bluuebunny/crossref_metadata_2025 huggingface dataset:
710-P: Material-Needs Security and Food Insecurity in Adults with Type 2 Diabetes in Lebanon
Authors: BASSIL MAYA , SUKKARIEH OLA , EGEDE LEONARD E.
Published: June 2023

Food insecurity is known to impair diabetes self-management and clinical outcomes. Little is known about the prevalence and social determinants of food insecurity among people with type 2 diabetes (T2DM) in the Middle East and North Africa (MENA) region. Thus, the aim of this study was to assess food insecurity and its relationship with material needs security in Lebanese adults with T2DM of low socioeconomic status. Subjects with T2DM (n=299) were recruited from primary health care centers in Lebanon; sociodemographic and material need variables were collected using self-reported questionnaires. Food insecurity was assessed using the validated US Household Food Security Survey Module: Six-Item Short Form (USDA, 2012). Around 25% of the sample were food insecure. Compared to the food secure group, there were significantly (p<0.05) more participants who were females (58% vs. 44%), and who had low education level (82% vs. 58%) low income (49% vs. 24%), and no health insurance (65% vs. 49%), compared to the food secure group. Sum of material needs security was lower in the food insecure group (7.8±2.0 vs. 9.4±2.1, p<0.05). Results from the fully adjusted logistic regression model showed that material needs security (OR: 1.26; 95% CI: 1.06-1.49; p<0.007) and higher income (OR: 3.34; 95% CI: 1.39-8.05; p<0.007) were independent predictors of food security. Our study highlights the importance of material needs in achieving food security in T2DM in the MENA region. Further research is needed to explore other social determinants of health in this population and potential pathways/mechanisms to guide programs for effective interventions.

Disclosure

M.Bassil: None. O.Sukkarieh: None. L.E.Egede: None.
714-P: Health-Related Quality of Life (HRQOL) in Young Adults with T1D
Authors: BAUDINO MARISSA , CARREON SAMANTHA A. , STREISAND RANDI , TANG TRICIA S. , LYONS SARAH , MCKAY SIRIPOOM , ANDERSON-THOMAS BARBARA J. , MINARD CHARLES G. , BUTLER ASHLEY , HILLIARD MARISA E.
Published: June 2023

Challenges of young adulthood with T1D include transitioning to adult care, increased self-management responsibility, and developmental changes. Recognizing patterns of HRQOL across demographically and clinically diverse young adults with T1D may help identify who needs additional support as they transfer to adult healthcare. We hypothesized that young adults from racially, ethnically, and socioeconomically marginalized groups and those with higher A1c would report lower HRQOL.

At baseline of a behavioral RCT (≤2 months after last pediatric T1D clinic visit), 82 young adults (Mage=19.9±1.3, MA1c=8.9±2.0%) self-reported demographics and HRQOL; A1c was analyzed via point of care or dried blood spot. ANOVAs, t-tests, and a regression model compare HRQOL by demographic (gender, race/ethnicity, insurance, school enrollment) and clinical variables (device use, A1c).

As detailed in the table, HRQOL was significantly higher for participants in school and men (p<.01). Pump-users reported higher HRQOL on the “Handling Diabetes Well” and “Peer Relationships” subscales (p<.05). Regression analyses yielded gender and school enrollment as significant predictors of HRQOL (p<.01).

Variability across groups of young adults with T1D suggests monitoring HRQOL may be helpful to identify T1D-specific psychosocial needs during this transition. Patterns suggest women and those not in school may benefit from additional support.

Disclosure

M.Baudino: None. M.E.Hilliard: None. S.A.Carreon: None. R.Streisand: None. T.S.Tang: Research Support; Juvenile Diabetes Research Foundation (JDRF), Speaker's Bureau; Abbott Diabetes, Insulet Corporation. S.Lyons: None. S.Mckay: None. B.J.Anderson-thomas: None. C.G.Minard: None. A.Butler: None.

Funding

National Institute of Diabetes and Digestive and Kidney Diseases (1R01DK119246 to M.E.H.)
716-P: Improving Provider–Patient Relationships in Treatment of Young Adult Type 1 Diabetes
Authors: DIAZ CRYSTAL N. , ONG ALLISON , CHEN CINDY
Published: June 2023

Aims: Type 1 diabetes mellitus (T1D) is a chronic illness that requires constant monitoring and management of one's blood glucose levels. This study focuses specifically on young adults aged 18-25 living with T1D in the United States and aims to identify strengths and areas of improvement for provider-patient relationships within young adult T1D care.

Methods: An online 15-question Qualtrics survey was distributed across social media over one month, and responses were studied using descriptive, inferential, and causal statistical analysis.

Results: Of the 48 responses, 56% strongly agreed that their provider listens to how they like to do things and conveys confidence in their ability to make changes, whereas 29% didn't feel trust and are unable to be open with their provider. Diabetes-specific stressors and diabetes burnout was the most selected topic that participants wanted their provider to address more often. 56.3% of participants have switched diabetes care providers due to dissatisfaction, and 47.9% have felt belittled or called a bad diabetic by a diabetes provider.

Discussion: Strong provider-patient relationships that facilitate trust, comfort, and connection were related to lower HbA1C, improved diabetes control, and improved diabetes-related stress.

Disclosure

C.N.Diaz: None. A.Ong: None. C.Chen: None.
72-OR: Higher Genetic Risk for Type 2 Diabetes Is Associated with Faster Decline of Beta-Cell Function
Authors: LEE HYUNSUK , CHOI JAEWON , SON HEEJUN , SOO PARK KYONG , CHO NAM H. , HEON KWAK SOO
Published: June 2023

Objective: Polygenic risk score (PRS) for type 2 diabetes (T2D) has been reported to be associated with beta cell function, but whether it is also associated with the longitudinal change of beta cell function is largely unknown. We aimed to evaluate the association of PRS and the trajectory of beta cell function in a community based prospective cohort.

Method: We analyzed 6,323 participants without T2D at baseline from Ansan-Ansung cohort with 75-g 2-hour oral glucose tolerance tests taken biennially for 14 years. Disposition index (DI), derived from insulinogenic index at 60 minutes and Matsuda index, was used as a marker for beta cell function. PRS was calculated using 1.2 million variants from trans-ancestry T2D genome-wide association study using Bayesian regression (PRS-CSx). Participants were stratified into low (1st quintile), intermediate (2nd to 4th quintiles) and high genetic risk (5th quintile). Lifestyle was categorized as unfavorable, intermediate and favorable lifestyle according to Life’s Essential 8. Linear mixed model was applied.

Result: During a median follow-up of 13 years, 379 (30.6%), 875 (23.0%) and 171 (13.4%) participants developed T2D in high, intermediate and low genetic risk group, respectively. Participants in high genetic risk group, compared to low genetic risk group, had a 33% lower DI at baseline (53 [95% CI 50, 56] vs 79 [74, 84]; P = 7.9×10-15), and a 1.7-fold faster rate of decline in log2(DI) per year (-0.035 [-0.028, -0.042] vs -0.020 [-0.013, -0.027]; P = 0.0026). Notably, we found significant interaction between the rate of decline in DI and T2D PRS (P = 8.5×10-5). Healthy lifestyle was associated with decreased rate of decline in DI across all genetic risk group.

Conclusion: Having a high genetic risk for T2D was associated with not only a lower DI at baseline, but also a faster rate of decline in DI. Genetic information could be used to identify those at risk for rapid decline of beta cell function and emphasize lifestyle modification.

Disclosure

H.Lee: None. J.Choi: None. H.Son: None. K.Park: None. N.H.Cho: None. S.Kwak: None.

Funding

Ministry of Health & Welfare, Republic of Korea
720-P: Material Needs Security and Mental Health Outcomes in Adults with Type 2 Diabetes in Lebanon
Authors: SUKKARIEH OLA , BASSIL MAYA , EGEDE LEONARD E.
Published: June 2023

Despite their documented significance in type 2 diabetes (T2DM) management, social determinants of health (SDOHs) including material needs security and mental health outcomes (herein referred to as depression and diabetes fatalism) are understudied in the Middle East and North Africa (MENA) region. This study aims to assess the relation between material needs security and mental health outcomes in Lebanese adults with T2DM. Subjects with T2DM (N=299) were recruited from primary health care centers in Lebanon; sociodemographic, material need variables, depression measured by Patient Health Questionnaire (PHQ-9) and Diabetes Fatalism measured by Diabetes Fatalism Scale (DFS) were used. Depression and diabetes fatalism were used as outcome variables. Most of the participants were men, married and with lower educational levels. Multivariate analyses revealed that having material needs security was associated with diabetes fatalism (β=-0.63(-1.13; -0.12)), and depression (β=-0.46(-0.78; -0.13)) after controlling for all relevant confounding variables. Results from the fully adjusted logistic regression model showed that material needs security (OR: 0.82; 95% CI: 0.69; p<0.001). Our study highlights the importance of material needs security on mental health outcomes for adults with T2DM in the MENA region. Clinicians are encouraged to assess impact of material needs on mental health outcomes. Further research is needed to understand potential pathways/mechanisms and options for effective interventions and policy making.

Disclosure

O.Sukkarieh: None. M.Bassil: None. L.E.Egede: None.
726-P: Medication Adherence among American Indians with Type 2 Diabetes—Assessing the Quality of Electronic Health Record Data within a Large Tribal Health Care System
Authors: SCARTON LISA , NELSON TARAH N. , DEVAUGHAN CIRCLES ASHLEY , LEGASPI ANATOLIA , WILKIE DIANA J.
Published: June 2023

Electronic health record (EHR) systems within tribal healthcare facilities offer a rich but underutilized data source about medication adherence and its potential to predict HbA1c. The purpose of this analysis was to describe data quality issues for medication events in a dataset extracted from a large tribal healthcare EHR system. This analysis was a critical step prior to conducting a study of medication adherence among American Indians with type 2 diabetes (T2D). The EHR dataset from 2017-2021 included 10,506 patients who were enrolled adult tribal citizens, had T2D, and had at least one health system encounter. Tribal pharmacy refill data were linked to the EHR data and included information such as prescription regimen (e.g., drug, dose, route of administration, quantity), date new medication prescribed, date picked up, and refill dates. Data quality indicators were: duplicate data, missing data (e.g., dispense and fill dates, RX number), and data inconsistent with eligibility criteria. The mean age of the sample was 60.2 ±13.4 years and 52% were female. Out of the 1,400,593 patient medication fill/refill events we excluded 64,015 medication events due to a) duplicate prescription fill data (n=112); b) no dispense date (n=1,081); c) no order date (n=0); d) no fill date (n=0); e) no RX number (n=0); f) missing number of days dispensed (n=0); g) missing drug (n=0); h) missing dose (n=0); and i) data extracted not meeting the eligibility criteria (n=62,822). The date the medication was prescribed was not extracted from the EHR. Discovering these results was labor intensive taking more than 6 months. This analysis revealed few data-related concerns. With the exception of one missing variable, the dataset includes high quality data from which we will calculate medication adherence among American Indians with T2D.

Disclosure

L.Scarton: None. T.N.Nelson: None. A.Devaughan circles: None. A.Legaspi: None. D.J.Wilkie: Other Relationship; eNursing llc.

Funding

National Institutes of Health (1R01NR020386-01)
738-P: Lifestyle Intervention Program with Smartphone App Augmented by Intermittently Scanned Continuous Glucose Monitoring for People at High Risk of Diabetes—Randomized Controlled Trial
Authors: KITAZAWA MASARU , SUZUKI HIROSHI , HORIKAWA CHIKA , TAKEDA YASUNAGA , IKEDA IZUMI , HATTA MARIKO , IWANAGA MIDORI , YAMADA TAKAHO , FUJIHARA KAZUYA , SONE HIROHITO
Published: June 2023

We examined the effects of a lifestyle intervention program with a smartphone app augmented by intermittently scanned continuous glucose monitoring (isCGM) of persons at high risk of developing diabetes in a 12-week randomized open-label trial (UMIN00004640). The program monitored blood glucose fluctuations and lifestyle habits and displayed them in an easy-to-understand interface as well as provided personalized lifestyle intervention messages. The primary endpoint was the change in time in range (TIR) of 70-140 mg/dL between intervention (App) and control (C) groups. Among 168 patients (mean age 48.1 y, mean BMI 26.6 kg/m2, and male 80.4%), 82 and 86 were assigned to the App group and C group, respectively. After 12 weeks, TIR of 70-140 mg/dL significantly improved in the App group compared to the C group (-2.6 min/day vs. +31.5 min/day, p=0.03). Changes in time above range (>140 mg/dL; -20.9 min/day vs. -22.6 min/day, p=0.86) did not differ, whereas time below range (<70 mg/dL; +23.5 min/day vs. -8.9 min/day, p=0.02) improved in App compared to C. BMI (-0.26 vs. -0.59, p=0.017) and carbohydrate intake (-4.4 kcal/day vs. -22.7 kcal/day, p=0.049) also improved in App compared to C. Intervention with a smartphone app and isCGM increased glycemic control with a decrease in carbohydrate intake and weight loss.

Disclosure

M.Kitazawa: None. H.Sone: Research Support; Novo Nordisk, Astellas Pharma Inc., Kyowa Kirin Co., Ltd., Taisho Pharmaceutical Holdings Co., Ltd., Ono Pharmaceutical Co., Ltd., Eisai Co., Ltd., Takeda Pharmaceutical Co., Ltd. H.Suzuki: None. C.Horikawa: None. Y.Takeda: None. I.Ikeda: None. M.Hatta: None. M.Iwanaga: None. T.Yamada: None. K.Fujihara: None.
739-P: Metabolome Alterations Associated with 12-Week Sitting Time Reduction among Sedentary, Postmenopausal Latinas
Authors: PATTERSON JEFFREY , JASBI PANIZ , GU HAIWEI , ALLISON MATTHEW , REUTER CHASE , RANA BRINDA , NATARAJAN LOKI , SEARS DOROTHY D.
Published: June 2023

Background: Prolonged sitting is associated with health risk. The metabolic impact of replacing sitting time with standing is unknown. We explored metabolome changes after a 12-week standing intervention.

Methods: Sedentary postmenopausal Latinas with overweight (N=254; 55+ years of age; BMI ≥25 kg/m2) were randomized to an increased standing intervention or a health education control group. Clinical, behavioral and fasting plasma measurements were collected at baseline and 12-weeks. Sitting, standing and stepping time was assessed objectively by a thigh-worn inclinometer (activPAL). Aqueous metabolites and carnitines were measured using LC-MS/MS.

Results: Top tertile of intervention group Best Responders (N=43) was selected by criteria of change in mean sitting bout duration and total sitting time. Variable-Matched Controls (N=43) were selected from the control group using a random forest model trained to predict the Best-Responders. Best Responders changed sitting and standing time by -110.0 (11.0) and 104.6 (10.1) min, respectively, compared to the Matched Controls change of 7.1 (9.8) and -7.8 (9.0) min, respectively. A covariate-controlled GLM revealed significant group differences in change scores of 24 metabolites (FDR q = 0.048-2.1E-4) from baseline to 12-week follow-up. Enzyme enrichment predicted significant functional changes in enzymes involved in glutamate and histidine catabolism. Pathway analysis showed significant effects in 14 metabolites of aminoacyl tRNA biosynthesis, as well as 4 metabolites involved in phenylalanine, tyrosine, tryptophan, ubiquinone/terpenoid-quinone biosynthesis and beta-alanine metabolism (all p < 0.05). Metabolite change scores mapped to central carbon metabolism with significant elevation of 14 amino acids involved in pyruvate, acetoacetyl- and acetyl-CoA metabolism, and TCA cycle intermediate biosynthesis.

Conclusion: Standing intervention results in broad amino acid metabolism alterations.

Disclosure

J.Patterson: None. P.Jasbi: None. H.Gu: None. M.Allison: None. C.Reuter: None. B.Rana: None. L.Natarajan: None. D.D.Sears: None.

Funding

American Heart Association (16SFRN28420000)
74-LB: Transition from Basal Bolus to Once-Weekly Subcutaneous Semaglutide and Basal Insulin in Patients with Type 2 Diabetes Mellitus (TRANSITION-T2D)—A Prospective Randomized Controlled Trial
Authors: RODRIGUEZ PALOMA , BRESLAW NIKKI , BENA JAMES F. , XIAO HUIJUN , JENKINS KIMBERLY , ISAACS DIANA , ZHOU KEREN , GRIEBELER MARCIO L. , BURGUERA BARTO , PANTALONE KEVIN M.
Published: June 2023

Background: The treatment of type 2 diabetes (T2D) with multiple daily injections of insulin (MDI) is associated with a significant burden of disease management, along with a high risk of hypoglycemia and weight gain.

Objective: To test the ability of once-weekly subcutaneous (sc) semaglutide to safely replace prandial insulin in patients with T2D adequately controlled on a regimen of MDI.

Methods: This is a single-center, open-label, randomized controlled trial. Sixty subjects aged 18 to 75, with an HbA1c ≤ 7.5% on MDI (+/-metformin and/or SGLT-2i) were randomized 2:1 to insulin degludec + semaglutide 1.0 mg or to continue MDI with degludec + insulin aspart for 26 weeks. For the intervention arm, prandial insulin was stopped on the same day of the first dose of semaglutide. Semaglutide was initiated at 0.25 mg sc weekly, and increased monthly, as tolerated. The primary outcome was the percentage of subjects maintaining an HbA1c ≤ 7.5% at week 26. Secondary outcomes were mean change in HbA1c, weight, daily insulin requirement, and diabetes treatment satisfaction from baseline to week 26; the cumulative number of hypoglycemic events and percentage of subjects needing to resume prandial insulin through week 26.

Results and conclusions: To be presented at the 2023 ADA scientific sessions.

Disclosure

P. Rodriguez: None. K. M. Pantalone: Consultant; AstraZeneca, Bayer Inc., Corcept Therapeutics, Diasome, Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk, Sanofi, Research Support; Bayer Inc., Merck & Co., Inc., Novo Nordisk, Twin Health, Speaker's Bureau; AstraZeneca, Corcept Therapeutics, Merck & Co., Inc., Novo Nordisk. N. Breslaw: None. J. F. Bena: None. H. Xiao: None. K. Jenkins: None. D. Isaacs: Speaker's Bureau; Dexcom, Inc., Abbott, Eli Lilly and Company, Medtronic, Novo Nordisk. K. Zhou: None. M. L. Griebeler: None. B. Burguera: Research Support; Novo Nordisk.

Funding

Novo Nordisk
74-OR: Improving Performance of Type 2 Diabetes Polygenic Scores in African and Hispanic Ancestries
Authors: HUERTA ALICIA , KIM JOOHYUN , MANDLA RAVI , LU YINGCHANG , PETTY LAUREN E. , SUZUKI KEN , LEE SIMON S. , KIAT NG HONG , LOH MARIE , VUJKOVIC MARIJANA , VOIGHT BENJAMIN F. , SIM XUELING , LOOS RUTH J. , BELOW JENNIFER E. , GE TIAN , MILLION VETERAN PROGRAM VA , FLOREZ JOSE C. , MANNING ALISA , NG MAGGIE , MERCADER JOSEP M. , POLYGENIC RISK SCORES IN MULTIPLE ANCESTRIES (D-PRISM) DIABETES
Published: June 2023

Most polygenic scores (PS) are developed based on data from persons of European (EUR) ancestry and perform poorly in non-EUR populations. To improve the performance of type 2 diabetes (T2D) PS in the under-studied African (AFR) and Hispanic (HIS) ancestries, we created more comprehensive reference panels using the “Tagging Iterative of single nucleotide variant in multiple populations” (TagIt) method and aggregated genome-wide association study (GWAS) meta-analyses from 5 major continental ancestries (360K cases, 1.8M controls, 32% of non-EUR ancestry). We used PRS-CS and PRS-CSx to develop ancestry-specific and multi-ancestry PSs with HapMap3 (HM3) and TagIt panels and evaluated their performance based on the variance explained by the liability R2 (lR2). Trained models were then tested in independent datasets. Compared to HM3 panels, TagIt panels for AFR and HIS ancestries had 4X improved coverage for variants with minor allele frequency 1-5% and showed significant improvement of ancestry-specific PSs (p of difference<0.01). Multi-ancestry PSs based on linkage disequilibrium (LD) and GWAS data from 5 ancestries outperformed the ancestry-specific PSs (lR2 AFR: 0.024 AFR-based PS vs. 0.038 multi-ancestry PS, p of difference = 1.3×10-3; lR2 HIS: 0.017 HIS-based PS vs. 0.061 multi-ancestry PS, p of difference = 4×10-8). It also outperformed the PS based on the EUR GWAS and LD data (lR2 AFR: 0.024 EUR-based PS, p of difference = 0.003; lR2 HIS: 0.045 EUR-based PS, p of difference = 0.003). TagIt reference panels did not show significant improved performance when applying multi-ancestry PS. By leveraging existing GWAS data from multiple ancestries and building more comprehensive reference panels we can improve the performance of the PS for diverse ancestries. However, increasing available GWAS data from diverse ancestries is still needed to improve performance in non-EUR populations and reduce health disparities.

Disclosure

A.Huerta: None. M.Vujkovic: None. B.F.Voight: None. X.Sim: None. R.J.Loos: None. J.E.Below: None. T.Ge: None. Va million veteran program: n/a. J.C.Florez: Consultant; AstraZeneca, Novo Nordisk, Other Relationship; AstraZeneca, Merck & Co., Inc. A.Manning: None. M.Ng: None. J.Kim: None. J.M.Mercader: None. I.Diabetes polygenic risk scores in multiple ancestr: n/a. R.Mandla: None. Y.Lu: None. L.E.Petty: None. K.Suzuki: None. S.S.Lee: None. H.Ng: None. M.Loh: None.

Funding

American Diabetes Association (11-22-ICTSPM-16 to J.M.M.); National Human Genome Research Institute (U01HG011723)
743-P: Delayed Diabetes with Proinsulin mRNA Vaccines in NOD Mice
Authors: FOSTER TIMOTHY P. , HALLER MICHAEL J. , SCHATZ DESMOND , WASSERFALL CLIVE , SAYOUR ELIAS
Published: June 2023

Objective: In type 1 diabetes, an immunomodulatory, antigen-specific therapy may abrogate autoimmunity and support immune tolerance to prevent β-cell destruction and disease progression. This study aims to assess the efficacy of a novel proinsulin II mRNA multi-lamellar liposome vaccine in preventing diabetes in the non-obese diabetic (NOD) mouse. We hypothesized that proinsulin mRNA vaccines would restore immunotolerance and delay diabetes.

Methods: Proinsulin II was cloned into plasmids for in vitro RNA transcription. mRNA was loaded into DOTAP liposomes. mRNA expression was validated in HEK293 cell line transfection. NOD/ShiLtJ strain mice were obtained at 4 weeks of age. Group 1 received three IV tail vein injections of mRNA vaccines every other day at 8 weeks and one dose at 23 weeks of age. Group 2 remained untreated. Mice were checked weekly for diabetes (glucose ≥250 mg/dl on two measurements one day apart). Kaplan-Meier survival curves, hazard ratio, median time to diabetes, and t-tests were used to compare time to diabetes.

Results: The diabetes rate by 32 weeks was 64.2% (9/14) in group 1 compared to 78.6% (11/14) in group 2 (Hazard ratio 1.60 95% CI 0.66-3.86). By 15 weeks, the treatment group had no diabetes compared to 35.7% untreated (p=0.04). Median time to diabetes was 23 weeks in the treatment group and 21 weeks in untreated.

Conclusions: Proinsulin II mRNA multi-lamellar liposome vaccines temporarily delay diabetes in NOD mice.

Disclosure

T.P.Foster: None. M.J.Haller: Board Member; SAB Biotherapeutics, Inc., Consultant; Sanofi, MannKind Corporation. D.Schatz: Advisory Panel; Medtronic, Avotres Inc., QuLab Medical Ltd., Kriya Therapeutics. C.Wasserfall: None. E.Sayour: None.

Funding

Endocrine Fellows Foundation
747-P: Duration of Sustained Weight Loss in Clinical Trials Evaluating Tirzepatide vs. Comparators—An Exploratory Analysis of SURPASS 1–5
Authors: TIMOTHY GARVEY W. , BATTERHAM RACHEL L. , ROSENSTOCK JULIO , LIU MINZHI , THIEU VIVIAN , DALY JACK , BERGMAN BRANDON
Published: June 2023

Sustained weight loss of ≥5% is highly beneficial in T2D. Here we assess the time spent with weight loss ≥5% in participants with T2D randomized to the GIP/GLP-1 receptor agonist tirzepatide (TZP) vs comparators in SURPASS 1-5.

Participants were randomized to TZP (5, 10, or 15 mg) or comparator (placebo in SURPASS 1 and 5, semaglutide (SEMA) 1 mg in SURPASS 2, insulin degludec in SURPASS 3, and insulin glargine in SURPASS 4) with primary treatment durations of 40 or 52 weeks (wks). Continuous time spent with weight loss ≥5% was descriptively analyzed in all participants on treatment without rescue medication, with missing data imputed in this post-hoc analysis.

In SURPASS 1-5, 54-88% of T2D participants randomized to all doses of TZP achieved body weight loss of ≥5%. TZP-treated participants experienced longer time with weight loss ≥5% than those randomized to comparators (Table 1). TZP dose-dependently increased time spent with weight loss ≥5% with the greatest durations observed in the 15 mg group (median: 24 and 40 wks in studies of 40 and 52 wks duration, respectively). Whereas, in the SURPASS 2 trial, those randomized to SEMA 1 mg spent a median of 10 weeks with weight loss ≥5%.

In conclusion, TZP led to a longer continuous time spent with weight loss ≥5% compared with placebo, SEMA 1 mg, and basal insulins in participants with T2D.

Disclosure

W.Garvey: Advisory Panel; Boehringer-Ingelheim, Novo Nordisk, Eli Lilly and Company, Merck & Co., Inc., Alnylam Pharmaceuticals, Inc., Fractyl Health, Inc., Inogen, Research Support; Novo Nordisk, Eli Lilly and Company, Epitomee, Pfizer Inc., Neurovalens. R.L.Batterham: Advisory Panel; Novo Nordisk, GlaxoSmithKline plc., Gila Therapeutics Ltd, Pfizer Inc., Consultant; Eli Lilly and Company, Novo Nordisk, Epitomee, Speaker's Bureau; Eli Lilly and Company, Novo Nordisk, GlaxoSmithKline plc. J.Rosenstock: Advisory Panel; Applied Therapeutics Inc., Boehringer Ingelheim Inc., Eli Lilly and Company, Novo Nordisk, Oramed Pharmaceuticals, Sanofi, Zealand Pharma A/S, Intarcia Therapeutics, Inc., Hanmi Pharm. Co., Ltd., Research Support; Applied Therapeutics Inc., Boehringer Ingelheim Inc., Eli Lilly and Company, Merck & Co., Inc., Novartis, Novo Nordisk, Pfizer Inc., Sanofi, Intarcia Therapeutics, Inc. M.Liu: Consultant; Eli Lilly and Company. V.Thieu: None. J.Daly: Employee; Eli Lilly and Company. B.Bergman: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company.

Funding

Eli Lilly and Company
755-P: A Phase 2 Evaluation of a Novel GLP-1 Analog Ecnoglutide (XW003) for Glycemic Control in Adults with Type 2 Diabetes
Authors: ZHU DALONG , QIN HONG H. , ZHENG QING , NING JING , ZHU ZHIYI , MENGYING GUO , BU YUE , JONES CATHERINE , FENAUX MARTIJN , XU SUSAN , JUNAIDI MOHAMMED K.
Published: June 2023

Ecnoglutide (XW003) is a novel, long-acting GLP-1 analog being developed for the treatment of type 2 diabetes mellitus (T2DM) and obesity. We conducted a Phase 2 randomized, double-blind, placebo-controlled study of ecnoglutide, which enrolled 145 adults at over 20 hospital-based sites in China. Eligible participants had T2DM that was inadequately controlled by lifestyle or a single oral hypoglycemic agent. Participants were randomized to receive 0.4, 0.8, or 1.2 mg ecnoglutide or placebo as once weekly injections for 20 weeks, including dose escalation. Change in mean HbA1c, body weight, and BMI, as well as safety and tolerability were evaluated. At baseline, participants had mean HbA1c of 8.55 ± 0.707 % and BMI of 26.27 ± 3.308 kg/m2. At the end of treatment, participants receiving ecnoglutide achieved significant HbA1c reductions of 1.81% to 2.39% from baseline (P<0.0001 for all cohorts vs placebo). At end of treatment, up to 67% of participants in the ecnoglutide cohorts achieved HbA1c levels ≤6.5% and up to 33% had body weight reductions ≥5% from baseline (Figure). Ecnoglutide was generally safe and well tolerated. There were no treatment-related ≥Grade 3 AEs and no treatment-related SAEs. The proportion of participants reporting any AE ranged from 72.2 to 78.4% for ecnoglutide and 58.3 % for placebo. The most frequently reported AEs were gastrointestinal, including diarrhea and nausea.

Disclosure

D.Zhu: None. S.Xu: Employee; Sciwind. M.K.Junaidi: None. H.H.Qin: Employee; Sciwind Biosciences, Sichuan Anerobic Biotech. Q.Zheng: Employee; Sciwind Biosciences. J.Ning: None. Z.Zhu: Employee; Sciwind Biosciences. G.Mengying: None. Y.Bu: Employee; Sciwind Biosciences. C.Jones: Employee; Sciwind Biosciences. M.Fenaux: Employee; Sciwind Biosciences, Stock/Shareholder; Terns Pharmaceuticals.

Funding

Sciwind Biosciences
757-P: Efficacy and Safety of Supaglutide Monotherapy in Patients with Type 2 Diabetes
Authors: WANG QINGHUA , ZHOU YUE , WANG WEIMIN , TONG GUOYU , JIA WEINA , LI LIANG , CHENG ZHIFENG , LU YIBING , SHI BIMIN , BIAN FANG , WANG YIHUA , SHI XIAOXIA , LI QINGJU , SU XIUHAI , WANG KUN , YUAN GUOYUE , LI LIPING , LING HONGWEI , HU XIAOLIN , WANG YANGANG , ZHAO NAIQING , YANG YEHONG , MA JIANHUA , LI YIMING , ZHU DALONG
Published: June 2023

GLP-1 is an incretin hormone with broad pharmacological potential. GLP-1 receptor agonists (GLP-1RAs) are successfully in clinical use for T2D and obesity. Several GLP-1-based therapies are in clinical evaluation for treating metabolic diseases. Supaglutide (supa), a novel GLP-1RA, is in late-stage development for T2D. The efficacy and safety of supa is being investigated in 297 patients with newly diagnosed T2D inadequately controlled with diet and exercise in this randomized, double-blind, placebo-controlled phase 3 clinical trial (NCT04994288). Supa treatment resulted in a statistically and clinically significant reduction from baseline in HbA1c at Week 24 of -1.73% and -2.15% with 1 and 3 mg QW dosing, respectively (p<0.001). Body weight was decreased by 0.97% and 3.14% from baseline in the supa 1 and 3 mg groups, respectively, with a significant difference for supa 3 mg versus 1 mg group (p<0.001). Supa also significantly improved glucose excursion, and increased meal-stimulated insulin and C-peptide secretion as determined by MMTT, suggesting improved glucose tolerance and enhanced β-cell function. The most common TEAEs with supa were GI symptoms, such as nausea, vomiting, diarrhea and decreased appetite, mostly in mild or moderate severity. Our data showed that supa improved glycemic and metabolic control and was well tolerated in T2D, suggesting supa as a novel alternative therapy for T2D and metabolic disorders.

Disclosure

Q.Wang: None. F.Bian: None. Y.Wang: None. X.Shi: None. Q.Li: None. X.Su: None. K.Wang: None. G.Yuan: None. L.Li: None. H.Ling: None. X.Hu: None. Y.Zhou: None. Y.Wang: None. N.Zhao: None. Y.Yang: None. J.Ma: None. Y.Li: None. D.Zhu: None. W.Wang: None. G.Tong: None. W.Jia: None. L.Li: None. Z.Cheng: None. Y.Lu: None. B.Shi: None.
768-P: Effect of Dulaglutide Therapy Initiation on the Course of Coronavirus Infection and the Dynamics of Inflammatory Markers in Hospitalized Patients with Type 2 Diabetes
Authors: MARKOVA TATIANA , STAS MUKHAMED , ANCHUTINA ANASTASIA
Published: June 2023

Aim: To determine the impact of initiation of dulaglutide therapy on the course of COVID-19 and the dynamics of inflammatory markers in hospitalized patients with type 2 diabetes mellitus (T2DM).

Methods: The inclusion criteria were history of T2DM, BMI > 27 kg/m2, PCR-confirmed diagnosis of COVID-19. The intervention group of 53 patients started dulaglutide therapy (1.5 mg once weekly) during the first 24 hours of admission, the control group consisted of 50 patients, who proceeded with glucose-lowering therapy. In both groups we compared COVID-19 outcomes (mortality/survival rate, ICU admission, need for assisted ventilation) and the duration of hospitalization. On days 3 and 7 of hospitalization we assessed laboratory parameters (FPG, CRP, ALT, AST, LDH, lymphocyte levels, D-dimer).

Results: The initiation of dulaglutide therapy reduced the risk of death and transfer to assisted ventilation by 3.5 times in the intervention group compared to the control one (5.7% vs 20.0%, p=0.038). No differences were found in the risk of ICU admission (17.0% vs 28.0%, p=0.18) and the duration of hospitalization (10 bed-days vs 11-bed days, p=0.26).

The groups were comparable in respect to carbohydrate metabolic compensation. Compared to those in the control group, patients on dulaglutide therapy demonstrated a lower CRP level (15.8 vs 24.6 mg/L, p=0.035), higher lymphocyte levels (1.2 vs 0.9 × 10*9/L, p=0.049) on day 3 of hospitalization, and a significantly lower LDH concentration level on day 7 (261.6 vs 326.1 U/L, p=0.016). There were no differences in ALT, AST, and D-dimer levels.

Conclusion: The initiation of dulaglutide therapy in hospitalized patients with T2DM and COVID-19 decreased the risk of lethal outcomes and transfer to assisted ventilation, as well as proved effective in regards to inflammatory markers (CRP, lymphocytes levels).

Disclosure

T.Markova: None. M.Stas: None. A.Anchutina: None.
77-LB: A Novel Glucagon-Like Peptide-1 (GLP-1R) and Glucagon (GCGR) Receptor Dual Agonist, Mazdutide (IBI362), Attenuates Hyperuricemia in Hyperuricemic Rats
Authors: JIANG HONGWEI , ZHANG YANZHAO , SHUANG REN YAN
Published: June 2023

Introduction: Existing studies have not conclusively proven that GLP-1RA drugs can attenuate hyperuricemia, and dual agonist drugs such as Tirzepatide have also not been reported. But in previous studies, we unexpectedly found that the statistically significant reduction in serum uric acid levels in participants receiving Mazdutide. So we designed animal experiments to verify this result.

Methods: Male 12-week-old adult SD rats were given potassium oxyzincate 1000 mg/kg and adenine 100 mg/kg used to maintain hyperuricemia status and were divided into different groups (Table1). Statistical and metabolomic, proteomic, and phosphoproteomic analyses were performed after 18 days of intervention, respectively.

Results: The Mazdutide and allopurinol groups showed varying degrees of decrease in serum uric acid, while there was no change in the semaglutide group (Table1). The specific mechanism will be analyzed after the histological results are available.

Conclusion: The degree of reduction of hyperuricemia by Mazdutide on rats was comparable to that of allopurinol. A slight increase in UUA may mean that the drug is working by promoting uric acid excretion. We conclude that Mazdutide has a safety and effectiveness profile similar to GLP-1 receptor agonist and has potential therapeutic benefit in the treatment of hyperuricemia.

Disclosure

H. Jiang: None. Y. Zhang: None. Y. Ren: None.

Funding

First Affiliated Hospital; College of Clinical Medicine of Henan University of Science and Technology
78-OR: Adipose Lysosomal Acid Lipase Is Indispensable for Starvation- and Cold-Induced Lipolysis
Authors: YEH YU-SHENG , RAZANI BABAK
Published: June 2023

Lipolysis is a metabolic process by which triglycerides (TGs) are hydrolyzed into free fatty acids (FFAs) and glycerol to serve as fuels during fasting or cold-induced nonshivering thermogenesis. Cytoplasmic lipases are thought to be the predominant mechanism of liberating FFA from lipid stores. However, lysosomes also contain lipolytic activity via lysosomal acid lipase (Lipa). In adipocytes, the primary lipid-storing cell in the body with significant involvement in metabolism, the roles of Lipa and lysosomal lipolysis are unclear. We found that Lipa expression increases in the adipose tissue of mice in response to fasting, cold exposure, and CL316,243 (CL) treatment, a mimic of cold-induced lipolysis. Similar results were obtained in cultured adipocytes with nutrient-depletion or isoproterenol treatment, mimicking fasting or cold, respectively. Treatment of C57BL/6J mice with Lalistat (Lali), a specific inhibitor of Lipa, impaired thermogenesis, as evidenced by suppression of cold- and fasting-enhanced increases in plasma FFAs levels during cold exposure or CL treatment. Lipolysis was inhibited by Lali treatment in cultured adipocytes and fresh adipose tissue of C57BL/6J mice under fasting- or cold-mimic conditions. To conduct more detailed in vivo studies, we developed adipose-specific Lipa knockout (A-Lipa) mice, which exhibited lower plasma FFAs when challenged with fasting, cold exposure, or CL treatment. Furthermore, A-Lipa mice were significantly thermogenesis-impaired with exposure to cold or treatment with CL. To determine whether autophagy is involved in these phenomena, adipose-specific Atg5 knockout (A-Atg5) mice were challenged with fasting, cold exposure, or CL treatment. As was found in A-Lipa mice, A-Atg5 mice had lower levels of plasma FFAs and obliteration of stress-induced thermogenesis. Overall, our data suggest a previously unrecognized contribution of lysosomal lipolysis in adipocytes, possibly involving autophagy-related lipophagy.

Disclosure

Y.Yeh: None. B.Razani: None.

Funding

American Heart Association (897628); National Institutes of Health (DK131188)
789-P: Real-Life Effectiveness of iGlarLixi (Insulin Glargine 100 U/ml and Lixisenatide) in People with Type 2 Diabetes (T2D) according to Prior Insulin Use
Authors: SEUFERT JOCHEN , FREEMANTLE NICK , GUJA CRISTIAN , HALUZIK MARTIN , BIGOT GREGORY , TOURNAY MATHILDE , BONNEMAIRE MIREILLE , KIS JANOS T.
Published: June 2023

Little is known in real life clinical practice about the effectiveness and safety of iGlarLixi in insulin naïve compared to insulin treated people with T2D. In the European REALI pooled database, we analyzed patient-level data of 1317 people with T2D initiating a 24-week iGlarLixi treatment: 718 were insulin naïve (55%) and 598 insulin treated (45%), with a median treatment duration of 2.5 years. Demographics were similar among groups with an overall mean±SD age of 61±9 years and BMI 32.2±5.5 kg/m². Median T2D duration was 8 years in the naïve group and 10 years in the treated group. At Baseline, mean HbA1c was 9.39% in the naïve and 8.76% in the treated (p<0.001). The least square (LS) mean HbA1c change from Baseline to Week 24 (using MMRM) was -1.57% in the naïve and -1.29% in the treated (Fig 1); the LS mean [95% CI] fasting plasma glucose change was -52.5 [-54.9; -50.1] and -50.4 [-53.4; -47.5] mg/dL, respectively. Mean±SD body weight decreased by 1.8±4.6 kg at Week 24, with no difference between groups. Mean iGlarLixi daily dose at Baseline was 14.3U in the naïve and 24.4U in the treated, and reached 30.7U and 36.4U, respectively, at Week 24. Symptomatic hypoglycemia reports and gastrointestinal side effects were low in both groups. This analysis demonstrated effectiveness and safety of iGlarLixi in both insulin naïve and insulin treated people with T2D in clinical practice.

Disclosure

J.Seufert: Advisory Panel; Abbott Diabetes, Boehringer Ingelheim Pharma GmbH&Co.KG, Sanofi-Aventis Deutschland GmbH, Speaker's Bureau; Abbott Diabetes, Bayer Inc., Boehringer Ingelheim Pharma GmbH&Co.KG, Merck Sharp & Dohme Corp., Sanofi-Aventis Deutschland GmbH, Novartis, Novo Nordisk. N.Freemantle: Advisory Panel; AstraZeneca, Research Support; Galderma, ALK-Abelló A/S, Ipsen Biopharmaceuticals, Inc., Vertex Pharmaceuticals Incorporated, Thea, Speaker's Bureau; Abbott Singapore, ALK Shanghai. C.Guja: Advisory Panel; AstraZeneca, Boehringer-Ingelheim, Eli Lilly and Company, Novo Nordisk A/S, Sanofi, Speaker's Bureau; AstraZeneca, Boehringer-Ingelheim, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi, Servier Laboratories, Viatris Inc. M.Haluzik: Advisory Panel; Novo Nordisk, Lilly Diabetes, Boehringer-Ingelheim, Research Support; Sanofi, Speaker's Bureau; Abbott, AstraZeneca. G.Bigot: None. M.Tournay: None. M.Bonnemaire: Employee; Sanofi, Stock/Shareholder; Sanofi. J.T.Kis: None.

Funding

Sanofi
796-P: Real-World Persistence with GLP-1 RA Treatment in Patients with Type 2 Diabetes Mellitus (T2DM) and Advanced Chronic Kidney Disease (CKD)
Authors: SIDRA FNU , XIE DONGLU , AGARWAL SHUBHAM , LINGVAY ILDIKO
Published: June 2023

Guidelines (ADA 2023 and KDIGO 2020) recommend treatment with GLP-1RAs in advanced CKD and ESRD because of their cardiovascular benefits, low risk of hypoglycemia, and potential renal benefits. GLP-1RA are vastly under-prescribed in this population, mainly due to concerns related to tolerability. We compared persistence rate with GLP-1RA vs dipeptidyl peptidase 4 inhibitors (DPP-4i) in this population. We extracted EHR data from a university health system from patients with T2DM and GFR <30 treated with either GLP-1RA or DPP-4i (2012- 2022). All charts were manually reviewed to confirm treatment start & stop date and reason for discontinuation. At the time of treatment initiation, those treated with GLP-1RA (N=149) vs DPP-4i (N=87) were younger, more likely to be female (51% vs 44%) and had a higher BMI. Only 12.7% and 9.2% of patients discontinued treatment with GLP-1RA and DPP-4i, respectively, within 180 days of initiation. The average treatment duration was 1036 and 1109 days with 34.9% and 54% having discontinued treatment at the time of data extraction. The maximum tolerated dose of GLP-1RA were comparable to that expected in patients without CKD (Table). Persistence with GLP-1RA treatment in patients with T2DM and advanced CKD is similar to DPP-4i and the vast majority tolerated the highest approved dose of GLP-1RA, confirming their tolerability in this population.

Disclosure

F.Sidra: None. D.Xie: None. S.Agarwal: None. I.Lingvay: Advisory Panel; Novo Nordisk A/S, Lilly Diabetes, Boehringer-Ingelheim, Sanofi, Consultant; Carmot Therapeutics, Inc., Merck Sharp & Dohme Corp., Janssen Scientific Affairs, LLC, Pfizer Inc., Intercept, Intarcia, Valeritas, TargetRWE, Shionogi, Zealand Pharma, Structure, Bayer, Research Support; Novo Nordisk A/S, Boehringer-Ingelheim.
8-OR: Novel Mechanism of Lipoprotein Lipase Folding and Maturation in Adipocytes
Authors: WU SHUANGCHENG , QI LING
Published: June 2023

Lipoprotein lipase (LPL) plays a central role in systemic lipid clearance by catalyzing intravascular hydrolysis of lipoprotein triglycerides, hence representing an important target in the treatment of hyperlipidemia in diabetes. Nascent LPL protein undergoes folding and maturation in the endoplasmic reticulum (ER), with only the properly folded ones exiting the ER and reaching to the cell surface. However, the maturation process for nascent LPL in the ER remains largely unknown. Here we show that LPL maturation in the ER is controlled by compensatory actions of two ER protein quality control mechanisms, ER-associated degradation (ERAD) and ER-phagy, in adipocytes. Specifically, we show that LPL is misfolding prone and degraded by ERAD, and when ERAD is compromised, LPL forms aggregates which is cleared by ER-phagy. In adipocytes lacking both ERAD and ER-phagy, ER fragments containing LPL aggregates cluster and fuse to form a novel cellular architecture, termed as Coalescence of ER Fragments (CERFs), where LPL undergo soluble-to-insoluble phase transition catalyzed by disulfide bond-mediated interactions. Lastly, mice with adipocyte specific ERAD and ER-phagy deficiency exhibited postprandial hyperlipidemia. In summary, this study provides novel insights into not only LPL biogenesis, but also the crosstalk between protein quality control pathways in the maintenance of ER homeostasis, as well as the disease pathogenesis, more broadly, associated with protein folding defects in the ER.

Disclosure

S.Wu: None. L.Qi: None.
80-LB: Evaluation of the Pharmacokinetics of Glucagon-Like-Peptide-1 (GLP-1) Receptor Agonist Delivered through the BIOJET Oral Biotherapeutic Delivery Platform in Porcine Model
Authors: LEE SHAOYING N. , STORK CHERYL A. , VALENZUELA-RIVAS RENE O. , WALKER MICHELLE , SMITH BRYAN J. , SMITH JEFFREY A. , QUINTANA NELSON , WAHL CHRIS , SINGH SHARAT
Published: June 2023

Glucagon-like-peptide-1 (GLP-1) receptor agonists stimulate insulin secretion and suppress glucagon release. Semaglutide is a GLP-1 agonist currently injected subcutaneously or taken orally to treat type 2 diabetes and for weight management. However, oral administration of protein/peptide therapeutics has proven difficult due to the harsh conditions of the upper gastrointestinal tract (GIT) and poor absorption rates in the small intestine. The BIOJET™ oral biotherapeutic delivery platform is an ingestible drug-device combination developed to increase drug bioavailability via needleless jet injection in the proximal small intestine following oral administration. Previous testing of an earlier, autonomously triggered version of the device in animal models was presented at ACG 2022. In this study we evaluated the pharmacokinetics (PK) of semaglutide delivered through the BIOJET device in a porcine model. Due to prolonged and variable gastric residence times in the porcine model, devices filled with semaglutide (~1mg) were administered by intraduodenal (ID) endoscopic placement and activated in the proximal small intestine of Yucatan swine. PK blood sampling was performed from 0 to 240 hours post-dose to evaluate systemic exposure of semaglutide. Seven of eight (7/8) devices were successfully placed and activated in the duodenum. All seven animals showed detectable drug levels up to ten days post-dosing and had an oral bioavailability average of 37% ± 15% (CV: 40%), ranging from 19%-60% compared to IV control. No significant clinical signs were observed in the animals. This study demonstrated that administration of the BIOJET device has the potential to achieve a magnitude greater bioavailability than the currently marketed oral semaglutide (< 1%). The BIOJET device could provide an alternative for the oral administration of large molecules and may improve patient compliance.

Disclosure

S. N. Lee: Employee; Biora Therapeutics. C. A. Stork: Employee; Biora Therapeutics. R. O. Valenzuela-rivas: Employee; Biora Therapeutics. M. Walker: Employee; Biora Therapeutics. B. J. Smith: Employee; Biora Therapeutics. J. A. Smith: None. N. Quintana: None. C. Wahl: Employee; Biora Therapeutics. S. Singh: None.
80-OR: A New Cytoskeleton-Based Mechanism for Regulating Brown Adipose Tissue Physiology
Authors: AGUILLARD ASHLEY , ARRICASTRES JUNE , TZENG JOYCE , LORENZO DAMARIS
Published: June 2023

Human genetic variants in ANK2, encoding the scaffold protein ankyrin-B (AnkB), increase risk for T2D. We characterized the role of AnkB in white adipose tissue (WAT) in mice with AnkB deficiency in both WAT and brown adipose tissue (BAT) (AT-AnkB KO). We found that AnkB loss led to obesity and insulin resistance driven by its role in clathrin mediated endocytosis of GLUT4 in WAT. AT-AnkB KO mice also had lipid accumulation in BAT. However, the cell-autonomous roles of AnkB in BAT and its contribution to energy balance is unknown. To elucidate AnkB’s roles in BAT, we developed mice lacking AnkB in BAT (BAT-AnkB KO). Histology and TEM revealed lipid accumulation in BAT of 4-month-old BAT-AnkB KO mice housed at thermoneutrality. Consistent with this finding, brown adipocytes from AnkB deficient mice also have enlarged lipid droplets, suggesting an AnkB cell-autonomous role in BAT lipid homeostasis. Proteomic-MS revealed that AnkB forms complexes with lipolysis factors Atgl, Hsl and Plin1, and regulators of the PKA pathway, suggesting AnkB plays a role regulating BAT lipolysis. Interestingly, Hsl and Plin1 are elevated in BAT despite the enlarged LDs of BAT-AnkB KO mice, implying either lipolytic deficits or compensatory effects. These findings support RNA sequencing that revealed downregulation of PKA signaling genes, ATPase subunits, and mitochondrial calcium signaling genes in BAT of BAT-AnkB KO mice. Last, peri-droplet mitochondria (PDM), a mitochondria subpopulation with reduced beta-oxidation capacity that contacts LDs, form longer contact sites with BAT LDs from BAT-AnkB KO mice. Together, these findings suggest that early alterations in mitochondrial bioenergetics and lipolysis contribute to BAT LD accumulation. Along with this data, we will present findings on thermogenic regulation in vivo and physiological assays evaluating lipolysis and its major regulators.

Disclosure

A.Aguillard: None. J.Arricastres: None. J.Tzeng: None. D.Lorenzo: None.

Funding

American Diabetes Association (1-19-JDF-081 to D.L.); National Science Foundation; Burroughs Wellcome Fund (1022069)