bluuebunny/crossref_metadata_2025 huggingface dataset:
74-PUB: Knowledge, Attitude, and Practice of Individuals with Obesity—Insights from a Large Nationwide Survey
Authors: KAPOOR NITIN , GHOSH SUJOY , CHAWLA MANOJ S. , KESAVADEV JOTHYDEV , ANUJ MAHESHWARI , AGARWAL SANJAY , MAKKAR BRIJ , DESHPANDE NEETA
Published: June 2024

Introduction & Objective: Understanding the awareness and behaviour of the public towards obesity can assist in implementing obesity management programs. Accordingly, this large-scale study evaluates the knowledge, attitude, and practice of individuals with different BMI statuses towards obesity awareness and management.

Methods: This pan-Indian study was conducted in the Asian-Indian population and responses to questions pertaining to their demographics, lifestyle habits, and awareness towards obesity and its management were collected. Comparison was made between different BMI groups classified using the Asian criteria: Underweight (<18.5kg/m2), Normal (18.5-22.9kg/m2), Overweight (23.0-24.9 kg/m2), and Obese (>25kg/m2). The data was expressed as proportions or descriptive statistics as applicable, and significance was calculated at α=5%.

Results: The survey included responses from 60325 individuals, with majority being obese (67.3%) or being overweight (15.3%). Overall distribution of gender (P<0.0001) and education status (P<0.0001) was significantly different across the groups. Majority of individuals with obesity (56.7%) considered obesity as a disease. The willingness to receive weight loss information was unaffected by their BMI status. A higher incidence of diabetes mellitus (P=0.0313) and dyslipidaemia (P=0.0206) was noted in individuals with obesity. Inclination to lose weight was highest in the group with obesity (69%), but all groups displayed similar weight loss efforts. Lifestyle habits facilitating obesity including longer idle times during weekdays (P<0.0001), weekends (P<0.0001) and higher frequency of eating out (P<0.0001) were significantly higher among the obese compared to the normal group.

Conclusion: The majority of the participants had obesity and their admission of obesity as a disease indicates its impact on the quality of life in the Indian population and the need for devising treatment strategies.

Disclosure

N. Kapoor: None. S. Ghosh: None. M.S. Chawla: Advisory Panel; Novo Nordisk. Speaker's Bureau; Novo Nordisk. Advisory Panel; Biocon. Speaker's Bureau; Biocon. Advisory Panel; Eris Lifesciences Ltd. Speaker's Bureau; Eris Lifesciences Ltd. Advisory Panel; Torrent Pharmaceuticals Ltd. Speaker's Bureau; Torrent Pharmaceuticals Ltd. Advisory Panel; USV Private Limited, Lupin Pharmaceuticals, Inc. J. Kesavadev: None. M. Anuj: None. S. Agarwal: None. B. Makkar: None. N. Deshpande: None.
740-P: Persistence and Adherence of Once-Weekly GLP-1 Receptor Agonists in Patients with Type 2 Diabetes and Atherosclerotic Cardiovascular Disease in a Real-World Setting
Authors: DUNN TYLER , ZHU YONG , GRONROOS NOELLE , XIE LIN , NOONE JOSHUA , SARGENT ANDREW , YEDIGAROVA LARISA , BILLINGS LIANA K.
Published: June 2024

Introduction & Objective: Multiple clinical trials have shown cardiovascular benefits from glucagon-like peptide 1 receptor agonists (GLP-1 RAs) in patients with type 2 diabetes (T2D). This study describes persistence and adherence of once weekly (OW) GLP-1 RAs use by patients with T2D and atherosclerotic cardiovascular disease (ASCVD) in a real-world setting.

Methods: The study used data from the Optum Research Database from 01 Jan 2017 through 28 Feb 2023 and identified adult patients with T2D and ASCVD with ≥1 pharmacy claim for OW GLP-1 RAs. The date of the first claim was the index date and the start of a variable follow up period. Persistence was defined as the number of days from the index date to either discontinuation of OW GLP-1 RAs or end of variable follow up. Percentages of persistent patients (those without discontinuation) were reported at 6, 12, and 18 months, as well as over the full variable follow up period. Adherence, measured as proportion of days covered (PDC) over the full variable follow up period, was reported for patients with at least 6, 12, and 18 months of follow up.

Results: Among a total of 29516 patients, the mean follow up duration was 535 days and mean persistence was 371 days; 63.9% of patients were persistent throughout their variable follow up period. Basic demographic and clinical characteristics were similar between persistent and non-persistent patients. At 6 months, 80.2% of patients were persistent; the percentage was 63.2% and 54.3% at 12 and 18 months, respectively. PDC was 0.72, 0.68, and 0.66 among patients with at least 6, 12, or 18 months of follow up, respectively.

Conclusions: Patients had at least two-thirds of PDC and 63.9% of them were persistent throughout their follow up. Identifying factors influencing persistence and adherence is imperative to guide interventions aimed at enhancing these aspects, thereby maximizing the cardiovascular benefits derived from GLP-1 RAs.

Disclosure

T. Dunn: Employee; Novo Nordisk. Y. Zhu: Employee; UnitedHealth Group. Stock/Shareholder; UnitedHealth Group. Other Relationship; UnitedHealth Group, Novo Nordisk. N. Gronroos: Other Relationship; UnitedHealth Group, Novo Nordisk. Stock/Shareholder; UnitedHealth Group. Employee; UnitedHealth Group. L. Xie: None. J. Noone: Employee; Novo Nordisk. A. Sargent: Other Relationship; Novo Nordisk. Employee; UnitedHealth Group. Other Relationship; UnitedHealth Group. L. Yedigarova: Employee; Novo Nordisk. Stock/Shareholder; AbbVie Inc. L.K. Billings: Advisory Panel; Novo Nordisk, Pfizer Inc.

Funding

Novo Nordisk, Inc.
744-P: Dosing Patterns of Tirzepatide (TZP) in Patients with Type 2 Diabetes (T2D) from a Commercially Insured U.S. Population
Authors: MODY REEMA , DESAI KARISHMA , TENG CHIA-CHEN , REZNOR GALLY , STOCKBOWER GRACE , GRABNER MICHAEL , BENNEYWORTH BRIAN D.
Published: June 2024

Intro & Objective: Tirzepatide (TZP) is a once weekly glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 (GLP-1) receptor agonist (RA) approved in the US for treatment of T2D and obesity. The goal of this retrospective observational study was to understand the dosing patterns of TZP in people with T2D in a US commercially insured population.

Methods: Adult patients (pts) with T2D, with ≥1 Rx claim for TZP from 5/2022 to 8/2023, and ≥6 months of health plan enrollment before and after initiation were identified from the Healthcare Integrated Research Database (HIRD®). Baseline demographics and 6 months’ follow-up dosing patterns were described.

Results: The cohort included 15,665 pts (mean age 53 years, 59% female, 51% baseline GLP-1 RA use). Of the 96% of pts with a single prescription on each fill date, 43% started on 2.5 mg and 41% on 5 mg dose of TZP. The most common dose at 3rd fill was 5 mg (Figure 1). 70% of pts had ≥1 dose escalation; 56% on the 2nd and 23% on the 3rd fill. Median time to first escalation was 45 days; 33% escalated from 2.5 mg to 5 mg and 37% from 5 mg to 7.5 mg. Of the patients with no dose changes and ≥3 fills (n=2505), 57% stayed on the 5 mg dose and 26% of people on 2.5 mg.

Conclusion: Real-world evidence suggests that most patients with T2D had at least one dose increase for TZP, with 5 mg being the most prescribed and retained dose in the first 6 months of treatment with TZP.

Disclosure

R. Mody: Employee; Eli Lilly and Company. K. Desai: Employee; Carelon Research. Stock/Shareholder; Anthem, Inc. C. Teng: Employee; Carelon Research. G. Reznor: None. G. Stockbower: None. M. Grabner: Employee; Carelon Research. Stock/Shareholder; Anthem, Inc. B.D. Benneyworth: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company.
75-OR: In-Silico Replay of Insulin Degludec and Liraglutide Clinical Trial Data in Subjects with Type 2 Diabetes
Authors: GANJIARJENAKI MOHAMMADREZA , FABRIS CHIARA , EL FATHI ANAS , LV DAYU , KOVATCHEV BORIS , BRETON MARC D.
Published: June 2024

Introduction & Objective: The UVLab platform - equipped with a metabolic model and 6062 virtual subjects (VS) with type 2 diabetes (T2D) - describes T2D heterogeneity. This work evaluates UVLab's ability to replicate the findings from a 26-week phase 3 clinical trial (NCT01336023) comparing degludec (IDeg), liraglutaide (Lira), and a fixed-ratio combination of the two (IDegLira).

Methods: IDeg, Lira, and IDegLira were administered to the VS according to clinical trial protocol. Subpopulations matching early trial glycemic metrics were selected; later data were not used to inform the simulations. Hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), daily drug dose, and hypoglycemia events (HE) over the 26-week study were compared between clinical trial and simulations.

Results: Subpopulations of 208, 283, and 417 VS for the IDeg, Lira, and IDegLira arm, respectively, were selected using a method matching mean and standard deviation of HbA1c, FPG, and HE from trial baseline, week-4, and week-8 (IDegLira only) data. Figure 1 shows the evolution of glycemic metrics, comparing clinical trial and simulations. Overall median absolute relative error across all metrics and arms was 2.6% [0.6-11%].

Conclusion: UVLab effectively replicates trial outcomes, affirming its predictive capability for T2D treatment. This endorses in-silico models for treatment planning and enhancement of clinical trials.

Disclosure

M. Ganjiarjenaki: None. C. Fabris: Research Support; Novo Nordisk A/S. Other Relationship; Novo Nordisk A/S, Dexcom, Inc. A. El Fathi: None. D. Lv: None. B. Kovatchev: Research Support; Dexcom, Inc., Novo Nordisk, Tandem Diabetes Care, Inc. Other Relationship; Dexcom, Inc., Johnson & Johnson Medical Devices Companies, Novo Nordisk, Sanofi. M.D. Breton: Consultant; Dexcom, Inc. Research Support; Dexcom, Inc. Speaker's Bureau; Tandem Diabetes Care, Inc. Research Support; Tandem Diabetes Care, Inc., Novo Nordisk. Speaker's Bureau; Vertex Pharmaceuticals Incorporated. Consultant; PhysioLogic Devices. Advisory Panel; Sanofi. Speaker's Bureau; Sanofi.
754-P: Effect of Retatrutide on Kidney Parameters in People with Type 2 Diabetes and/or Obesity—A Post-Hoc Analysis of Two Phase 2 Trials
Authors: HEERSPINK HIDDO L. , LU ZEQING , DU YU , DUFFIN KEVIN L. , COSKUN TAMER , HAUPT AXEL , HARTMAN MARK L.
Published: June 2024

The prevalence of chronic kidney disease due to T2D and obesity is rapidly increasing. Retatrutide (RETA), an agonist of GIP, GLP-1 and glucagon receptors, showed marked effects in reducing body weight and HbA1c in people with T2D and/or obesity/overweight (OB). This post-hoc analysis assessed the impact of RETA on kidney parameters. Data from all participants in 2 phase 2 studies were included: T2D (N=281): RETA (0.5, 4, 8, 12 mg) vs dulaglutide 1.5 mg vs PBO (N=45-50/arm); OB (non-T2D; N=338): RETA (1, 4, 8, 12 mg) vs PBO (N=62-70/arm). Assessments included CKD-EPI creatinine eGFR (Cr-eGFR), cystatin C-based eGFR and urine albumin-to-creatinine ratio (UACR). Change from baseline was analyzed using mixed models for repeated measures; pairwise contrasts were used to compare RETA to PBO. At 36 wks in T2D, no difference was observed in Cr-eGFR between all RETA groups and PBO; UACR was significantly reduced vs PBO with RETA 12 mg (Fig). In OB, RETA 8 and 12 mg increased Cr-eGFR and decreased UACR compared to PBO at 48 wks. Results were similar when GFR was estimated from cystatin C. Blood pressure (BP) was significantly reduced in both studies. RETA 8 and 12 mg increased eGFR in people with OB but not in those with T2D. UACR and BP were reduced vs PBO with higher doses of RETA in both trials. These data suggest possible benefits on kidney function that warrant further investigation in larger populations.

Disclosure

H.L. Heerspink: Consultant; AstraZeneca, Bayer Inc., Boehringer-Ingelheim, CSL Behring, Eli Lilly and Company. Advisory Panel; Gilead Sciences, Inc. Consultant; Janssen Pharmaceuticals, Inc., Novartis AG, Novo Nordisk, Traveere Pharmaceuticals. Z. Lu: None. Y. Du: None. K.L. Duffin: Employee; Eli Lilly and Company. T. Coskun: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company. A. Haupt: Employee; Lilly Diabetes. Stock/Shareholder; Lilly Diabetes. M.L. Hartman: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company.

Funding

Eli Lilly and Company
756-P: Glucagon-Like Peptide-1 Receptor Agonists and the Risk of Endoscopy Failure or Aspiration—A Cohort Study
Authors: ALKABBANI WAJD , SUISSA KARINE , GU KRISTINE D. , JANE CROMER SARA , PAIK JULIE M. , BYKOV KATSIARYNA , HOBAI ION , WEXLER DEBORAH J. , PATORNO ELISABETTA
Published: June 2024

Introduction & Objective: Several cases of aspiration during endoscopy have been reported in glucagon-like peptide-1 receptor agonists (GLP1RA) users due to residual gastric contents. We conducted a population-based cohort study to assess whether GLP1RA use, compared to sodium-glucose cotransporter 2 inhibitors (SGLT2i), is associated with an increased risk of endoscopy discontinuation or aspiration.

Methods: Using two insurance claim databases, we identified adults with type 2 diabetes who underwent an endoscopy and were on either GLP1RA or SGLT2i within 30 days before the procedure. Outcomes were discontinued procedure, aspiration, or intubation, occurring within 24 hours after endoscopy. We estimated the risk ratio (RR) after 1:1 propensity score (PS) matching.

Results: We identified 29,384 PS-matched pairs (mean age 61 years; 52% female). Among GLP1RA users, the risk/1000 patients was 14.4 for procedure discontinuation, 2.5 for aspiration, and 2.9 for intubation. Compared to SGLT2i, GLP1RA use was associated with a slightly higher risk of endoscopy discontinuation (RR=1.25; 95% CI=1.09-1.44) and no increased risk of aspiration or intubation.

Conclusion: In this study, we observed no association between GLP1RA use and aspiration or intubation during endoscopy; however, GLP1RA users were more likely to have the procedure discontinued, compared to patients on SGLT2i.

Disclosure

W. Alkabbani: None. K. Suissa: None. K.D. Gu: None. S. Cromer: Other Relationship; Johnson & Johnson Medical Devices Companies. Advisory Panel; Alexion Pharmaceuticals, Inc. Other Relationship; Wolters Kluwer Health. J.M. Paik: None. K. Bykov: None. I. Hobai: None. D.J. Wexler: Other Relationship; Novo Nordisk. E. Patorno: Research Support; Boehringer-Ingelheim, Food and Drug Administration (FDA), National Institutes of Health, Patient-Centered Outcomes Research Institute.
761-P: Use of Tirzepatide in Type 1 Diabetes
Authors: CHILDS BELINDA P. , TADE MACKENZIE , SEBES JENNIFER , MOLT LISA , CHILDS ALLISON
Published: June 2024

In a retrospective chart review, we assessed the efficacy and safety of GLP1/GIP agonists, specifically tirzepatide, in managing Type 1 Diabetes (T1D). The study involved 15 patients (7 males, 8 females; average age 48 years; average diabetes duration 34 years), using Continuous Glucose Monitors (CGM). Among them, 8 on insulin pumps and 7 Multiple Daily Injections (MDI). Six had prior exposure to GLP1 agonists. The intervention, recognized as off-label, included careful insulin titration and ketone monitoring. Over 6-12 months, significant findings emerged: A1c levels significantly decreased at 6 months (Cohen's d = -0.79), indicating short-term effectiveness, but this change wasn't sustained at 1 year, suggesting the need for ongoing or modified approaches for long-term glycemic control. Additionally, there was a reduction in average Body Mass Index (BMI) with baseline 34.7, 6 month 31.7, 1 year 28.9 (Box and Whisker availble) and insulin requirements (attached) at both intervals, reflecting improved metabolic health and insulin sensitivity. Risks were mitigated through strategic insulin reduction. However, one patient discontinued due to severe hypoglycemia despite these adjustments. Mild nausea and constipation were reported in 3 patients. These findings, while preliminary, highlight the potential benefits of GLP1/GIP agonists in T1D management, warranting further investigation despite the risk of hypoglycemia and other side effects.

Disclosure

B.P. Childs: Research Support; Abbott. Advisory Panel; Provention Bio, Inc. M. Tade: None. J. Sebes: None. L. Molt: None. A. Childs: None.
78-PUB: Machine Learning–Assisted Segmentation of Pancreas MRI
Authors: TIRADO-VELEZ PEDRO L. , KANG SANGHOON , JU HUIWEN , CAMPBELL-THOMPSON MARTHA , KIM SARAH , LAMB DAMON
Published: June 2024

Introduction & Objective: Pancreas volume (PV) may be a useful biomarker for T1D, but manual segmentation of PV from an MRI is time consuming. The objective of this project was to develop and evaluate the efficiency of a machine-learning (ML) pipeline for pancreas MRI segmentation to calculate pancreas volume.

Methods: Manual and ML-assisted PV MRI segmentations were created from a sample of 68 including 15 controls (no diabetes) from an existing dataset (PMID: 30552130). We linked a local 3D Slicer (PMID: 22770690) instance with a hardware-accelerated MONAI Label server instance on the UF HiPerGator cluster for our ML-assisted segmentations. We evaluated the relative efficiency of ML-assisted vs. manual to create high quality segmentation of the pancreas.

Results: ML-assisted segmentations are of high-quality. ML-assisted segmentation resulted in a reduction of average time per segmentation by 5 minutes and a reduction of average total mouse-clicks by 28% when completed by a minimally-trained (non-radiologist) staff.

Conclusion: ML-assted segmentation can result in significant productivity gains for pancreas segmentation without loss of data quality or accuracy, reducing costs associated with radiological MRI segmentation for PV.

Disclosure

P.L. Tirado-Velez: None. S. Kang: None. H. Ju: None. M. Campbell-Thompson: None. S. Kim: None. D. Lamb: None.

Funding

JDRF (3-SRA-2022-1157-S-B)
781-P: Efficacy and Safety of Switching to iGlarLixi from Twice-Daily (BID) Premixed Insulin (PI) Administration in People with Type 2 Diabetes (T2D)—Subanalysis of Soli-SWITCH Study
Authors: HALUZIK MARTIN , MIN KYUNGWAN , CYPRYK KATARZYNA , ALVAREZ AGUSTINA , LAUAND FELIPE , REN YAN , BAKINER OKAN
Published: June 2024

Introduction & Objective: iGlarLixi is a once-daily injectable fixed-ratio combination of insulin glargine 100 U/mL plus lixisenatide. This sub-analysis of Soli-SWITCH (EudraCT number 2021-003711-25) assessed the efficacy and safety of switching from BID administration to once-daily iGlarLixi in people with T2D.

Methods: In this phase 4, 24-week, single-arm study, participants switched from PI to iGlarLixi at baseline. Key inclusion criteria included participants aged ≥18 years who had been diagnosed with T2D for ≥6 months and had received PI for ≥3 months and <10 years. In this sub-analysis we assessed the change in HbA1c (baseline to Week 24) in participants with previous BID PI dosing. The analyses also included the proportion of participants achieving HbA1c <7% at Week 24 and safety.

Results: Overall, 162 participants received iGlarLixi (88.3% BID PI dosing). In the overall population, mean PI dose at baseline was 39.5 units (U) (standard deviation [SD] 13.4), mean iGlarLixi dose at Week 24 was 40.6 U (SD 13.3). In evaluable participants with BID PI dosing at baseline and at Week 24 (n=126), mean HbA1c reduced from baseline to Week 24 by 1.2% (standard deviation [SD] 0.9%); similarly, in the total population, mean HbA1c reduced from baseline to Week 24 (n=145) by 1.2% ([SD] 0.9%). At Week 24, 36.2% of participants with prior BID PI dosing and 37.6% of participants in the total population achieved a HbA1c target of <7%. Confirmed symptomatic hypoglycemia occurred in 38.3% of all participants (ADA level 1: 35.8%; ADA level 2: 15.4%; ADA level 3: 0.0%). No new safety signals were observed in overall population.

Conclusion: iGlarLixi demonstrated improved glycemic outcomes in participants switching to iGlarLixi from BID PI dosing. These data suggest that iGlarLixi may be a potentially simplified treatment alternative for people with T2D currently receiving two daily injections of PIs.

Disclosure

M. Haluzik: Advisory Panel; Sanofi, Novo Nordisk, Eli Lilly and Company, AstraZeneca, Bayer Inc., Johnson & Johnson Medical Devices Companies. Consultant; Merck & Co., Inc., Sanofi, Novo Nordisk, Eli Lilly and Company, AstraZeneca, Bayer Inc., Boehringer-Ingelheim, Johnson & Johnson Medical Devices Companies, Novatin. Research Support; Sanofi. Speaker's Bureau; Sanofi, Novo Nordisk. K. Min: None. K. Cypryk: Research Support; Novo Nordisk, Sanofi. Speaker's Bureau; Novo Nordisk, Eli Lilly and Company, Sanofi, Merck & Co., Inc. A. Alvarez: Employee; Sanofi. Stock/Shareholder; Sanofi. F. Lauand: Employee; Sanofi. Stock/Shareholder; Sanofi. Y. Ren: Consultant; Sanofi. Employee; Aixial. O. Bakiner: None.

Funding

Sanofi
782-P: Insulin Therapy Deintensification with iGlarLixi—The IDEAL Randomized Controlled Trial
Authors: NOVODVORSKY PETER , THIEME LENKA , LANKOVA IVANA , VESELÁ ALICA , ZAHUMENSKY EMIL , EDELSBERGER TOMAS , LÖBLOVÁ MARIE , HRUBÝ FILIP , MRAZ MILOS , HALUZIK MARTIN
Published: June 2024

Introduction: Multiple daily injection (MDI) insulin therapy in people with type 2 diabetes (PwT2D) often leads to weight gain, increased risk of hypoglycemia and lower QoL. The Insulin therapy DE-intensificAtion with iglarLixi (IDEAL) trial examined the efficacy and safety of MDI de-intensification into once-daily administered FRC of insulin glargine U100 and GLP-1 RA lixisenatide (iGlarLixi) in PwT2D.

Methods: IDEAL was a 5-centre, open-label, parallel-group, phase 4 RCT with a 24-week treatment period. Eligible individuals (age 18-80 years, total daily dose of insulin [TDD] ≤ 0.8 IU/kg and fasting c-peptide above the lower limit of normal) were randomized in a 1:1 fashion into once-daily administered iGlarLixi or continuation with MDI, both titrated to fasting plasma glucose (FPG) ≤ 6 mmol/L (108 mg/dL). Primary outcome was HbA1c change at 24 weeks. Secondary outcomes were change in body weight (BW), TDD, FPG, postprandial glycemia (PPG), hypoglycemia, CGM-related metrics and QoL.

Results: Altogether 91 individuals (20/91, 22% women) with mean (SD) age 66 (9) years, diabetes duration 17 (9) years and BMI 33.5 (5.5) kg/m2 were analyzed. Mean change in HbA1c in the iGlarLixi group was non-inferior to the MDI group (-0.47 [0.91] % vs (-0.37 [0.77] %, p = 0.01 for non-inferiority, p = 0.25 for superiority). Mean reduction in BW in the iGlarLixi group was higher in comparison to the MDI group (-4.8 [4.3] kg vs -0.5 [3.7] kg, p < 0.001). TDD reduced in the iGlarLixi group (p < 0.0001) and remained unchanged in the MDI group (p = 0.233). The proportion of study visits at which hypoglycemia was reported was lower in the iGlarLixi vs MDI group (5.5% vs 9.6%, p = 0.029). No differences in FPG and PPG were observed.

Conclusion: Insulin therapy de-intensification from MDI into iGlarLixi is an efficient and safe treatment option for PwT2D that provides comparable glycemic control with the benefits of reduction of BW, TDD, number of insulin injections and lower proportion of visits as which hypoglycemia was reported.

Disclosure

P. Novodvorsky: Speaker's Bureau; Sanofi, Boehringer-Ingelheim. Advisory Panel; Boehringer-Ingelheim. Speaker's Bureau; Novo Nordisk A/S. Research Support; Sanofi. Speaker's Bureau; Abbott, Medtronic, Berlin-Chemie AG, Viatris Inc., Novartis AG. L. Thieme: None. I. Lankova: None. A. Veselá: None. E. Zahumensky: None. T. Edelsberger: None. M. Löblová: None. F. Hrubý: None. M. Mraz: None. M. Haluzik: Advisory Panel; Sanofi, Novo Nordisk, Eli Lilly and Company, AstraZeneca, Bayer Inc., Johnson & Johnson Medical Devices Companies. Consultant; Merck & Co., Inc., Sanofi, Novo Nordisk, Eli Lilly and Company, AstraZeneca, Bayer Inc., Boehringer-Ingelheim, Johnson & Johnson Medical Devices Companies, Novatin. Research Support; Sanofi. Speaker's Bureau; Sanofi, Novo Nordisk.

Funding

Sanofi
791-P: The Impact of Age on Response to Injectable Semaglutide—Insights from the Association of British Clinical Diabetologists’ Audit Programme
Authors: CRABTREE THOMAS S.J. , ADAMSON KAREN , BICKERTON ALEX , EVANS ALISON , PHILLIPS SUZANNE M. , GALLAGHER ALISON , BARNES DENNIS , DHATARIYA KETAN , FIELD BENJAMIN C.T. , IDRIS ISKANDAR R. , RYDER ROBERT E.
Published: June 2024

The ABCD Semaglutide (Ozempic) audit launched in 2019 to capture real-world outcomes in the UK. Pooled analysis from the SUSTAIN trials has demonstrated similar HbA1c and weight reducing efficacy in older populations compared younger. We report the impact of age on weight and HbA1c response to semaglutide.

Methods: Routinely collected clinical data was entered by participating centres into a secure online tool and included provided baseline and follow-up data were available. Age groups at commencement were defined as <40years, 40-64.9 years and ≥65years. Changes between baseline and follow-up were assessed using multivariate regression analysis to correct for potential confounders, with Bonferroni corrections for multiple comparisons. Analysis performed in Stata 16.

Results: In total 1,623 individuals (49.9% female) were included with baseline mean±SD age 58.9±11.0 years, HbA1c 9.4±1.7% and 107.1±23.5kg. Over a median follow-up of 0.7 years (IQR 0.4-1.0), HbA1c reduced by 1.2% (95%CI 1.1-1.3, P<0.001) and weight reduced by 4.7kg (95%CI 4.1-5.3, P<0.001). Baseline HbA1c levels were similar across age groups, but baseline weight was significantly lower with increasing age (mean±SD youngest group 115.5±28.6 vs. 101.8±19.5 in the oldest group, P<0.001). In those aged <40years HbA1c fell by 1.4% (95% 0.9-1.9) and weight reduced by 4.4kg (1.4-7.4); in age 40-64.9years HbA1c fell by 1.2% (1.0-1.3) and weight by 4.3kg (3.7-5.0) and in age ≥65years HbA1c reduced by 1.2% (1.0-1.4) and weight by 4.7kg (3.8-5.6) (P<0.001 for all). No significant differences between groups were noted for either change in HbA1c or weight.

Conclusions: Semaglutide is associated with HbA1c reductions across all ages. Weight reductions are also similar despite differences in baseline weight; this may be variably desirable in older individuals where weight maintenance may be preferred to prevent frailty.

Disclosure

T.S.J. Crabtree: Speaker's Bureau; Abbott, Novo Nordisk, Dexcom, Inc., Sanofi, Insulet Corporation, Lilly Diabetes. K. Adamson: Speaker's Bureau; Lilly Diabetes. A. Bickerton: None. A. Evans: None. S.M. Phillips: None. A. Gallagher: None. D. Barnes: None. K. Dhatariya: Other Relationship; AstraZeneca, Menarini, Boehringer-Ingelheim, Abbott Diagnostics, Eli Lilly and Company, Novo Nordisk. B.C.T. Field: Speaker's Bureau; AstraZeneca, Boehringer-Ingelheim, Eli Lilly and Company, Novo Nordisk, Sanofi. Consultant; Tape Specialities Limited. I.R. Idris: None. R.E. Ryder: Speaker's Bureau; Abbott, Besins Healtcare, BioQuest, GI Dynamics. Consultant; GI Dynamics. Other Relationship; Novo Nordisk.

Funding

Funded by ABCD
830-P: No Evidence of Increased Physical Activity–Related Hypoglycemia with Once-Weekly Insulin Icodec vs. Once-Daily Basal Insulin in Type 2 Diabetes—ONWARDS 1–5
Authors: RIDDELL MICHAEL C. , HELLER SIMON R. , ASONG MARISSE , CARSTENSEN LISBETH , WATT SARA K. , WOO VINCENT C.
Published: June 2024

Introduction & Objective: The ONWARDS (ON) phase 3a trials showed the efficacy and safety of once-weekly (OW) basal insulin icodec (icodec) vs once-daily (OD) basal insulin comparators. This post hoc analysis examined physical activity (PA)-related hypoglycemia, based on self-reported data, in adults with T2D in ON 1-5.

Methods: Hypoglycemia occurrence was evaluated in insulin-naive (ON 1, 3, 5) and insulin-treated (ON 2, 4) adults with T2D receiving icodec vs OD comparators. In each trial, participants who experienced hypoglycemic episodes were instructed to note any relation to PA in a digital diary.

Results: The number of PA-related level 2 or level 3 hypoglycemic episodes was low in all trials, except ON 4 (basal-bolus trial). The proportion of hypoglycemic episodes that were related to PA trended higher or was comparable with icodec vs OD comparators in insulin-naive T2D and trended lower or was comparable in insulin-treated T2D (Table). There were no statistically significant differences in the odds of experiencing a PA-related level 2 or level 3 hypoglycemia for icodec vs OD comparators.

Conclusion: The incidence of PA-related level 2 or level 3 hypoglycemia in T2D was low in these trials of basal insulins and was not worsened by treatment with icodec vs OD basal insulin comparators. Despite some uncertainty due to low incidences, these data are reassuring.

Disclosure

M.C. Riddell: Consultant; Eli Lilly and Company. Speaker's Bureau; Novo Nordisk. Advisory Panel; Supersapiens. Consultant; Dexcom, Inc. Speaker's Bureau; Sanofi. Advisory Panel; Zealand Pharma A/S. Speaker's Bureau; Dexcom, Inc. Stock/Shareholder; Zucara Therapeutics. S.R. Heller: Research Support; Dexcom, Inc. Speaker's Bureau; Novo Nordisk. Other Relationship; Eli Lilly and Company. Speaker's Bureau; Medtronic. Advisory Panel; Zealand Pharma A/S, Zucara Therapeutics, Vertex Pharmaceuticals Incorporated. M. Asong: Employee; Novo Nordisk A/S. Stock/Shareholder; Novo Nordisk A/S. L. Carstensen: Employee; Novo Nordisk A/S. Stock/Shareholder; Novo Nordisk A/S. S.K. Watt: Employee; Novo Nordisk. V.C. Woo: Advisory Panel; Novo Nordisk. Speaker's Bureau; Abbott. Advisory Panel; Boehringer-Ingelheim, Lilly Diabetes.

Funding

Novo Nordisk A/S
834-P: A Prospective Study on Switching from Basal Insulin to Insulin Degludec/Insulin Aspart, in Patients with Type 2 Diabetes Whose FPG Levels Are Lower Than Those Predicted by Their HbA1c
Authors: HONG EUNSHIL , NA JANG HAN , LEE SEONGOK , SEUL YANG YE , HEON KWAK SOO , SOO PARK KYONG , CHUL JANG HAK , SEUNG JUNG HYE
Published: June 2024

Objective: Benefits of once-daily insulin degludec/aspart (IDegAsp) compared with basal insulin in patients with type 2 diabetes (T2D) have not been established. As we have observed that a low ratio of fasting plasma glucose (FPG) to mean glucose was associated with superior response to IDegAsp by a retrospective study, we aimed to confirm it by a prospective design.

Methods: A randomized, open-label, cross-over trial was conducted in patients on a basal insulin therapy with FPG lower than predicted FPG (=12.6 x HbA1c (%) + 30, drawn from our previous study). Participants were assigned 1:1 ratio to IDegAsp or insulin glargine (IGlar) arm. After 20 weeks, the treatments were exchanged for the next 20 weeks. The primary endpoint was treatment difference of HbA1c changes from the baseline. Additionally, self-reported hypoglycemic events were collected, and a professional CGM was applied for 1 week prior to completion of each treatment.

Results: The study included 55 subjects (male 40 %, age 64.6 ± 9.5 years, FPG 102.6 ± 19.5 mg/dL, HbA1c 8.3 ± 0.6 %). After 20 weeks, the HbA1c significantly decreased to 7.8 ± 0.8 % by IDegAsp (0.40 ± 0.17 U/kg) and to 8.0 ± 0.7 % by IGlar (0.39 ± 0.18 U/kg). The mean estimated treatment difference of changes in HbA1c was not statistically significant (-0.22% point, 95% CI [-0.52, 0.08], p=0.078). In the CGM analyses, IDegAsp significantly reduced glucose levels after breakfast and before lunch, compared to IGlar. TIR, TBR, and hypoglycemic events were not significantly different between the treatments.

Conclusion: Compared to basal insulin, once-daily IDegAsp demonstrated a marginal benefit in reducing HbA1c in patients with lower FPG than predicted by their HbA1c, though the glycemic excursions after breakfast were significantly improved. More indices would be needed to tell those expected to have significant benefits by switching from basal insulin to IDegAsp. UTN#: U1111-1241-6269

Disclosure

E. Hong: None. H. Jang: None. S. Lee: None. Y. Yang: None. S. Kwak: Employee; SNUH Venture. K. Park: None. H. Jang: Consultant; Novo Nordisk. H. Jung: Research Support; Novo Nordisk.

Funding

Novo Nordisk, NRF (2022R1A2C2004570)
851-P: Whole Body Digital Twin (WBDT) Enabled Diabetes Reversal—U.S. Real-World Findings
Authors: SHAH LISA , JOSHI SHASHANK R. , MOHAMMED JAHANGIR , MOHAMED MALUK , THAJUDEEN MOHAMED , KAUFMAN FRANCINE R. , WILLIS BREE
Published: June 2024

The WBDT is a digital model of metabolism, created using sensors, the Internet of Things, artificial intelligence and machine learning, providing an individualized comprehensive lifestyle intervention to improve and reverse T2D and its comorbidities. With an easy-to-use app, patients (pts) and the care team are given daily individualized guidance across nutrition, sleep, and activity. This study assessed medication (meds) use and metabolic markers over 1 yr in 256 T2D pts using WBDT commercial program data. Continuous variables were analyzed with paired t-test or Wilcoxon signed-rank test. At 1 yr, A1C decreased from 7.73±1.38 to 6.22±0.62; 71.9% had A1C <6.5%. T2D reversal (A1C <6.5% with no T2D meds except metformin) was achieved by 55.5%. At entry, 5.9% were not on T2D meds, 32.8% on 1, 35.9% on 2, and 25.4% on ≥3. At 1 yr, 29.7% were not on T2D meds, 37.5% on 1, 25.8% on 2, and 7.0% on ≥3. The Table shows the 1 yr changes in metabolic parameters. These data suggest the WBDT program leads to diabetes reversal, reduction in meds, and improvement or normalization of multiple metabolic parameters. The WBDT program may be an effective strategy to reduce the overall burden of T2D and its comorbidities.

Disclosure

L. Shah: Employee; Twin Health. S.R. Joshi: Consultant; Twin Health, Marico, Franco Indian, Zydus Cadila, Glenmark Pharmaceuticals. Other Relationship; Novo Nordisk, Sanofi, MSD, Abbott Nutrition, Abbott, Biocon, Alkem, USV Private Limited, Boehringer-Ingelheim. J. Mohammed: Employee; Twin Health. M. Mohamed: None. M. Thajudeen: None. F.R. Kaufman: Employee; Senseonics. Consultant; Twin Health. B. Willis: Employee; Twin Health.
857-P: Real-World Impact of Once-Weekly Injectable Semaglutide on Weight, BMI, and HbA1c Outcomes in Type 2 Diabetes—An Observational Study (PAUSE)
Authors: AMAMOO JAMES , DOSHI RIDDHI P. , NOONE JOSHUA , XIE LIN , GAMBLE CORY L. , GUEVARRA MICO , DIVINO VICTORIA , CHEN JUSTIN , KING AARON A.
Published: June 2024

Introduction & Objective: This study aimed to determine the real-world effectiveness of injectable semaglutide once weekly (sema OW) on weight and HbA1c outcomes among people with type 2 diabetes (T2D) in the US.

Methods: This observational cohort study involved adults with uncontrolled T2D (HbA1c ≥7%) initiating sema OW from January 2018—February 2022 (first prescription = index) using IQVIA PharMetrics® Plus and Ambulatory Electronic Medical Records databases. Change in weight, BMI and HbA1c outcomes from baseline to 1-year post-index were descriptively compared overall, as well as for subgroups of those persistent (≤60-day gap in treatment, subgroup 1), those receiving maintenance dose ≥1 mg (subgroup 2), and those who were persistent and receiving dose ≥1 mg (subgroup 3).

Results: Among the final sample (n=772) and all subgroups, a significant mean change from baseline was seen in weight, BMI and HbA1c (all p<0.0001; Fig.). Mean changes in weight and BMI were numerically greatest in subgroup 3 (Fig.). The proportion of patients with obesity (BMI ≥30 kg/m2) significantly decreased from 84.0% at baseline to 77.1% post-index (p<0.0001).

Conclusion: Adults with T2D initiating sema OW had statistically significant decreases in weight, BMI and HbA1c after 1 year, with better weight outcomes in patients persistent to treatment and receiving maintenance dose ≥1 mg.

Disclosure

J. Amamoo: None. R.P. Doshi: None. J. Noone: Employee; Novo Nordisk. L. Xie: None. C.L. Gamble: Employee; Novo Nordisk. M. Guevarra: Stock/Shareholder; Novo Nordisk. V. Divino: Employee; IQVIA Inc. J. Chen: None. A.A. King: Speaker's Bureau; Abbott, MannKind Corporation, Novo Nordisk. Advisory Panel; Novo Nordisk. Speaker's Bureau; Lilly Diabetes. Advisory Panel; Lilly Diabetes. Speaker's Bureau; Dexcom, Inc. Advisory Panel; Dexcom, Inc. Speaker's Bureau; Astellas Pharma Inc.

Funding

Novo Nordisk
862-P: Efficacy and Safety of Orlistat in People with Overweight/Obese and Hyperuricemia—Results of a Randomized, Double-Blind, Placebo-Controlled Trial
Authors: LIU SHUANG , QU SHEN , CHEN HAIBING
Published: June 2024

Objective: Obesity is associated with elevated serum uric acid (SUA) and frequent gout flares. Losing weight can lower SUA and reduce gout flares. In this study, we investigated the effects of orlistat on SUA and gout flares compared to placebo in people with overweight/obese and hyperuricemia (HUA).

Methods: A total of 72 Chinese people with overweight/obese and HUA were randomly divided into placebo group and orlistat group for 12 weeks. The primary endpoints were relative changes in SUA, as well as gout flares.

Results: All participants with overweight/obesity and HUA were randomly assigned to placebo group (35, 48.61%) and orlistat group (37, 51.39%). There were 26 (74.29%) and 29 (78.38%) participants with gout in the two groups, respectively. Orlistat was associated with a significantly lower proportion of people with gout flares (log-rank p = 0.023, hazard rate = 0.31, 95% CI 0.11-0.85). There was no significant change in SUA levels in both groups. The weight loss of participants in the orlistat group (2.85kg) was significantly higher than that in the placebo group (0.76kg).

Conclusions: This study demonstrates for the first time that orlistat has no direct effect on SUA levels in people with overweight/obese and HUA. The value of orlistat as an adjunct therapy to prevent gout flares during weight loss in people with HUA was emphasized.

Disclosure

S. Liu: None. S. Qu: None. H. Chen: None.

Funding

National Natural Science Foundation of China (81870606)
863-P: Genetically Proxied GLP-1 Receptor Agonism Improves Kidney Function—A Mendelian Randomization Study
Authors: CHOI JAEWON , LEE HYUNSUK , LEE JEONGEUN , PARK JONGSEOK , JO YEEUN , SUNG JOOHON , LEE SEUNGGEUN , HEON KWAK SOO , KHO MINJUNG
Published: June 2024

Recently, the use of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) has been associated with prevention of kidney function decline and reducing the risk of chronic kidney disease (CKD). However, it is not clear whether GLP-1 receptor agonism has a direct causal effect on renal function. We aimed to investigate the causal association between GLP-1 receptor agonism, kidney function, and the risk of CKD using the Mendelian randomization approach. We constructed genetic instruments for GLP-1 receptor agonism using expression quantitative trait loci (eQTL), focusing on those with significant associations between genetic variants and gene expression in pancreatic tissue from the GTEx database. The inverse variance weighted model was utilized to estimate causal associations, and summary genetic association estimates for the estimated glomerular filtration rate (eGFR)(N=33,152) and CKD (N=117,165) were obtained from a mixed-ancestry genome-wide association study (GWAS) from the CKD Gen Consortium. We identified 7 genetic variants, or eQTL, that were significantly associated with GLP1 receptor mRNA expression in pancreatic tissue. Using these as instrumental variables we observed that genetically predicted GLP1 receptor agonism was significantly associated with improved kidney function as estimated by eGFR (beta 1.97×10-3, 95% CI 6.08×10-4-3.33×10-3, P=5.38×10-3). However, we were not able to find any causal association between genetically predicted GLP1 receptor agonism and reduction in risk of CKD (OR=0.99, 95% CI 0.95-1.03, P=0.65). There was no evidence of horizontal pleiotropy, as indicated by MR-Egger intercept and no obvious heterogeneity (all P>0.05) was observed in each analysis.

In conclusion, genetic evidence suggests that GLP-1 receptor agonism is likely to improve kidney function in the general population. Further studies are warranted to determine the impact of GLP-1 receptor agonism on reducing the risk of CKD especially in people with diabetes.

Disclosure

J. Choi: None. H. Lee: None. J. Lee: None. J. Park: None. Y. Jo: None. J. Sung: None. S. Lee: None. S. Kwak: Employee; SNUH Venture. M. Kho: None.

Funding

National Research Foundation of Korea grant funded by the Korean Ministry of Science and ICT (RS-2023-00262002)
871-P: One-Year Real-World Evidence of Effectiveness of Carbohydrate Restricted Nutrition Therapy in Adults with Type 2 Diabetes across Age and Gender
Authors: ROBERTS CAROLINE G.P. , ADAMS REBECCA N. , ATHINARAYANAN SHAMINIE J. , VOLK BRITTANIE M. , ZOLLER ALISON R. , MCKENZIE AMY L.
Published: June 2024

Type 2 diabetes (T2D) affects 12% of US adults, with a growing presence in young adults. Virta Health provides carbohydrate restricted nutrition therapy (CRNT) through continuous remote care (CRC) to US adults with T2D, but the impact of the program across age and gender groups is unknown. This retrospective real-world study assessed differences in health marker change over one year between age groups, and secondarily between genders, with linear mixed effects models. One year retention was high across age groups (64%, 76%, 76%; ages 18-44, 45-64, 65+) and gender (76% male, 73% female), and a random sample (N=750) of patients enrolled one year was selected for this analysis. Broadly, all age groups and both genders improve over time in multiple health markers (weight, A1c, triglycerides, HDLc, liver enzymes) with no change in Total Cholesterol or LDLc, and with few differences between groups. Mean A1c in all age groups and both genders is <7% at one year. These results provide real-world evidence that CRNT favorably impacts glycemic control, cardiometabolic health, and hepatic function in adults with T2D across age groups and in both men and women. The A1c reduction in the youngest age group is notable, as early glycemic control may confer legacy effects on complication rates for many decades.

Disclosure

C.G.P. Roberts: Other Relationship; Virta Health Corp. R.N. Adams: Employee; Virta Health Corp. Stock/Shareholder; Virta Health Corp. S.J. Athinarayanan: Employee; Virta Health Corp. B.M. Volk: Employee; Virta Health Corp. Stock/Shareholder; Virta Health Corp. A.R. Zoller: Employee; Virta Health Corp. Stock/Shareholder; Virta Health Corp. A.L. McKenzie: Employee; Virta Health Corp. Stock/Shareholder; Virta Health Corp. Employee; Abbott.
882-P: A Novel Angiogenesis Role of GLP-1(32-36) to Rescue Diabetic Ischemic Lower Limbs via GLP-1R–Dependent Glycolysis
Authors: ZHANG YIKAI , WANG SHENGYAO , ZHOU QIAO , XIE YI , ZHENG CHAO
Published: June 2024

Our initial experiments revealed that GLP-1(32-36), an end-product of GLP-1, did not affect insulin secretion, but could significantly rescue angiogenic function and blood perfusion in ischemic limb of STZ-induced type 1 diabetes mellitus (T1DM) mice, a function similar to its parental GLP-1. We hypothesized that GLP-1(32-36) might exert its angiogenetic effects by an unknown mechanism independent of the insulinotropic activity. We demonstrate that GLP-1(32-36) ameliorated high glucose (HG)-induced excessive mitochondrial fission by resorting to aerobic glycolysis. GLP-1(32-36)-mediated angiogenesis in T1DM mice after hindlimb ischemia (HLI) were dependent on GLP-1R expression. GLP-1R, though not involved in GLP-1(32-36) entry into the cells, was required for GLP-1(32-36)-mediated pro-angiogenetic activities, including mitochondrial homeostasis, activation of the eNOS/cGMP/PKG pathway, and enhanced glycolysis via PFKFB3. Thus, our study provides a novel mechanism with which GLP-1(32-36) acts in modulating metabolic reprogramming towards glycolytic flux in partnership with GLP-1R for improved angiogenesis in HG-exposed EPCs and T1DM murine models. We propose that GLP-1(32-36) could be used as a monotherapy or add-on therapy with existing treatments for peripheral arterial disease.

Disclosure

Y. Zhang: None. S. Wang: None. Q. Zhou: None. Y. Xie: None. C. Zheng: None.

Funding

National Natural Science Foundation of China(82100862, 82070833)
889-P: Type 2 Diabetes Treatment Algorithm Study
Authors: MOHAN RAMANARAYANAN SHIVAA
Published: June 2024

Clinical inertia is a global challenge affecting >50% of individuals with type 2 diabetes(T2DM). T2TA study is an initiative towards Algorithm development for T2DM treatment initiation or intensification based on FBS and PPBS outcomes to avoid clinical inertia. This study included individuals (N=200) with uncontrolled, untreated Newly diagnosed T2DM (NDDM) and Previously diagnosed T2DM (PDDM) on treatment, aged >18 years subjected to various drug combinations on Day 0. Therapy included DPP4 inhibitor (DPP4i), SGLT2 inhibitor (SGLT2i), Sulfonylurea (SU), Metformin (MET), Insulin (INS). Difference between Day 0 and Day 5 FBS, PPBS values were termed Glycemic reduction capacity (GRC) of a therapy. Therapy achieving a GRC frequently was termed the treatment of choice for initiation/intensification. GRC values were categorized into 9 glucose ranges from 1-449mg/dl. In NDDM the mean FBS, PPBS values on Day 0 were 243 ± 81 mg/dl, 350 ±106 mg/dl.On Day 5 of treatment it was 136 ± 30 mg/dl, 187 ± 69 mg/dl, with a significant reduction of mean glucose by 107 ± 82 mg/dl,164 ± 104 mg/dl. Among PDDM the mean FBS, PPBS values on Day 0 were 206 ± 62 mg/dl, 304 ± 87 mg/dl. On Day 5 of treatment it was 131 ± 35 mg/dl, 191 ± 50 mg/dl with a significant reduction of mean glucose by 76 ± 48 mg/dl, 114 ± 76 mg/dl. High GRC treatment of T2TA study can be used to develop an algorithm for treatment initiation or intensification in T2DM with significant glycemic reduction as early as Day 5 to avoid clinical inertia

Disclosure

S. Ramanarayanan: None.
89-OR: GPSM1 Regulates ER Ca2+-Myosin II Axis and Promotes Adipocyte Browning and Metabolic Health
Authors: YAN JING , HU CHENG
Published: June 2024

Introduction & Objective: Adaptive thermogenesis offer crucial potential to combat metabolic diseases. We have proved G-protein-signaling modulator 1 (GPSM1) regulated metabolic inflammation in macrophages, however, it remains unclear whether GPSM1 mediates thermogenic fat function.

Methods: We generate adipocyte-specific GPSM1 KO and transgenic mice, subject them to a NCD or HFD to monitor thermogenic and metabolic phenotypes. By using molecular, biochemical analyses, and primary cell culture to reveal the role of GPSM1 in adipocytes and elucidate the underlying mechanisms of GPSM1 in regulating thermogenesis.

Results: Adipocyte-specific KO of GPSM1 in mice impairs a broad thermogenesis of adipocytes, including decreased energy expenditure, cold tolerance and UCP1 levels, exacerbates diet-induced obesity, insulin resistance, glucose dysregulation and hepatic steatosis. Mechanistically, GPSM1 controls ER Ca2+ store, resulting in enhanced intracellular Ca2+ levels and consequential promoting Ca2+-dependent myosin II activation, thus mediating mitochondrial respiration and thermogenesis in adipocytes. In contrast, mice with transgenic overexpression of GPSM1 show improved energy expenditure, better cold tolerance, and ameliorated metabolic dysfunctions.

Conclusions: we uncover a novel function of GPSM1 as a positive regulator of adipocyte thermogenesis and metabolic homeostasis.

Disclosure

J. Yan: None. C. Hu: None.

Funding

the National ScienceFoundation of China (82370879); Shanghai Rising-Star Program (23QA1407400)