bluuebunny/crossref_metadata_2025_split huggingface dataset:
160-LB: Age-Related Adipose Tissue Fibrosis and Neuropathy in the Genetically Diverse HET3 Mouse
Authors: WILLOWS JAKE , MISHRA GARGI , BLASZKIEWICZ MAGDALENA , TOWNSEND KRISTY L. 
Published: May 2022

Changes in adipose tissue's extracellular matrix, as with fibrosis, inhibits the tissue's ability to shrink and expand as needed, resulting in sheer stress on adipocytes and chronic inflammation, as well as decreased insulin sensitivity. With aging, a state of metabolic dysregulation and increased incidence of insulin resistance, we have observed a reduction in adipose innervation. This ‘adipose neuropathy' likely poses a physiological challenge for tissue metabolic function and glucose homeostasis, as has been observed in adipose denervation studies. Using second-harmonic generation label-free imaging of adipose collagen and advanced image co-localization techniques, we found that obese adipose tissue exhibits higher co-localization of nerves with collagen fibers, indicating that changes in tissue fibrosis may tie mechanistically with tissue neuropathy. We compared C57BL/6J mice with the more genetically diverse HET3 mouse model that is used by the NIA's intervention testing program, to investigate age-related neuropathy and adipose fibrosis. We found that HET3 mice displayed mitigated neuropathy phenotypes in skin, muscle and adipose, compared to inbred C56BL/6J mice. Tissue fibrosis was significantly increased with age in subcutaneous and visceral white adipose depots of both strains of mice. Using birefringence imaging, we found that the relative distribution of type I / thick filament collagen increased with age while type III / thin filament collagen decreased. Gene expression by qPCR revealed significant increases in collagen genes Col1a1, Col3a1, and Col5a1 in adipose with age. Despite its success as a longevity treatment, the mTOR inhibitor rapamycin had little to no effect on reducing or preventing the onset of neuropathy in HET3 aged mice, and importantly it worsened the fibrotic phenotype with increased type 1 collagen in adipose. Together, we found that rapamycin's longevity effects are uncoupled from healthspan producing effects, with detrimental impacts on adipose fibrosis that may impact age-related insulin resistance.

Disclosure
J. Willows: None. G. Mishra: None. M. Blaszkiewicz: None. K. L. Townsend: Other Relationship; Neuright, Inc.

Funding
American Heart Association (AHA) Collaborative Sciences Award (18CSA34090028)
160-OR: Effects of Bariatric Surgery on Early Postprandial Glucose Turnover Assessed through a Dual Tracer Study
Authors: SCHIAVON MICHELE , TRIPYLA AFRODITI , HERZIG DAVID , THOMAS ANDREAS , BALLY LIA , MAN CHIARA DALLA 
Published: May 2022

Postbariatric hypoglycemia (PBH) is a complication of bariatric surgery, mainly Roux-en-Y bypass (GB) . Surgery-induced changes in the gastrointestinal anatomy affect nutrient passage, absorption kinetics and may contribute to PBH. Here we aim to explore early postprandial glucose turnover in GB subjects with confirmed PBH vs. unaffected operated and non-operated controls. A total of 32 subjects (age = 48 [32,53] y, BMI = 29 [25,32] kg/m2; median [IQR]) , belonging to 4 matched (age/BMI/sex) groups (GB with PBH [GB-PBH] and unaffected [GB], sleeve gastrectomy [SG] and non-operated controls [C]) , ingested 15g of labeled [U-13C]-glucose (t=0 min) , 100 min after initiation of a primed constant infusion (30 μg/kg/min) of [6,6-2H2]-glucose. Plasma glucose and enrichments were measured, allowing the calculation of postprandial glucose fluxes, i.e. rates of meal glucose appearance (Rameal) , endogenous glucose production (EGP) and glucose disappearance (Rd) , together with insulin concentration. iAUC (0-20 min) of plasma glucose was significantly higher in both GB groups than C (GB-PBH: 36 [29,38], GB: 38 [31,40], C: 9 [17,19] mmol/L*min; p&lt;0.01) . This was also the case for Rameal normalized to glucose dose (GB-PBH: 39 [34,42], GB: 42 [35,44], C: 20 [16,27] %; p&lt;0.03) and Rd normalized to basal (GB-PBH: 56 [19,83], GB: 65 [54,76], C: -8 [-20,21] %; p&lt;0.03) but not EGP, which was similarly suppressed in all groups. Finally, iAUC (0-20 min) of plasma insulin was significantly higher in GB and SG than C (GB: 657 [534,826], SG: 563 [351,822], C: 265 [192,310] μU/mL*min; p&lt;0.03) while GB-PBH failed to reach significance (477 [384,631] μU/mL; p=0.06) . After a small dose (15g) of oral glucose, early postprandial glucose exposure, Rameal and Rd were faster in GB subjects than C, while insulin exposure was higher in almost all operated groups vs. C. However, no difference between GB groups was observed, underscoring the multifactorial etiology of PBH.

Disclosure
M.Schiavon: None. A.Tripyla: None. D.Herzig: None. A.Thomas: None. L.Bally: None. C.Dalla man: Research Support; Becton, Dickinson and Company, Sanofi-Aventis Deutschland GmbH.

Funding
MIUR (Italian Minister for Education) under the initiative "Departments of Excellence" (Law 232/2016) and Swiss National Science Foundation (SNSF) PCEGP3_186978
168-LB: Presentation of New Onset Diabetes in Youth during the COVID-19 Pandemic
Authors: CITRON KATE , STEIN CHERYL R. , ILKOWITZ JENIECE , GONZALEZ JUANA E. , JOSEPH VANESSA , PAT GALLAGHER MARY 
Published: May 2022

Background: Early research suggests during the COVID-19 pandemic there was an increase in new onset diabetes mellitus (DM) and greater severity at presentation. We examined pandemic related trends of new onset DM among patients at a pediatric diabetes center in New York, NY.
Methods: We conducted a retrospective chart review of 168 youth 0-26 years old presenting with new onset DM from January 2019 to October 2021. We used chi-square statistics, t-tests, and ANOVAs to compare aspects of presentation by year of diagnosis, overall and type 2 DM (T2D) versus type 1 DM (T1D) .
Results: The number of patients presenting with new onset DM increased throughout this time, with 43 in 2019, 57 in 2020, and 68 in 2021. This increase was primarily driven by an increase in T2D (8 in 2019, 16 in 2020, 27 in 2021) . Patients with T2D had higher mean BMI percentile at presentation compared to T1D (97.5 vs. 42.9; p&lt;.001) . The mean BMI percentile of all patients increased (p for trend=0.02) and was higher in 2021 (67.8) compared to 2019 (50.1; p=0.02) . These differences, however, were not statistically significant when examined by DM type. There was no significant difference in severity of presentation based on HbA1C, DKA frequency or severity, lowest potassium level, or length of stay (LOS) . For example, among all patients in DKA, the prevalence of severe DKA was 53% in 2019, 62% in 2020, and 55% in 2021 (p=0.89) . Although numbers were small, there was a qualitative increase in LOS and decrease in bicarbonate level in patients with new onset T2D between 2019 and 2021.
Conclusions: In this population, the number of pediatric new onset DM increased during the COVID-19 pandemic. Cases of T2D increased by a greater degree than T1D which may explain the increased mean BMI percentile at diagnosis. There was no change in severity of DM presentation when examining multiple markers of severity. Further research is needed to understand if lifestyle changes during the pandemic may have impacted BMI and how this may relate to new onset pediatric DM, particularly T2D.

Disclosure
K. Citron: None. C. R. Stein: None. J. Ilkowitz: None. J. E. Gonzalez: None. V. Joseph: None. M. Gallagher: None.
169-LB: Structural Echocardiographic Abnormalities in T2D —Mexico Cohort of Take Care of Me Program
Authors: SAHAGUN-SANCHEZ GUILLERMO , GUTIÉRREZ-FAJARDO PEDRO , MEZA-LEDEZMA OMAR , RODRIGUEZ-VALADEZ FLORISA , LAVALLE-GONZALEZ FERNANDO J. , VAZQUEZ-MENDEZ ESTEFANIA 
Published: May 2022

Rationale: Due to gaps in detecting subclinical cardiac abnormalities in T2D, we evaluated prevalence and clinical manifestations of early echocardiographic (echo) abnormalities in primary care in Mexico.
Methods: Mexico cohort of the ongoing ‘Take CaRe of Me program’ enrolled 2760 people with T2D (between 7 Dec 2020 - 10 Dec 2021) and no cardiorenal disease per index visit history. We present descriptive data of documented echo performed by cardiologists as routine clinical care (499) in high-risk T2D identified by Systematic Coronary Risk Evaluation (ESC 2019) .
Results: With mean age of 54.2±11.4 years, 55.4% were females and 189 patients (37.9%) had echo abnormalities — left ventricular hypertrophy (21%, 105) , left atrial enlargement (24.2%, 121) , diastolic dysfunction (6.8%, 34) , pulmonary hypertension (5.4%, 27) and valvular disease (4.8%, 24) . Substantial proportion of people with echo abnormalities had high or very high CV risk (Table) . Overall, 23 people had presumptive diagnosis of pre-HF based on symptoms and echo. Per documented data, 18 people had HF with preserved ejection fraction (EF) , 4 had mid-range EF and 1 had reduced EF.
Conclusion: Structural abnormalities are prevalent in 37.9% of people with T2D referred for an echo, even in absence of symptoms. Timely diagnosis of silent structural heart abnormalities in T2D is an opportunity for using novel cardiorenal pharmacotherapy for preventing HF.

Disclosure
G. Sahagun-sanchez: None. P. Gutiérrez-fajardo: None. O. Meza-ledezma: None. F. Rodriguez-valadez: None. F. J. Lavalle-gonzalez: Speaker's Bureau; Abbott Diagnostics, AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Novo Nordisk, Sanofi, Servier Laboratories. E. Vazquez-mendez: None.

Funding
TCoM study was funded by AstraZeneca International. We are thankful to the cardiologists at the investigation centers for performing echocardiography and primary care physicians of Clinicas del Azcar for recruiting the patients.
17-LB: Antihyperglycemic Use in Hemodialysis-Dependent Kidney Failure
Authors: KLEIN KLARA , PATE VIRGINIA , ASSIMON MAGDALENE M. , STÜRMER TIL , BUSE JOHN B. , FLYTHE JENNIFER 
Published: May 2022

Background: At least two-thirds of people with hemodialysis-dependent kidney failure have comorbid diabetes which associates with higher mortality. Some GLP-1 receptor agonists (RA) do not require renal dosing and could uniquely benefit dialysis patients, individuals with tremendous cardiovascular disease burden.
Methods: Using data from a national surveillance system for kidney failure in the U.S. that includes Medicare Part D prescription drug claims, we: 1) calculated the quarterly prevalence of antihyperglycemic use among diabetic hemodialysis patients from 2012 to 2017 and 2) characterized antihyperglycemic users in October 2017.
Results: Among the 129,865 hemodialysis patients with comorbid diabetes, insulin was the most prescribed agent (33%) , followed by sulfonylureas (SU, 7%) and DPP4 inhibitors (DPP4i, 5%) in October 2017. SU use fell, and DPP4i use rose from 2012 to 2017. Less than 5% of patients received combination therapy (insulin + a 2nd agent; Figure 1) . Disregarding kidney disease as an atherosclerotic cardiovascular disease (ASCVD) risk factor, 64% of patients met American Diabetes Association ASCVD criteria and 98% were at high risk for ASCVD in 2017. GLP-1 RA were prescribed to &lt;1% of patients, 20% of whom had an endocrinology claim in the prior 6 months.
Conclusions: GLP-1 RA use by hemodialysis patients is limited. There is compelling need to establish the safety and efficacy of GLP-1 RA in this high-risk population.

Disclosure
K. Klein: None. V. Pate: None. M. M. Assimon: None. T. Stürmer: Research Support; Novo Nordisk. Stock/Shareholder; Novartis AG, Novo Nordisk, Roche Pharmaceuticals. Other Relationship; AbbVie Inc., Boehringer Ingelheim International GmbH, GlaxoSmithKline plc., Takeda Pharmaceutical Company Limited, UCB, Inc. J. B. Buse: Consultant; Alkahest, Anji, AstraZeneca, Boehringer Ingelheim International GmbH, Cirius Therapeutics, Inc., Eli Lilly and Company, Fortress biotech, GentiBio, Glycadia, Glyscend, Janssen Pharmaceuticals, Inc., Mellitus Health, Moderna, Inc., Pendulum Therapeutics, Praetego, LLC, Stability Health, Valo, Zealand Pharma A/S. Research Support; AstraZeneca, Dexcom, Inc., Eli Lilly and Company, Novo Nordisk, vTv Therapeutics. Stock/Shareholder; Glyscend, Mellitus Health, Pendulum Therapeutics, PhaseBio Pharmaceuticals, Inc., Praetego, LLC, Stability Health. Other Relationship; Adocia, AstraZeneca, Eli Lilly and Company, Intarcia Therapeutics, Inc., MannKind Corporation, Novo Nordisk, Sanofi, Senseonics, vTv Therapeutics. J. Flythe: Advisory Panel; Fresenius Medical Care. Consultant; AstraZeneca. Research Support; Fresenius Medical Care.
170-OR: Outcomes of a Digital Health Coaching Program Integrating Food Delivery for a Population of Adults with T2DM at Risk of Food Insecurity
Authors: RUTLAND SARAH , MOORE JASMINE , TRAN VANESSIA T. , ALLISON MATTHEW , BURTON B. STEPHEN , PATEL DHIREN 
Published: May 2022

Background: Recent reviews suggest that concurrent Type 2 Diabetes Mellitus (T2DM) and food insecurity contributes to poorer outcomes, including worse glycemic control and increased healthcare use. We present outcomes from a real-world program involving digital health coaching (DHC) and bi-weekly food delivery for individuals with T2DM screened for food insecurity.
Methods: Individuals with T2DM were enrolled in a payor-supported DHC program and screened for food insecurity through social worker, provider, or payor records. A retrospective analysis compared data from baseline to 3-months of enrollment to evaluate T2DM-related outcomes.
Results: Of the 1093 individuals who completed baseline assessments, 75% completed 3 months of DHC. This population was primarily female (74%) , racially/ethnically diverse (38% Black, 54% white, 8% other or multi-racial) , with an average age of 53. At 3 months, there were significant improvements in mean scores on the Diabetes Distress Score (2.76 to 2.09, p&lt;0.001) , HbA1c (8.22 to 7.52, p&lt;0.001) , and USDA Food Security Survey (2.49 to 1.39, p&lt;0.001) among evaluable participants (n=710) .
Conclusions: A DHC program with integrated food delivery demonstrated promising results, suggesting that addressing basic needs such as food security may contribute to improved clinical and quality of life outcomes for individuals with T2DM.

Disclosure
S.Rutland: Employee; Pack Health. J.Moore: None. V.T.Tran: None. M.Allison: None. B.Burton: None. D.Patel: None.
171-LB: Estimating the Immunological Risk for Type 1 Diabetes from a CGM-Based One Week Self-Administered Home Test
Authors: MONTASER ESLAM , VILLARD ORIANNE , FABRIS CHIARA , LOBO BENJAMIN , BROWN SUE A. , DEBOER MARK D. , KOVATCHEV BORIS , FARHY LEON 
Published: May 2022

Background and aims: Detection of immunological risk (IR) for type 1 diabetes (T1D) requires testing for presence of islet autoantibodies (AB) . However, who and when to test is challenging. Our goal is to develop a (pre) screening technology to estimate the T1D IR from a simple continuous glucose monitoring (CGM) home test.
Methods: Data from a NIH TrialNet ancillary study with 53 healthy relatives to T1D with (N=35) or without (N=18) AB, mean±SD age of 25.4±10.7, HbA1c of 5.1±0.3%, and BMI of 22.9±5.2 (kg/m2) were used. Subjects wear CGM for a week and consumed 3 caloric drinks (Boost) . Nine glycemia features were extracted from the 75 minutes post-Boost CGM traces and used for IR classification. K-fold cross-validation with eight different classification models (i.e., linear, nonlinear, advanced, etc.) was used to develop an IR classifier. Receiver operating characteristic (ROC) curves, sensitivity, and specificity were used to select the best performing classification model.
Results: IR classifier based on a neural network (NN) model with upsampling and 10-fold cross-validation achieved the best performance between different classification models: an AUC-ROC of 0.93, a sensitivity of 89%, and a specificity of 75%. A random forest model-based classifier performed almost equally well. The Naive Bayes model achieved the best sensitivity of 100%, but had an AUC-ROC of 0.78, and specificity of 32%. On the other hand, the support vector machines models achieved the worst performance with the best being AUC-ROC of 0.63, a sensitivity of 65%, and a specificity of 54%.
Conclusion: We have developed a new methodology, which combines a dedicated one-week CGM home test with a neural network-based classifier that reliably predicts the individual IR in terms of presence or absence of islet AB. The test is self-administered, does not require a visit to a hospital or a lab, and can be used as an alternative or in addition (e.g., for prescreening) to the standard test for presence of islet autoantibodies.

Disclosure
E. Montaser: None. O. Villard: None. C. Fabris: None. B. Lobo: Other Relationship; Dexcom, Inc., Research Support; Dexcom, Inc. S. A. Brown: Research Support; Dexcom, Inc., Insulet Corporation, Roche Diagnostics USA, Tandem Diabetes Care, Inc., Tolerion, Inc. M. D. Deboer: Research Support; Dexcom, Inc., Tandem Diabetes Care, Inc. B. Kovatchev: Other Relationship; Dexcom, Inc., Johnson & Johnson, Novo Nordisk, Sanofi, Research Support; Dexcom, Inc., Novo Nordisk, Tandem Diabetes Care, Inc., Speaker's Bureau; Dexcom, Inc., Tandem Diabetes Care, Inc. L. Farhy: Research Support; Dexcom, Inc., Novo Nordisk.

Funding
NIH DP3DK106907 (TrialNet ancillary study) and CRCF Award MF20-007-LS
173-OR: Associations between Post-Discharge Care (PDC) and Cognitive Impairment-Related Hospital Readmissions for Ketoacidosis and Severe Hypoglycemia in Adults with Diabetes
Authors: WANG YEHUA , ZHANG PING , FANG RUOGU R. , BROWN JOSHUA D. , JIAO TIANZE , GUO JINGCHUAN , SHAO HUI 
Published: May 2022

Cognitive Impairment (CI) is associated with an increased risk of ketoacidosis (DKA) and severe hypoglycemia (SH) in persons with diabetes (DM) . Post-discharge Care (PDC) in nursing homes and home care facilities provides continuous medical care after hospital discharges. This study examined whether PDC is associated with lower CI-related hospital readmission for DKA and SH in US adults with DM (age &gt;18) . Our study population includes 43,467 and 166,221 adults admitted for DKA and SH from the 2016-2018 National Readmission Database, among which 1492 (3.43%) and 822 (0.49%) had CI, respectively. Readmission was defined as hospitalization for all causes within 30 days after discharge. CI-related readmission risk was estimated by comparing those with and without CI using a multiple logistic regression model, adjusting for age, sex, primary payer, income level, disease severity, mortality risk at the index discharge, and PDC status. PDC as an effect modulator was tested as an interaction term of PDC and CI. For patients initially admitted for DKA, CI was associated with 62% (adjusted odds ratio (aOR) =1.62, 1.25-2.11) higher odds of readmission among those who were discharged to home. The CI-related increase in readmission risk disappeared if patients received PDC (aOR=1.05, 0.88-1.26) . For patients initially admitted for SH, CI was associated with 34% (aOR=1.34, 95% CI 1.08-1.66) higher odds of readmission among those discharged to home and a 32% lower odds of readmission if patients received PDC (aOR=0.68, 0.59-0.81) . CI was associated with increased readmission risks for SH and DKA among adults with DM discharged to home. This CI-related readmission risk was substantially lower in patients who received PDC, indicating the importance of PDC for people with DM and CI.

Disclosure
Y.Wang: None. P.Zhang: None. R.R.Fang: None. J.D.Brown: None. T.Jiao: None. J.Guo: None. H.Shao: Board Member; BRAVO4HEALTH, LLC.
174-OR: Identify Effect Modulators of Intensive Glucose Control in Preventing Cognitive Function Decline among Individuals with Type 2 Diabetes: A Revisit to the ACCORD MIND Trial
Authors: KIANMEHR HAMED , GUO JINGCHUAN , FONSECA VIVIAN , SHI LIZHENG , SHAO HUI 
Published: May 2022

This study aimed to identify patient characteristics associated with the effectiveness of intensive glucose control (i.e., A1c&lt;6.0% vs. A1c 7-8%) in preventing cognitive function decline (CFD) among individuals with type 2 diabetes (T2D) in the ACCORD trial. The Memory in Diabetes (MIND) study was sub trial of the ACCORD study, including 2,977 participants without a history of cognitive impairment or dementia. We applied the causal forest (CF) and causal tree (CT) algorithm to identify participant characteristics that modulate the effectiveness of intensive glucose control in preventing CFD from a list of 58 candidate variables (demographics, disease histories, medications, and biomarkers) at the study baseline. The study outcome was the change of cognitive function from the baseline to the 40th month, assessed through the Digit Symbol Substitution Test (DSST) , Rey Auditory Verbal Learning Test (RAVLT) , Mini-Mental State Examination (MMSE) , and Stroop test. A computer-driven approach identified a close relationship between renal function and the effectiveness of intensive glycemic control in preventing CFD: study participants with the urinary albumin less than 0.4 mg/dl (absolute function change (AFC) : 0.43 in MSSE) or urinary creatinine 120-200 mg/dl (AFC: 0.30 in RAVLT) had slower CFD associated with intensive glycemic control, while participants with GFR&lt;60 (AFC:-0.51 in RVALT) , or GFR&lt;90 (AFC:-1.7 in Stroop) had a faster CFD associated with intensive glycemic control. In addition, only participants with age below 60 years old benefited from the intensive glucose control (AFC:1.23 in DSST) in preventing CFD. All p&lt;0.05. Our study tied renal function to the effectiveness of intensive glycemic control in preventing CFD. Clinicians may consider these individualized characteristics for better-targeted A1c goal setting, especially those at risk for CFD.

Disclosure
H.Kianmehr: None. J.Guo: 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. L.Shi: None. H.Shao: Board Member; BRAVO4HEALTH, LLC.
175-LB: Patient Determinants of Mortality with Severe DKA and/or HHS during the COVID Pandemic Differ from the Prepandemic
Authors: YANG ALMIRA J. , FIREK MATTHEW A. , MUNIR IQBAL , TRAN ANH , FIREK ANTHONY 
Published: May 2022

Background: SARS CoV-2 has been linked to higher mortality rate among DM patients who present with diabetic ketoacidosis (DKA) and/or hyperosmolar hyperglycemic state (HHS) . The Riverside University Health System Medical Center (RUHS-MC) -DKA Outcomes Group initiated a study to determine outcomes and risk factors before and during the pandemic in patients hospitalized at RUHS-MC with DKA and/or HHS.
Methods: This was a retrospective cohort study reviewing medical records of non-pregnant adults age 18 or older admitted to the RUHS-MC for DKA and/or HHS from 03/2020 to 02/2021 (“pandemic”) compared to 3 years before the pandemic (“pre-pandemic”) . Descriptive statistics were used to determine the clinical characteristics. Logistic regression was used to assess the impact of the parameters on the death rate.
Results: The mortality rate of DKA and/or HHS was 9% (30/335) during pandemic vs. 1.8% (15/855) during pre-pandemic. Six out of 30 patients died without COVID-19 infection, consistent with the pre-pandemic mortality rate. Pre-existing myocardial infarction and lower beta-hydroxybutyrate level were associated with increased mortality (Table 1) .
Discussion: At our institution, the mortality rate of DKA and/or HHS during pandemic was significantly higher, specifically associated with COVID-19 infection. Our study suggests concomitant COVID-19 is a highly lethal and independent factor in patients that develop DKA. The gender disparity in mortality is unexplained and requires additional studies.

Disclosure
A. J. Yang: None. M. A. Firek: n/a. I. Munir: None. A. Tran: None. A. Firek: None.