bluuebunny/crossref_metadata_2025_split huggingface dataset:
885-P: Impact on Glycaemic Variability in Newly Onset T2DM Patients Initiating Dapagliflozin Plus Metformin vs. Metformin Alone, a Randomized Open Label Clinical Study—The MAGNNIFY Trial
Authors: GUERRERO-CASTILLO ANNA P. , SIGFRIDO BENITEZ-RENTERIA ALBERTO , CUEVAS-RAMOS DANIEL , GUADALUPE LÓPEZ-CARRASCO MARÍA , SILVA ALEJANDRA , BRITO GRISELDA X. , PALACIOS-BAEZ LUCIA , MANJARREZ-MARTÍNEZ ILIANA , RODRIGUEZ-CARRANZA SANDRA I. , JUAREZ-COMBONI SONIA C. , GÓMEZ-PEREZ FRANCISCO J. , GOMEZ-SAMANO MIGUEL A. 
Published: June 2023

Background: The aim of this study is to compare the effect of dapagliflozin (DAPA) in addition to metformin (MET) at maximum tolerated dose in glycaemic variability (GV) on drug naïve T2DM patients. ClinicalTrials.gov Identifier: NCT04090580
Methods: Newly diagnosed T2DM patients with HbA1c ≥ 7.5% - ≤ 12%, BMI &gt; 25 - &lt;45 kg/m2, were randomized 1:1 to receive DAPA 10 mg + MET or MET alone for 12 weeks. Both groups were monitored using a CGM system for 7 days at baseline and week 12. Primary outcome was defined as the mean difference of MAGE (Mean Amplitude of Glycaemic Excursions). Additional secondary endpoints included mean difference of serum insulin, HbA1c, weight, and time in range.
Results: 80 patients completed follow-up at week 12 (DAPA+MET, n=41; MET, n=39). Baseline characteristics included mean age 52.2±10.4 years, weight 80.6±16.5 kg, SBP 133.3±19.3 mmHg, HbA1c 9.3±1.5 %, eGFR 100.5±15.4 ml/min/1.73m2, MAGE 4.2±1.4 mmol/L. Patients treated with DAPA+MET had lower GV at week 12 measured by MAGE (-0.79 [-0.86 DAPA+MET vs -0.06 MET; p=0.018]) and higher time in range (+22.9% [35.8 DAPA+MET vs 12.9 MET; p=0.002]). DAPA group had lower insulin plasma levels (-4.5 µU/mL [-2.8 DAPA+MET vs +1.6 MET; p=0.029]) and body weight (-3.2 kg [-3.22 DAPA+MET vs -0.6 MET; p&lt;0.001]); nominal reductions were observed in HbA1c (-1.82 DAPA+MET vs -1.61 MET; p=0.919) and SBP (-4.96 mmHg [-4.35 DAPA+MET vs +0.60 MET; p=0.277].
Conclusions: Patients with new onset T2DM treated with DAPA + MET during a 12-week period had improvements in glycaemic variability measured by MAGE (-19.63%) and achieved longer periods within target range for glycaemic control in comparison with patients treated only with MET. Plasmatic insulin levels, and weight reduction were also significantly reduced with DAPA; nominal reductions in HbA1c and SBP were observed. All these findings support the early dapagliflozin use in patients with newly onset T2DM.

Disclosure
A.P.Guerrero-castillo: None. S.C.Juarez-comboni: Employee; AstraZeneca. F.J.Gómez-perez: None. M.A.Gomez-samano: Research Support; AstraZeneca. A.Benitez-renteria: Employee; AstraZeneca. D.Cuevas-ramos: None. M.López-carrasco: None. A.Silva: Stock/Shareholder; AstraZeneca. G.X.Brito: None. L.Palacios-baez: None. I.Manjarrez-martínez: None. S.I.Rodriguez-carranza: None.

Funding
AstraZeneca Mexico
890-P: Efficacy and Safety of Dapagliflozin Add-on Therapy to Evogliptin plus Metformin Combinations in Inadequately Controlled Patients with Type 2 Diabetes—A 24-Week, Randomized, Double-blind, Placebo-Controlled, Parallel-Design, Phase 3 Trial
Authors: JEONG IN-KYUNG , MOOK CHOI KYUNG , AH HAN KYUNG , KIM KYOUNG-AH , JOO KIM IN , JIN HAN SEUNG , LEE WON-YOUNG , JIB YOO SOON 
Published: June 2023

Background and Aims: We aimed to evaluate the efficacy and safety of dapagliflozin versus placebo as add-on therapy in patients with type 2 diabetes and inadequate glycemic control with evogliptin and metformin combinations.
Materials and Methods: In this multi-center, double-blind, randomized, placebo-controlled phase 3 trial, patients with HbA1c ≥7.0% and ≤10.5% who had received stable-dose (≥1000 mg) metformin and evogliptin 5mg for at least 8 weeks were randomized to receive dapagliflozin 10mg or placebo once daily for 24 weeks. All patients continued treatment with metformin and evogliptin 5 mg. The primary endpoint was the change from baseline in HbA1c after 24 weeks of double-blind treatment.
Results:198 patients were randomized and 195 patients were included in efficacy analyses (dapagliflozin: 96, placebo: 99). At week 24, dapagliflozin significantly reduced HbA1c. The least square [LS] mean difference in the change from baseline with dapagliflozin versus placebo was -0.70% (95% confidence interval [–0.91, –0.48], p&lt;0.0001). The proportion of patients achieving HbA1c &lt;7% was higher in dapagliflozin group (42.71% versus 16.16% in placebo; p=0.0002). Compared to placebo, dapagliflozin treatment significantly reduced fasting plasma glucose, mean daily glucose, fasting insulin and HOMA-IR at week 24. Adiponectin was significantly increased from baseline over 24 weeks with dapagliflozin. Adverse event rates were similar between groups (dapagliflozin: 27.55%, placebo:27.27%) including hypoglycemia and genital infection.
Conclusions: Triple combination with dapagliflozin add-on to evogliptin plus metformin improved glycemic control and is well tolerated in patients with type 2 diabetes who are not adequately controlled with evogliptin and metformin combination.

Disclosure
I.Jeong: None. K.Choi: None. K.Han: None. K.Kim: None. I.Kim: None. S.Han: None. W.Lee: None. S.Yoo: None.
9-LB: PDZK1 Inhibits Fatty Acid Uptake in Renal Tubular Epithelial Cell through FATP2 to Ameliorate Diabetic Kidney Disease
Authors: YANG LONGYAN , WANG YAN , XU YONGSONG , KE JING , ZHAO DONG 
Published: June 2023

Background: Renal tubular injury is the driving force of diabetic kidney disease (DKD) and their targeting may be an effective means for prevention. PDZK1 is a scaffold protein that is highly expressed in proximal renal tubules and participates in renal tubular reabsorption. However, the role of PDZK1 in DKD with disorder of glucose and lipid metabolism is unclear.
Methods: We generated mice lacking the Pdzk1 gene specifically in renal tubular epithelial cells by crossing Pdzk1 floxed mice with Pax8-Cre mice. We observed renal tubular injury and renal fibrosis in Pdzk1 Pax8-cre+ and Pdzk1 Pax8-cre- mice induced by high fat diet and streptozotin. In vitro, we elucidated that PDZK1 regulates fatty acid uptake and renal tubular injury.
Results: In this study, proteomic analysis found that compared with the control, the expression of PDZK1 in kidney of DKD mice was significantly reduced. Compared with non-DKD patients, PDZK1 was also lower in renal tissue samples of patients with DKD. Pdzk1 Pax8-cre+ mice significantly increased lipid deposition of renal tubules, renal tubular injury and renal fibrosis compared with Pdzk1 Pax8-cre- mice induced by high fat diet and streptozotin. Knocked down PDZK1 increased intracellular lipid deposition in renal tubular epithelial cells stimulated with high glucose and palmitic acid. Knockdown PDZK1 could promote fatty acid uptake in renal tubular epithelial cells. PDZK1 interacted with fatty acid transporter 2 (FATP2) and inhibited the expression and localization of FATP2 on cell membrane.
Conclusion: Diabetes stimulates the decreased expression of PDZK1 in renal tubular epithelial cells. The decrease of PDZK1 attenuates the inhibition of FATP2 localization on cell membrane, promoting ectopic lipid deposition and renal tubular injury, leading to DKD. This study will reveal the new regulatory mechanism of renal tubular injury and provide a new target for the treatment of DKD.

Disclosure
L. Yang: None. Y. Wang: None. Y. Xu: None. J. Ke: None. D. Zhao: None.

Funding
National Natural Science Foundation of China (82170454)
900-P: Patient-Reported Outcomes of Adults with Type 1 Diabetes Using Do-It-Yourself Compared with Commercial Automated Insulin Delivery Systems
Authors: LEBBAR MAHA , WU ZEKAI , BONHOURE ANNE C. , MESSIER VIRGINIE , BRAZEAU ANNE-SOPHIE , RABASA-LHORET RÉMI 
Published: June 2023

Introduction: We aim to assess the difference between open-source do-it-yourself (DIY) and commercial automated insulin delivery (AID) systems in patient-reported outcomes (PRO) of adults with type 1 diabetes (T1D).
Methods: Analysis from a prospective, non-inferiority, non-randomized, parallel-cohort study involving 78 non-pregnant adults with T1D, AID users ≥3 months and living in Canada. Participants (25 DIYAID and 53 commercial AID users, 60.3% females, mean age 41.2±14.6 years, mean T1D duration 27.0±14.7 years, median [Q1, Q3] duration of AID use 15.6 [7.8, 27, 4] months, mean HbA1c 6.7±0.7%, median time in range [TIR 70-180 mg/dl] 74.3% [66.8, 81.0]) completed the following validated PRO questionnaires: Diabetes Distress Scale (DDS, high distress level defined as &gt;2.0), Diabetes Treatment Satisfaction Questionnaire (DTS-Q), An Audit of Diabetes-Dependent Quality of Life (ADD-QoL), Hypoglycemia Fear Score II (HFS-II, fear of hypoglycemia defined as scoring ≥3 in any worry subscale item), Pittsburgh Sleep Quality Index (PSQI, poor sleep defined as &gt;5), Clarke and Gold score (hypoglycemia unawareness defined as either score ≥4).
Results: DIYAID users reported better sleep quality (66.7% vs 33.3%, p=0.02) and lower HFS-II worry subscale score (28.2 vs 33.2, p=0.03) than commercial AID users, but results did not remain significant after adjusting for sex, age, level of education, T1D and AID use duration, HbA1c, and TIR. The two groups were otherwise comparable in other PROs. Overall, one third of participants reported diabetes distress, 88.3% reported poor sleep, 20.8% reported impaired hypoglycemia awareness and 80.5% reported fear of hypoglycemia.
Conclusion: Similar broad QoL and other PROs were observed between DIYAID and commercial AID users, with a persistent and significant diabetes burden for all, despite advanced diabetes technology use and optimal glycemic management.

Disclosure
M.Lebbar: None. Z.Wu: Other Relationship; Eli Lilly and Company. A.C.Bonhoure: Consultant; Dexcom, Inc. V.Messier: None. A.Brazeau: Other Relationship; Dexcom, Inc., Diabète québec, Ordre des diététistes nutritionnistes du Québec, Research Support; Canadian Institutes of Health Research, Fonds de recherche du Québec en Santé. R.Rabasa-lhoret: Consultant; Dexcom, Inc., Abbott, Janssen Pharmaceuticals, Inc., Novo Nordisk Canada Inc., Sanofi, Lilly, Tandem Diabetes Care, Inc., Insulet Corporation.

Funding
Canadian Institutes of Health Research (148464)
915-P: Euglycemic Ketoacidosis in Type 1 Diabetes on an Automated Insulin Delivery System after Bariatric Surgery—A Case Series
Authors: PASQUA MELISSA-ROSINA , TSOUKAS MICHAEL , HU WEN 
Published: June 2023

Obesity is an increasing concern in patients with type 1 diabetes. Bariatric surgery is an effective option for weight loss and is associated with an improvement in metabolic complications. We report 2 cases of adults with type 1 diabetes using automated insulin delivery where laparoscopic sleeve gastrectomy was complicated post-operatively by euglycemic ketoacidosis. The first case was of a 28-year-old man using Control-IQ (HbA1c 7.3%, body mass index 40, and insulin requirements 0.98 Units/kg/day). His insulin requirements and carbohydrate intake decreased from 108 units and 208 grams respectively to 44 units and 8 grams during the preoperative liquid diet. His lack of carbohydrate consumption continued post-operatively. Two days after his surgery, he presented to the emergency department with nausea, where his glucose level was 12.8 mmol/L, venous pH level 7.30, venous bicarbonate concentration 20.9 mmol/L, and plasma beta-hydroxybutyrate 4.5 mmol/L. He was treated with intravenous hydration with supplementation dextrose with observation. The second case was of a 33-year-old woman using the MiniMed 770G (HbA1c 7.0%, body mass index 44, insulin requirements 0.4 units/kg/day). Post-operative day 16, she presented to the emergency department with nausea and vomiting. Her glucose level was 11.9 mmol/L venous pH was 7.31, venous bicarbonate was 17 mmol/L, and positive urinary ketones. Daily insulin requirements had reduced (from preoperatively to post-operatively) from 35.8 to 16.3 Units per day, with her carbohydrate intake from 86 to 33 grams. She was treated with intravenous insulin. Though euglycemic ketoacidosis is documented after bariatric surgery and starvation, automated insulin delivery (particularly unnoticed insulin changes) may have influenced glycemia and acidosis. Careful review of insulin administration, carbohydrate intake, and ketone monitoring is recommended in these cases.

Disclosure
M.Pasqua: None. M.Tsoukas: Speaker's Bureau; Novo Nordisk Canada Inc., Boehringer Ingelheim (Canada) Ltd., Eli Lilly and Company, Janssen Scientific Affairs, LLC, AstraZeneca, Sanofi. W.Hu: None.
921-P: Improved Glycemic Control in Pregnancy Using Continuous Subcutaneous Infusion of Concentrated Insulin
Authors: MON NANDAR , KRISHNASAMY SATHYA 
Published: June 2023

Maternal and fetal complications are high in preexisting uncontrolled type 2 diabetes mellitus (T2DM). There is limited data on the use of concentrated insulin in continuous subcutaneous insulin infusion (CSII) during pregnancy. We report a case of 22-year-old woman G4P0030 with T2DM since 10 years of age who was admitted for preterm premature rupture of membrane at 26 weeks gestation. Preconception HbA1c was 12.1% on metformin, and basal bolus insulin. Severe hyperglycemia following betamethasone administration for fetal lung maturity required insulin drip initially which was transitioned to basal bolus insulin. Despite total daily insulin dose &gt;480 units, glucose control was suboptimal. Decision was made to initiate CSII with basal U-500 concentrated regular insulin and U-100 prandial insulin injections. She was started on Dexcom for CGM and Omnipod Dash with basal rate 1.3 units/hour (6.5 units/hour U-500), insulin sensitivity factor 27 mg/dl (5.4 mg/dl with U-500), carb ratio 1 unit lispro to 2 g. Glycemic control improved as noted in CGM even after adjusting the pregnancy target (70-140mg/dl). Patient delivered a male infant (2090 grams) by emergency C-section at 30 weeks gestation due to preterm labor with fetal malpresentation. She was discharged home with U-100 basal bolus insulin regimen on day 3 postpartum. Concentrated insulin in CSII is effective for uncontrolled T2DM in pregnancy.

Disclosure
N.Mon: None. S.Krishnasamy: None.
926-P: Implementation of a Novel AutoBolus Feature in an Automated Insulin Delivery (AID) System
Authors: NARAYANASWAMI RANGARAJAN , ZHENG YIBIN , WHITELEY WILLIAM J. , SEVIL MERT , SALAVATI SAEED 
Published: June 2023

AID systems aim to reduce mental burden experienced by people with diabetes by automatically adjusting insulin delivery in response to real-time glucose levels; however, systems still require pre-meal boluses for optimal outcomes. A system providing an automatic bolus response (‘AutoBolus’) to rising glucose levels (e.g., after meals) lessens user burden and reduces hyperglycemic events by compensating for missed or under-estimated pre-meal boluses. We propose a novel method to deliver an AutoBolus based on rising glucose levels via a machine learning based meal detection algorithm. AutoBolus meal detection is paired with a two-part novel insulin delivery scheme with an immediate safe upfront delivery, followed by temporarily tuning AID algorithm parameters to progressively respond to the post-prandial glucose response by delivering additional insulin. If a decreasing glucose condition is detected, the AID algorithm parameters revert to baseline. In-silico simulation demonstrates AutoBolus increases time in euglycemia by as much as 11% in adolescents, 8% in adults, and 6% in children for missed boluses for three meals in a 24-hour period. Our results show that the proposed AutoBolus insulin delivery partially compensates for missed pre-meal boluses increasing time in euglycemia, reducing user burden. Figure. Illustrative diagram showing the two-part novel insulin delivery scheme upon meal detection.

Disclosure
R.Narayanaswami: None. Y.Zheng: Employee; Insulet Corporation. W.J.Whiteley: Employee; Insulet Corporation. M.Sevil: None. S.Salavati: Employee; Insulet Corporation.
937-P: CGM Metrics and HbA1c Are Differentially Associated with Complications and Plasma Metabolites in Long-Duration Type 1 Diabetes
Authors: GREGORY YU MARC , VISHVA TEJA JANGOLLA SURYA , GAUTHIER JOHN , ZIEMNIAK NOLAN A. , SHAH HETAL , KING GEORGE L. 
Published: June 2023

Continuous glucose monitor (CGM)-derived metrics evaluate aspects of glycemic variability that are not assessed with HbA1c alone. However, the comparative contributions of these measures to chronic complications in long-duration Type 1 diabetes (T1D) have not been reported. From the Joslin Medalist Study composed of people with T1D≥50 years, a consecutive 14-day block of CGM data was obtained from a subset of CGM users (n=102) after performing usual activities. In linear regression models, mean historical HbA1c was associated with glucose management indicator (GMI), mean glucose, and time above range (TAR)&gt;250 mg/dL; and inversely with time in range (TIR) 70-180 mg/dL and time below range (TBR)&lt;70 mg/dL (all p&lt;0.001). Medalists with GMI significantly greater (≥0.5%) than mean historical HbA1c also had greater coefficient of variability (p=0.04) and TAR (p=0.01). While retinopathy, nephropathy, and neuropathy were associated with GMI, mean glucose, and TAR (p&lt;0.05), only neuropathy was associated with TBR (p=0.02). In contrast, HbA1c was associated only with self-reported cardiovascular disease in the overall Medalist cohort (n=952; p&lt;0.05). Plasma global metabolomics studies (n=95) revealed that amino acid activation pathways, particularly asparagine and glutamine, were associated with lower TAR and higher TIR; while bile acid synthesis was associated with lower TBR (p&lt;0.05). Meanwhile, amino acid metabolism pathways were associated with lower mean historical HbA1c (p&lt;0.05). Our results suggest that while HbA1c and CGM metrics are closely related in long-duration T1D subjects, they provide differential contributions to the development of complications. Additionally, this is the first study to comprehensively characterize plasma metabolomics with both HbA1c and CGM metrics, which provided novel insights on potential therapeutic targets for glycemic control and variability in T1D, as well as potential protection from complications.

Disclosure
M.Yu: None. S.Jangolla: None. J.Gauthier: None. N.A.Ziemniak: None. H.Shah: None. G.L.King: Research Support; Janssen Research & Development, LLC.

Funding
American Diabetes Association (9-18-CVD1-005 to M.C.Y.); Mary K. Iacocca Family Foundation; Thomas J. Beatson, Jr. Foundation
954-P: A New Portable HbA1c Meter—Red Blood Cell Deformability–Based HbA1c Test
Authors: PARK EUNYOUNG , KANG SEUNGJIN , KO UNGHYEON 
Published: June 2023

In the United States, more than 1 in 5 people with diabetes do not know they have diabetes, and they are at higher risk of severe health complications by diabetes management failure. Early diagnosis and management of diabetes through HbA1c monitoring can address these public health issues, but many people still do not benefit from the HbA1c test due to its limited accessibility. Alternatively, a portable HbA1c meter, which lay users can easily use, could be a valuable solution to monitor their HbA1c levels without visiting the doctor. However, the current HbA1c test requires precise sample volume and temperature-sensitive maintenance, reducing its usability for lay users.
In this study, as a solution for portable HbA1c meters, we proposed a new HbA1c assay that can be free from sampling error and maintenance by estimating RBC deformability. This novel system employed a microfluidic channel, evaluating RBCs deformability via detecting the velocity of individual RBCs in a fluidic channel with a narrower width than RBC. The results showed that RBC deformability was inversely correlated with HbA1c level and successfully converted the HbA1c level from estimated RBC deformability data. In conclusion, RBC deformability-based HbA1c test has the potential to revolutionize the HbA1c test assay and could benefit individuals beyond the limits of current point-of-care devices.

Disclosure
E.Park: Board Member; Orange Biomed Ltd., Co. S.Kang: Board Member; Orange Biomed Ltd., Co. U.Ko: Board Member; Orange Biomed Ltd., Co.

Funding
Orange Biomed Ltd., Co.
959-P: Hands-On Continuous Glucose Monitor Training for Primary Care Providers in a Rural Family Medicine Residency Clinic
Authors: PRUDENCIO JARRED , KIM MICHELLE , CHAN CHRISTINE 
Published: June 2023

Continuous glucose monitors (CGMs) are helpful tools in managing diabetes, and it is important that primary care providers (PCPs) receive adequate training on how to use them. There are various on-demand lectures about CGMs that are available for clinicians, but these programs lack a hands-on component. In a rural Family Medicine residency clinic, two clinical pharmacists created a training program for PCPs which included an educational module, a hands-on experience wearing an intermittently-scanned CGM for 2 weeks, and a debriefing module. This study describes and evaluates this training program. The investigators created a questionnaire aimed to measure PCPs confidence and knowledge of CGMs. PCPs were given the identical questionnaire at baseline, after the educational module (midpoint), and after the debriefing module (final). Descriptive statistical analysis was performed to assess differences in confidence and knowledge levels throughout the program. A total of 21 PCPs completed the program, including 13 medical residents, six physician faculty, and two nurse practitioners. On a scale from 1 to 10, PCP’s rated their average baseline knowledge of CGMs at 3.8. This increased to 5.3 at midpoint, and 7.9 at final. For the knowledge-based portion of the questionnaire, PCPs scored an average of 20.35% at baseline, and this increased to 75.32% at midpoint, and 90.48% at final. After completion of the training program, all 21 participants either agreed or strongly agreed that having the opportunity to wear a CGM provided them with more confidence in working with patients with CGMs, compared to a lecture-based training program alone. This study demonstrates that a training program including a hands-on experiential component can improve PCPs confidence and knowledge levels regarding CGMs.

Disclosure
J.Prudencio: None. M.Kim: None. C.Chan: None.

Funding
Abbott Medical Education (2182022)