bluuebunny/crossref_metadata_2025_split huggingface dataset:
1815-LB: Lower Limb Vascularity Indices for Major Adverse Limb Events and Mortality in Individuals with Diabetic Foot Ulcer
Authors: GUPTA ASHISH , RASTOGI ASHU 
Published: June 2024

Objectives: We aimed to assess correlation between baPWV and ABI, specifically role of baPWV in participants with normal ABI for major adverse limb events (MALE) and mortality in people with diabetes and first diabetic foot ulcer (DFU).
Research Design and Methods: A total of 16000 patients with type 2 diabetes were screened and 2186 individuals followed until 31st December 2022 or the time of death, whichever occurred earlier. A detailed demographic and diabetes complications were recorded. Whole cohort was divided into three groups based on the presenting ABI: group A: ABI 0.7-0.9, group B-ABI: 0.9-1.2 and Group C:ABI&gt;1.2. Presenting baPWV was divided into quartiles as &lt;1642cm/sec, 1642-1896cm/sec,1897-2210 cm/sec and &gt;2210cm/sec for all individuals.. A stepwise logistic regression was used to determine the most relevant predictors of MALE and all-cause mortality.
Results: Median age of participants was 61(53-67) years, duration of diabetes 10(6-15)years and follow up duration of 6(2-8) years. In comparison with participants having a baPWV&lt;1642 cm/sec, the odds for mortality was significantly higher in individuals with baPWV &gt;2210 cm/sec [OR 1.745(1.315-2.315); p&lt;0.001]. At baPWV 1678 cm/sec, sensitivity was 68% and specificity of 62% for predicting mortality. On multivariate logistic regression predictors of mortality were- Age&gt;57.5 years [OR 1.285(1.007-1.639), p-0.004], eGFR&lt;71.5 ml/min/1.73 m2 [OR 1.434(1.128-1.824); p -0.003], any amputation [OR 1.290(1.002-1.660), p-0.049] and bAPWV &gt;2210cm/sec [OR 1.603(1.160-2.214); p&lt;0.001].
Conclusion: High baPWV is a significant predictor of mortality in people with diabetes presenting with a DFU despite a normal ABI.

Disclosure
A. Gupta: None. A. Rastogi: None.
1818-LB: The Influence of COVID-19 Pandemic on Diabetic Foot Amputations in a Western Amazon Hospital
Authors: CARMO HERCULES M. 
Published: June 2024

Introduction: Diabetes mellitus is a multifactorial chronic condition, including dietary habits, lifestyle and social, genetic and economic factors, which affects approximately 3% of the global population. In Brazil, around 17 million people have diabetes, with extensive growth projections. Diabetic foot is a serious and prevalent complication, contributing to over 50% of lower limb amputations, especially in developing countries. The COVID-19 pandemic has exacerbated this situation, directly impacting the lives of patients, leading to lifestyle changes, and altering the medical care of individuals with diabetes.
Objective: Investigate the impact of COVID-19 pandemic on amputations due to diabetic foot complications in the last five years.
Methods: This is a cross-sectional study that investigated the frequency of lower limb amputations due to diabetic foot complications from 2017 to 2022 at the Emergency Hospital of Rio Branco (Brazil), considering the impact of the COVID-19 pandemic.
Results: There was an increase in the quarterly average of surgeries of almost 30% after the start of the Covid-19 pandemic and a significant increase in amputations above the foot was observed when compared to the previous period (p=0,0011). The most affected age group was 40 to 79 years. In the analysis by age group, younger patients tended to have lower-level amputations, while older patients had higher-level amputations, indicating a significant correlation (p=0,0023).
Conclusion: This study found an increase in the prevalence of amputation surgeries due to diabetic foot in Acre during the COVID-19 pandemic. This can be attributed to the suspension of control and educational activities in Primary Care due to social distancing measures, transportation restrictions, and fear of virus exposure. The research emphasizes the need for early screening and treatment, both for physical and psychological health, including health agents, to improve the care of diabetic foot patients.

Disclosure
H.M. Carmo: None.

Funding
CNPQ
182-OR: The Triglyceride-Glucose Index and the Presence of Coronary Artery Disease are Mutually Independent Predictors for the Development of Type 2 Diabetes Mellitus
Authors: PLATTNER THOMAS , LARCHER BARBARA , MADER ARTHUR , VONBANK ALEXANDER , LEIHERER ANDREAS , MUENDLEIN AXEL , DREXEL HEINZ , SAELY CHRISTOPH H. 
Published: June 2024

The Triglyceride-Glucose-Index (TyG-Index) is a predictor of cardiovascular event risk and is associated with the metabolic syndrome as well as with type 2 diabetes (T2DM). Whether this parameter also predicts incident diabetes in subjects who do not yet have diabetes is less clear; this issue is adressed in the present study. We prospectively recorded incident diabetes over 4 years in 1296 consecutive nondiabetic Caucasian patients who underwent coronary angiography for the evaluation of established or suspected stable coronary artery disease (CAD). Diabetes was diagnosed according to ADA criteria. At baseline, 701 (54.1%) of our patients had significant CAD with lumen narrowing ≥50% at angiography; the TyG-Index was significantly higher in patients with than in those without significant CAD (8.7 [8.3-9.1] vs 8.6 [8.2-8.9] p=0.003). During follow-up, diabetes was newly diagnosed in 204 patients, i.e. in 15.7% of the study population. The TyG-Index strongly predicted diabetes both univariately (OR 1.72 [1.47-2.00]; p&lt;0.001) and after multivariate adjustment including age, sex, smoking, BMI and HbA1c (OR 1.57 [1.33-1.86]; p&lt;0.001). When we further adjusted for the presence of significant CAD, the TyG-Index remained predictive of incident diabetes (OR 1.54 [1.30-1.83]; p&lt;0.001), while CAD predicted incident diabetes in this model independently of TyG-Index (OR 1.61 [1.14-2.28]; p=0.007). We conclude that the TyG-Index and the presence of CAD are mutually independent predictors for the development of T2DM.

Disclosure
T. Plattner: None. B. Larcher: None. A. Mader: None. A. Vonbank: None. A. Leiherer: None. A. Muendlein: None. H. Drexel: None. C.H. Saely: None.
1825-LB: Reproductive Health (RH) and Gestational Diabetes (GDM) Knowledge Mediates the Intervention Effect on the Intention to Communicate in Dyads of American Indian and Alaska Native (AIAN) Female Adolescents and Young Adults (FAYA) at Risk for GDM and their Adult Female Caregivers
Authors: SEREIKA SUSAN M. , MOORE KELLY R. , STOTZ SARAH A. , PEI XUEYING , WANG YOUJIA , CHARRON-PROCHOWNIK DENISE , STOPPING GDM STUDY GROUP THE 
Published: June 2024

AIAN women are unduly impacted by GDM. This secondary analysis of Stopping GDM trial data explored possible mechanisms of action of a psycho-behavioral educational intervention targeting healthy behaviors to reduce GDM risk from pre- to post-test among AIAN FAYA. Dyads of FAYA and their adult female caregivers were recruited from 5 sites. Each dyad member independently completed questionnaires regarding RH and GDM knowledge, health beliefs, and intention to initiate discussion with healthcare providers (HCPs) and their corresponding dyad member. Between assessments intervention participants viewed a 45-minute video, the initial component of the intervention. Dyadic mediation analysis was conducted using the Actor-Partner Interdependence Model extended to Mediation (APIMeM) assuming distinguishable dyad members. The sample (N=149 dyads; intervention; n=79; control: n=70) included FAYA (mean age 16.7±3.0 years) and adult female caregivers (mean age 44.1±9.3 years; 81.0% being mothers of FAYA). APIMeM revealed a positive actor indirect effect of the intervention for improvement in the FAYA’s intention to initiate discussion through increases in FAYA’s RH and GDM knowledge (1.53, 95%CI=[0.27, 2.98]). A positive partner indirect effect was also observed for the intervention on the improvement in the FAYA’s intention to initiate discussion through increases in the adult caregiver’s RH and GDM knowledge (0.61, 95%CI=[0.042, 1.42]). No effects were found for changes in health beliefs of FAYA or adult caregivers as mediators of intervention effects on FAYA’s and adult caregiver’s intention to initiate discussion. These results suggest that enhancing RH and GDM knowledge may improve key downstream outcomes such as communication between FAYA, adult caregivers and HCPs for AIAN FAYA at risk for GDM.

Disclosure
S.M. Sereika: None. K.R. Moore: None. S.A. Stotz: None. X. Pei: None. Y. Wang: None. D. Charron-Prochownik: None.

Funding
National Institutes of Health (R01-NR014831)
1833-LB: Methylation of MicroRNAs in Human Skeletal Muscle following Acute Exercise
Authors: ZAPATA BUSTOS ROCIO , ROUST LORI R. , FUNK JANET K. , COLETTA DAWN K. 
Published: June 2024

Introduction & Objective: MicroRNAs (miRNAs) are non-coding RNAs that act as epigenetic modulators by regulating gene expression post-transcriptionally. Given their regulatory role in gene expression, epigenetic modifications such as DNA methylation to the miRNA, may affect their expression. Previous work from our group has focused on DNA methylation of protein-coding genes, but recently, we have been exploring the methylation status of miRNAs. This study aimed to identify methylation changes in genes coding for miRNAs following a single exercise session.
Methods: We studied 14 sedentary participants (7 male/7 female): age = 34.5 ± 3.1 years, body mass index = 29.3 ± 1.9 kg/m2 and HbA1c = 5.3 ± 0.1 %. We performed VO2peak tests to determine exercise capacity (VO2peak = 25.5 ± 1.6 mL per Kg per minute) and euglycemic hyperinsulinemic clamps (Rd value = 5.9 ± 0.8 mg per Kg per minute) with vastus lateralis muscle biopsies before and 30 minutes after exercise. We extracted DNA from the muscle biopsies and performed reduced representation bisulfite sequencing followed by MethylSig analysis.
Results: An acute exercise bout resulted in 171 differentially methylated cytosines (P &lt; 0.05 and methylation change ≥ 5%), corresponding to 110 unique miRNA genes. Among them, 101 were hypomethylated, and 70 were hypermethylated following exercise. Hypomethylated miRNAs included Hsa-mir-1225 (5 DMCs, 10-25% decrease) and Hsa-mir-3187 (8 DMCs, 6-14% decrease). Hypermethylated miRNAs included Hsa-mir-375 (2 DMCs, 15-19% increase) and Hsa-mir-1915 (3 DMCs, 14-15% decrease). Enrichment analysis of the miRNAs revealed pathways related to ECM and membrane receptors, immune responses, DNA damage responses, STAT3 signaling, and others.
Conclusion: Our study reveals that an acute exercise bout induces alterations in the DNA methylation of various genes coding for miRNAs. Additional work is needed to elucidate how these methylation alterations influence gene expression and biological pathways.

Disclosure
L.R. Roust: Other Relationship; Fractyl Health, Inc. J.K. Funk: None. D.K. Coletta: None.

Funding
This study was funded by the National Institutes of Health (R01DK094013).
1836-LB: Real-World Impact of a Remote, Digitally Enabled Lifestyle Program with Diabetes-Specific Formula as Part of Low-Calorie Diet among People with Obesity and Type 2 Diabetes—The RESET Study
Authors: TRENELL MICHAEL , TAYLOR LOUISE C. , KERR KIRK W. , RUEDA RICARDO , SULO SUELA 
Published: June 2024

Background: Weight management strategies are central to the control and remission of type 2 diabetes (T2D). Yet, scalable interventions remain elusive. We report the real-world outcomes of a scalable, digitally-enabled lifestyle program utilizing diabetes-specific nutrition formula (DSNF) as part of a low-calorie diet for people with obesity and T2D.
Methods: 185 adult participants with recently diagnosed T2D and 27 ≤BMI≤ 45 kg/m2 were recruited from 28 primary care practices (Newcastle upon Tyne, UK). The 12-week weight loss phase included the use of a DSNF (Glucerna®, Abbott) as part of a low-calorie diet (900-1000 kcal/day). The diet was personalized, allowing use of Glucerna® for meal replacement, real food, or a combination of both. Anti-hyperglycemic medication was withdrawn while clinical care remained with the primary clinicians. Behavioral coaching was offered digitally alongside educational content, interactive quizzes, and diet planners.
Results: Participants (55±9 years, 53% male, 70% White) engaged well with the digital service, with 78% (n=145) completing the weight loss phase. Content engagement was high (average 360 minutes content read; 60 minutes 1:1 coaching across five sessions); Glucerna® adherence was &gt;80%. A significant 10% weight loss reduction (-10 kg [95%CI: -12, -8]) and ~1% HbA1c reduction (10.9 mmol/mol [95%CI: -11,-7]) were reported at 3 months. Significant reduction in blood pressure was also reported (p-values&lt;0.01). No significant differences were observed between intent-to-treat and evaluable cohorts.
Conclusions: A remote, digitally-enabled lifestyle program using a DSNF as part of a low-calorie diet significantly improved body weight and diabetes control in people with obesity and T2D.

Disclosure
M. Trenell: Consultant; Changing Health, Abbott Nutrition. L.C. Taylor: Employee; Changing Health Ltd. K.W. Kerr: Employee; Abbott. Stock/Shareholder; Abbott. R. Rueda: Employee; Abbott Nutrition. S. Sulo: Employee; Abbott Nutrition.

Funding
Financial support for this study was provided by Abbott and UK Research and Innovation.
185-OR: The Role of Optical Coherent Tomography in the Estimation of Cardiovascular Risk in Asymptomatic Patients with Type 1 Diabetes
Authors: DUBSKY MICHAL , ROLAND ROBERT , MARHEFKOVÁ NATÁLIA , WOHLFAHRT PETER , NOVODVORSKY PETER , KARMAZIN VLADIMIR , HALUZIK MARTIN , PAZDERNIK MICHAL 
Published: June 2024

Introduction & Objective: Data on cardiovascular (CV) risk in patients with type 1 diabetes (T1D) is lacking. Our study aimed to assess coronary arteries in high-risk T1D patients using optical coherent tomography (OCT) to estimate their CV risk.
Methods: Sixty-two patients with T1D &gt; 10 years, age 30-67 years, with no history of CVD were examined by carotid ultrasound and coronary artery calcium (CAC) score. Twelve patients were recognized as high-risk defined as CAC score &gt;400 and/or presence of ≥2 carotid plaques. Patients were subsequently examined by coronary angiography and OCT.
Results: Mean age was 64.5±1.8 years, T1D duration 36±11.5 years, HbA1c 7.5±0.8 % and baseline LDL 88.9±21.3 mg/dl. Thin-cap fibroatheroma (TCFA [Figure-A]) was identified in 7/12 (58.3%) patients and very high-risk plaque (TCFA with lumen area &lt; 3.5 mm2 [B], lipid arch &gt; 180° and macrophages [C]) was present in 4/12 (33.3%) patients. We saw intraluminal thrombus [D] and cholesterol crystal [E] in 3/12 (25%) patients. A strong correlation between OCT stenosis and CAC score at the left anterior descending artery (Pearson’s r=0.75, p=0.005) was identified.
Conclusion: Our study showed that asymptomatic T1D patients with high CAC score and carotid plaques had very severe OCT findings. We observed a significant proportion of high-risk lesions potentially associated with plaque rupture and risk of CV death.

Disclosure
M. Dubsky: None. R. Roland: None. N. Marhefková: None. P. Wohlfahrt: None. P. Novodvorsky: Speaker's Bureau; Sanofi, Boehringer-Ingelheim. Advisory Panel; Boehringer-Ingelheim. Speaker's Bureau; Novo Nordisk A/S. Research Support; Sanofi. Speaker's Bureau; Abbott, Medtronic, Berlin-Chemie AG, Viatris Inc., Novartis AG. V. Karmazin: None. M. Haluzik: Advisory Panel; Sanofi, Novo Nordisk, Eli Lilly and Company, AstraZeneca, Bayer Inc., Johnson & Johnson Medical Devices Companies. Consultant; Merck & Co., Inc., Sanofi, Novo Nordisk, Eli Lilly and Company, AstraZeneca, Bayer Inc., Boehringer-Ingelheim, Johnson & Johnson Medical Devices Companies, Novatin. Research Support; Sanofi. Speaker's Bureau; Sanofi, Novo Nordisk. M. Pazdernik: None.

Funding
Supported by the project National Institute for Research of Metabolic and Cardiovascular Diseases (Programme EXCELES, Project No. LX22NPO5104) - Funded by the European Union - Next Generation EU.
1852-LB: “I realized that I could control my health with better eating habits and exercise”—Significant Improvements in Psychosocial Health and Lifestyle in People with Prediabetes Using Dexcom rtCGM
Authors: CRAWFORD MARGARET A. , HICKS CHRISTIAN , SINGH HARSIMRAN 
Published: June 2024

CGM supports diabetes self-management and related behavior modification. We investigated the impact of CGM on psychosocial health and lifestyle behaviors in a prediabetes population.
Glucose data were collected in an observational 12-week US study involving adults with prediabetes or at high risk for diabetes (Study 1, N=47). Patient-reported outcomes (PROs) assessing psychosocial health were collected at baseline and study-end. A subset of Study 1 participated in a qualitative follow-up (Study 2, N=17) and shared their experiences using the Dexcom G6. Qualitative data were analyzed using thematic and content analyses.
Study 1 participants were 63% female, 59% White, median (IQR) age 54 (44, 66), BMI 32 (26, 38) kg/m2, medication count=6 (3, 10). TIR remained high for the duration of the study (100% (96, 100)). PROs reflected significantly improved emotional well-being and self-efficacy for health management and reduced perceived severity of prediabetes using Dexcom CGM. Primary qualitative themes are presented in Table 1.
Use of Dexcom CGM was associated with improved psychosocial health and self-care behaviors in participants with prediabetes. Findings emphasize the value of Dexcom CGM as a behavior modification tool irrespective of individuals’ diabetes and glycemic status.

Disclosure
M.A. Crawford: Employee; Dexcom, Inc. C. Hicks: Employee; Dexcom, Inc. H. Singh: Employee; Dexcom, Inc.
1886-LB: Safety, PK, and Preliminary Efficacy of the Liver-Targeted Mitochondrial Protonophore TLC-6740—A Phase 1 Study
Authors: GANE EDWARD , HUSS RYAN S. , SUR JANE , MURAKAMI EISUKE , WENG STEVE , KIRBY BRIAN J. , SHAH AMRIK , SHULMAN GERALD I. , SUBRAMANIAN MANI , VIJAYAKUMAR ARCHANA , MYERS ROBERT P. 
Published: June 2024

Background: Mitochondrial uncoupling is a validated approach to weight loss, however, toxicity due to systemic uncoupling has restricted clinical use. To enhance safety, TLC-6740 was developed as a liver-targeted protonophore (&gt;40x liver/plasma ratio) for the treatment of obesity.
Methods: In this randomized, double-blind Ph 1 study (NCT05822544), healthy subjects received single (SAD; n=48) or multiple ascending doses (MAD; n=60) of TLC-6740 (3-120 mg) PO once daily for 10 days (n=6-8 active vs n=2 placebo/group) while fasting. Eight subjects received TLC-6740 15 mg fasted and then fed to evaluate food effect.
Results: In the MAD cohorts, the proportion of subjects with adverse events (AEs) was 58% with placebo and 50-88% with TLC-6740. All AEs were mild except 3 moderate AEs unrelated to treatment (anal fissure, 30 mg; heating pad burn, 120 mg; viral illness, placebo). No drug-related discontinuations, lab abnormalities, or temperature increases were observed. TLC-6740 had a median steady-state half-life of 18-33 hrs; AUC and Cmax increased in a dose-dependent manner with no impact of food or body weight. TLC-6740 caused significant, dose-dependent reductions in serum total and LDL-C (Figure).
Conclusion: In this Ph 1 study, the liver-targeted protonophore TLC-6740 was well tolerated and led to dose-dependent improvements in lipids, supporting its potential for treatment of obesity.

Disclosure
E. Gane: None. R.S. Huss: None. J. Sur: Employee; OrsoBio, Inc. E. Murakami: Employee; OrsoBio, Inc. S. Weng: Employee; OrsoBio, Inc. B.J. Kirby: Consultant; OrsoBio, Inc. A. Shah: Consultant; OrsoBio, Inc. G.I. Shulman: None. M. Subramanian: Board Member; OrsoBio, Inc. A. Vijayakumar: Employee; OrsoBio, Inc. R.P. Myers: Employee; OrsoBio, Inc.
1892-LB: Impact of Ongoing Treatment with High Concentration Capsaicin Topical System on Affective Distress and Quality of Life in Patients with Painful Diabetic Neuropathy—A Retrospective Cohort Study
Authors: UEBERALL MICHAEL A. , QUANDEL TAMARA , ENGELEN SYLVIA , FREITAS RITA , GARCÍA LUCÍA , ALLEN SAMUEL , EERDEKENS MARIE-HENRIETTE 
Published: June 2024

Introduction: Pain, depression, anxiety, and sleep disturbance reduce Quality-of-Life (QoL) in painful diabetic peripheral neuropathy (pDPN).1 Prevalence of affective distress in pDPN is 51.4%.2 It is unclear if emotional distress is impacted by analgesic treatment.3 This analysis evaluates the effect of high concentration capsaicin topical system (HCCTS) on affective distress, QoL and sleep in clinical practice, to analyze predictors of treatment response.
Method: Data of all pDPN patients treated with ≥ 1 HCCTS and followed up for a year, were taken from the German Pain eRegistry (283 pain centers). Assessments included pain rating (VAS), Depression, Anxiety and Stress Scale (DASS-21), Veterans RAND-12, modified pain disability index (mPDI) sleep item and suicidal ideation.
Results: This analysis included 826 patients. Patients with strong/severe symptoms of depression, anxiety, stress (DAS-21) decreased from 33.6%, 38.3 %; 47.5% at baseline to 4.7%, 6.5%, 4.6% after treatment 4, respectively. All results showed significant improvements in patients who received 4 HCCTS treatments (Table 1). Tolerability was consistent with the HCCTS profile.
Conclusion: Ongoing HCCTS treatment results in progressive improvement across assessments of pain, affective distress, sleep, suicidal ideation and QoL.

Disclosure
M.A. Ueberall: Research Support; AbbVie Inc. Speaker's Bureau; Almirall, S.A., GlaxoSmithKline plc. Research Support; Grünenthal. Speaker's Bureau; Kyowa Kirin Co., Ltd., Nestlé Health Science, Teva. Research Support; Dermapharm, Recordati. Speaker's Bureau; Esanum. T. Quandel: None. S. Engelen: Employee; Grunenthal GmbH. R. Freitas: Employee; Novartis Pharmaceuticals Corporation, Grunenthal S.A. L. García: Employee; Grunenthal Pharma S.A. S. Allen: Employee; Averitas Pharma, Inc., Lundbeck. M. Eerdekens: Employee; Grünenthal GmbH.
1897-LB: Active Surveillance of Patients at Risk for Euglycemic Diabetic Ketoacidosis from Sodium–Glucose Cotransport 2 Inhibitors—A Quality Improvement Project
Authors: MCCLURE ELIZABETH B. 
Published: June 2024

Introduction: The prescriptions rates of SGLT2 inhibitors have increased last decade both for the management of diabetes as well as heart failure management. With this increase there has been a rise in incidence of euglycemic diabetic ketoacidosis (eDKA) in hospitalized patients. The purpose of this quality improvement project was to determine if active surveillance of at risk patients would reduce time to diagnosis and improve patient outcomes.
Methods: A best practice alert was generated within the electronic health record that would fire for any patients with SGLT2-I on home medication list or taken while hospitalized, with a specific list of lab criteria. For this QI project, a provider from the endocrine team monitored a generated report and reached out to the primary team with diagnostic and treatment recommendations. Teams were instructed to place an Endocrine specialty consult if further guidance or management was needed.
Results: During the five-week trial, 34 patients were identified by the BPA with a wide variety of services identified. Of the 34 patients identified as at risk for eDKA, 41% had diagnosis confirmed with further lab evaluation and 12% definitively did not have euglycemic DKA. Of the fourteen patients with confirmed EKDA, eleven received treatment with dextrose containing IVF and IV insulin as needed. Three patients recovered without treatment or with aggressive oral nutrition repletion. During the five-week trial one patient required transfer to intensive care unit for management. The average time to diagnosis with active surveillance was less than 24 hours.
Conclusion: Active surveillance of the BPA lead to prompt diagnosis and treatment of patient with e-DKA from SGLT-2 inhibitors. The QI project also increased awareness of the BPA as well as the diagnosis of eDKA based on provider feedback. There were also several system-wide opportunities noted to reduce patient risk of development of eDKA.

Disclosure
E.B. McClure: None.