bluuebunny/crossref_metadata_2025 huggingface dataset:
817-P: Identifying Modulators of Treatment Benefits of Albiglutide (GLP-1 RA) in Preventing Major Adverse Cardiovascular Events (MACE) among Individuals with Type 2 Diabetes in the HARMONY Trial Using Machine Learning
Authors: KIANMEHR HAMED , LIN YILU , SHI LIZHENG , FONSECA VIVIAN , GUO JINGCHUAN , SHAO HUI
Published: May 2022

This study aimed to identify patient characteristics associated with the effectiveness of albiglutide in preventing MACE among patients with type 2 diabetes (T2D) in the HARMONY trial. The HARMONY trial was a randomized, double-blind, placebo-controlled trial to examine the effectiveness of albiglutide in reducing the risk of cardiovascular disease in 9,463 individuals with T2D. We used the causal forest (CF) and causal tree (CT) algorithm to identify participant characteristics that modulate the effectiveness of albiglutide in preventing MACE from a list of 16 candidate variables (demographics, disease histories, medications, and biomarkers) at the study baseline. A computer-driven approach identified that study participants with baseline A1c level above 8.0% (absolute risk change (ARC) : -2.77%, 95% confidence interval [-4.21% to -1.28%]; relative risk (RR) : 0.74 [0.62 to 0.87]) , or diabetes duration less than 15 years (ARC: -2.55% [ -3.85% to -1.04%]; RR: 0.70 [0.58 to 0.85]) , or DBP higher than 70 mmHg (ARC: -2.40% [-3.68% to -1.21%]; RR: 0.73 [0.62 to 0.86]) , or heart rate below 70 per hour (ARC: -2.88% [-4.76% to -1.04%]; RR: 0.70 [0.56 to 0.88]) , or ALP level below 70 U/L (ARC: -3.10% [-3.10% to -1.30%]; RR: 0.65 [0.52 to 0.81]) , or serum creatinine level below 90 umol/L (ARC: -1.99% [-3.33% to -0.81%]; RR: 0.74 [0.61 to 0.88]) benefited from albiglutide in reducing the risk of MACE. In contrast, their counterparts who did not have these characteristics did not receive statistically significant MACE risk reduction from albiglutide. Our study identified clinical features that may result in greater benefits of albiglutide on MACE than what would be expected from a population average. Clinicians may consider these individualized characteristics for better-targeted albiglutide treatment. However, future GLP-1 trials may help to confirm this approach to optimize outcomes.

Disclosure

H.Kianmehr: None. Y.Lin: None. L.Shi: None. V.Fonseca: Consultant; Abbott, Asahi Kasei Corporation, Bayer AG, Novo Nordisk, Sanofi, Research Support; Fractyl Health, Inc., Jaguar Gene Therapy, Stock/Shareholder; Abbott, Amgen Inc., BRAVO4Health, Mellitus Health. J.Guo: None. H.Shao: Board Member; BRAVO4HEALTH, LLC.
821-P: Randomized Clinical Trial on the Renoprotective Effect of CU01-10in Patients with Diabetic Kidney Disease (DKD)
Authors: MOON JUN SUNG , WON KYU CHANG , KIM MIN-JI , LEE IN-KYU , KWON SO HEE , PYO JUNG-IN , KANG JI-HYE , KWON YOUNG-GUEN , SEO HEEWON
Published: May 2022

Background: One of the leading causes of chronic kidney disease, DKD is associated with increased oxidative stress and chronic inflammation. CU01-10is dimethyl fumarate (DMF) which being developed for treatment of DKD. DMF attenuated renal fibrosis via the Nrf2-mediated inhibition of TGF-b/Smad3 signaling in an antioxidant response element independent manner in preclinical model, suggesting that DMF can be potentially effective against kidney damage. In this study, we investigated the efficacy and safety of CU01-10in patient with DKD.

Methods: For this randomized, double-blinded phase 2a clinical trial for the efficacy and safety assessment, we enrolled 42 adults with DKD (estimated glomerular filtration rate (eGFR) 30 to 89 ml/min/1.73m2) with albuminuria to be treated with CU01-10 (120mg twice a day) or placebo. We measured the change from baseline in urine albumin creatinine ratio (uACR) and eGFR at 12 weeks for primary outcomes.

Results: A total of 39 patients were evaluated for primary efficacy analysis. CU01-10group showed significant increase of eGFR (+ 3.80±8.72 ml/min/1.73m2at week 12, from baseline) , and there was a significant intergroup difference of eGFR at 6 and 12 weeks (p=0.0349 and p=0.0121, respectively) . CU01-10group was statistically significantly decreased in the mean ACR (p=0.0441) but not for placebo group (p=0.1336) , and after 12 weeks, CU01-10group (-39.65 mg/g) showed lower median uACR from the baseline than placebo (-16.90 mg/g) . In DMF group, no severe adverse events were reported during the trial and the most common adverse events were nausea (n=3) and skin flushing (n=3) .

Conclusion: CU01-10showed an improvement of uACR and eGFR compared to placebo for patients with DKD, with no major drug-related adverse events.

Disclosure

J.Moon: None. K.Won: None. M.Kim: None. I.Lee: n/a. S.Kwon: None. J.Pyo: None. J.Kang: None. Y.Kwon: None. H.Seo: None.
822-P: The Harmine and Exendin4 Combination Markedly Expands Human Beta-Cell Mass In Vivo in Diabetic Mice
Authors: BELIARD KARA A. , ROSSELOT CAROLINA , LI YANSUI , ALVARSSON ALEXANDRA , WANG PENG , THAKKAR KEYA , GUEVARA DANIELA , DEVITA ROBERT J. , STEWART ANDREW F. , STANLEY SARAH , GARCIA-OCANA ADOLFO
Published: May 2022

Diabetes results from diminished functional β-cell mass. Small molecule inhibitors of Dual Specificity Tyrosine Phosphorylation Regulated Kinase 1A (DYRK1A) markedly increase human β-cell replication in vitro and in vivo. Furthermore, combination of DYRK1A inhibitors such as Harmine (H) with widely clinically used glucagon-like peptide 1 receptor agonists such as Exendin-4 (E) further enhance human β-cell proliferation. However, whether H+E combination increases human β-cell mass and improves glucose homeostasis in diabetic immunosuppressed mice transplanted with a marginal number of human islets is unknown. Human islets from 5-6 different adult healthy donors were transplanted under the kidney capsule (200 islets per kidney) of streptozotocin-induced diabetic immunodeficient Rag1-/- mice. At the time of transplantation, osmotic Alzet minipumps were implanted for continuous delivery of vehicle V, H, E and H+E for a period of 12 weeks. At the end of the study, human islet-bearing kidneys were harvested, labeled with insulin antisera and cleared using a modification of the iDISCO+ method. Imaging and analysis of the β-cell volume was done using the Light-sheet Ultramicroscope II and Imaris software. Transplanted diabetic mice who received the combination of H+E showed a significant increase of human β-cell volume up to 600% compared with mice treated with V or the drugs alone. This increase correlated with a significant increase in plasma human insulin levels, sustained normalization of blood glucose levels and significantly improved glucose tolerance. Our studies provide unequivocal documentation that treatment with the harmine and exendin-4 combination can lead to actual increases in human β-cell mass in diabetic conditions suggesting that β-cell replenishment might be possible in humans with diabetes.

Disclosure

K.A.Beliard: None. S.Stanley: None. A.Garcia-ocana: Consultant; Sun Pharmaceutical Industries Ltd. C.Rosselot: None. Y.Li: None. A.Alvarsson: None. P.Wang: None. K.Thakkar: None. D.Guevara: None. R.J.Devita: None. A.F.Stewart: None.

Funding

NIH/NIDDK 1R01DK105015-05.
828-P: Preservation of ß-Cell Function in Pancreatic Insufficient Cystic Fibrosis (CF) with Highly Effective CFTR Modulator Therapy
Authors: FLATT ANNELIESE , SHEIKH SABA , PELECKIS AMY J. , GALLAGHER KATHRYN , ALVARADO PAOLA , HADJILIADIS DENIS , STEFANOVSKI DARKO , GALLOP ROBERT J. , RUBENSTEIN RONALD C. , RICKELS MICHAEL R. , KELLY ANDREA
Published: May 2022

CF related diabetes is common with pancreatic insufficient CF (PI-CF) . Highly effective modulator therapy enhances aberrant CF transmembrane conductance regulator (CFTR) function and improves pulmonary and nutritional status. Ivacaftor therapy for indicated CFTR mutations enhanced insulin secretion to glucose-potentiated arginine (GPA) testing; however the effects of elexacaftor/tezacaftor/ivacaftor (ETI; Trikafta™) on β-cell function have not been assessed. We retrospectively compared changes in GPA measures performed on two visits in individuals with PI-CF without diabetes and who were 1) initiated on ETI after the baseline visit (ETI group) vs. 2) not treated with CFTR modulator therapy (controls) .

ETI participants (mean±SD age 27±9 years) and 8 matched controls were followed up after a median (IQR) 5.8 (3.7-6.7) and 2.7 (1.9-3.0) years, respectively (p=0.001) , with ETI initiation 1.1 (0.2-1.2) years before the follow-up visit. Weight increased in both groups, but by more in the ETI group (p<0.01) . No differences in lung function or HbA1c were observed; however, improvement in oral glucose tolerance test 2-hour glucose was observed in the ETI group (p<0.05) that was different by trend from the change seen in controls (p=0.09) .

Acute insulin and C-peptide responses to glucose-potentiated arginine deteriorated in controls (p<0.05) but not in the ETI group, while C-peptide changes differed between groups (p<0.05) . A trend towards lower acute proinsulin response was seen in the ETI group (p=0.07) with the change different between groups (p<0.05) . Deterioration in the proinsulin secretory ratio was observed in the control (p<0.05) but not the ETI group (between group change, p=0.01) .

ETI therapy appears to preserve β-cell function in CF through effects on glucose-dependent insulin secretion and proinsulin processing. Further work should determine whether early intervention with ETI can prevent deterioration of glucose tolerance in PI-CF.

Disclosure

A.Flatt: None. M.R.Rickels: Advisory Panel; Sernova, Corp., Vertex Pharmaceuticals Incorporated, Zealand Pharma A/S, Consultant; L-Nutra Inc. A.Kelly: Research Support; vTv Therapeutics. S.Sheikh: None. A.J.Peleckis: None. K.Gallagher: None. P.Alvarado: None. D.Hadjiliadis: Advisory Panel; AstraZeneca, Research Support; Mylan N.V. D.Stefanovski: None. R.J.Gallop: None. R.C.Rubenstein: None.

Funding

Public Health Service research grants (RDK97830; K23 DK107937; UL1 TR001878) and National Institutes of Health (P30 DK19525) .
83-OR: The LDIFLARE Method Predicts the Development of Incipient Diabetes Polyneuropathy: Results of the Five-Year Longitudinal Ipswich NeuroDiab Study
Authors: SHARMA SANJEEV , CROSS JEN , RAYMAN GERRY
Published: May 2022

Aims: The LDIFLARE method has been previously shown to be a sensitive measure of small fibre function. In this longitudinal 5-year study, we evaluated the LDIFLARE as a method to predict the development of DPN.

Methods: From the cohort of 160 people with type 1 and 2 diabetes recruited at baseline, 58 patients who did not have DPN at onset and completed 5 years of follow up were studied. Incident DPN was defined as progression to a Neurology Disability Sore (NDS) of ≥3. All subjects underwent comprehensive neurological review including electrophysiology. We used duration-dependent receiver operating characteristic (ROC) curves to calculate the predictive validity of the baseline LDIFLARE for the development of a NDS of ≥3.

Results: Of the 58 subjects without DPS who completed 5yr follow up, 34 had Type-1 and 24 had Type-2 diabetes; 35 females. Mean age (±SD) was 47.1±8.8 years. Mean follow up time was 5.4 years. Of these, 24 (T1Dm & 14 T2DM) progressed to a NDS of ≥3 (41%; 7.7 events per 100 subject-years) . There was a strong correlation with older age, longer duration of diabetes, raised HbA1c and raised triglycerides (significance: p<0.05) but no effect of BMI or blood pressure. The linear rate of fall of LDIFLARE from baseline in newly diagnosed DPN was 0.16 cm2/yr for T1DM and 0.22cm2/yr for T2DM. The area under the ROC curve for LDIFLARE ranged between 0.66 and 0.75. The optimal diagnostic threshold for a baseline LDIFLARE of 5.05cm2 was associated with 71% sensitivity, 74% specificity, and a hazard ratio of 3.73 (95% CI 2.14-6.73; P < 0.01) for new-onset DPN.

Conclusions: We conclude that the LDIFLARE method with a cut-off of 5.cm2 showed good predictive validity for identifying people with diabetes who are at risk of developing DPN. We suggest that as a measure of small fibre function, the LDIFLARE method may be preferred over conventional large fibre methods in predicting the later development of clinical DPN.

Disclosure

S.Sharma: None. J.Cross: None. G.Rayman: None.
851-P: Oral Long-Acting Menin Inhibitor Normalizes Type 2 Diabetes Mellitus (T2DM) in Two Rat Models
Authors: BUTLER THOMAS , LI WEIQUN , LAW BRIAN , ARCHER TENLEY , KINOSHITA TAISEI , SOMANATH PRIYANKA
Published: May 2022

Menin is a scaffold protein that has been recognized for its role in T2DM as a key regulator of β-cell proliferation. Menin inhibition has previously been shown to improve glycemic control in diabetic mice. Herein, we report the first evidence that BMF-219, an orally bioavailable, selective, irreversible menin inhibitor, restores glycemic control in Zucker Diabetic Fatty (ZDF) Rat and Streptozotocin-induced Rat (STZ) models of T2DM. Rats were treated daily with BMF-219, vehicle, or pioglitazone for 16 days. BMF-2was well tolerated throughout the conduct of the study. BMF-2treatment resulted in a significant 50% reduction in fasting and non-fasting blood glucose levels, reduced serum insulin and c-peptide levels (p<0.05) , and reduced HOMA-IR (p<0.001) after two weeks of treatment in ZDF rats. BMF-2decreased glucose levels at all timepoints during an oral glucose tolerance test at Day 15 (AUC reduction of 54%, p<0.001) and at Day 29 (AUC reduction of 40%, p<0.05, ∼2 weeks after the last dose) in the ZDF model, indicating prolonged glycemic control. Strikingly, BMF-219, but not pioglitazone, reduced blood glucose levels during an OGTT in STZ animals (AUC reduction of 41%, p<0.05, see figure) . Significant reductions in blood lipemic levels (p<0.01) and body weight were observed in both models. Collectively, our data indicate the novel and marked potential of BMF-2as an oral, long-acting treatment for T2DM.

Disclosure

T. Butler: Employee; Biomea Fusion Inc. W. Li: None. B. Law: Stock/Shareholder; Biomea Fusion Inc., Mirum Pharmaceuticals. T. Archer: Employee; Biomea Fusion. T. Kinoshita: None. P. Somanath: Employee; Biomea Fusion, Inc. Stock/Shareholder; Biomea Fusion, Inc.
852-P: Precision of the Afinion HbA1c Dx Point-of-Care Test in CLIA Waived Settings
Authors: CLENDENIN MARTA , KUPFER KENNETH , GREEN CHRISTOPHER L. , FORTNER KYLE S. , BAILEY TIMOTHY S. , BRICK STEPHEN , SMILEY SARAH I. , STRAUSS GUY S. , THORSELL ASHLEY A. , AHMED NASEER
Published: May 2022

There is limited data on the performance of point of care HbA1c assays when fingerstick samples are tested by intended users in CLIA waived settings.

This study evaluated the precision of the Afinion HbA1c Dx (Afinion) when performed at CLIA waived sites (N=5) by operators with no laboratory training. The operators (N=12) self-trained using the materials provided with test purchase, had no prior Afinion system experience, and did not observe one another during testing. For each subject enrolled in the study (N=115) , 2 operators each obtained 2 fingerstick samples (4 total fingersticks per subject) and tested one sample on each of 2 Afinion instruments. The repeatability, between-operator, and between-instrument components of variance were calculated using the REML method for each of 4 HbA1c concentration intervals. The total imprecision was calculated as a composite of 6 relevant components of variance, including a) the components of variance estimated here (repeatability, between-operator, and between-instrument) , and b) components of variance estimated in prior studies (between-run, between-day, and between-lot) .

The repeatability was the dominant component, ranging from 0.83-1.14% CV across the HbA1c concentration intervals. The between-operator component was 0.00% CV for 3 out of the 4 HbA1c intervals, and was only 0.19% CV in the remaining interval, indicating the precision of the test is not operator dependent. The between-instrument component ranged from 0.22-0.39% CV. When combined with the other components of variance estimated in prior studies, the total imprecision does not exceed 1.80% CV, which is below the National Academy of Clinical Biochemistry’s (NACB) recommendation for a single method, interlaboratory CV of <3%. The results were similar to those obtained by trained operators testing fingerstick samples with the Afinion system.

These results indicate that the precision of the Afinion is comparable to many laboratory HbA1c assays, and suitable for use in CLIA waived settings.

Disclosure

M.Clendenin: Employee; Abbott. N.Ahmed: Employee; Abbott. K.Kupfer: Employee; Abbott. C.L.Green: Employee; Abbott Diagnostics, Siemens. K.S.Fortner: Employee; Abbott. T.S.Bailey: Advisory Panel; Abbott Diabetes, CeQur SA, MannKind Corporation, Medtronic, Novo Nordisk, Consultant; LifeScan, Sanofi, Research Support; Abbott Diabetes, Abbott Diagnostics, Biolinq, Capillary Biomedical, Inc., Dexcom, Inc., Eli Lilly and Company, Kowa Research Institute, Inc., Livongo, MannKind Corporation, Medtronic, Novo Nordisk, REMD Biotherapeutics, Sanofi, Sanvita Medical, Senseonics, ViaCyte, Inc., vTv Therapeutics, Zealand Pharma A/S, Speaker's Bureau; Becton, Dickinson and Company, Medtronic, Sanofi. S.Brick: None. S.I.Smiley: None. G.S.Strauss: None. A.A.Thorsell: None.
857-P: Mechanisms of Dapagliflozin to Reduce Intraglomerular Pressure in Patients with Type 2 Diabetes
Authors: BARKHORDARIAN MARYAM , TRIPLITT CURTIS L. , SOLIS-HERRERA CAROLINA , ADAMS JOHN M. , DEFRONZO RALPH A. , CERSOSIMO EUGENIO
Published: May 2022

Aim: To examine the renal hemodynamic effects of SGLT-2i therapy in type 2 diabetes patients [T2D].

Design & Methods: T2D (n=20) with normal GFR measured with 24-hour creatinine clearance [CrCl>100ml/min/1.73m2], who were not receiving ACEi or ARB, had renal blood flow (RBF) measured using PAH clearance divided by (1-Hct) and mean arterial pressure [MAP] to calculate renal vascular resistance [RVR] prior to and 4 months after Dapagliflozin 10mg/day (DAPA, n=10) . Results were compared to T2D treated with metformin ± glipizide to achieve similar glycemic control (Control, n=10) .

Results: HbA1c decreased equally in DAPA (8.6±0.5% to 7.4±0.3%) and CONTROL (8.7±0.3 to 7.5±0.2%) . There was a non-significant increase in RBF (ml/min) in DAPA compared to Control. MAP (mmHg) decreased by 8.5% from 98.4±2.9 mmHg to 90.0±2.0 mmHg and RVR by 21.4% from 87.9±5.1 mmHg/l/min to 69.1±5.2 mmHg/l/min in the DAPA group, while MAP & RVR remained unchanged in CONTROL group. Data at baseline [Pre-Rx] and after 4 months of therapy [Post-Rx] are shown in the table.

Conclusion: These findings show that, with equivalent glycemic control, dapagliflozin, but not metformin/glipizide, is accompanied by a decrease in renal vascular resistance, without significant change in RBF. Unlike studies in T1D, our results suggest that in T2D patients post-glomerular vasodilatation is the primary reno-protective mechanism of SGLT-2i therapy.

Disclosure

M.Barkhordarian: None. C.L.Triplitt: Consultant; Bayer AG, Speaker's Bureau; Eli Lilly and Company, Novo Nordisk. C.Solis-herrera: Speaker's Bureau; Novo Nordisk. J.M.Adams: None. R.A.Defronzo: Advisory Panel; AstraZeneca, Boehringer Ingelheim International GmbH, Intarcia Therapeutics, Inc., Novo Nordisk, Research Support; AstraZeneca, Boehringer Ingelheim International GmbH, Merck & Co., Inc., Speaker's Bureau; AstraZeneca. E.Cersosimo: Research Support; AstraZeneca.

Funding

AstraZeneca
858-P: Predictors of HbA1c and Weight Response to Sodium–Glucose Cotransporter 2 Inhibitors (SGLT2i) in the Association of British Clinical Diabetologist (ABCD) UK Nationwide Audit
Authors: CRABTREE THOMAS S.J. , GALLAGHER ALISON , SIVAPPRIYAN SIVA , DHATARIYA KETAN , RAGHAVAN RAJEEV P. , BICKERTON ALEX , ELLIOTT JACKIE , CULL MELISSA L. , RAYMAN GERRY , GALLEN IAN W. , IDRIS ISKANDAR R. , RYDER ROBERT E.
Published: May 2022

SGLT2i treatment is associated with weight and Hba1c reduction. Previous work has demonstrated clinical predictors of HbA1c and weight reduction with canagliflozin. We aim to analyse predictors of HbA1c and weight change across the class.

Methods: People with type 2 diabetes treated with any SGLT2i in the ABCD nationwide audit and available baseline and follow-up data were included. Multiple linear regression model was used to assess independent predictors of Hba1c and weight change. Analysis was performed using Stata 16.

Results: Data for 275individuals were included (n=13925 Empagliflozin, n=106Dapagliflozin, n=2976 Canagliflozin) . Baseline (mean±SD) were: age 59.8±10.5 years, baseline Hba1c 9.1±1.6%, weight 97.7±22.2kg, BMI 33.8±6.9kg/m2 and eGFR 81.8±13.6. Median (IQR) diabetes duration was 8.3 years (4.4-12.7) and follow-up time 1.5 years (0.7-2.7) . 61.3% were men. HbA1c fell by 0.87% (95%CI 0.85-0.89; p<0.01) . Factors associated with greater Hba1c reductions include: older age (ß=0.01, p<0.01) ; shorter diabetes duration (ß=-0.01, p<0.01) ; higher HbA1c (ß=0.65, p<0.01) ; greater weight loss (ß=0.02, p<0.01) ; higher alanine aminotransferase (ALT) (ß=0.005, p<0.01) ; higher baseline eGFR (ß=0.002, p<0.01) and canagliflozin or empagliflozin use (vs. dapagliflozin; p<0.05) . Weight fell by 3.0kg (95%CI 2.2-3.8; p<0.01) . Predictors of greater weight reductions include: older age (ß=0.05, p<0.01) ; lower HbA1c (ß=-0.29, p<0.01) ; higher weight (ß=0.03, p<0.01) or BMI (ß=0.17, p<0.01) and larger HbA1c reductions (ß=0.41, p<0.01) . Empagliflozin was superior to dapagliflozin (p=0.01) - no other differences between drugs were noted.

Conclusion: Our models demonstrate that baseline characteristics can help predict clinical outcomes with SGLT2i. Individual patient levels factors appear to provide only weak predictive value but may still be useful in assisting therapeutic choices.

Disclosure

T.S.J. Crabtree: Other Relationship; Abbott Diabetes, Novo Nordisk, Sanofi. A. Gallagher: Other Relationship; Dexcom, Inc. S. Sivappriyan: None. K. Dhatariya: Advisory Panel; AstraZeneca, Boehringer Ingelheim International GmbH. R.P. Raghavan: Speaker's Bureau; Novo Nordisk. Other Relationship; Lilly Diabetes, Novo Nordisk. A. Bickerton: None. J. Elliott: Advisory Panel; Abbott. Speaker's Bureau; Abbott, Dexcom, Inc., Insulet Corporation, Novo Nordisk. G. Rayman: None. I.W. Gallen: None. I.R. Idris: None. R.E. Ryder: None.

Funding

The ABCD SGLT2 audits are funded by unrestricted grants from Boehringer Ingelheim, AstraZeneca and Napp Pharmaceuticals
861-P: Differences in Heart Failure Hospitalization Risk following Initiating SGLT2 Inhibitors vs. DPP4 Inhibitors across Race/Ethnicity and Rural/Urban Areas
Authors: GUO JINGCHUAN , LI YUJIA , BIAN JIANG , LACKLAND DANIEL T. , KIMMEL STEPHEN , SCHATZ DESMOND , WINTERSTEIN ALMUT G.
Published: May 2022

Objective: Racial and rural disparities exist in the adoption of newer antidiabetic agents, including SGLT2 inhibitors. We aimed to evaluate whether the effectiveness of SGLT2 inhibitors varied across race/ethnicity and rural/urban areas.

Methods: Using claims data from 15% samples of national Medicare beneficiaries, we identified individuals who had type 2 diabetes and initiated SGLT2 inhibitors or DPP4 inhibitors (as the active control) between 1/1/2017-12/31/2018. Cohort entry was the day of the first filled prescription of any SGLT2 inhibitors or DPP4 inhibitors, defined as no use of either in the prior year. The outcome was hospitalization for heart failure (HHF) . Inverse probability treatment weighting (IPTW) Cox regressions were applied, controlling for pre-exposure covariates. IPTW models were fitted separately across subgroups.

Results: Cohort, mean age was 72 (SD 10) , 53% were women and 2.2% (2,577 / 116,751) experienced HHF over a median follow up of 363 days. Compared with DPP4 inhibitors, SGLT2 inhibitors were associated with a lower risk of HHF (HR, 0.73; CI, 0.65-0.80) . In the subgroup analyses, the beneficial effect of SGLT2 inhibitors vs. DPP4 inhibitors were comparable across non-Hispanic White (HR, 0.77; CI, 0.68-0.87) , non-Hispanic Black (HR, 0.67; CI, 0.49-0.91) and Hispanic (HR, 0.68; CI, 0.50-0.92) groups. SGLT2 inhibitors associated decreased risk of HHF was only seen in individuals living in urban areas (HR, 0.69; CI, 0.61-0.78) but not rural areas (HR, 0.95; CI, 0.76-1.19) .

Conclusion: Use of SGLT2 inhibitors, vs. DPP4 inhibitors, was associated with a lower risk of HHF and the effectiveness were comparable across racial and ethnics groups. However, SGLT2 inhibitors’ HHF benefit appeared to have been attenuated in those living in rural areas. Future studies are warranted to understand the mechanisms underlying the potential rural-urban disparities in treatment outcomes.

Disclosure

J.Guo: None. Y.Li: None. J.Bian: None. D.T.Lackland: None. S.Kimmel: Other Relationship; Janssen Pharmaceuticals, Inc. D.Schatz: Advisory Panel; Abbott Diabetes, Medtronic. A.G.Winterstein: Consultant; Genentech, Inc., Research Support; Merck & Co., Inc.
874-P: Potential Anti-Inflammatory Effects of Canagliflozin in Tumour Necrosis Factor-α and Interferon-ϒ-Stimulated Endothelial Cells
Authors: ALSHNBARI AFNAN S. , KHAN RAHEELA N. , IDRIS ISKANDAR R.
Published: May 2022

Background: This study investigates the potential direct anti-inflammatory effects of the SGLT2 inhibitors (canagliflozin, C; dapagliflozin D; or empagliflozin, E) on cultured endothelial cells.

Methods: Human umbilical vein endothelial cells (HUVECs) or Human cardio microvascular endothelial cells (HCMECs) were pre-incubated in the presence or absence of C (0.5μM, 1μM, and 10μM) , D (0.5μM, 1μM, and 10μM) and E (0.5μM, 1μM, and 10μM) for 1 hr and NaCl (150 mM) for 24 hr. The cells were then stimulated with TNF-α (ng/mL) and IFN-Υ (ng/mL) for 24 hrs. Expression of IL-6 and was analysed using Quantikine ELISA kits. The expression of SGLT2 mRNA was assessed using RT-PCR in cDNA prepared from two independent cultures of HUVECs and HCMECs using cDNA from human kidney cortex as a positive control.

Results: TNF-α and IFN-Υ and significantly induced expression of IL-6 in both HUVECs and HCMECs compared to controls (p = <0.0001) . The effects were significantly inhibited by canagliflozin 0.1μM, 1μM, and 10μM (p=0.0099, p< 0.0001, and p<0.0001, respectively) in HUVECs. In HCMECs, C, (0.5μM, 1μM, and 10μM) significantly inhibit the TNF-α and IFN-Υ IL-6 secretion (p< 0.0001, p< 0.0001, and p<0.0001, respectively) . No significant effect of D and E was observed. High NaCl had no influence on C (0.5μM, 1μM, and 10μM) inhibition of TNF-α and IFN-Υ induced of IL-6 secretion, and high salt alone had no influence on the secretion of IL-6 secretion. SGLT2 mRNA levels were below the detection level in HUVECs and HCMECs alone and on high glucose and TNF-α and IFN-Υ conditions.

Conclusion: This result indicates that SGLT2-I directly inhibits endothelial pro-inflammatory cytokines secretions. This striking anti-inflammatory of the SGLT2 inhibitor class merits further mechanistic research.

Disclosure

A.S.Alshnbari: None. R.N.Khan: None. I.R.Idris: None.
877-P: Safety of Dapagliflozin in Patients with Type 2 Diabetes Mellitus in China: Results from the DONATE Study
Authors: GUO LIXIN , WANG JING , LI LI , YUAN LIN , CHEN SHENG , WANG HUI , LI TONGHUAN , QI LIN , YANG HONG
Published: May 2022

Background: Dapagliflozin significantly improves glycemic control, body weight and blood pressure in Asian patients with type 2 diabetes mellitus (T2DM) , but safety data from studies with a large population are lacking. The DONATE study investigated the real-world safety of dapagliflozin in Chinese patients with T2DM.

Methods: This observational study enrolled patients with T2DM from 88 hospitals in China, who had received ≥1 dose of dapagliflozin between August 2017 and July 2020. Patients were followed for 6 months, or 7 days after discontinuing study drug. Primary outcome was the incidence of adverse events (AEs) and serious adverse events (SAEs) , particularly urinary tract infections (UTIs) , genital tract infections (GTIs) and hypoglycemia. Exploratory outcomes included the incidence of AEs of specific interest (AESI) and absolute changes in metabolic factors. Results: Of 3000 patients enrolled, 2990 patients were included in the safety analysis set; 1059 (35.4%) reported ≥1 AE, including 186 (6.2%) with ≥1 SAE. Adverse drug reaction was reported in 268 (9.0%) patients. In total, there were 70 (2.3%) , 39 (1.3%) and 32 (1.1%) patients with UTI, GTI and hypoglycemia, respectively. The occurrence of other AESIs was also low: polyuria (0.7%) , volume depletion (0.3%) , renal impairment (0.3%) , hepatic impairment (0.2%) , haematuria (0.2%) and diabetic ketoacidosis (0.1%) . There were no abnormal electrolytes events reported. At Week 24 (metabolic analysis set) , mean change from baseline in HbA1c was −1.318%; 161/417 (38.6%) achieved HbA1c <7.0%; Mean change from baseline in FPG, 2h-PPG, weight and waist circumference was −1.826 mmol/L, −5.466 mmol/L, −1.89 kg and -2cm, respectively.

Conclusion: Dapagliflozin showed a good safety profile in real-world clinical practice in China, with a low incidence of AEs, especially AESI. Meanwhile, a trend of improvement was found in blood glucose control as well as other metabolic factors.
887-P: Productivity and Medical Costs Due to Diabetes in Adults Aged 18–64 Years with Large Employer-Sponsored Insurance
Authors: PARK JOOHYUN , LUMAN ELIZABETH , ZHANG PING
Published: May 2022

Despite a substantial economic burden of type 2 diabetes (T2D) on the working population, the costs of T2D for employers are not well characterized. We estimated productivity losses and medical costs due to T2D among employees aged 18-64 years using 2018-20MarketScan® databases. We estimated missed days due to absences, short-term disability (STD) , and long-term disability (LTD) attributable to T2D, overall and by age and sex. We converted these losses into costs by multiplying them by an average hourly wage. We used two-part and generalized linear models (controlling for age, sex, state of residence, employer industry type, and Charlson Comorbidity Index score) to estimate the productivity costs and medical costs in total and by service type. All costs were in 20USD. Overall, employees with T2D had 68% higher costs measured in productivity losses and medical services than those without diabetes (Table) , yielding a total cost attributable to T2D of $6,933. Most of the extra cost (90%) was from medical costs, followed by productivity costs due to STD (7%) , absences (2%) , and LTD (1%) . The youngest group had higher STD days and outpatient costs. Females had more absences and STD days and higher outpatient costs than males. Our estimates may assist employers in assessing potential financial gains from improved efforts to prevent and manage T2D in the workplace.

Disclosure

J.Park: None. E.Luman: None. P.Zhang: None.
891-P: Health Care Economic Burden and Resource Utilization in Adults with Type 2 Diabetes and Myocardial Infarction
Authors: KING AARON A. , RAJPURA JIGAR J. , LIANG YUANJIE , PAPROCKI YUREK M. , UZOIGWE CHIOMA
Published: May 2022

Objectives: To evaluate health care resource utilization and cost in adults with type 2 diabetes mellitus (T2DM) and myocardial infarction (MI) .

Methods: We conducted a retrospective cohort study using the Optum® Clinformatics® Data Mart claims database. Patients ≥ 18 years of age with T2DM, with or without incident MI, were identified between January 1, 2012 and December 31, 2020. Healthcare resource utilization and cost were measured in the 12 months following index. MI was defined as a hospitalization with a qualifying primary discharge diagnosis code. Patient cohorts were compared using an inverse probability of treatment weighting approach.

Results: Incidence of MI was 0.7% (n = 13,681) in the one year following T2DM diagnosis. For the weighted analysis, 9,474 patients with T2DM and incident MI (mean age, 73.6; mean Charlson comorbidity index [CCI], 4.6) were compared to 9,536 patients with T2DM alone (mean age, 73.7; mean CCI, 4.7) . Compared to patients with T2DM alone, patients with T2DM and MI were more likely to have an inpatient (IP) visit (adjusted rate ratio [ARR], 5.4; 95% CI, 5.2-5.6; p < 0.01) , outpatient (OP) visit (ARR, 1.6; 95% CI, 1.6-1.6; p < 0.01) , or emergency room (ER) visit (ARR, 1.8; 95% CI, 1.7-1.8; p < 0.01) , and had longer IP length of stay (ARR, 5.4; 95% CI, 5.4-5.5; p < 0.01) . Healthcare costs from IP visits, OP visits, ER visits, and pharmacy costs were all higher in patients with T2DM and MI compared to patients with T2DM alone (Total costs, $10,929 per patient per month [PPPM] vs. $2,997 PPPM; p < 0.01) . In a hypothetical health plan population of one million adults with T2DM, we project patients with T2DM and MI would have +$676 million higher annual costs than patients with T2DM alone.

Conclusions: Having MI in addition to T2DM increased healthcare resource utilization and costs. Proactively managing patients’ T2DM to reduce risk of MI and the increased healthcare utilization and costs associated with MI may improve clinical outcomes and reduce overall costs.

Disclosure

A.A.King: Advisory Panel; Novo Nordisk, Board Member; JDRF, Speaker's Bureau; Abbott, Dexcom, Inc., Lilly Diabetes, MannKind Corporation, Medtronic, Novo Nordisk. J.J.Rajpura: Employee; Novo Nordisk. Y.Liang: Employee; Novo Nordisk. Y.M.Paprocki: Employee; Novo Nordisk, Stock/Shareholder; Novo Nordisk. C.Uzoigwe: Employee; Novo Nordisk, Stock/Shareholder; Novo Nordisk.
895-P: External Validation of the BRAVO Diabetes Model Using Data from the EXSCEL Study
Authors: SHAO YIXUE , NIU SHU , SHI LIZHENG , FONSECA VIVIAN , SHAO HUI
Published: May 2022

We developed an individual-level discrete-time microsimulation model, namely the Building, Relating, Assessing, and Validating Outcomes (BRAVO) diabetes model. The BRAVO model was externally validated using cohort-level data in people with type 2 diabetes (T2D) . This study further externally validated the BRAVO diabetes model using patient-level data from the Exenatide Study of Cardiovascular Event Lowering Trial (EXSCEL) . Baseline characteristics and trajectories of key biomarkers, including A1c, LDL, SBP, and BMI, were retrospectively extracted from the EXSCEL study database. To protect patients’ private information, variables of age and BMI were masked in ranges from the EXSCEL study (e.g., BMI 35 coded as BMI>30) . To convert the ranges back into specific values to support the simulation, we used the National Health and Nutrition Examination Survey (NHANES) data for the data imputations. We used the median value for each population subgroup from NHANES to replace the ranges. The BRAVO diabetes model was applied to the EXSCEL baseline data to predict the 7-year EXSCEL study outcomes. We assessed the BRAVO model’s discrimination power using C-statistics and calibration using the Brier score. The model demonstrated good discrimination and calibration in predicting the first occurrence of non-fatal myocardial infarction (C-index 0.620 [95% CI 0.590-0.650] and Brier Score (BS) 0.080 [0.074-0.085]) , non-fatal stroke (C-index 0.696 [0.634-0.758] and BS 0.031 [0.028-0.034]) , heart failure (C-index 0.700 [0.666-0.733] and BS 0.037 [0.034-0.041]) , revascularization (C-index 0.664 [0.590-0.738] and BS 0.036 [0.033-0.039]) , and all-cause mortality (C-index 0.746 [0.711-0.781] and BS 0.102 [0.098-0.106]) , respectively. Although the majority of the data obtained from EXSCEL trial was obtained in range instead of specific values, the BRAVO model remained robust in prediction performance in diabetes complications and mortality.

Disclosure

Y.Shao: None. S.Niu: None. L.Shi: None. V.Fonseca: Consultant; Abbott, Asahi Kasei Corporation, Bayer AG, Novo Nordisk, Sanofi, Research Support; Fractyl Health, Inc., Jaguar Gene Therapy, Stock/Shareholder; Abbott, Amgen Inc., BRAVO4Health, Mellitus Health. H.Shao: Board Member; BRAVO4HEALTH, LLC.

Funding

Astrazeneca
908-P: Shared Decision-Making for Diabetes Prevention: 24-and 36-Month Results from the Prediabetes Informed Decision and Education (PRIDE) Trial
Authors: DURU O. KENRIK , MOIN TANNAZ , TURK NORMAN , TSENG CHIHONG , NORRIS KEITH C. , MANGIONE CAROL
Published: May 2022

Background: Intensive lifestyle change (e.g., the Diabetes Prevention Program) and metformin reduce type 2 diabetes risk, but uptake is low. Our team has shown that shared decision-making (SDM) for diabetes prevention resulted in greater uptake of DPP and/or metformin and weight loss at 12 month follow-up. In this analysis, we examine weight loss at 24 and 36 month follow-up.

Methods: We led a pragmatic cluster RCT in 20 primary care clinics in a regional health system. We enrolled 5overweight/obese adults with prediabetes (BMI ≥ 24 kg/m2, HbA1c 5.7-6.4%) from intervention clinics. We used propensity score matching to select 1,502 control patients from usual care clinics. We assessed the difference in follow-up weight between groups as recorded in the EHR. We adjusted for age, sex, race, and ethnicity and trimmed the top and bottom 2.5% of change in weight to remove outliers. Intervention: A single SDM visit with a pharmacist who used a decision aid to discuss diabetes prevention options: DPP, DPP +/- metformin, metformin only, usual care.

Results: The greater mean 12-month weight loss among intervention participants versus controls (-4.0 lbs, 95% CI -5.1, -2.9) persisted with ongoing follow-up, although there was some weight regain. Specifically, intervention participants maintained greater mean weight loss than controls at 24 months (-3.1 lbs, 95% CI -4.2, -1.9) and 36 months (-2.7 lbs, 95% CI -3.9, -1.4) .

Conclusion: An intervention with a single SDM session increased engagement in evidence-based diabetes prevention, resulting in weight loss that was largely maintained for three years. Prediabetes SDM is a promising approach to enhance prevention among patients at increased diabetes risk. To achieve greater and more sustained weight loss, periodic reinforcement may be required.

Disclosure

O.Duru: None. T.Moin: None. N.Turk: None. C.Tseng: None. K.C.Norris: None. C.Mangione: n/a.

Funding

National Institutes of Health (R18DK105464)
909-P: Diabetes Assessment in El Paso, Texas, Using ADA Chronic Care Model
Authors: BAJPEYI SUDIP , CONCHA JEANNIE B. , PORTILLO DENISE N.
Published: May 2022

Hispanics are affected at a greater rate, with 14.3% diagnosed or predicted to have type 2 diabetes, and 50% more likely to die from diabetes compared to non-Hispanic Whites. El Paso, located at the border region of Texas and Mexico, have predominantly Hispanic population (∼87%) , faces significant health concerns associated with diabetes. Purpose: 1) to determine whether appropriate community resources exist to meet the American Diabetes Association (ADA) recommended standards of medical care and 2) to identify community/culture-centered strategies for the County of El Paso to best meet the recommended standards of care. Methods: The ADA Chronic Care Model (CCM) were used to develop interview guides. Focus groups were conducted with three certified diabetes care and education specialists (CDCES) and people with diabetes (PWD) . A survey was sent out to members of the focus groups and the members of the Diabetes leadership council to rank the ADA standards (S) based on priority and feasibility for the city of El Paso. Results: Interviews revealed that the ADA standard to refer PWD to diabetes community resources and DSMES programs (S1, S5) are not fully met. CDCES noted the need for mental health assessments and referrals to resources (S4) . PWD indicated promotion and awareness about diabetes resources is needed. PWD ranked S1 (Improving Care and Promoting Health in Populations) (29%) , S2 (Diabetes Diagnosis) (24%) and S3 (Diabetes Prevention and Delay) (19%) as the top three standards. CDCES ranked S1 (29%) and S3 (24%) as top two and S4 (Comprehensive Medical Evaluations) , S5 (Lifestyle Management) and S6 (Obesity Management) (14%) as the third priority. Diabetes Leadership Council ranked S6 (29%) , S5 (24%) and S3 (17%) as the top standards. Conclusion: There are several diabetes community resources and existing evidence based programs in El Paso. Leveraging CDCES professionals as a critical component to the education bridge between the Health System and the Community may help meet the diabetes Standards of Care.

Disclosure

S.Bajpeyi: n/a. J.B.Concha: n/a. D.N.Portillo: None.
916-P: Evaluation of an Enhanced Primary Care Team Model to Improve Diabetes Care
Authors: HERGES JOSEPH , MATULIS JOHN , KESSLER MAYA , RUEHMANN LISA L. , MARA KRISTIN , MCCOY ROZALINA G.
Published: May 2022

Purpose: Primary care practices manage most patients with diabetes, and face significant operational, regulatory, and reimbursement pressures to improve care quality. The Enhanced Primary Care Diabetes (EPCD) model was developed to leverage the expertise of care team registered nurses and pharmacists to improve diabetes care.

Methods: Utilizing a retrospective, interrupted time series design, we evaluated the EPCD model’s impact on a composite publicly reported quality measure of diabetes care (D5) , including indicators of glycemic control, blood pressure control, low-density lipoprotein, tobacco use, and aspirin use. We compared three groups of practices (32 total) that care for adults (age 18-75 years) with diabetes: staff clinician (physician and Advanced Practice Provider) practices with access to EPCD (5761 patients) , resident physician practices with access to EPCD (1887 patients) , and staff clinician practices without access EPCD (10,079 patients) . The primary outcome was a comparison of the pre-implementation trend (7 months) to the post-implementation trend (months) in the three groups for the percentage meeting the D5.

Results: There was a positive difference in pre to post-implementation trends for patients meeting the D5 in the staff clinician practices in the EPCD group (Pre IRR 0.995, Post IRR 1.005; P= 0.01) . There was no difference in the trend for the trainee physician practices with access to EPCD (Pre IRR 0.999, Post IRR 1.011; P= 0.14) , and a significant negative trend in the staff clinician practices without access to EPCD (Pre IRR 1.001, Post IRR 0.994; P= 0.05) .

Conclusion: The EPCD model significantly improved diabetes care quality. Further study of proactive, multidisciplinary chronic disease management led by care team nurses integrating clinical pharmacists is warranted.

Disclosure

J.Herges: None. J.Matulis: None. M.Kessler: None. L.L.Ruehmann: None. K.Mara: None. R.G.Mccoy: Consultant; Emmi.

Funding

National Institute of Diabetes and Digestive and Kidney Diseases (K23DK114497)
958-P: Associations between Effect of Body-Mass Index (BMI) and HbA1c among Children and Young Adults with Type 1 Diabetes: A U.S. Based Multicenter Study
Authors: MEKHOUBAD ALLISON B. , HSIEH SUSAN , NOOR NUDRAT , EBEKOZIEN OSAGIE , ROMPICHERLA SAKETH , OSPELT EMMA L. , ROBERTS ALISSA J. , SANCHEZ JANINE , FERRO DIANA , MIYAZAKI BRIAN , LEE JOYCE M.
Published: May 2022

Background: The primary objective of this U.S. based multi-center study was to examine the association of overweight and obesity with A1c levels for children and adolescents with type 1 diabetes (T1D) .

Methods: Electronic health record data spanning 2017-2021 for children and adolescents from the T1D Exchange Quality Improvement (T1DX-QI) Collaborative was analyzed. BMI percentiles were calculated using the Centers for Disease Control and Prevention growth curves, and children were categorized into normal weight, overweight, obese and severely obese groups. Normal weight was defined as a BMI < 85th percentile for age and sex. Overweight was defined as a BMI ≥ 85th to < 95th percentile. Obesity was defined as having a BMI <120% of the 95th percentile whereas severe obesity was defined as having BMI ≥120% of the 95th percentile. HbA1c levels and BMI were from last in-person encounter.

Results: Of 14,484 T1D patients aged < 18 years, 2,063 (14%) were underweight, 9,320 (65%) normal weight, 1,769 (12%) overweight, 977 (7%) obese and 333 were severely obese (2%) . More people of Black (12%) and Hispanic (18%) race/ethnicity were in the obese group relative to the normal weight group (8% and 10% respectively; p<0.001) . HbA1c levels were higher in the obese/severely obese group compared to normal weight patients (HbA1c Mean (SD) : Obese (9.1 (2.3)) /severely obese (9.1 (2.2) vs. Normal weight: 8.7 (2.0) ; p<0.001) .

Conclusion: In this extensive real-world study, we found obese children and adolescents with T1D were more likely of Black or Hispanic race/ethnicity and have higher HbA1c levels compared to those with healthy weight.

Disclosure

A.B.Mekhoubad: None. B.Miyazaki: None. J.M.Lee: Advisory Panel; GoodRx, Consultant; Tandem Diabetes Care, Inc. S.Hsieh: None. N.Noor: None. O.Ebekozien: None. S.Rompicherla: None. E.L.Ospelt: None. A.J.Roberts: None. J.Sanchez: None. D.Ferro: None.

Funding

The Leona M. and Harry B. Helmsley Charitable Trust
97-OR: Fatty Liver Index (FLI) Is an Independent Risk Factor for All-Cause Mortality and Cardiovascular Events in Type 1 Diabetes (T1D) : A 10-Year Observational Study
Authors: GAROFOLO MONIA , LUCCHESI DANIELA , GUALDANI ELISA , FALCETTA PIERPAOLO , GIAMBALVO MASSIMO , FRANCESCONI PAOLO , DEL PRATO STEFANO , PENNO GIUSEPPE
Published: May 2022

Nonalcoholic fatty liver disease (NAFLD) increases overall and CVD mortality. We prospectively observed 774 T1D to assess impact of FLI (based on BMI, waist, GGT and triglycerides) on all-cause death and CVD (MI, stroke, amputation, revascularizations) risk. Over a 11-year follow-up, 57 subjects died (7.4%) and 49 CV events (6.7%) occurred among 736 T1D with retrievable incidence data. FLI was <30 in 515 T1D (66.5%) , ≥30-60 in 169 (21.8%) , ≥60 in 90 (11.6%) . Mortality increased with FLI: 3.9, 10.1, 22.2% (K-M p<0.0001) . In unadjusted Cox, risk of death in FLI ≥30-60 (HR 2.85, 95% CI 1.49-5.45, p=0.002) and in FLI ≥60 (6.07, 3.27-11.29, p<0.0001) increased respect to FLI <30. Adjusting for Steno Type 1 Risk Engine (ST1-RE: age, sex, DD, sBP, LDL-chol, A1c, ACR, GFR, smoking and exercise) , HRs was 1.52 (0.78-2.97, p=0.222) for FLI ≥30-60 and 3. (1.59-5.82, p=0.001) for FLI ≥60. Inclusion of prior CVD modified HRs slightly. FLI effect was confirmed in 733 T1D without prior CVD (noCVD) . Adjusting for EURODIAB Risk Engine (EURO-RE: age, A1c, WHR, ACR and HDL-chol) did not alter FLI effect (≥30-60: HR 1.24, 0.62-2.48; ≥60: 2.54, 1.30-4.95, p=0.007) even after inclusion of prior CVD, or by restricting the analysis to noCVD subjects. CVD incidence events increased with FLI: 3.5, 10.5, 17.2% (K-M p<0.0001) . In unadjusted Cox, HR was 3.24 (1.65-6.34, p=0.001) for FLI ≥30-60 and 5.41 (2.70-10.83, p<0.0001) for ≥60. After ST1-RE adjustment, HRs was 1.80 (0.90-3.61, p=0.096) for FLI ≥30-60 and 2.98 (1.45-6.13, p=0.003) for FLI ≥60, with trivial modification with prior CVD inclusion. FLI was not a significant predictor in noCVD subjects. EURO-RE adjustment instead of ST1-RE confirmed an independent FLI role (≥30-60: 1.49, 0.73-3.03; ≥60: 2.44, 1.1-5.09, p=0.017) , even after inclusion of prior CVD. This is the first prospective study to demonstrate that FLI is associated with higher all-cause mortality and increased risk of incident CV events in T1D.

Disclosure

M.Garofolo: Employee; Eli Lilly and Company. D.Lucchesi: None. E.Gualdani: None. P.Falcetta: Speaker's Bureau; Abbott Diabetes. M.Giambalvo: None. P.Francesconi: None. S.Del prato: Advisory Panel; Applied Therapeutics, Eli Lilly and Company, Novartis Pharmaceuticals Corporation, Novo Nordisk A/S, Sanofi, Consultant; Menarini Group, Research Support; AstraZeneca, Boehringer Ingelheim International GmbH, Speaker's Bureau; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck & Co., Inc., Sanofi, Stock/Shareholder; Novo Nordisk A/S. G.Penno: Advisory Panel; Eli Lilly and Company.