bluuebunny/crossref_metadata_2025 huggingface dataset:
847-P: SGLT2 Inhibitors and GLP-1s Are Falling Short of Expectations among Patients with Type 2 Diabetes Newly Initiating Therapy
Authors: HOLLEMAN CLAIRE , XU EMILY , COX EVELYN , BRISTOW TRACY L.
Published: June 2023

SGLT-2s and GLP-1s have demonstrated significant glucose lowering, cardiorenal, and weight loss benefits. However, the exisiting research on patients’ perception of these benefits is limited. Thus, the present study aims to identify and compare new users' expectations of SGLT-2s and GLP-1s and the degree to which their expectations have been met.

In September 2022, 3,785 adults living with T2D took an online survey in which they indicated their SGLT-2 and GLP-1 usage and start date. Those who initiated SGLT-2 (n=108) or GLP-1 (n=128) use in the past year reported their expected changes upon starting the therapy. Participants were then asked the degree to which their expectations were met for each expectation held. Met expectations were calculated based on the percent of people selecting a 9 or 10 on a 10-point Likert scale.

New SGLT-2 users expected lower A1c, increased protection against kidney disease, and weight loss (76%, 43%, and 40%, respectively), although less than a third of SGLT-2 new users expecting a lower A1c and weight loss felt that their expectations were met (29% and 28%, respectively). GLP-1 new users expected lower A1c, weight loss, and fewer instances of hyperglycemia (80%, 74%, and 48%, respectively). Only a third of new users felt their expectations of lower A1c and weight loss were met (34% and 33%, respectively). Expectations of A1c lowering were similar between GLP-1s and SGLT-2s (80% vs. 76%); however, weight loss expectations were significantly higher among GLP-1 users compared to those on SGLT-2s (74% vs. 43%, p<.01).

Among patients initiating SGLT-2 or GLP-1 therapy, A1c lowering and weight loss expectations were not met for the majority of participants. These findings emphasize the need for improved expectation management and realistic goal setting. Future research is needed to understand how failed expectations translate into clinical outcomes and medication adherence, and to identify steps to better align patient expectations and outcomes.

Disclosure

C.Holleman: Employee; Close Concerns, Other Relationship; Abbott Diabetes, Eli Lilly and Company, LifeScan Diabetes Institute, Tandem Diabetes Care, Inc., Medtronic, Ascensia Diabetes Care, MannKind Corporation, dQ&A. E.Xu: Employee; dQ&A. E.Cox: Employee; dQ&A. T.L.Bristow: Employee; dQ&A.
85-OR: Swi/Snf Controls Transcriptional Programs Required for ß-Cell Development and Postnatal Islet Function
Authors: DAVIDSON REBECCA K. , KANOJIA SUKRATI , OSMULSKI MEREDITH E. , SPAETH JASON
Published: June 2023

A key feature of diabetes is insufficient functional β-cell mass. Strategies to augment functional β-cell mass include directed differentiation of stem cells towards a β-cell fate, which requires extensive knowledge of transcriptional programs governing differentiation in vivo. Pdx1, an essential transcription factor involved in β-cell differentiation, dynamically recruits coregulators to drive different gene expression programs. A recent study identified the ATP-dependent Swi/Snf chromatin remodeling complex as an important Pdx1-interacting partner. In the developing pancreas, conditional removal of the Brg Swi/Snf ATPase subunit compromised final pancreas mass, and loss of both ATPase subunits, Brg1 and Brm, led to glucose dyshomeostasis. While Swi/Snf is essential during early pancreas development and mature β-cell function, the role of Swi/Snf during endocrine cell development has yet to be explored. Here, we generated a conditional knockout of either Brg1 (Brg1ΔendoBrm+/-), Brm (Brg1Δendo/+Brm-/-), or both subunits (DKOΔendo) during endocrine development using Neurogenin 3 Cre. Four-week-old Brg1ΔendoBrm+/- mice are glucose intolerant, hyperglycemic, and hypoinsulinemic, with no phenotype observed in Brg1Δendo/+Brm-/-mice. Impaired glucose homeostasis of Brg1ΔendoBrm+/- mice was due in part to reduced islet number, impaired insulin secretion, and altered gene expression programs. DKOΔendo mice have not been found at weaning; however, postnatal day 6 DKOΔendo mice are severely hyperglycemic with reduced plasma insulin levels. Single-cell RNA-Seq of embryonic day 15.5 lineage-labeled cells revealed reduced insulin and glucagon transcript in the β-cell and α-cell clusters, respectively, in both Brg1ΔendoBrm+/- and DKOΔendo mice and reduced Neurogenin 3­ transcript in DKOΔendo endocrine progenitor clusters. These data suggest Swi/Snf plays a critical role in governing gene-expression programs essential for endocrine cell development.

Disclosure

R.K.Davidson: Employee; Eli Lilly and Company. S.Kanojia: None. M.E.Osmulski: None. J.Spaeth: None.

Funding

National Institutes of Health (R01DK129287, R03DK127129)
853-P: Effect of Ketogenic Diet with Weight Maintenance in Type 2 Diabetes (T2D)
Authors: MEROVCI AURORA , FINLEY BRITTANY , CHAVEZ ALBERTO , HANSIS-DIARTE ANDREA A. , NEPPALA SIVARAM , TRIPATHY DEVJIT , DEFRONZO RALPH A.
Published: June 2023

Aim: To examine the effect of ketogenic diet in T2D patients on glucose tolerance, beta cell function, insulin sensitivity and body fat content.

Methods: 29 T2D subjects were randomized to receive for 10 days a weight maintaining diet containing: GROUP I - 30% protein, 50% CHO, 20% fat (n=8); GROUP II - isocaloric ketogenic diet with 15% protein, 5% CHO, 80% fat (n=10); GROUP III - isocaloric ketogenic diet plus ketone ester of β-OH-B, 8 grams every 8h (n=11). Subjects ate breakfast daily in the TDI Metabolic Kitchen and picked up food for lunch and dinner.

Results: After 10 days, body weight remained constant: Group I (89.0 vs 89.0 kg), II (93.0 vs 92.5) and III (96.0 vs 97.0), as did body fat content. HbA1c and fructosamine did not change in any of the 3 groups. During OGTT, FPG, 2-h PG, mean PG, fasting PI, mean PI, [Delta]I/[Delta]G, and Matsuda index of insulin sensitivity did not change in Groups I, II, III. Subjects received a 2-step euglycemic insulin clamp (20 and 60 mU/m2.min) with 3-3H-glucose and indirect calorimetry. Before and after 10 days basal HGP and suppression of HGP (step I) were similar in all 3 groups. Insulin-stimulated glucose disposal (step 2) did not change in group I (4.23 vs 4.38 mg/kg.min), II (3.62 vs 3.55), or III (3.26 vs 3.35). After 10 days, basal lipid oxidation increased, while CHO oxidation decreased (both P<0.01) in groups II and III and was unchanged in group I.

Disclosure

A.Merovci: None. B.Finley: None. A.Chavez: None. A.A.Hansis-diarte: None. S.Neppala: None. D.Tripathy: None. R.A.Defronzo: Advisory Panel; AstraZeneca, Bayer Inc., Boehringer-Ingelheim, Novo Nordisk, Research Support; AstraZeneca, Boehringer-Ingelheim, Merck & Co., Inc., Speaker's Bureau; AstraZeneca.
872-P: Utilization of Empagliflozin in Patients with Type 2 Diabetes Mellitus and Congestive Heart Failure
Authors: ALVAREZ CARLOS A. , PERKINS AARON , SIGLER MEREDITH A. , YANG HUI , CABERWAL HARJEET , EBRAHIMI RAMIN
Published: June 2023

Intro: Diabetes (DM) and heart failure (HF) are an epidemic. Randomized controlled trials demonstrated sodium glucose cotransporter 2 inhibitors (SGLT2i) are beneficial in these patients. Guidelines suggest SGLT2i, such as empagliflozin, as potential first line therapy. We sought to determine utilization patterns and compliance to empagliflozin.

Methods: We assessed utilization and compliance in patients with DM and HF from the Veterans Affairs national database from 2015-2022. Initiation was calculated as the number of new empagliflozin prescriptions per 1,000 eligible patients. Compliance was calculated using the proportion of days covered (PDC). Compliance to empagliflozin was defined as PDC > 80%.

Results: A total of 44,608 patients exposed to empagliflozin were included. The majority of patients are white (n=33,663; 75.5%) male (n=43,335; 97.1%). A total of 6.6% were Hispanic or Latino (n=2,955). Table 1 shows incident empagliflozin prescription by year. The average proportion of days covered (PDC) was 0.83 (SD 0.21). The proportion of empagliflozin compliant patients was 66.2%.

Conclusions: Empagliflozin prescriptions have increased exponentially since 2015. Compliance to empagliflozin was moderate necessitating a potential intervention to increase compliance.

Disclosure

C.A.Alvarez: Research Support; Boehringer Ingelheim Inc. A.Perkins: None. M.A.Sigler: None. H.Yang: None. H.Caberwal: Employee; Boehringer Ingelheim Inc. R.Ebrahimi: Consultant; Pfizer Inc., Speaker's Bureau; Novo Nordisk.

Funding

Boehringer Ingelheim
884-P: Decentralized N=1 Study—A Feasible Approach to Evaluate Individual Therapy Response to Dapagliflozin
Authors: BEERNINK JELLE , LAVERMAN GOZEWIJN D. , HEERSPINK HIDDO L. , JONGS NIELS
Published: June 2023

Background: The SGLT2 inhibitor dapagliflozin reduces kidney function decline and urine albumin:creatinine ratio (UACR) on a population level. However, there is marked heterogeneity in the efficacy among individual patients. We conducted a decentralized (i.e. at home) N=1 trial to assess the effect of dapagliflozin in individual patients and the feasibility of remote data collection.

Methods: Twenty patients with type 2 diabetes, UACR >20 mg/g and eGFR >30 mL/min/1.73m2 entered the randomized placebo-controlled double-blind N=1 trial. Patients were randomly assigned to two periods of 1-week treatment with dapagliflozin 10 mg/day and two periods of 1-week treatment with placebo in random order with 1-week wash-out periods in between. Patients collected and sent their own data with automatic uploading to an online platform and sent early morning urines 5 times/week to the laboratory for albumin and creatinine assessment. Primary outcome was UACR change from baseline (mixed effects model). The study had 80% power to detect a correlation in UACR change between first and second dapagliflozin period of 0.6.

Results: Patients had a mean eGFR of 70.2 mL/min/1.73m2 and median UACR of 94.7 mg/g. During the study, dapagliflozin compared to placebo reduced albuminuria by 15.1% (95%CI 3.3 - 28.2; p=0.013). There was a marked variation in the change from baseline in UACR during dapagliflozin treatment periods (range first and second exposure -26.9 to -4.7% and -30.5 to -5.8%, respectively). The individual change in UACR during the first and second exposure correlated in the dapagliflozin periods (r=0.50; p=0.026) but not in the placebo periods (r=0.09; p=0.69). Of all scheduled urine collections (N=816), only 5 collections (0.61%) were not delivered in the laboratory.

Conclusion: The individual UACR response to dapagliflozin varies among individual patients and is consistent upon re-exposure. Remote data collection was very reliable with nearly any missed urine collection.

Disclosure

J.Beernink: None. G.D.Laverman: Advisory Panel; AstraZeneca, Vifor Pharma Management Ltd., Boehringer Ingelheim Inc., Astellas Pharma Inc., Lilly, Other Relationship; Sanofi, AstraZeneca. H.L.Heerspink: Consultant; AstraZeneca, Boehringer Ingelheim International GmbH, Bayer Inc., Eli Lilly and Company, Chinook Therapeutics Inc., CSL Behring, Gilead Sciences, Inc., George Clinical, Merck & Co., Inc., Janssen Research & Development, LLC, Traveere Pharmaceuticals, Novo Nordisk. N.Jongs: Speaker's Bureau; AstraZeneca.
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 > 25 - <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<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<0.0001). The proportion of patients achieving HbA1c <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 >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 >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 >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)>250 mg/dL; and inversely with time in range (TIR) 70-180 mg/dL and time below range (TBR)<70 mg/dL (all p<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<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<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<0.05). Meanwhile, amino acid metabolism pathways were associated with lower mean historical HbA1c (p<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)
96-LB: Dorzagliatin Improves Beta-Cell Function in Patients with Type 2 Diabetes
Authors: ZHANG YUANHUI , FENG LINGGE , CHEN LI , LIU DONGYANG
Published: June 2023

Objective: The oral minimal model (OMM) is a powerful tool to assess beta-cell function, including both the dynamic and static states. Dorzagliatin, a novel dual-acting glucokinase activator, has been reported the potential to improve pancreatic function in patients with type-2 diabetes mellitus (T2DM). In this study, we aimed to evaluate the effects of dorzagliatin on beta-cell function by using OMM.

Methods: A randomized, double-blind, placebo-controlled study of dorzagliatin following multiple ascending doses in T2DM was completed (NCT02077452) and the data collected were used for beta-cell function parameters (Φb, Φd, Φs, and Φtot) estimation by using the SAAM II package integrating OMM. These parameters represent the non-glucose stimulated index, the dynamic responsivity of insulin secretion, the static responsivity of insulin secretion, and the global index of beta-cell responsivity, respectively.

Results: All treatments except for the 200 mg dose group, compared with baseline, were associated with higher beta-cell function indices. Among them, Φb was significantly higher in the 25, 50, 100, and 150 mg dose groups (p < 0.05, p < 0.01, or p < 0.001), indicating basal beta-cell responsivity improved. Φd has an increase in the 25 and 100 mg dose groups (p < 0.05), indicating promptly releasable insulin responsivity improved. Φs was higher in the 25, 50, 100, and 150 mg dose groups (p < 0.05 or p < 0.01), indicating insulin secretion responsivity at steady state improved. Φtot significantly increased in the 25, 50, 100, and 150 mg dose groups (p < 0.05 or p < 0.001), indicating total beta-cell responsivity improved. No statistically significant difference was observed within the placebo group.

Conclusions: This study suggested dorzagliatin can improve postprandial glucose control through its positive effects on beta-cell function.

Disclosure

Y. Zhang: None. L. Feng: Employee; Hua Medicine. L. Chen: Employee; Hua Medicine. D. Liu: None.
964-P: Real-World Comparison of Rural and Urban Cohorts Using the Bigfoot Unity System for 6 Months
Authors: TILLMAN JOHN , OLSON BYRON P. , VAUGHAN SARAH , NAUREEN SHEIKH F. , MALONE JAMES K.
Published: June 2023

Background: The Bigfoot Unity® System incorporates CGM data, real-time alerts, and clinician-directed dose recommendations. Clinicians use a web portal to view patient data remotely. Our objective was to analyze real world data from rural and urban subgroups.

Methods: A 6-month retrospective analysis was done using a prespecified analysis plan for commercial users with ≥50% CGM data at 6 months (N=127, 24 clinics). A baseline A1C was obtained from clinic medical records (N=118). Glycemic and System engagement outcomes for those living in urban (N=102) and rural (N=25) zip codes were compared.

Results: Most in urban and rural groups had T2D (82 v 84%); mean age was 65 and 61 years, respectively. Urban users had mean baseline A1C of 8.4±1.6% and 7.5±0.8% mean GMI at 6 months; rural users had baseline A1C of 8.5±1.9% and 6-month GMI of 7.2±0.8%. Subgroup outcomes are shown (Table). Using GMI as an A1C proxy, pairwise comparisons of 6 month GMI to baseline A1C in the overall cohort (N=118) show a 1.1±1.4% improvement (P <0.05).

Discussion: Overall, both groups were primarily older adults with T2D using MDI and having suboptimal glycemic control before System use. Given concerns with disparity in diabetes management in rural areas, we evaluated rural and urban users of Bigfoot Unity. The rural cohort was small but data suggests that for both groups, using the System resulted in similar improved and durable glycemic control at 6 months.

Disclosure

J.Tillman: Employee; Bigfoot Biomedical, Inc. B.P.Olson: Employee; Bigfoot Biomedical, Inc. S.Vaughan: Employee; Bigfoot Biomedical, Inc. F.Sheikh: Employee; Bigfoot Biomedical, Inc. J.K.Malone: Employee; Bigfoot Biomedical, Inc.

Funding

Bigfoot Biomedical, Inc.
983-P: GluClose—Collaboratively Designing a More Personalized Continuous Glucose Monitoring (CGM) Onboarding Experience
Authors: CHAO EDWARD C. , ZHANG MINGJIN , HOULE MARY A. , RATAJ HEIDI
Published: June 2023

Current resources for acclimating patients to continuous glucose monitoring (CGM) may not be convenient or individualized. We examined if design thinking could better understand patients’ challenges, to uncover insights to facilitate more personalized onboarding for individuals living with type 1 diabetes mellitus (T1DM) new to CGM.

Design Thinking seeks to understand the user, challenge assumptions, and discover strategies that might not be initially apparent. This iterative working process generates solutions. A 10-week sprint started with immersion in current devices, including wearing a demonstration CGM. After directly observing in a DM clinic CGM onboarding for T1DM patients, we interviewed 4 newly-diagnosed and 4 previously-diagnosed individuals with T1DM: ages 2-65, diagnosed 5 months to 58 years ago; and 2 health care professionals (HCP). Patients’ pain points included: being overwhelmed with technology, and feeling a lack of ongoing support.

Individuals’ journey maps and user personas informed low-fidelity prototypes for patient testing, which guided a high-fidelity prototype for GluClose. Key features included: recording goals; tracking progress; and providing a forum to ask questions and share information, with vetting for accuracy.

The Standard Usability Score was 74 (from 7 participant responses), which is above average for acceptability.

This early design thinking study of improving CGM onboarding demonstrates that our patient-driven prototype, GluClose, has high usability. Entering and tracking goals and questions could serve as a springboard for enhancing engagement and communication with other patients and HCP. Balancing participants’ preferences on interacting with HCP on GluClose with time and safety considerations can be both a challenge and an opportunity. Connecting T1DM patients with HCP, DM community members, and design thinkers could spark new questions and solutions, to further tailor and improve CGM onboarding.

Disclosure

E.C.Chao: None. M.Zhang: None. M.A.Houle: Other Relationship; Insulet Corporation. H.Rataj: None.

Funding

University of California San Diego
991-P: Reduction in Diabetes-Related Hospitalizations and Medical Costs after Real-Time Continuous Glucose Monitor (rtCGM) Initiation in Patients with Type 2 Diabetes (PWT2D) on Intensive Insulin Therapy (IIT)
Authors: HANNAH KATIA , NEMLEKAR POORVA , NORMAN GREGORY J.
Published: June 2023

This study evaluated changes in diabetes-related hospitalizations and healthcare resource utilization (HCRU) costs after rtCGM initiation in PWT2D on IIT. Retrospective analysis of US healthcare claims data using Optum’s Clinformatics® database was conducted. The cohort included CGM naïve PWT2D on IIT who initiated rtCGM (Dexcom G6) between 8/1/2018 through 3/31/2021 (index date=earliest observed pharmacy claim). Diabetes-related (e.g., diabetic ketoacidosis, hyperglycemia and hypoglycemia) hospitalizations (ER and inpatient visits) and associated HCRU costs were assessed 12-months pre- and post-index. Hospitalizations were expressed as changes in the number of visits. Changes in diabetes-related HCRU costs were reported as per-person-per-month (PPPM) costs. Hospitalizations and HCRU costs were defined as claims with a diabetes-related diagnosis code in the 1st or 2nd position on the claim. A total of 790 PWT2D (average age=52.8 (sd=10.5) years, 46.7% female) rtCGM users on IIT with commercial health insurance met inclusion criteria. A 50% reduction (p<0.0001) in the number of diabetes-related inpatient visits after rtCGM initiation was observed (baseline n=132, follow-up n=66). Similarly, after rtCGM initiation, a 47% reduction (p<0.05) in the number of diabetes-related ER visits occurred (baseline n=85, follow up n=45). Average PPPM diabetes-related hospitalization medical costs decreased by $329.53 (p<0.05). HCRU cost reductions were driven by reduced diabetes-related inpatient medical costs (-$308.46 PPPM). Payer claims showed that hyperglycemia and ketoacidosis were the most common reasons for hospitalizations 12-months pre- and post-device initiation. Findings suggest that rtCGM initiation may contribute to reduced HCRU for PWT2D on IIT by way of improving glycemic control.

Disclosure

K.Hannah: Employee; Dexcom, Inc. P.Nemlekar: Employee; Dexcom, Inc. G.J.Norman: Employee; Dexcom, Inc.

Funding

Dexcom, Inc.
Metformin for Treatment of Acute COVID-19: Systematic Review of Clinical Trial Data Against SARS-CoV-2
Authors: Erickson Spencer M. , Fenno Sarah L. , Barzilai Nir , Kuchel George , Bartley Jenna M. , Justice Jamie Nicole , Buse John B. , Bramante Carolyn T.
Published: June 2023

BACKGROUND

Observational and preclinical data suggest metformin may prevent severe coronavirus disease 2019 (COVID-19) outcomes.

PURPOSE

We conducted a systematic review of randomized, placebo-controlled clinical trials of metformin treatment for COVID-19 to determine whether metformin affects clinical or laboratory outcomes in individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and present a structured summary of preclinical data.

STUDY SELECTION

Two independent reviewers searched PubMed, Scopus, Cochrane COVID-19 Study Register, and ClinicalTrials.gov on 1 February 2023 with no date restrictions for trials where investigators randomized adults with COVID-19 to metformin versus control and assessed clinical and/or laboratory outcomes of interest. The Cochrane Risk of Bias 2 tool was used to assess bias.

DATA EXTRACTION

Two reviewers extracted data pertaining to prespecified outcomes of each interest from each included trial.

DATA SYNTHESIS

The synthesis plan was developed a priori and was guided by Synthesis Without Meta-analysis (SWiM) guidelines. Summary tables and narrative synthesis were used (PROSPERO, 2022, CRD42022349896). Three randomized trials met inclusion criteria. In two of the trials investigators found that metformin improved clinical outcomes (prevented need for oxygen and prevented need for acute health care use), and in the third trial a larger portion of adults with diabetes were enrolled but results did show a direction of benefit similar to that of the other trials in the per-protocol group. In the largest trial, subjects were enrolled during the delta and omicron waves and vaccinated individuals were included. The certainty of evidence that metformin prevents health care use due to COVID-19 was moderate per Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria. Many preclinical studies have shown metformin to be effective against SARS-CoV-2.

LIMITATIONS

Limitations include inclusion of only three trials and heterogeneity between trials.

CONCLUSIONS

Future trials will help define the role of metformin in COVID-19 treatment guidelines.
Variable Outcome of Immunotherapy in Advanced Multiple Cutaneous Squamous Cell Carcinomas in Two Patients with Recessive Dystrophic Epidermolysis Bullosa
Authors: Trefzer Laura , Hess Maria E. , Scholten Lena , Technau-Hafsi Kristin , Meiss Frank , Boerries Melanie , Has Cristina , Rafei-Shamsabadi David
Published: June 2023

Cutaneous squamous cell carcinoma (cSCC) is a major complication of recessive dystrophic epidermolysis bullosa (RDEB) that has high morbidity and mortality rates and unmet therapeutic needs. The aim of this study was to evaluate the molecular pattern of cSCC and the clinical course of immunotherapy in 2 RDEB patients with multiple advanced cSCC. Clinical course and disease staging were evaluated retrospectively. The tumour tissues were subjected to immunohistochemical staining. DNA from the blood and cSCC samples was subjected to massive parallel sequencing, and somatic mutations were determined. Patient 1 survived for over 2 years as disease control was achieved with cemiplimab and intralesional interleukin-2. The target advanced cSCC demonstrated a high rate of somatic mutations and strong expression of the immune markers, indoleamine 2,3-dioxygenase, programmed cell death protein ligand 1, and lymphocyte-activation gene 3. The patient ultimately succumbed to complications of oesophageal carcinoma. Patient 2 had an undifferentiated cSCC on the foot, which displayed a low mutational burden and did not express immune markers. The tumour progressed quickly even with cemiplimab therapy. These 2 cases underscore the challenges of cSCC treatment for RDEB. Multiple tumours with different molecular and immune profiles occur concomitantly or sequentially, and surgical excision is not always possible because of the anatomical and tissue constraints imposed by the disease itself. In conclusion, programmed cell death protein 1 inhibitors are approved and effective in treating metastatic and locally advanced cSCC. Our experience and the literature suggest that cemiplimab is an option in patients with RDEB if surgery is not. Somatic mutations and the immune microenvironment should be characterized to predict therapeutic response, particularly in aggressive undifferentiated tumours.
Design of a predictive control system for the smart regulation of renewable climatization systems
Authors:   IGNIS Energía. Madrid. Spain, Felez R. , Castro J. , Felez J. ,   ETS Ingenieros Industriales, Universidad Politécnica de Madrid. Spain
Published: June 2023

The objective of this Project is to design a predictive controller for Heating Ventilation and Air Conditioning in residential buildings is designed. A realistic residential home has been designed, establishing the dynamics of the temperature according to a theoretical model that has been elaborated, being the basis for the actuation of the temperature-regulation controller. Several simulations have been carried out, defining the objective function and the constraints associated, together with the controller parameters that allow an optimal performance, taking into account different criteria such as thermal comfort and reduction of power consumption for different scenarios. In addition, electricity selfgeneration has been also contemplated, integrating it into the controller actuation for leveraging the increase in economic savings.