bluuebunny/crossref_metadata_2025_split huggingface dataset:
1091-P: Impact of Metabolic Syndrome and Metabolic Dysfunction-Associated Fatty Liver Disease on Cardiovascular Risk in People with and without Type 2 Diabetes
Authors: MATSUBAYASHI YASUHIRO , FUJIHARA KAZUYA , YAMADA MAYUKO H. , YAGUCHI YUTA , YAMAMOTO MASAHIKO , ISHIGURO HAJIME , KITAZAWA MASARU , IWANAGA MIDORI , YAMADA TAKAHO , KODAMA SATORU , SONE HIROHITO 
Published: May 2022

This study aims to examine the impact of the association between metabolic syndrome (MetS) and metabolic dysfunction-associated fatty liver disease (MAFLD) , which both have insulin resistance and are pathophysiologically similar, on the development of new-onset cardiovascular disease, with and without type 2 diabetes mellitus (T2DM) A total of 570,426 participants without a history of cardiovascular disease who were enrolled in the nationwide claims database from 2008-2016 were included in this study. Participants were classified according to the presence or absence of MetS and/or MAFLD, and the risk of developing coronary artery disease (CAD) and/or cerebrovascular disease (CVD) in each category was analyzed using a multivariate Cox proportional hazard model. The same analysis was performed with stratification by the presence or absence of T2DM. During a median follow-up of 5.2 years, 2,252 CAD and 3,128 CVD events occurred. The hazard ratio (HR) (95% CI) for CAD, compared with the group with neither MAFLD nor MetS, was 1.46 (1.32-1.62) for MAFLD only (without MetS) , 2.02 (1.51-2.70) for MetS only (without MAFLD) , and 2.33 (2.10-2. 58) for MAFLD + MetS. For CVD, The HR was 1.41 (1.28-1.55) for MAFLD only, 1.67 (1.38-2.02) for MetS only, and 1.89 (1.72-2.08) for MAFLD + MetS. These results were similar for non-T2DM participants but different for T2DM participants, with no significant increased risk for CAD in MetS only and a significant increased risk for CVD only when both MAFLD and MetS coexisted. The predictive ability for cardiovascular disease development in patients with MetS and MAFLD differed depending on the presence or absence of T2DM. These results suggest that distinguishing between the diagnosis of MetS and MAFLD, taking into account the presence or absence of T2DM, may lead to more accurate identification of patients at high risk of developing cardiovascular disease.

Disclosure
K. Fujihara: None. M.H. Yamada: None. M. Yamamoto: None. H. Ishiguro: None. M. Kitazawa: None. M. Iwanaga: None. S. Kodama: None. H. Sone: Research Support; Astellas Pharma Inc., Eisai Co., Ltd., Kyowa Kirin Co., Ltd., Novo Nordisk, Ono Pharmaceutical Co., Ltd., Taisho Pharmaceutical Holdings Co., Ltd., Takeda Pharmaceutical Company Limited.

Funding
The Japan Society for Promotion of Science (JSPS) KAKENHI Grant Number JP 20K19706)
1093-P: Vascular Health across the Lifespan in Women with and without Type 1 Diabetes (TID)
Authors: CHARTIER-LOGAN CATHERINE J. , ALMAN AMY C. , SHAH VIRAL , SNELL-BERGEON JANET K. 
Published: May 2022

Introduction: Cardiovascular disease (CVD) is the leading cause of death in people with T1D, and women with T1D are disproportionately affected. However, few studies have examined how T1D affects vascular health in women across the lifespan.
Methods: Women ages 18-79 with (N=309) and without T1D (n=351) were examined cross-sectionally for markers of CVD: pulse wave velocity (PWV) , augmentation index (AiX) , pulse height (PH) , brachial artery distensibility (BrachD) , subendocardial viability index (SVI) , and carotid intima thickness (cIMT) . Menopausal status was self-reported. Body composition was measured by Dual Xray Absorptiometry. CVD markers were examined by diabetes status and age using linear regression models adjusted for menopausal status.
Results: Age did not differ in women with and without diabetes (49 ± 12 vs. 50±14 years, p=0.32) . Women with T1D had higher systolic blood pressure (SBP) , cIMT, PWV and PH, and lower BrachD and SVI than non-diabetic women (Table 1) . Changes in blood pressure, cIMT, AiX, and SVI with age differed by diabetes status, as demonstrated by a significant interaction. While SBP and Aix were increased more in women with T1D at younger ages, cIMT and SVI worsened with age to a greater extent in T1D.
Conclusions: Women with T1D have worse CVD markers than women without diabetes across the lifespan, with more arterial stiffness at younger ages and more atherosclerosis and lower SVI later in life.

Disclosure
C.J.Chartier-logan: None. A.C.Alman: None. V.Shah: Advisory Panel; Medscape, Sanofi, Consultant; Dexcom, Inc., Research Support; Dexcom, Inc., Eli Lilly and Company, Insulet Corporation, Novo Nordisk. J.K.Snell-bergeon: Stock/Shareholder; GlaxoSmithKline plc.
1094-P: Awareness of Cardiovascular Disease Risk in People with Type 2 Diabetes
Authors: IMRISEK STEVEN D. , HOY-ROSAS JAMILLAH R. , LAVAYSSE LINDSEY M. , LEE MATTHEW , DACHIS JEFF , SEARS LINDSAY 
Published: May 2022

Objective: Independent of other risk factors, type 2 diabetes (T2D) increases the risk of heart attack or stroke two-to-threefold and the risk of death twofold. Poorly managed diabetes and commonly comorbid conditions such as hypertension and hyperlipidemia multiply this risk. This cross-sectional study investigates differences in cardiovascular disease (CVD) risk awareness in a sample of people with T2D.
Methods: Participants with T2D paying for a subscription to One Drop for diabetes management completed a survey on their health. Three groups were identified: those who did not know their CVD risk, those who reported no risk, and those who reported being at risk for CVD. One-way ANOVA and chi-square tests compared groups on CVD risk factors (comorbidities, health behaviors, A1C, BMI) , self-care knowledge and interest in knowing more about risk.
Results: Of the 165 participants, 20.6% did not know their risk, 32.7% indicated no risk and 46.7% indicated they were at risk for CVD. The unknown risk group had the most interest in knowing more about their CVD risk (81.3%; p&lt;.001) and the least engagement in diabetes self-care behaviors (p’s&lt;.05) . The group self-reporting no risk had the lowest rates of hypertension (44% vs. 60%+, p&lt;.02) and hyperlipidemia (26% vs. 50%+, p&lt;.001) , the least knowledge of diabetes self-care behaviors (p=.004) , and the least interest in learning more about their CVD risk (34%; p&lt;.001) . The group self-reporting risk had moderate interest in learning more about their risk (58%) . Groups did not differ on self-reported A1C (p=.23) or BMI (p=.18) .
Discussion: Over half of the sample reported unknown or no risk for CVD. Those who did not know their risk had high interest in knowing more about their risk but low engagement in risk-mitigating behaviors. Those reporting no risk had lower rates of comorbidities; however, there was no difference in diabetes-related risk factors between groups. These findings suggest that CVD prevention programs should be developed to complement diabetes-focused programs.

Disclosure
S.D.Imrisek: Employee; One Drop. J.R.Hoy-rosas: None. L.M.Lavaysse: Employee; One Drop. M.Lee: Employee; One Drop. J.Dachis: Board Member; One Drop, Employee; One Drop, Stock/Shareholder; One Drop. L.Sears: Employee; One Drop.
11-LB: A Prediction Model on Incident CKD among Individuals with T2D in the United States
Authors: LIN YILU , SHAO HUI , ANDERSON AMANDA H. , FONSECA VIVIAN , BATUMAN VECIHI , SHI LIZHENG 
Published: May 2022

CKD is highly prevalent and costly in individuals with diabetes. Clinicians need to have a tool for early identification and prediction of incident CKD in individuals with diabetes. This study aimed to predict incident CKD among individuals with diabetes. A time-varying Cox model was derived from the ACCORD clinical trial data to predict the risk of incident CKD, defined as eGFR&lt;60 mL/min/1.73 m2 or UACR&gt;30 mg/g lasting for 3 months. A list of candidate variables was chosen based on literature reviews and experts’ consultation, including demographic characteristics, physical exam, laboratory, medical history, drug use, and healthcare utilization. Predictors were selected from candidate variables using a stepwise algorithm. Data were split into training and validation set. Model performance was evaluated by Brier score (BS) and C statistics. Confidence intervals (CI) was calculated using a bootstrap method. Decomposition analysis was conducted to assess the predictor contribution. External validation was performed on patient-level data of HARMONY Outcome clinical trial. A total of 6,006 diabetes patients free of CKD at baseline were used for model development, with a median follow-up of 3 years and 2,257 new onset CKD events. The CKD risk model identified age at T2D diagnosed, smoking status, BMI, HDL, VLDL, ALT, eGFR, UACR, hypoglycemia event, retinopathy event, CHF event, CHD history, antihyperlipidemic drug use, antihypertensive drug use, and hospitalization. The model demonstrated good discrimination (C-statistics 0.828 [95% CI 0.812-0.845]) and calibration (BS 0.0552 [95% CI 0.0474-0.0593]) performance. UACR, eGFR, and CHF event were the top 3 factors that contributed most to the prediction. A total of 8,221 patients free of CKD was selected from HARMONY Outcome trial with 1,288 CKD events and median follow-up of 2 years. The model demonstrated acceptable discrimination (C-statistics: 0.772 [95% CI 0.767-0.805]) and calibration (BS: 0.0504 [95% CI 0.0477-0.0531]) in external data. A risk prediction of incident CKD among T2D patients was developed and validated for use in decision support of CKD prevention.

Disclosure
Y. Lin: None. H. Shao: Board Member; BRAVO4HEALTH, LLC. A. H. Anderson: 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. V. Batuman: None. L. Shi: None.
110-LB: Management of Alpelisib-Induced Hyperglycemia
Authors: WEINTRAUB MICHAEL , LIU DAZHI , FLORY JAMES 
Published: May 2022

The phosphoinositide 3-kinase (PI3K) pathway is a common target for oncologic therapies and mediates much of insulin’s action. The PI3Kα inhibitor alpelisib is effective in advanced breast cancer but causes hyperglycemia in up to 80% of patients. The FDA label recommends metformin as first-line treatment of alpelisib-induced hyperglycemia. There is no consensus on other options. This is a single-center, retrospective review of new alpelisib users at a cancer center in 2021. Manual chart review for periods of exposure to alpelisib and antidiabetic drugs identified 67 patients newly started on alpelisib. Average age was 59 years. Median exposure time to alpelisib was 103 days. Antidiabetic drugs were prescribed in 48% (32/67) of patients, with 25% (17/67) using 2 or more. Of patients who stopped alpelisib, 14% (5/35) were primarily due to hyperglycemia. Hyperglycemia was a contributing cause in another 3 cases. The only antidiabetic drugs significantly associated with glucose reduction in multivariable analysis were metformin (26 mg/dL reduction, 95% CI 6.4 - 45.6) and SGLT2 inhibitors (74 mg/dL reduction, 95% CI 42 - 104) . Diabetic ketoacidosis (DKA) occurred in 6% (4/67) of patients. There was a higher rate of DKA among SGLT2 inhibitor users compared to nonusers (p=0.019) . SGLT2 inhibitors are effective as second-line to metformin for alpelisib-induced hyperglycemia but with a higher rate of DKA.

Disclosure
M. Weintraub: None. D. Liu: Consultant; Invitae Corporation. J. Flory: None.

Funding
P30 CA008748
1101-P: Cardiovascular Risk Factors and Intraoperative Hypotension Predicted Development of Insulin Deficiency and Diabetes after Pancreatectomy
Authors: MOON SEOIL , LEE JUN SUH , SOHN HEEJU , HAN YOUNGMIN , KIM HONGBEOM , KWON WOOIL , YOON YOO-SEOK , HAN HO-SEONG , OH TAE JUNG , PARK KYONG SOO , JANG HAK CHUL , JANG JIN-YOUNG , JUNG HYE SEUNG 
Published: May 2022

Objective: Ischemia in pancreatic islets is critical to beta cell function, however, clinical evidences on the implications for diabetes are lacking. Pancreatectomy can induce diabetes, but the mechanisms are not clearly elucidated. Therefore, we examined if cardiovascular disease (CVD) risk factors and intraoperative ischemia, which could cause perfusion insufficiency in pancreatic islets, are associated with insulin deficiency and diabetes after pancreatectomy.
Methods: From 2 prospective cohorts of pancreatectomy since 2007, participants were enrolled who had pre-operative HbA1c &lt; 7% without antidiabetes. As for proximal pancreatectomy, those were selected whose HOMA-R increased after surgery. Insulin secretion was assessed by changes in HOMA-B for 1 year (ΔB) . The participants were divided into low- and high-ΔB groups, with stratification by operation type, pre-operative HbA1c, HOMA-B, HOMA-R, and ΔR. Then CVD risk factors and intraoperative ischemic events were compared between the 2 groups, and evaluated for diabetes incidence.
Results: A total of 237 patients were enrolled (men 44%, age 56 years, HbA1c 5.6% in average) . Low-ΔB (median -32% of baseline) and high-ΔB (5%) groups showed comparable baseline metabolic variables. According to logistic regression analyses and Cox regression model, a composite of IGT, hypertension, dyslipidemia and a reduction in intraoperative systolic BP significantly decreased HOMA-B after 1 year (RR, 9.52; 95% CI, 1.14-79.3) , and increased diabetes incidence (HR, 3.3; 95% CI, 1.2-8.9) , after adjustment with age, sex, BMI, HbA1c and operation.
Conclusion: We observed that chronic ischemia suggested by CVD risk factors and intraoperative ischemic insult were linked to development of insulin deficiency and diabetes after pancreatectomy.

Disclosure
S.Moon: None. K.Park: None. H.Jang: None. J.Jang: None. H.Jung: Advisory Panel; Novo Nordisk, Research Support; Jeil Pharmaceutical Co., Novo Nordisk. J.Lee: None. H.Sohn: None. Y.Han: None. H.Kim: None. W.Kwon: None. Y.Yoon: None. H.Han: None. T.Oh: None.

Funding
National Research Foundation of Korea (2019R1A2C1007397)
111-OR: Response to COVID-Vaccination and Infection in Islet Transplant Recipients
Authors: JUENGEL BRADEN , BACHUL PIOTR J. , PEREZ-GUTIERREZ ANGELICA , BASTO LINDSAY , PEREA LAURENCIA , WANG LINGJIA , TIBUDAN MARTIN , BARTH ROLF , FUNG JOHN , WITKOWSKI PIOTR 
Published: May 2022

Background: Since response to COVID-vaccine among transplant recipients remains diminished comparing to general population, we decided to assess effect of COVID-specifically among islet transplant patients.
Methods: Response to COVID-infection and vaccine was assessed in a cohort of 20 islet transplant recipients: N=13 after islet transplant alone (ITx) , N=7 with islet after kidney (IAK) or pancreas after islet transplantation (PAI) . The median age was 48 years (25-62) . Maintenance immunosuppression included tacrolimus and an antimetabolite in addition to 5mg of Prednisone in IAK and PAI recipients. Nine patients received booster.
Results: Seven patients (38%) chose not to be vaccinated and 4 (57%) of them remained COVID-free with no SARS-CV-2 Spike total antibody (Spike ab) present in their blood. The other three patients (43%) developed only mild symptoms of infection with a high level of Spike ab (&gt;2,500 U/ml) afterwards. In contrast, all remaining 13 patients (62%) , who were vaccinated while on immunosuppression for a median of 7 years (0.5-16) , remained COVID-free (p=0.11, Fischer) . The level of Spike ab in response to vaccine varied: undetected- (N=4) , in range 1-100U/ml (N=6) , around 400U/ml (N=2) , and above 2,500U/ml (N=1) . Presence of 5mg of Prednisone did not affect the outcomes. Booster was administered in patients and increased the level of Spike ab above 100U/ml in all of them, in 7 (78%) to over 2,500 U/ml. One patient responded neither to vaccine nor to booster. There were no SAEs related to the vaccination or booster. Islet graft function remained stable in all but one patient after initial vaccination or COVID-19.
Conclusion: Nearly half of unvaccinated islet transplant recipients developed Covid-19, however, all of them presented only with mild symptoms. In contrast, none of vaccinated transplant patients developed COVID-infection with 69% rate of seroconversion. Booster increased level of the Spike ab in those patients who responded to the original vaccination.

Disclosure
B.Juengel: None. P.Witkowski: Advisory Panel; Sernova, Corp., Vertex Pharmaceuticals Incorporated. P.J.Bachul: None. A.Perez-gutierrez: None. L.Basto: None. L.Perea: None. L.Wang: None. M.Tibudan: None. R.Barth: None. J.Fung: n/a.

Funding
NIDDK P30 DK020595
112-OR: Metabolic Outcomes One Year after Total Pancreatectomy with Islet Autotransplantation after Early Pump Initiation
Authors: TELLEZ SIOBHAN E. , HORNUNG LINDSEY , COURTER JOSHUA D. , ABU-EL-HAIJA MAISAM , NATHAN JAIMIE D. , LAWSON SARAH , ELDER DEBORAH A. 
Published: May 2022

Background: We previously published that insulin pump initiation immediately after IV insulin therapy was associated with improved post-surgical glycemic outcomes compared to multiple daily injections (MDI) in pediatric patients following total pancreatectomy with islet autotransplantation (TPIAT) . We investigated metabolic outcomes of this population at 1 year post-TPIAT to assess if the improved outcomes in the early pump group were sustained over time.
Methods: We retrospectively reviewed 40 patients post-TPIAT previously studied at days post-surgery (14 used MDI and 26 used pump therapy immediately post-ICU, all discharged on pump therapy) . Data analyzed included: demographics, islet equivalents per kilogram (IEQ/kg) transplanted, exogenous insulin use, and baseline vs. 1 year (via mixed meal testing) HgA1C, fasting glucose, insulinogenic index and area under the curve (AUC) for insulin and c-peptide.
Results: More patients were off insulin at 1 year in the early pump group compared to the MDI group (43% vs. 14%, p=0.08) . Of all patients off insulin, 100% of the early pump users weaned off by 6 months post-TPIAT compared to 30% of the MDI users. Two known variables associated with favorable insulin outcomes, lower age and higher IEQ/kg were not significantly different between groups. Fasting glucose was lower in the early pump group compared to the MDI group (median 97.5 vs. 122 mg/dL, p=0.01) while AUC c-peptide was greater in early pump users at 1 year post-TPIAT but did not reach significance (median 65.3 vs. 49.5 ng/mL x minutes, p=0.07) . Other metabolic outcomes did not differ between groups.
Conclusion: Despite lower median age and higher IEQ/kg in the MDI group, the early pump group had a lower fasting glucose. Though not significant, the early pump group had a higher proportion off insulin and greater AUC c-peptide secretion. This study was limited by sample size. Early pump use may have long term benefits in post-TPIAT endogenous insulin secretion.

Disclosure
S.E.Tellez: None. L.Hornung: None. J.D.Courter: None. M.Abu-el-haija: None. J.D.Nathan: None. S.Lawson: None. D.A.Elder: None.
1120-P: Pilot Study Comparison of Newly Developed Pastry Sugar Tolerance Test with the OGTT: Africans in America Study
Authors: DUHUZE-KARERA M GRACE , YANG SHANNA , SCHENK BLAYNE R. , WENTZEL ANNEMARIE , PATTERSON ARIELLE , WALDMAN ZOE C. , DUBOSE CHRISTOPHER , MABUNDO LILIAN , JAGANNATHAN RAM , COURVILLE AMBER B. , SUMNER ANNE E. 
Published: May 2022

As undiagnosed diabetes (DM) rises in Africa and A1C performs suboptimally, attention turns to the OGTT. Obtaining Glucola (75g glucose) for the OGTT is difficult. Analyzing Africans in America data, we previously found that duplicate OGTT were highly reproducible for DM detection (k=0.84) ; and moderate for preDM (k=0.51) . Diagnostic reproducibility for preDM was lowest if fasting glucose was 90-1mg/dL (OR: 5, P=.02) . In the current study, 12 Africans had an OGTT and 1 week later a Pastry Sugar Tolerance Test (PSTT) with pastry sugar (75g glucose) which is inexpensive and widely available (Figures 1 & 2) . DM reproducibility was excellent (k=0.99) , and moderate for preDM (k=0.40) . The three individuals who transitioned out of preDM had fasting glucose of 90-99 mg/dL. For detecting DM, the PSTT may become an OGTT alternative.

Disclosure
M. Duhuze-Karera: None. S. Yang: None. B.R. Schenk: None. A. Wentzel: None. Z.C. Waldman: None. C. DuBose: None. L. Mabundo: None. R. Jagannathan: None. A.B. Courville: None. A.E. Sumner: None.
1121-P: The Combination of the ELF and FIB-4 Scores Have High Predictive Performance for Significant or Advanced Fibrosis in Patients with NAFLD
Authors: YOUNOSSI ZOBAIR , FELIX SEAN , JEFFERS THOMAS , YOUNOSSI ELENA , NADER FATEMA , RACILA ANDREI , LAM BRIAN P. , STEPANOVA MARIA 
Published: May 2022

Background: Patients with nonalcoholic fatty liver disease (NAFLD) and fibrosis stage ≥ 2 (F2-F4) are at risk for adverse outcomes and considered to be candidates for clinical trials. We aimed to use two NITs combined to rule in and rule out fibrosis stages F2-F4 among patients with NAFLD.
Methods: Data were collected from patients with NAFLD diagnosis. The Enhanced Liver Fibrosis (ELF) and FIB-4 NITs were calculated. Liver biopsies were read by 1 hepatologist; scored by NASH CRN criteria. Significant fibrosis stage was ≥ F2, advanced fibrosis was ≥ F3.
Results: There were 463 NAFLD patients: 48±13 years old, 31% male, 35% type 2 diabetes, 39% had significant fibrosis and 24% advanced fibrosis. In comparison to those without significant fibrosis, patients with significant fibrosis were older (mean age 52 vs. 45 years) , more commonly male (38% vs. 26%) , and had more components of metabolic syndrome (type 2 diabetes, hypertension, hyperlipidemia) as well as higher ELF and FIB-4 scores; similar trends were observed for patients with vs. without advanced fibrosis (p&lt;0.05) . The performance of the two NITs in identifying NAFLD patients with significant fibrosis was as follows: AUC (95% CI) = 0.78 (0.74-0.82) for ELF, 0.79 (0.75-0.83) for FIB-4; for advanced fibrosis AUC = 0.81 (0.77-0.85) for ELF, 0.83 (0.79 - 0.86) for FIB-4. A combination of ELF score ≥9.8 and FIB-4 ≥1.96 returned PPV of 95% which can reliably rule in significant fibrosis (sensitivity 22%, specificity &gt;99%) , while an ELF score ≥7.7 and FIB-4 ≥0.30 had NPV of 95% which can be used to rule out significant fibrosis (sensitivity 98%, specificity 22%) . For advanced fibrosis, similar rules were ELF ≥9.8 and FIB-4 ≥2.90 (PPV 95%, sensitivity 18%, specificity &gt;99%) to rule in; ELF ≥7.2 and FIB-4 ≥0.74 (NPV 95%, sensitivity 92%, specificity 49%) to rule out.
Conclusions: The combination of ELF and FIB-4 can provide an easy algorithm with high predictive value to detect significant or advanced fibrosis in NAFLD.

Disclosure
Z.Younossi: Consultant; Bristol-Myers Squibb Company, Gilead Sciences, Inc., Intercept Pharmaceuticals, Inc., Madrigal Pharmaceuticals, Inc., Merck & Co., Inc., Novartis Pharmaceuticals Corporation, Novo Nordisk, Quest Diagnostics, Siemens. S.Felix: None. T.Jeffers: Stock/Shareholder; Neurometrix. E.Younossi: None. F.Nader: None. A.Racila: None. B.P.Lam: Consultant; Intercept Pharmaceuticals, Inc. M.Stepanova: None.