bluuebunny/crossref_metadata_2025_split huggingface dataset:
255-OR: Postpartum Weight Retention and the Early Evolution of Cardiovascular Risk over the First 5 Years after Delivery
Authors: KRAMER CAROLINE K. , YE CHANG , HANLEY ANTHONY , CONNELLY PHILIP W. , ZINMAN BERNARD , RETNAKARAN RAVI 
Published: June 2023

The cumulative effect of postpartum weight retention from each pregnancy in a woman’s life may contribute to her risk of ultimately developing cardiovascular (CV) disease and type 2 diabetes. However, there is limited direct evidence supporting this hypothesis. Thus, we sought to characterize the impact of postpartum weight retention on the trajectories of cardiometabolic risk factors over the first 5 years after pregnancy. Three-hundred-and-thirty women underwent cardiometabolic characterization in pregnancy and at 3-months, 1-yr, 3-yr, and 5-yrs postpartum. They were stratified into 3 groups based on the magnitude of weight change between pre-pregnancy and 5-yrs postpartum as follows: weight gain &lt;0% (n=100), weight gain 0-6% (n=110), and weight gain &gt;6% (n=120). CV risk factors did not differ between these groups at 1-yr postpartum but showed a stepwise worsening across the groups at 3- and 5-yrs (Fig). Specifically, adverse lipids, insulin resistance, and CRP progressively worsened from the weight gain &lt;0% group to weight gain 0-6% to weight gain &gt;6% (all p&lt;0.05). On logistic regression analyses of prediabetes/diabetes at 5-years postpartum, weight gain &gt;6% was shown to be significant (adjusted OR 3.40 [1.63 to 7.09]). In conclusion, postpartum weight retention predicts trajectories of enhanced CV risk and rising glycemia over the first 5-yrs after delivery.

Disclosure
C.K. Kramer: Research Support; Boehringer Ingelheim Inc. C. Ye: None. A. Hanley: None. P.W. Connelly: None. B. Zinman: Consultant; Abbott Diabetes, Eli Lilly and Company, Novo Nordisk A/S, Novo Nordisk Canada Inc., Boehringer Ingelheim Inc., Merck & Co., Inc. R. Retnakaran: Research Support; Boehringer Ingelheim/Mount Sinai Hospital, Novo Nordisk. Other Relationship; Sanofi, Eli Lilly and Company.
257-LB: Defining the Stage-Dependent Transcriptome and Methylome in the Mouse Liver during Perinatal Metabolic Maturation
Authors: YANO SEIICHI , SATO NAOICHI , ARAKI HIROMITSU , MIURA FUMIHITO , ITO TAKASHI , OGAWA YOSHIHIRO 
Published: June 2023

A mammalian liver serves as an extramedullary hematopoietic organ during fetus, and matures into a metabolic organ after birth, thereby adapting to the changes in nutritional environment. PPARα-dependent DNA demethylation upregulates hepatic fatty acid β-oxidation (FAO) genes in the postnatal mouse liver to produce energy from breast milk lipids. However, the detailed interaction between DNA methylation (DNAme) and gene expression in the liver through perinatal stages remain poorly understood. Here, we perform an integrative analysis of transcriptome and methylome of the mice liver at fetal, neonatal, and postweaning stages. While the level of global DNAme gradually increased from fetal to postweaning stages, we found a drastic loss of DNAme in specific regions that are associated with metabolic pathways such as FAO, gluconeogenesis, and amino acid metabolism within the neonatal stage in concordance with the activation of such metabolic processes. Moreover, in silico analysis predicted transcription factors, such as HNF4α, PPARα, NR1H2, and NR1H3, as key epigenetic regulators within lactation period. We also observed an inactivation of erythrocyte development with a concordant gain of DNAme. This analysis extends the epigenetic landscape for understanding the hepatic maturation during early life, and suggests the importance of lactation period in epigenetic regulation.

Disclosure
S. Yano: None. N. Sato: None. H. Araki: None. F. Miura: None. T. Ito: None. Y. Ogawa: None.
257-OR: Diabetic Kidney Disease (DKD) and Nonalcoholic Fatty Liver Disease (NAFLD) Confer Worsening All-Cause Mortality and Cardiovascular Disease (CVD) Risk in Type 2 Diabetes (T2D)
Authors: GAROFOLO MONIA , LUCCHESI DANIELA , GIAMBALVO MASSIMO , CAPOBIANCO MARTINA , FRANCESCONI PAOLO , PENNO GIUSEPPE , DEL PRATO STEFANO 
Published: June 2023

Aim: In T2D, the prevalence of NAFLD is 56-60% and approximately 40% have DKD; thus, a sizable proportion of subjects may have both conditions. We explored to which extent the coexistence of the two could further worsen mortality and CVD risk in T2D.
Methods: We recorded vital status and data for major CVD (the latter available for 98.5% subjects) were retrieved on December 31st, 2017. DKD (eGFR &lt;60 ml/min/1.73 m2 and/or ACR ≥30 mg/g) and NAFLD (fatty liver index ≥60) effects assessed by Kaplan-Meier curves and hazard ratios (HR, 95% CI) by adjusted Cox regressions.
Results: Distributions of NAFLD and DKD are reported in Table. HbA1c was similar in subgroups; NAFLD had worse metabolic and inflammatory profile, DKD higher hypertension rate. Over a follow-up of 13.1±2.8 years, we recorded 229 deaths (23.8%) and 273 major CV (28.8%). Rates of other outcomes are reported in Table. Death rate was 16.3, 21.8, 25.6 and 43.8% (p&lt;0.0001) across groups with full adjusted HR (Model 2), of 1.50 (1.07-2.10, p=0.020) in NAFLD only, 1.15 (0.58-2.27, p=0.697) in DKD only, and 2.73 (1.90-3.93, p&lt;0.0001) in DKD/NAFLD. Table reports effects of DKD-NAFLD combinations on CV outcomes.
Conclusions: DKD and NAFLD concur increasing mortality and CVD risk in T2D patients. Monitoring and managing DKD and NAFLD is required to prevent CVD and reduce mortality.

Disclosure
M.Garofolo: Consultant; Novo Nordisk, Employee; Eli Lilly and Company. D.Lucchesi: None. M.Giambalvo: None. M.Capobianco: None. P.Francesconi: None. G.Penno: Advisory Panel; Eli Lilly and Company, Bayer Inc., Consultant; Novo Nordisk, AstraZeneca, Boehringer Ingelheim Inc. S.Del prato: Advisory Panel; Abbott Diagnostics, Altimmune, Amarin Corporation, Applied Therapeutics Inc., Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk A/S, Vertex Pharmaceuticals Incorporated, Novartis, Consultant; A. Menarini Diagnostics, Research Support; AstraZeneca, Boehringer Ingelheim International GmbH, Speaker's Bureau; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk A/S, Sanofi.
258-OR: Type 2 Diabetes and Chronic Kidney Disease as Predictors of Cardiovascular Mortality in Patients with Established Cardiovascular Disease
Authors: SPRENGER LUKAS , MAECHLER MAXIMILIAN , VONBANK ALEXANDER , LARCHER BARBARA , MADER ARTHUR , PLATTNER THOMAS , LEIHERER ANDREAS , MUENDLEIN AXEL , DREXEL HEINZ , SAELY CHRISTOPH H. 
Published: June 2023

This study aims to investigate the single and joint effects of T2DM and CKD on cardiovascular mortality in patients with established cardiovascular disease. We prospectively investigated 1755 patients with established cardiovascular disease, angiographically proven coronary artery disease (CAD) or sonographically proven peripheral artery disease (PAD), over 10.8±5.0 years. Cardiovascular death occurred more frequently in T2DM patients (n=568) than in nondiabetic subjects (30.4% vs 18.1%, p&lt;0.001) and in patients with CKD (eGFR&lt;60ml/min/1.73m2; n=300) than in those without CKD (35.7% vs 19.3%, p=0.001). When both T2DM and CKD were considered, 1015 subjects had neither T2DM nor CKD, 440 had T2DM but not CKD, 172 did not have diabetes but had CKD, and 128 had T2DM and CKD. Compared to the incidence of cardiovascular death among patients with neither T2DM nor CKD (15.8%), cardiovascular death occurred more frequently in patients with T2DM who did not have CKD (27.4%; p&lt;0.001) as well as in nondiabetic patients with CKD (31.6%; p&lt;0.001); the incidence of cardiovascular death was highest in patients with T2DM and CKD (41.3%; p&lt;0.001), in whom it was higher than in those with T2DM but not CKD (p&lt;0.001) or those without T2DM but with CKD (p=0.039); the incidence of cardiovascular death did not differ significantly between nondiabetic CKD patients and T2DM patients who did not have CKD (p=0.075). In Cox regression analysis, T2DM (HR 1.78 [1.43-2.21]; p&lt;0.001) and CKD (HR 1.74 [1.36-2.23]; p&lt;0.001) proved to be mutually independent predictors of cardiovascular mortality after multivariate adjustment for age, sex, BMI, history of smoking, hypertension, LDL-C and HDL-C. We conclude that T2DM and CKD in patients with established cardiovascular disease are mutually independent predictors of cardiovascular mortality. Cardiovascular disease patients with both CKD and T2DM are at an extremely high risk for cardiovascular death.

Disclosure
L. Sprenger: None. M. Maechler: None. A. Vonbank: None. B. Larcher: None. A. Mader: None. T. Plattner: None. A. Leiherer: None. A. Muendlein: None. H. Drexel: None. C.H. Saely: None.
259-OR: Arterial Stiffness and Diabetes-Associated Complications in the SEARCH for Diabetes in Youth Study
Authors: BRADY RYAN , URBINA ELAINE M. , GAO ZHIQIAN , DOLAN LAWRENCE M. , DABELEA DANA , LUSTIGOVA EVA , MOTTL AMY K. , PIHOKER CATHERINE , REYNOLDS KRISTI , SANCRAINTE LEANNE , SHAH AMY S. 
Published: June 2023

Arterial stiffness and vascular complications contribute to the burden of disease in diabetes, and it is unclear how they relate to each other. The relationship between arterial stiffness, an early marker of cardiovascular disease, and microvascular complications has not been comprehensively assessed in youth-onset diabetes. This study included 1226 individuals (mean age 22.8 years, 58% female, 53% Non-Hispanic White, 22% Non-Hispanic Black, 20% Hispanic) with type 1 (n=999) and type 2 (n=227) diabetes. Arterial stiffness measures included pulse wave velocity for carotid-femoral (PWVcf), carotid-radial (PWVcr), and femoral-foot (PWVff) and augmentation index (AIx). Microvascular complications included diabetic kidney disease, peripheral neuropathy, and retinopathy. Logistic regression was used to analyze associations between arterial stiffness and microvascular complications. PWVcf and AIx were associated with higher odds of having any microvascular complication, p&lt;0.05 (Table). PWVcf, PWVff, and AIx were each associated with diabetic kidney disease. PWVcf was associated with peripheral neuropathy and PWVcr and AIx were associated with retinopathy. Arterial stiffness is related to diabetes microvascular complications in youth-onset diabetes. Future work will determine whether arterial stiffness is a marker for early onset and progression of microvascular complications.

Disclosure
R.Brady: None. L.Sancrainte: None. A.S.Shah: None. E.M.Urbina: Advisory Panel; Astellas Pharma Inc., Other Relationship; Targus Medical, Inc. Z.Gao: None. L.M.Dolan: None. D.Dabelea: None. E.Lustigova: None. A.K.Mottl: Advisory Panel; Bayer Inc., Chinook Therapeutics Inc., Consultant; Bayer Inc., Research Support; Bayer Inc., Alexion Pharmaceuticals, Inc., Pfizer Inc., Boehringer Ingelheim Inc., Calliditas. C.Pihoker: None. K.Reynolds: Research Support; Novartis Pharmaceuticals Corporation.

Funding
National Institute of Diabetes and Digestive and Kidney Diseases (1R01DK127208-01); Centers for Disease Control and Prevention (00097, DP-05-069, DP-10-001)
262-LB: Fasting Intact Insulin by Liquid Chromatography–Tandem Mass Spectrometry (LC-MS/MS) as a Predictor of Nonalcoholic Fatty Liver Disease in Pediatric Patients
Authors: HUNEAULT HELAINA , AYINDE DAMILOLA , HE ZHULIN , RAMIREZ ANA M. , COHEN CATHERINE C. , MCPHAUL MICHAEL J. , VOS MIRIAM B. 
Published: June 2023

Background: Recent research in adults has shown fasting intact insulin levels measured by mass spectrometry can predict nonalcoholic fatty liver disease (NAFLD) in patients without diabetes; however, there is limited research in children. This study aimed to evaluate fasting intact insulin by LC-MS/MS as a predictive biomarker of NAFLD in adolescents.
Methods: This retrospective, cross-sectional study was based on data from four previously conducted studies. Existing clinical laboratory values included fasting intact insulin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), C-peptide, and the insulin resistance (IR) score. Hepatic fat was assessed by magnetic resonance imaging proton density fat fraction (MRI-PDFF) or MR spectroscopy (MRS). NAFLD was defined as intrahepatic fat of ≥5%.
Results: A total of 73 children were included in the analysis (64% male; 13.9 ± 2.8 years of age; body mass index (BMI) 29.1 ± 8.5 kg/m2; 56% with NAFLD). Intact fasting insulin, C-peptide, AST, ALT, and IR scores were higher in children with NAFLD compared to non-NAFLD children (P&lt;0.05). Fasting intact insulin measurements predicted NAFLD (area under the receiver operating characteristic curve [AUROC] of 0.83 [95%CI, 0.73-0.93]). When combined with ALT (intact insulin (μU/mL) × ALT (× U/L)), the combined biomarker slightly improved the prediction of NAFLD (AUROC 0.89 [0.81-0.96]), with positive and negative predictive values of 79% and 100%, respectively. Based on maximizing Youden's index, the optimal cutoff points to predict NAFLD were 13.0 μU/mL for intact insulin and 380 μU/mL × U/L for intact insulin × ALT.
Conclusion: Our findings support that fasting intact insulin alone, or combined with ALT (intact insulin × ALT), show promise as predictive biomarkers for pediatric NAFLD with high positive and negative predictive values. Additional studies are needed to validate these findings in other pediatric populations.

Disclosure
H. Huneault: None. D. Ayinde: None. Z. He: None. C. C. Cohen: None. M. J. McPhaul: Employee; Quest Diagnostics. M. B. Vos: Consultant; Boehringer Ingelheim International GmbH, BMS, Intercept Pharmaceuticals, Inc., Novo Nordisk, ProSciento, Eli Lilly and Company. Research Support; Quest Diagnostics, TARGET PharmaSolutions, Inc.

Funding
National Institutes of Health (R01DK125701); Georgia Clinical Translational Science Alliance (UL1TR002378)
263-LB: Food Intake Impacts on Insulin Secretion, Resistance, and Glucose Variability in Free-Living Individuals with Type 2 Diabetes Mellitus
Authors: PAULA COMARELLA ANA , BELFORT-DEAGUIAR RENATA 
Published: June 2023

Changes in eating habits and physical activity are the cornerstone of treatment of type 2 diabetes mellitus (T2D). Dietary composition has important effects on the postprandial glucose and insulin response, but little is known about its impact in a real-life context. We analyzed the self-reported daily food composition of 13 individuals with obesity and T2D not on insulin (7F/6M, age 48±9, BMI 33±2, A1C 7±1) with ASA24 (NIH), while wearing continuous glucose monitor (Dexcom G4) for 3±1 days. They also underwent an oral glucose tolerance test to explore correlations with standard indices of insulin secretion and sensitivity. The mean consumption per meal of total calorie was: 534±110Kcal, carbohydrate: 51±19g, total grains: 1.78±0.66g (refined 1.61±0.59g, whole 0.17±0.18g), total fat: 25±6g (10±3.17g monounsaturated fat), and protein: 24±7g. We observed a positive correlation between average intake of total and monounsaturated fat with the insulin secretion index (ρ= 0.630, p=0.02,) and Disposition Index (DI) (p=0.001, ρ=0.821). An inverse relationship between the consumption of total and refined grains was noted with the insulin sensitivity indexes (p=0.01, ρ= -0.663); as well as with whole grains and DI (p=0.03, ρ= -0.601). We documented glycemic variability (GV) related to meal nutrient intake through macro program: CGM peak and nadir analysis, Microsoft Excel. Total and monounsaturated fats correlated with lower GV (p=0.02), while total and refined grains were associated with greater GV (p&lt;0.03). Glucose nadir after a meal and glucose at the time of the meal inversely correlated with insulin secretion indexes and with DI (p&lt;0.05). These data suggest, in a real-life context, the impact of food composition on modulation of GV, with fats being associated with greater insulin secretion and refined grains with decreased insulin sensitivity, reinforcing the importance of the effect of diet on management of diabetes.

Disclosure
A. Comarella: None. R. Belfort-DeAguiar: Research Support; Fractyl Health, Inc., Silver Palate Kitchens.

Funding
National Institutes of Health (DK098286-02)
265-LB: Human Skeletal Muscle Mitochondrial Dynamics across the Insulin-Sensitivity Spectrum
Authors: AXELROD CHRISTOPHER L. , DANTAS WAGNER S. , ZUNICA ELIZABETH R.M. , BELMONT KATHRYN , HEINTZ ELIZABETH C. , DAVULURI GANGARAO , MEY JACOB T. , ERICKSON MELISSA , FUJIOKA HISASHI , FEALY CIARAN , HOPPEL CHARLES L. , KIRWAN JOHN P. 
Published: June 2023

Introduction: There is immense dispute as to whether perturbations in skeletal muscle mitochondrial function contribute to the onset and progression of type 2 diabetes (T2D). The purpose of this study was to examine differences in mitochondrial dynamics, structure, and energetic function in humans across the spectrum of insulin sensitivity.
Methods: 58 sedentary adults (37±12 years) were enrolled into one of three groups based upon the following criteria: (1) healthy weight without T2D (HW; BMI: 22.6±1.8 kg/m2 and HbA1c: 5.0±1.1 %); (2) overweight/obesity without T2D (Ov/Ob; BMI: 32.6±3.3 kg/m2 and HbA1c: 5.6±0.4 %); or (3) overweight/obesity with T2D (T2D; BMI: 36.1±6.5 kg/m2 and HbA1c: 6.9±0.9 %). Participants underwent a 3-day inpatient stay consisting of body composition (DXA), aerobic capacity (VO2MAX), and insulin sensitivity (hyperinsulinemic euglycemic clamp). Prior to insulin sensitivity testing, a skeletal muscle biopsy was obtained for determination of mitochondrial dynamics (Western blot), DNA content (qPCR), ultrastructure (electron microscopy), and respiratory capacity (respirometry). Comparisons were made using a one-way ANOVA with contrasts.
Results: Insulin sensitivity and aerobic capacity were lower in Ov/Ob and T2D compared to HW. Markers of mitochondrial fission were higher in T2D (Drp1Ser616, MiD49), and fusion lower in T2D and Ov/Ob (Mfn2). The mitophagy marker Parkin was higher in T2D only while Pink1 was lower in T2D relative to Ov/Ob but not HW. The autophagy marker LC3II was higher in Ov/Ob. Mitochondrial content was lower in Ov/Ob and T2D relative to HW. Mitochondrial respiratory capacity was similar between groups.
Conclusions: T2D is associated with heightened expression of proteins required for mitochondrial quality control and reduced mitochondrial volume despite intact respiratory function. These data support the notion that mitochondria adapt to progressive insulin resistance by increasing fragmentation to maintain bioenergetic capacity.

Disclosure
C. L. Axelrod: None. C. Fealy: Employee; Mission Therapeutics. C. L. Hoppel: None. J. P. Kirwan: None. W. S. Dantas: None. E. R. M. Zunica: None. K. Belmont: None. E. C. Heintz: None. G. Davuluri: None. J. T. Mey: None. M. Erickson: None. H. Fujioka: None.

Funding
National Institutes of Health (DK108089, GM104940)
265-OR: Effectiveness of a Virtual Diabetes Clinic in a Racially Diverse Population
Authors: WARING AVANTIKA C. , SCHANDL BERNHARD , HEINEMANN LUTZ , HOFNER MICHAEL , GEEVARGHESE PAUL 
Published: June 2023

Objective: To evaluate the outcome of a novel virtual diabetes clinic on glycemic control in a diverse group of patients with type 2 diabetes.
Methods: 86 patients completed a medical questionnaire, which generates recommendations based on clinical algorithms. All participants had at least one physician consult and unlimited access to a virtual care team (RDs, RN, and PharmD). Participants self-identify race, insurance status, prior conditions and medications. HbA1c levels were documented when joining the program (patient-reported from prior lab or an initial result obtained as part of the program). Subsequent HbA1c results were measured through the lab program (dried blood spot or in-home phlebotomy) or were confirmed results from a non-integrated lab. We compared the first and last HbA1c levels using a paired t-test. In addition, we evaluated the percentage of participants whose HbA1c levels were lowered to target (from &gt;7% to ≤7%).
Results: Participants were highly diverse, with 45.4% self-identifying as non-white. During the study period, 21 of 86 participants received at least one new generic medication or dose adjustment. Among the 24 patients (27.9%) with an initial HbA1c &gt;8%, there was a significant improvement in HbA1c (mean decline 1.7, from 9.5% to 7.8%, p&lt;0.01). Upon joining the program, 39 (45%) participants had an HbA1c &gt;7%; at the end of the study period (ave. 148 days), only 24 (27.9%) had an HbA1c &gt;7% (p=0.018, X2-test).
Conclusions: Participation in a virtual diabetes clinic improved HbA1c significantly over a 3-6 month period in a racially and ethnically diverse population. Prospective studies are needed to confirm the initial effectiveness of a virtual clinic for diabetes over longer periods. Approximately 50% of program members are uninsured and pay an affordable monthly fee. This initial effectiveness suggests that affordable cash-pay virtual clinic solutions may be an efficient and convenient option for patients with diabetes who experience barriers to accessing traditional care.

Disclosure
A.C.Waring: Employee; 9amHealth. B.Schandl: Employee; mySugr, Roche Diabetes Care, Stock/Shareholder; Boydsens, 9amHealth Inc. L.Heinemann: Consultant; 9am.health. M.Hofner: Consultant; 9amHealth Inc. P.Geevarghese: Employee; 9amHealth, Roche Diabetes Care.
266-OR: Development of an EMR Dashboard to Enable Remote Patient Monitoring and Proactive Diabetes Care
Authors: LYONS SARAH , SONABEND RONA Y. , SCHWARTZ DAVID D. , TIMMONS KELLY D. , DESALVO DANIEL 
Published: June 2023

We developed a pediatric T1D remote patient monitoring (RPM) program, ROCKET T1D (Remote Outreach & Care for Kids’ Empowerment and Technology use in T1D), with the aims of supporting youth at risk for chronic hyperglycemia and DKA and their families to leverage emerging technology, improve self-management habits, and achieve self-care goals to thrive with T1D. The ROCKET T1D program, supported by diabetes educators and social workers, includes a proactive “Launch Phase” with frequent virtual touchpoints for education, psychosocial support, and therapy adjustments, followed by an “Orbit Phase” with a less frequent remote data review and therapy adjustments. Prior to ROCKET T1D go-live, we developed an electronic medical record (EMR)-based diabetes registry with dashboards to enable remote monitoring, visualization of a validated DKA risk score and clinical data (e.g., pump/CGM use, A1C, etc.) to quickly assess clinical progress and facilitate targeted outreach. Patients are added to the ROCKET T1D Registry via the EMR’s “FYI Flag” feature, which allows visualization of progress through the Launch and Orbit Phases in the dashboard (Figure 1). We are actively working on automated integration of CGM data into ROCKET T1D dashboards to enable proactive outreach to patients at highest glycemic risk, with intent to optimize time in range and prevent DKA.

Disclosure
S.Lyons: None. R.Y.Sonabend: None. D.D.Schwartz: None. K.D.Timmons: None. D.Desalvo: Consultant; Dexcom, Inc., Research Support; Insulet Corporation.

Funding
The Leona M. and Harry B. Helmsley Charitable Trust (2206-05307)