications using a multiple linear regression in Stata 16 . Baseline ALT levels were used to perform a stratified analysis as follows: normal (ALT 0-29U/L) , mildly elevated (30-59 U/L) and significantly elevated (≥60U/L) . Missing data were multiply imputed.
Results: Data for 1,623 individuals (50.2% men) were included with baseline (mean±SD) : age 58.9±11.0 years, HbA1c9.4±1.7%, weight 104.6±2.8kg, BMI 37.1±7.4kg/m2 and median (IQR) diabetes duration 10.9 years (6-15.4) and ALT 26U/L (19-36) . Median (IQR) follow-up was 8.2 months (5-12) . At follow-up, changes in HbA1c and weight were -1.2% (95%CI -1.0, -1.3; p&lt;0.001) and -2.4kg (95%CI -1.7, -3.1; p&lt;0.001) respectively. No significant change in ALT was seen across the entire cohort (p=0.172) . However, ALT rose in the normal group (+14.6U/L; 95%CI 10.4, 18.8; p&lt;0.001) and fell in the significantly elevated group (-16.2U/L; 95%CI -11.8, -20.5; p&lt;0.001) . No change was noted in the mildly elevated group (p=0.33) . The differences between groups were statistically significant (p&lt;0.0001) .
Conclusion: Among patients with significantly raised ALT, semaglutide was associated with ALT reduction, but this finding may result from regression to the mean. Measurement in parallel of further biomarkers of liver fibrosis will be required to assess the potential of semaglutide as a NAFLD therapy.

Disclosure
T.S.J. Crabtree: Other Relationship; Abbott Diabetes, Novo Nordisk, Sanofi. D.K. Sennik: Speaker's Bureau; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Novo Nordisk, Sanofi. D. Barnes: None. S. Sivappriyan: None. K. Adamson: None. S.M. Phillips: None. A. Evans: None. N. Larsen: None. A. Panesar: None. I.W. Gallen: None. I.R. Idris: None. R.E. Ryder: None.

Funding
The ABCD audit is support by an unrestricted grant from NovoNordisk
757-P: Perioperative Fully Closed-Loop vs. Standard Insulin Therapy in Adults Undergoing Pancreatic Surgery
Authors: HERZIG DAVID , SUHNER SIMON , CECCHINI LUCA , ROOS JONATHAN L. , SCHÜRCH DANIEL , NAKAS CHRISTOS , BELDI GUIDO , GLOOR BEAT , WILINSKA MALGORZATA E. , HOVORKA ROMAN , VOGT ANDREAS , BALLY LIA 
Published: May 2022

Background and Aims: Pancreatic surgery challenges perioperative glucose management by abrupt changes in endogenous insulin stores, surgical stress, medication and nutritional support. We hypothesize that fully closed-loop (CL) insulin delivery, compared to usual care, may better accomodate the complex needs of this population.
Methods: In this subpopulation analysis of a randomized controlled trial (NCT04361799) we compared the CamAPS HX fully CL system using subcutaneous faster insulin aspart (CL) with standard insulin treatment (control) in patients undergoing pancreatic surgery. Glucose control was assessed using the Dexcom G6 continuous glucose monitoring (blinded in the control group) from hospital admission to discharge (max 20 days) .
Results: Twelve patients (6 per group, 58% female, mean±SD age 69±18 years, BMI 27.3±3.9 kg/m2, HbA1C 7.8±2.0 %, 66 % total pancreatectomy) were analyzed. Median [IQR] %time in target glucose range (5.6-10.0mmol/L) was 76.5 [75.3; 80.3] % with CL vs. 45.6 [24.1; 55.5] % with control (P=0.005) . Time in hypoglycemia (&lt;3.9mM and &lt;3.0mM) did not differ between groups (P=0.81 and P=0.46) . No study-related serious adverse events occurred in either group.
Conclusions: Perioperative fully CL in patients undergoing partial or total pancreatectomy improves glucose control compared to standard insulin therapy without a higher risk of hypoglycemia.

Disclosure
D.Herzig: None. R.Hovorka: Advisory Panel; Eli Lilly and Company, Other Relationship; CamDiab Ltd., Research Support; Abbott Diabetes, Dexcom, Inc., Medtronic, Speaker's Bureau; Dexcom, Inc., Eli Lilly and Company, Novo Nordisk. A.Vogt: None. L.Bally: None. S.Suhner: None. L.Cecchini: None. J.L.Roos: None. D.Schürch: None. C.Nakas: None. G.Beldi: None. B.Gloor: None. M.E.Wilinska: Consultant; CamDiab Ltd.

Funding
Swiss Helmut Horten Foundation;Swiss Foundation for Anaesthesiology and Intensive Care;Product support by Dexcom Inc.;
768-P: Clinical Outcomes of Euglycemic DKA with a Computerized Insulin Algorithm: Descriptive Analysis of a Nationwide Cohort
Authors: MESSLER JORDAN , VELLANKI PRIYATHAMA , BOOTH ROBERT 
Published: May 2022

Euglycemic DKA (euDKA) is an underdiagnosed endocrine emergency and may not be treated appropriately treated due to lower than expected glucose levels. EuDKA has been increasing in prevalence due to the use of SGLT2-inhibitors. Glycemic or insulin outcomes for hospitalized patients with euDKA have been limited to case reports and series and have not been reported in a large cohort. Individual-level data were extracted from the Glytec Inpatient Database from 154 hospitals across the United States from (2017-2021) . All patients were on Glucommander IV, a computerized continuous insulin infusion (CII) algorithm, for at least 1 hour, to examine glycemic outcomes and insulinometrics. EuDKA was defined as patients with age ≥18 years with a BG &lt; 250 mg/dl and who met the following criteria on admission: bicarbonate &lt;18 mmol/L, pH &lt;7.3, with ketones present in serum or urine. All patients had an ICD of Eor Eor A1c &gt;6.5%. We identified 533 patients with euDKA (Table) . Time to HCO3 &gt; 18 mEq/L was 14.1 hours. The incidence of hypoglycemia was low. Analysis of a nationwide cohort shows that euDKA can be safely and effectively treated with a computerized algorithm in the hospital, as patients achieved rapid time to target, resolution of DKA, and low mortality.

Disclosure
J.Messler: Employee; Glytec, LLC. P.Vellanki: n/a. R.Booth: Employee; Glytec, LLC.
773-P: Impact of Six Months of Hybrid Closed-Loop Use on Sleep in Youth with Type 1 Diabetes and Their Parents
Authors: COBRY ERIN C. , KARAMI ANGELA J. , VIGERS TIMOTHY B. , PYLE LAURA , JOST EMILY , MELTZER LISA J. , WADWA R. PAUL 
Published: May 2022

Many youth with T1D and their parents do not achieve sufficient sleep duration or quality. While HCL use improves nocturnal glycemic control, it is unclear whether sleep duration and quality are impacted. The objective of this study was to measure sleep outcomes in children with T1D and parents after HCL initiation.
Youth with T1D starting the Tandem Control-IQ (CIQ) and a parent enrolled in an observational study. Actigraphy data (sleep duration, sleep efficiency, and wake after sleep onset (WASO)) and sleep surveys (Pittsburgh Sleep Quality Index (PSQI) , PROMIS Pediatric Sleep Disturbance and Sleep-Related Impairment) were collected at baseline and 3- and 6-months after CIQ initiation.
Thirty-nine youth (11.1±3.6 yrs (range 3-17) , T1D duration 2.5±3.0 yrs, 54% male) and parents (42.5±6.7 yrs, 18% male) participated. Parents significantly improved WASO at 3- and 6-months (p=0.0 and 0.007) and sleep quality at 3-months (p=0.011) . No significant changes in subjective or objective sleep outcomes for children occurred other than a decrease in PROMIS Sleep-Related Impairment parent proxy at 3 months (p=0.041) .
Youth with T1D and their parents experience insufficient sleep duration and poor sleep quality. Parent subjective sleep quality and WASO improved with CIQ use. Improving sleep quality is complex and further research is needed to identify causes of sleep disruptions and intervention methods.

Disclosure
E.C.Cobry: None. A.J.Karami: None. T.B.Vigers: None. L.Pyle: None. E.Jost: Other Relationship; Tandem Diabetes Care, Inc. L.J.Meltzer: None. R.Wadwa: Advisory Panel; Dompé, Consultant; Beta Bionics, Inc., Other Relationship; Tandem Diabetes Care, Inc., Research Support; Dexcom, Inc., Eli Lilly and Company, Tandem Diabetes Care, Inc.

Funding
National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases (K12DK094712)
778-P: Variations in Insulin Pump Use across Pediatric Endocrinology Centers in the U.S.
Authors: MUNGMODE ANN , ADAMS BLAKE V. , DOCTER OLIVIA , FOGEL NAOMI R. , ILKOWITZ JENIECE T. , IZQUIERDO ROBERTO , LEE JOYCE M. , MIYAZAKI BRIAN , NEYMAN ANNA , RECKSON ISABEL , SCHMITT JESSICA , EBEKOZIEN OSAGIE 
Published: May 2022

Background: The T1D Exchange Quality Improvement Collaborative (T1DX-QI) is a learning network of over forty US type 1 diabetes clinics. Clinics share best-practice ideas for quality improvement and use data for population health research. This study benchmarks insulin pump use across pediatric clinics in the T1DX-QI.
Method: T1DX-QI clinics report monthly on critical metrics, including the percentage of patients with HbA1c &lt;7% or using a pump, and other quality metrics. Median values for each site were calculated using Lahey P run charts between July 2020 and June 2021. These results are shared non-anonymized internally among participating T1DX-QI clinics.
Results: Across 17 T1DX-QI clinics, the percentage of patients using pumps ranged from 23% to 79% (Figure 1, A; mean and median pump use were 51.5% and 49.0%, respectively) . Clinic-specific average percentage of patients with HbA1c &lt; 7% ranged from 35% to 12% (Figure 1, B) . There were no observed differences in pump use by patient population size.
Conclusion: The T1DX-QI benchmarks key clinical metrics to support quality improvement, share best practices, and promote learning across clinics.

Disclosure
A. Mungmode: None. B.V. Adams: None. O. Docter: None. N.R. Fogel: None. R. Izquierdo: None. J.M. Lee: Advisory Panel; GoodRx. Consultant; Tandem Diabetes Care, Inc. B. Miyazaki: None. A. Neyman: None. I. Reckson: None. J. Schmitt: None. O. Ebekozien: None.

Funding
The Leona M. and Harry B. Helmsley Charitable Trust
78-OR: LRH-1/NR5A2 Agonism Triggers an Anti-Inflammatory Phenotypic Switch of Immune Cells from Patients with Type 1 Diabetes and Improves Islet Engraftment/Function
Authors: COBO-VUILLEUMIER NADIA , RODRIGUEZ-FERNANDEZ SILVIA , LORENZO PETRA I. , LOPEZ LIVIA , DORRONSORO AKAITZ , LACHAUD CHRISTIAN C. , ALMENARA-FUENTES LIDIA , RAMOS-RODRÍGUEZ MIREIA , MERIDA ISABEL , AGUILAR-DIOSDADO MANUEL , NANO RITA , PIEMONTI LORENZO , PASQUALI LORENZO , MARTIN FRANZ , GARCIA-SANCHEZ ISABEL , MARTINEZ-BROCCA MARIA ASUNCION , VIVES-PI MARTA , GAUTHIER BENOIT R. 
Published: May 2022

Administration of the LRH-1 agonist BL0refrains hyperglycemia in 3 mouse models of type 1 diabetes (T1DM) . This antidiabetes action correlated with beta cell mass preservation and the presence of anti, rather than pro, inflammatory immune cells, indicating tolerization. Herein, we sought to translate these data to human immune cells of T1DM patients to demonstrate BL0benefits to re-educate the immune system and to assess its therapeutic value on human islet engraftment/function. Blood mononuclear cells purified from blood samples (healthy and T1DM) were derived in culture into 1) pro-inflammatory macrophages (MDM1) , 2) mature dendritic cells (mDCs) , 3) T-cells and 4) B-cells. Cells were then treated with BL0 and processed for 1) cell surface marker profiling, 2) cytokine secretome profiling, 3) T-cell proliferation and 4) RNAseq. In T1DM samples, BL0reduced the expression of pro-inflammatory markers on MDM1 (CD80) and mDCs (CD54 and CXCR4) and the secretion of the pro-inflammatory cytokines, CXCL6 and CCL24 (MDM1) as well as IL7 (mDCs) . Moreover, in these samples, BL0also increased Tregs, but not B-cells. T-cell proliferation was blunted by BL001-treated mDCs and Tregs. RNAseq analysis of BL001-treated MDM1 revealed increased expression of genes encoding components of complex I, III, IV, and V of the respiratory chain consistent with a transition from a glycolytic driven MDM1 to an oxidative phosphorylation driven MDM2 anti-inflammatory phenotype. BL0administration to STZ-treated mice transplanted with human islet improved survival correlating with reduced hyperglycemia, increased circulating human C-peptide, preserved beta cell mass, and reduced CD4+ T-cell infiltration. Our results establish that BL0can induce a pro-to-anti-inflammatory phenotypic switch to human immune cells, and improve human islet engraftment/function, supporting the therapeutic benefits of BL0in human.

Disclosure
N. Cobo-Vuilleumier: None. S. Rodriguez-Fernandez: Employee; Ahead Therapeutics SL. P.I. Lorenzo: None. A. Dorronsoro: None. C.C. Lachaud: None. L. Almenara-Fuentes: Employee; Ahead Therapeutics SL. M. Ramos-Rodríguez: None. I. Merida: None. M. Aguilar-Diosdado: None. L. Piemonti: None. L. Pasquali: None. F. Martin: None. I. Garcia-Sanchez: None. M. Martinez-Brocca: None. M. Vives-Pi: Research Support; Ahead Therapeutics S.L. B.R. Gauthier: None.

Funding
JDRF (2-SRA-2019-837-S-B) Consejeria de Salud y Familia, junta de Andalucia (PI-0001-2020)
788-P: Development of an Extended-Wear Infusion Set with Angled Cannula
Authors: ZHANG GINA , ANSELMO EVAN , ORTIGOZA JESSICA L. , CHATTARAJ SARNATH 
Published: May 2022

Objective: Medtronic Mio™ 30 infusion set (M30IS) is a single-use consumable for pump users with pre-loaded inserter, utilizing a 30° insertion angle, and labeled for 3-day use. The M30IS wear duration is impacted by initial local trauma caused by insertion & cannula and sustained inflammation mostly by insulin infusion (especially insulin aggregates and other impurities in the infusate) , with the latter being predominant. Recently, a 7-day Medtronic Extended Infusion Set (MEIS) based on 3-day Mio™ Advance IS with a 90° soft cannula was developed and commercialized in Europe, by improving insulin formulation stability in the fluid path. This study is focused on applying the extended wear (EW) technology from MEIS to the M30IS to develop an EW set with angled cannula (the EM30IS) .
Method: This is a cross over study of M30IS and EM30IS on drug-induced Type 1 diabetic Yucatan pigs. Each animal wore both sets multiple times with one each time on the abdomen that was continuously infused with Novolog™ subcutaneously via a pump for 1-week or until failure. Blood glucose were measured 5 times/day. Physical examination and serum panel tests were conducted for safety evaluation.
Result: Fourteen wears were completed for each device. No significant safety concern was identified. Compared to the 90° cannula sets tested on the same model having occlusion alarm rate of 0∼20% for MEIS and ∼40% for 3-day sets at 7 days, no occlusion alarm was detected in either M30IS or EM30IS. Survival rate of EM30IS (86%, similar to MEIS) trended higher than that of M30IS (71%) . Average total daily dose of insulin increased with time for M30IS (Day 1: 14.4 U, Day 6: 18.1U) , whereas remained nearly unchanged for EM30IS (Day 1: 14.9 U, Day 6: 15.6 U) .
Conclusion: The data indicated that the EM30IS is safe and efficacious on the diabetic porcine model for subcutaneous insulin infusion for 7 days. The EW technology is equally safe and effective on extending the wear duration of M30IS. The EM30IS is moving to the next phase of product development.

Disclosure
G.Zhang: Employee; Medtronic. E.Anselmo: Employee; Medtronic. J.L.Ortigoza: Employee; Medtronic. S.Chattaraj: Employee; Medtronic.