bluuebunny/crossref_metadata_2025_split huggingface dataset:
267-OR: ADA Presidents' Select Abstract: Combining an SGLT Inhibitor with a Glucagon Receptor Agonist (GRA) in Subjects with Type 1 Diabetes—A Randomized Clinical Trial
Authors: BOEDER SCHAFER C. , ROUX MELISSA J. LE , GIOVANNETTI ERIN R. , ARMSTRONG ADRIENNE , CARTER LESLIE , THOMAS ROBERT L. , GREGORY JUSTIN M. , PETTUS JEREMY 
Published: June 2023

SGLTi treatment improves glycemic control and reduces insulin dosing but increases the risk of diabetic ketoacidosis (DKA). Combination therapy (SGLTi + GRA) could augment glycemic and insulin dosing benefits while mitigating DKA risk.
Subjects with T1D (n=12) received 4-week insulin-adjunctive treatments with (a) SGLTi (dapagliflozin 10 mg) + placebo and (b) SGLTi + GRA (volagidemab 70 mg) in a cross-over, double-blind design. At baseline and end of each treatment, CGM and insulin dosing were recorded, and subjects completed an 8-hr insulin withdrawal test (IWT).
Average glucose improved with both SGLTi (138 mg/dL; P &lt; 0.01) and SGLTi + GRA (131 mg/dL; P &lt; 0.01) compared to Baseline (150 mg/dL). Total daily insulin dose was reduced with SGLTi (0.52 U/kg/day) compared to Baseline (0.56 U/kg/day; P = 0.06) and was reduced further with SGLTi + GRA treatment (0.41 U/kg/day; P &lt; 0.01 vs SGLTi). Peak beta-hydroxybutyrate (BHB) concentrations during IWT were lower with SGLTi + GRA treatment (2.03 mmol/L) than with SGLTi alone (2.44 mmol/L; P = 0.04); there was no significant difference in peak BHB with either treatment vs Baseline (2.14 mmol/L).
Treatment with SGLTi + GRA improved glycemic control, reduced insulin use, and mitigated ketosis during hypoinsulinemia. These data suggest that combination adjunctive therapy may be effective to address multiple metabolic abnormalities in T1D.

Disclosure
S.C.Boeder: Consultant; Cecelia Health, Research Support; Dexcom, Inc., REMD Biotherapeutics, Eli Lilly and Company. M.J.Le roux: None. E.R.Giovannetti: None. A.Armstrong: None. L.Carter: None. R.L.Thomas: None. J.M.Gregory: Advisory Panel; Eli Lilly and Company, vTv Therapeutics, Other Relationship; Medtronic. J.Pettus: Advisory Panel; Sanofi, Novo Nordisk, Lilly, MannKind Corporation, Consultant; Carmot Therapeutics, Inc., Diasome.

Funding
National Institutes of Health (P30DK063491, UL1TR001442); Diabetes Research Connection
27-LB: A Prediction Model for Diabetic Retinopathy Based on Plasma Adipokines among Patients with Type 2 Diabetes
Authors: AN YAXIN , KE JING , ZHAO DONG 
Published: June 2023

Background: Accumulating evidence has suggested a link between adipokines and diabetic retinopathy (DR). This study aimed to investigate the risk factors for sight-threatening DR (STDR) and establish a prognostic model for predicting STDR among patients with type 2 diabetes mellitus (T2DM).
Methods: In the case-control set, principal component analysis (PCA) was performed to select optimal predictive cytokines for STDR. Support vector machine (SVM) was used to examine the possible combination of baseline plasma adipokines to discriminate the mild participants who will later develop STDR. An individual prospective cohort with a follow-up period of 3 years was used for the external validation.
Results: In both training and testing sets, comprised of 306 patients with DR, median levels of plasma adiponectin, leptin, and fatty acid-binding protein 4 (FABP4) were significantly higher in the STDR group than those in mild DR. Except for adipsin, the other three adipokines, FABP4, adiponectin, and leptin, were selected by PCA and integrated into SVM. The accuracy of the multivariate SVM classification model was acceptable in both the training set (AUC = 0.81, sensitivity = 71%, specificity = 91%) and the testing set (AUC = 0.77, sensitivity = 61%, specificity = 92%). 110 T2DM mild NPDR patients were enrolled for external validation. High- and low-risk groups were grouped by the median value of adiponectin, FABP4, and leptin. More STDR occurred in the high-risk group than in the low-risk group among the three predictors. SVM demonstrated acceptable performance, with the AUC, sensitivity, and specificity of 0.77, 64%, and 91%, respectively.
Conclusions: Adiponectin, leptin, and FABP4 were demonstrated to be associated with the severity of DR and maybe good predictors for STDR, suggesting that adipokines may play an important role in the pathophysiology of DR development.

Disclosure
Y. An: None. J. Ke: None. D. Zhao: None.
271-OR: Capillary Blood Ketone Level and Future Ketoacidosis Risk in Type 1 Diabetes Using Sodium–Glucose Linked Transporter Inhibitors
Authors: BAPAT PRIYA , DHALIWAL SHARON , SONG CIMON , BUDHRAM DALTON R. , BAKHSH ABDULMOHSEN M.K. , SCARR DANIEL , WEISMAN ALANNA , FRALICK MICHAEL , IVERS NOAH , CHERNEY DAVID , MUMFORD DOUG , TOMLINSON GEORGE , ERIK LOVBLOM LEIF , PERKINS BRUCE A. 
Published: June 2023

Adjunctive-to-insulin Sodium-Glucose Linked Transporter inhibitors (SGLTi) improve metabolic control in T1D but cause diabetic ketoacidosis (DKA). We aimed to determine if time-varying ketone levels could predict future DKA. We explored data on 1194 participants randomly assigned to empagliflozin in a T1D trial program (NCT02414958 and NCT02580591). Protocol called for fasted capillary blood ketone levels 2-3 times/week, categorized into maximum, mean, and last values for sequential 1-month ‘index test’ periods during 6-12-month follow-up. Trial-adjudicated DKA/Ketosis was determined in subsequent 1-month ‘outcome’ periods. Area under the Receiver Operator Characteristic curves (AROC) were calculated. Gradient-boosted trees determined if prediction could be improved. Participants had mean age 44.3 years, HbA1c 8.14±0.60 percent, and contributed 3.70±2.97 ketone measurements/week. 617 outcomes (568 ketosis, 49 DKA events) occurred over follow-up. On-treatment ketone levels were higher for index test periods preceding an outcome period with an event compared to those without (for example, maximum ketone was 1.32±1.03 vs 0.80±0.71 mmol/l, respectively, p&lt;0.001). AROC for maximum, mean and last ketone levels were 0.764, 0.755, and 0.682 respectively. Maximum ketone level ≥ 0.9 mmol/l had sensitivity 59%, specificity 84%, likelihood ratio positive 3.65, likelihood ratio negative 0.49, and diagnostic odds ratio 7.39. Inclusion of the other ketone measures (mean or last) or clinical variables did not improve the predictive validity of maximum ketone levels on their own. Routine surveillance of morning capillary ketone levels in T1D patient using SGLTi can predict 1-month risk of DKA/Ketosis and could allow for interventions to mitigate risk.

Disclosure
P.Bapat: None. D.Cherney: Other Relationship; Boehringer Ingelheim-Lilly, Merck, AstraZeneca, Sanofi, Mitsubishi-Tanabe, Abbvie, Janssen, Bayer, Prometic, BMS, Maze, Gilead, CSL-Behring, Otsuka, Novartis, Youngene, Lexicon and Novo-Nordisk, Research Support; Boehringer Ingelheim-Lilly, Merck, Janssen, Sanofi, AstraZeneca, CSL-Behring and Novo-Nordisk. D.Mumford: None. G.Tomlinson: None. L.Lovblom: None. B.A.Perkins: Advisory Panel; Dexcom, Inc., Insulet Corporation, Novo Nordisk, Sanofi, Vertex Pharmaceuticals Incorporated, Other Relationship; Abbott, Medtronic, Sanofi, Research Support; Novo Nordisk, Bank of Montreal (BMO). S.Dhaliwal: None. C.Song: None. D.R.Budhram: None. A.M.K.Bakhsh: None. D.Scarr: None. A.Weisman: None. M.Fralick: None. N.Ivers: Consultant; Novo Nordisk Canada Inc., IQVIA Inc.

Funding
Diabetes Canada (OG-3-21-5572-BP)
272-LB: Obesity-Induced Mitochondrial Fragmentation in White Adipocytes Is Controlled by the Small GTPase RalA
Authors: XIA WENMIN , VEERAGANDHAM PREETHI , CAO YU , XU YAYUN , RHYNE TORREY E. , JONES YING , YU RUTH T. , RYDÉN MIKAEL , WABITSCH MARTIN , SALTIEL ALAN 
Published: June 2023

Mitochondrial dysfunction has been implicated in the development of obesity, insulin resistance and fatty liver disease. Here we report that mitochondria undergo fragmentation and reduced oxidative capacity specifically in inguinal white adipose tissue after high fat diet, and that this process is regulated by the small GTPase RalA. RalA mRNA, protein and GTP binding activity are increased in inguinal white adipose tissue after HFD feeding. Targeted deletion of Rala in white adipocytes prevents the obesity-dependent fragmentation of mitochondria, and produces mice who are resistant to HFD-induced weight gain via increased energy expenditure, as well as improvements in glucose homeostasis and liver metabolism. In vitro studies revealed that RalA suppresses mitochondrial oxidative function in adipocytes by increasing fission through reversing the inhibitory phosphorylation of the mitochondrial fission protein Drp1. This reduced phosphorylation results from the recruitment of the regulatory subunit of protein phosphatase PP2A, which acts as a bona fide effector of RalA, leading to the specific dephosphorylation of the inhibitory Ser637 residue on Drp1, rendering the protein active. Thus, RalA plays a key role in repressing energy expenditure in obese adipose tissue through maintaining mitochondrial fission, contributing to weight gain and related metabolic dysfunction, including glucose intolerance and fatty liver, and may explain in part how energy expenditure is repressed in prolonged obesity.

Disclosure
W. Xia: None. A. Saltiel: Board Member; Elgia Therapeutics. P. Veeragandham: None. Y. Cao: None. Y. Xu: None. T. E. Rhyne: None. Y. Jones: None. R. T. Yu: None. M. Rydén: Advisory Panel; Boehringer-Ingelheim, Eli Lilly and Company, Consultant; Sigrid Therapeutics, Other Relationship; Novo Nordisk Foundation, Speaker's Bureau; Sanofi, Novo Nordisk. M. Wabitsch: None.
272-OR: The Efficacy of Sotagliflozin on Heart-Failure Related Outcomes Is Independent of Baseline A1C
Authors: AGGARWAL RAHUL , BHATT DEEPAK L. , SZAREK MICHAEL , DAVIES MICHAEL J. , BANKS PHILLIP L. , PITT BERTRAM , STEG PHILIPPE G. 
Published: June 2023

Background: SGLT inhibitors reduce the risk of cardiovascular (CV) events in patients with heart failure (HF) and chronic kidney disease regardless of diabetes status. Although the SOLOIST-WHF and SCORED trials enrolled high CV risk patients with T2DM, participants had a wide range of baseline A1C values. Thus, the present analysis evaluated the effects of sotagliflozin relative to placebo on cardiovascular (CV) death and total HF-related outcomes by baseline A1C range.
Methods: SOLOIST-WHF had no baseline A1C entry criteria (baseline median = 7.1%, range = 4.5, 15.0%), while SCORED randomized patients with T2DM and an A1C ≥7% at screening (8.3%, 6.5, 17.3%). Natural cubic splines from Poisson regression models estimated the relationships between continuous A1C and the primary endpoint for both studies: total number of CV deaths, hospitalizations for HF, and urgent visits for HF.
Results: Within each trial, patients with higher baseline A1C experienced higher event rates (spline effect p=0.0349 and 0.0014 for SOLOIST-WHF and SCORED, respectively). Sotagliflozin reduced the primary outcome in each trial (p for treatment &lt;0.0001 for both SOLOIST-WHF and SCORED) and this did not differ across A1C (p for interaction &gt;0.10; Figure).
Conclusion: Sotagliflozin was effective in reducing the risk of CV death and HF-related events independent of baseline A1C.

Disclosure
R.Aggarwal: None. D.L.Bhatt: Board Member; Bristol-Myers Squibb Company, Research Support; Lexicon Pharmaceuticals, Inc., Sanofi, Lilly, Boehringer Ingelheim Inc., AstraZeneca, Novo Nordisk. M.Szarek: Consultant; Amarin Corporation, ESPERION Therapeutics, Inc., Other Relationship; Janssen Pharmaceuticals, Inc., Research Support; Lexicon Pharmaceuticals, Inc., Regeneron, Sanofi, Bayer Inc. M.J.Davies: Employee; Lexicon Pharmaceuticals, Inc. P.L.Banks: Employee; Lexicon Pharmaceuticals, Inc. B.Pitt: Consultant; Bayer Inc., AstraZeneca, Boehringer Ingelheim International GmbH, Vifor Pharma Management Ltd., Lexicon Pharmaceuticals, Inc., PhaseBio Pharmaceuticals, Inc., KBP Bioscience, Merck & Co., Inc. P.G.Steg: Advisory Panel; Merck & Co., Inc., Consultant; Sanofi, Amarin Corporation, Amgen Inc., BMS, PhaseBio Pharmaceuticals, Inc., Idorsia Pharmaceuticals Ltd., Novartis AG, Janssen Pharmaceuticals, Inc., AstraZeneca, Research Support; Lexicon Pharmaceuticals, Inc.
275-LB: Mitochondrial Fission Factor Can Be a Key Factor in the Regulation of Hepatic Lipid Metabolism
Authors: TAKEICHI YUKINA , MIYAZAWA TAKASHI , OGAWA YOSHIHIRO 
Published: June 2023

Nonalcoholic fatty liver disease (NAFLD) develops into nonalcoholic steatohepatitis (NASH) when fat accumulates in the liver, leading to hepatocyte apoptosis, inflammation and fibrosis. No effective treatments for NASH have been established. Mitochondria are important organelles that play a central role in de novo lipogenesis and fatty acid β-oxidation. We have shown that mitochondrial fission is enhanced by short-term high-fat diet (HFD) loading, but is impaired by long-term. We speculated that mitochondrial fission inhibition is associated with the development of NASH and generated mice deletion of hepatocyte-specific mitochondrial fission factor (KO) mice. Conditioning HFD, KO mice showed inhibition of hepatocyte mitochondrial fission, increased ER stress and decreased triglyceride secretion from the liver. The hepatic triglyceride contents had significantly increased in KO mice compared to control (CONT), and histological analysis showed a marked increase in large lipid droplets (LDs). In addition to marked fat accumulation, hepatic apoptosis, inflammation and fibrosis were increased in the livers of KO mice, indicating the development of NASH. We noted that large LDs were increased in KO mice and added an additional analysis to determine how mitochondrial fission inhibition is involved in LDs formation in the liver. Oleic acid is a representative monounsaturated fatty acid that promotes LDs deposition in hepatocytes and is mildly cytotoxic by inducing ER stress and apoptosis. Loading primary cultured hepatocytes (PH) with oleic acid increased the number of smaller LDs in PH of CONT mice, whereas LDs in cells of KO mice became larger. Gene expression of Cidec, which acts on the fusion of LDs, was increased in the liver of KO mice, suggesting that inhibition of mitochondrial fission may induce the fusion of LDs and the enlargement of intracellular LDs in the liver. Further analysis is planned, as inhibition of mitochondrial fission may be involved in changes of LDs morphology.

Disclosure
Y. Takeichi: None. T. Miyazawa: None. Y. Ogawa: None.
278-LB: The Effect of Combining Very-Low-Calorie Diet with Semaglutide on Beta-Cell Function in Individuals with Type 2 Diabetes
Authors: ANYIAM OLUWASEUN , PHILLIPS BETHAN E. , WILKINSON DANIEL J. , SMITH KEN , ATHERTON PHILIP J. , IDRIS ISKANDAR R. 
Published: June 2023

Type 2 diabetes (T2D) is characterised by the loss of the first phase response of insulin-producing pancreatic beta cells. Recently, Very-low calorie diets (VLCD - defined as less than 800 kilocalories per day) have been shown to restore this first phase response to induce remission of T2D, while Glucagon-like peptide-1 agonists also improve the first phase response by enhancing postprandial insulin secretion. Here, we present interim results of an investigation exploring the effect of combining these two interventions on beta cell function, in individuals with T2D.
Eighteen individuals with T2D and body mass index &gt;27kg.m-2 were randomly allocated into 3 groups: i) Semaglutide (S), ii) VLCD (V), and iii) Semaglutide-plus-VLCD (SV). Semaglutide was administered once weekly gradually up titrated to a maximum dose of 1mg and VLCD regime was provided by LighterLife® total meal replacement. Beta cell function was assessed using intravenous glucose tolerance tests (IVGTT) performed at baseline and 12 weeks. First-phase insulin response was calculated as the incremental area under the suprabasal plasma insulin concentration curve during 0-10 minutes of the IVGTT (µU.min.ml-1). Data were analysed using GraphPad Prism 9.5.0 (La Jolla, USA).
All groups were equally matched at baseline. Mean weight loss was 6.4, 14.1 and 14.9 kg in S, V and SV, respectively. A significant improvement in first phase response was observed in all groups (S: +398.5; V: +88.4; SV: +547.8 µU.min.ml-1, all p&lt;0.05 vs. baseline). At 12 weeks, first phase response in SV was significantly higher than in V (583.9 vs. 169.2 µU.min.ml-1 respectively, p&lt;0.05).
These data suggest that combination of VLCD and Semaglutide results in a significantly greater improvement in first phase response than VLCD alone. This approach could result in a more robust remission of T2D in the longer-term, and may have important implications for the future design of interventions for the clinical management of T2D.

Disclosure
O. Anyiam: None. B. E. Phillips: None. D. J. Wilkinson: None. K. Smith: None. P. J. Atherton: None. I. R. Idris: None.

Funding
Medical Research Council Confidence in Concept Scheme
278-OR: Impact of a Parameter Change in DBLG1 System
Authors: ADENIS ALICE , VESIN AURÉLIEN , ROMERO-UGALDE HECTOR M. , LOUIS MAXIME , HUBER CLÉMENT V. , POU LIM-SYLVIE , TOURKI YOUSRA , HUNEKER ERIK , BENHAMOU PIERRE Y. 
Published: June 2023

In DBLG1 System, multiple parameters can be customized. This study aims at analyzing the impact of a change of the normoglycemia aggressiveness (NA), the hyperglycemia aggressiveness (HA) and the glucose target (GT) on the glycemic control of T1D patients. Data is collected from 5977 adult patients who gave their consent (3/2021 to 11/2022). Periods of 14 days before and after a single parameter change are collected. Conditions of 70% of data availability and of 75% of time spent in closed loop are requested for each period. The time in range 70-180 mg/dL (TIR), the time below range 70 mg/dL (TBR), the mean sensor glucose (MG), the coefficient of variation (CV) and the mean daily insulin dose (MDI) of the two periods are compared for each parameter using a Wilcoxon Signed-Rank test. Control for the multiple tests is done using the Benjamini-Hochberg procedure. The size effect is inferred using Cohen’s d. The results are summarized in the table below. On average, an increase of HA or NA improves the TIR and reduces the MG. The TBR appears to increase when the HA is increased and to decrease when HA or NA are reduced. A decrease of the GT increases TIR, TBR and CV, and decreases MG, conversely an increase of the GT decreases TIR, TBR and CV, and increases MG. The size effect is small. The impact on MDI is small or not significant. The most impactful parameter seems to be the GT which affects the MG proportionally. HA and NA had a lower than expected impact.

Disclosure
A.Adenis: Employee; Diabeloop SA. A.Vesin: Employee; Diabeloop SA. H.M.Romero-ugalde: Employee; Diabeloop SA. M.Louis: Employee; Diabeloop SA. C.V.Huber: Employee; Diabeloop SA. L.Pou: None. Y.Tourki: Employee; Diabeloop SA. E.Huneker: Employee; Diabeloop SA. P.Y.Benhamou: Advisory Panel; Eli Lilly and Company, Insulet Corporation, Novo Nordisk, Consultant; Dexcom, Inc., Employee; Diabeloop SA.
279-OR: Placental IGFBP1 Is Associated with Insulin Sensitivity during Pregnancy and Is an Early Biomarker for Gestational Diabetes
Authors: HIVERT MARIE-FRANCE , WHITE FRÉDÉRIQUE , ALLARD CATHERINE , JAMES KAITLYN , MAJID SANA , FLOREZ JOSE C. , EDLOW ANDREA , BOUCHARD LUIGI , JACQUES PIERRE-ETIENNE , ANANTH KARUMANCHI S. , POWE CAMILLE E. 
Published: June 2023

Pregnancy is associated with a profound reduction in insulin sensitivity (IS) that contributes to gestational diabetes (GDM), but the placental factors that lower IS in pregnancy are not fully known. We conducted genome-wide RNA sequencing in 450 placenta samples from a prospective pregnancy cohort (Gen3G). Participants provided plasma samples in the 1st trimester and completed 75g oral glucose tolerance tests in the late 2nd trimester, from which IS was estimated via the Matsuda index. We used regression analyses to test differential expression of 15,232 placental genes related to maternal IS, adjusting for gestational age at delivery, fetal sex, maternal age, gravidity, BMI, and 37 surrogate variables (to account for technical variability). Among the top differentially expressed genes, lower placental expression of IGFBP1 was significantly associated with lower maternal IS (P=1.7×10-4). In 837 Gen3G women, lower IGFPB1 circulating protein was strongly associated with lower IS (r=0.50, P&lt;0.001) and predicted GDM risk (1st trimester median levels: 23,884 pg/mL in no GDM vs 14,363 pg/mL in GDM, adjusted OR=0.55 [0.39-0.75] per quartile increase; P=1.5×10-4). The association between plasma IGFBP1 and IS was replicated in two pregnancy cohorts: SPRING (n=165 with GDM risk factors, r=0.54, P&lt;0.001) and MOMS (n=97 matched GDM cases and controls, r=0.55, P&lt;0.001). The association of lower plasma IGFBP1 with greater risk of GDM was replicated in SPRING (adjusted OR=0.66 per quartile increase, P=0.07) and MOMS (adjusted OR=0.45 per quartile increase, P&lt;0.001). In SPRING, plasma IGFBP1 protein were markedly elevated in the 1st and 2nd trimesters compared to postpartum (P&lt;0.001), consistent with placental origin. Our results suggest that the placenta expresses high levels of IGFBP1, which influences IGF-1 bioavailability and is released in maternal circulation to regulate IS in pregnancy, highlighting it as a promising early plasma biomarker of GDM risk.

Disclosure
M.Hivert: None. S.Karumanchi: None. C.E.Powe: Consultant; Mediflix, Inc., Other Relationship; Wolters Kluwer Health. F.White: None. C.Allard: None. K.James: None. S.Majid: None. J.C.Florez: Consultant; AstraZeneca, Novo Nordisk, Other Relationship; AstraZeneca, Merck & Co., Inc. A.Edlow: Consultant; Mirvie, Inc, Research Support; Merck & Co., Inc. L.Bouchard: None. P.Jacques: None.

Funding
Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD094150)
281-LB: The Association between Pericardial Fat Volume and Mortality—The Multi-Ethnic Study of Atherosclerosis
Authors: SHIL HONG EUN , BRUMBACK LYNDIA , ALLISON MATTHEW 
Published: June 2023

Background: Pericardial fat, a specific measure of ectopic fat, is associated with incident cardiovascular disease (CVD). Both coronary artery calcium (CAC) and body mass index (BMI) may modify the effect of ectopic fat on mortality. However, there are few studies on the association between pericardial fat and mortality and if this association can be modified by CAC and BMI.
Objective: We examined the association between pericardial fat volume (PFV) and all-cause and CVD mortality.
Methods: This study ascertained PFV using cardiac computed tomography in 6,785 participants without pre-existing cardiovascular disease from the Multi-Ethnic Study of Atherosclerosis (MESA). Cox proportional hazards regression was used to evaluate the association between PFV and mortality. We tested for effect modification in these associations by CAC and BMI categories.
Results: The mean age of the analytic sample was 62.1 ± 10.0 years and 53% were female. The mean PFV was 79.6 ± 42.0 cm3. Over a 16.9-year median follow-up, there were 1,701 (25%) all-cause deaths and 411 CVD-related deaths (6%). In unadjusted model, every 1-SD (42 cm3) increase in PFV was associated with a 2-fold higher rate of all-cause mortality (HR=1.99, 95% CI=1.81-2.20). After adjusting for demographics, CV risk factors, income, and waist-to-hip ratio, this association was attenuated but remained significant (HR=1.20, 95% CI=1.06-1.36). Similarly, PFV was associated with CVD mortality in unadjusted model (HR=2.38, 95% CI=1.95 - 2.91) but was no longer statistically significant after multivariable adjustment (HR=1.26, 95% CI=0.97-1.62). There were no significant interactions by CAC. However, a significant interaction by BMI was found (p value for interaction = 0.013); the HR of BMI≥35kg/m2 was 2.4-times higher than the HR of BMI&lt;25kg/m2.
Conclusions: In this large, community-based, prospective cohort study, pericardial fat was associated with a higher risk of all-cause mortality especially among obese participants.

Disclosure
E. Hong: None. L. Brumback: None. M. Allison: None.