bluuebunny/crossref_metadata_2025_split huggingface dataset:
45-LB: A Qualitative Study to Understand Why People Living with Obesity and General/Family Practitioners Experience Therapeutic Inertia in Obesity
Authors: LAU DAVID C. , PATTON IAN , LAVJI REENA , BELLOUM ADEL , NG GINNIE , MODI RENUCA 
Published: May 2022

Medical nutrition therapy and physical activity are often used exclusively for obesity treatment despite the availability of effective adjunctive interventions, including psychological intervention, pharmacological therapy, and bariatric surgery. We conducted a qualitative study through interviews with people living with obesity (PwO) and general/family practitioners (GP/FPs) to better understand the factors contributing to healthcare decision-making and therapeutic inertia in obesity management. Phone interviews were conducted by the same investigator using discussion guides informed by the Theoretical Domains Framework (TDF) . Eligibility criteria for PwO included having a BMI over 30 kg/m2.
A total of 20 PwO and 20 GP/FPs across Canada were interviewed with representation across gender and ethnicity. PwO also varied in obesity classification and experience with management strategies. GP/FPs varied in practice type, local community, and awareness of the 2020 Canadian Adult Obesity Clinical Practice Guidelines.
Themes related to therapeutic inertia mapped to all 14 TDF domains. Both PwO and GP/FPs often perceived obesity to be a secondary health priority that is associated with negative emotions, which had pervasive influence on obesity management. PwO were hesitant to explore new strategies due to financial barriers, access to support, and concerns of adverse side-effects, effectiveness, and sustainability of interventions that support eating and physical activity behavioral changes. GP/FPs were limited in time and resources, and were hesitant to recommend specific treatments due to concerns of risks, effectiveness, and accessibility. GP/FPs were also hesitant to make referrals due to skepticism of whether other healthcare providers can provide better care. Future research will validate these themes in a larger, national sample of PwO and GP/FPs to understand how individuals can overcome the therapeutic inertia.

Disclosure
D. C. Lau: Advisory Panel; Amgen Canada, Novartis Canada, Novo Nordisk Canada Inc., Board Member; Canadian Association of Bariatric Physicians and Surgeons, Consultant; Pfizer Inc., Viatris Inc., Research Support; Novo Nordisk Canada Inc., Speaker’s Bureau; AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Canadian Collaborative Research Network, CME at Sea, Eli Lilly and Company, HLS Therapeutics Inc., Novo Nordisk Canada Inc., Obesity Canada. I. Patton: None. R. Lavji: Employee; Novo Nordisk Canada Inc., Stock/Shareholder; Moderna, Inc., Novo Nordisk, Pfizer Inc. A. Belloum: None. G. Ng: Other Relationship; Novo Nordisk Canada Inc. R. Modi: Advisory Panel; Bausch Health, Canada, Eli Lilly and Company, Novo Nordisk Canada Inc., Other Relationship; Takeda Canada.
450-P: Soluble Guanylate Cyclase Stimulator Praliciguat Promotes Ischemic Leg Reperfusion in db/db Mice
Authors: FOUSSARD NINON , BUYS EMMANUEL S. , MOHAMMEDI KAMEL , RENAULT MARIE-ANGE 
Published: May 2022

Background: Lower-limb peripheral artery disease (PAD) is a prevalent and challenging complication of diabetes, requiring innovating therapies. Praliciguat is an orally available stimulator of soluble guanylate cyclase reported to have favorable effects on metabolic and hemodynamic endpoints in preclinical and clinical studies, suggesting the potential for benefit in PAD. We evaluated the effect of praliciguat on hindlimb ischemia recovery in a mouse model of diabetes.
Methods: Hindlimb ischemia was induced in db/db mice by ligation and excision of the left femoral artery. Praliciguat 10mg/kg/day (N=mice) or vehicle (N=10) were administered in the diet for 31 days. Foot perfusion was assessed with a Laser Doppler Imager and reported as a ratio in the ischemic versus non-ischemic limb. Ischemic leg function was assessed with a 4-point scale: 0, plantar/toe flexion in response to tail traction; 1, plantar but not toe flexion; 2, no flexion; 3, foot dragging.
Results: Ischemic foot perfusion and function were better 28 days after surgery in praliciguat than in vehicle treated mice (mean ± SD: perfusion 1.± 0.23 vs. 0.38 ± 0.16; p&lt;0.0001; function 1.14 ± 0.36 vs. 1.73 ± 0.80; p=0.03) . Praliciguat did not impact angiogenesis. Arteriolar diameter was higher (9.88 ± 0.96 vs. 8.57 ± 0.64 µm; p=0.004) and ICAM-1 expression lower (186 ± 41 vs. 403 ± 177 % of healthy muscle; p=0.005) in the ischemic limb of mice treated with praliciguat than with vehicle. Praliciguat attenuated accumulation of oxidative pro-angiogenic and pro-inflammatory muscle fibers. In cultured myoblasts praliciguat significantly downregulated Myh2 and Cxcl12 mRNA expression. Conditioned medium from praliciguat-treated myoblast decreased ICAM-1 mRNA expression in HUVECs.
Conclusion: These results suggest that praliciguat restored perfusion and function in the ischemic muscle of db/db mice by increasing arteriolar diameter and decreasing ICAM-1 expression in endothelial cells via downregulation of Cxcl12 in myocytes.

Disclosure
N.Foussard: None. E.S.Buys: Employee; Cyclerion Therapeutics, Inc. K.Mohammedi: Board Member; Lilly, Novo Nordisk, Sanofi, Research Support; Cyclerion Therapeutics, Inc., Speaker's Bureau; Abbott, AstraZeneca. M.Renault: None.
456-P: HMGB1 Inhibition Protects Schwann Cells from High Glucose–Induced Cytotoxicity
Authors: SHI MIN , SONG JING , CHEN YANNA , GU WENSHA , LIU YUTING , ZHANG HONG 
Published: May 2022

Objective: Damage to Schwann cells play a crucial role in diabetic peripheral neuropathy (DPN) . To observe whether HMGB1 inhibitor (Glycyrrhizic acid, GA) can prevent diabetic Schwann cells damage and its potential mechanisms.
Methods: RSC96 cells were divided into 5 groups: NG group (5.6 mmol/L) and HG group (25.0 mmol/L) , HG+GA (1μM) group, HG+GA (10μM) , HG+GA (100μM) . Small interfering RNA was used to knock out HMGB1. CCK8 assay was used to detect the proliferation of RSC96 cells. The levels of inflammatory factors were determined by ELISA. The mRNA expression of NGF and neuritin-1 was detected by qRT-PCR. The expression levels of NSE, cleaved-caspase-3, RAGE, p38MAPK, ERK, JNK and NF-κBp65 in cells were measured by western blot.
Results: GA at the concentration of μM for 24h had significant inhibitory effect on HMGB1 synthesis and secretion (P&lt;0.05) . Schwann cell viability in high glucose was restored due to GA and siHMGB1 (P&lt;0.05) . GA intervention and siHMGB1 potently prevented inflammatory substance generation (TNF-α, IL-1β, IL-6, MCP-1 and ICAM-1) , alleviated the neurotrophic factor reduction (NGF and neuritin-1) , and suppressed cellular apoptosis related protein activation (cleaved caspase-3) in Schwann cells exposed to high glucose ambience (P&lt;0.05) . Moreover, we found that RAGE expression, p38MAPK phosphorylation and nuclear NF-κBp65 expression in high glucose-stimulated Schwann cells was reversed by GA or siRNA interference with HMGB1 (P&lt;0.05) .
Conclusions: GA and siHMGB1 can not only inhibit HMGB1 expression in Schwann cells exposed to high glucose, but also enhance cell viability. GA and siHMGB1 restored neurotrophic factors level and reduce cleaved caspase-3 expression in Schwann cell due to its anti-inflammatory ability, which may be related to the inhibition of RAGE/p38MAPK/nuclear NF-κBp65 pathway. HMGB1 may implicate in Schwann cells lesion in high glucose milieu and HMGB1 inhibition protects Schwann cells from high glucose induced cytotoxicity.

Funding
National Natural Science Foundation of China Grant Award (81700723)
460-P: Cellular Communication of Schwann Cell Subtypes in Metabolically-Acquired Neuropathy
Authors: EID STEPHANIE , NOURELDEIN MOHAMED H. , MENDELSON FAYE , FELDMAN EVA L. 
Published: May 2022

The prevalence of the metabolic syndrome (MetS) is increasing worldwide due in part to the increased consumption of a Western diet. MetS is associated with peripheral neuropathy (PN) . PN develops in a cell non-autonomous manner with involvement of axons, Schwann cells (SC) and nerve tissue- infiltrating macrophages (TIM) . SC are divided into subtypes with different roles in nerve injury. Our aim in the current study was to determine how gene expression of different types of SC and macrophages are affected in MetS and how these cells communicate with one another. C57BL6/j male mice (6-weeks old) were fed either a standard diet (SD, 10% fat) or high fat diet (HFD, 60%) for 17 weeks. Metabolic and PN phenotyping were performed for all mice and SC were extracted from sciatic nerves for single cell RNA sequencing (scRNA-seq) . Cellular communication was determined using the CellChat tool. Mice on HFD had higher fasting blood glucose (FBG) , glycated hemoglobin (HbA1c) and decreased nerve conduction velocities and intraepidermal nerve fiber densities consistent with PN compared to mice on SD. Analysis of SC scRNA-seq data revealed unique RNA expression signatures for TIM and 4 subpopulations of SC denoted as myelinating SC (mySC) , non-myelinating SC (nmSC) , SC precursors (SCP) and regenerating SC. Inflammatory genes such as Ptprc and Il1b were significantly more expressed in both TIM and mySC in HFD mice compared to SD mice. CellChat analysis of cellular communication revealed more crosstalk between TIM and various types of SC in HFD animals and identified multiple metabolic and inflammatory pathways that were activated in HFD compared to SD mice.
In conclusion, our study shows that there are many subtypes of SC that behave differently in MetS. Their communication with each other and with TIM strongly implicates these two cell types in the pathogenesis of metabolically acquired PN.

Disclosure
S.Eid: None. M.H.Noureldein: None. F.Mendelson: None. E.L.Feldman: None.

Funding
Funding was provided by the National Institutes of Health (NIH) (1R24082841 to ELF) , Novo Nordisk Foundation (NNF14OC0011633 to ELF) , the Nathan and Rose Milstein Research Fund (to SAE) , NeuroNetwork for Emerging Therapies at the University of Michigan (to SAE, MHN, and ELF) , and the A. Alfred Taubman Medical Research Institute (to SAE, MHN, and ELF) .
462-P: Improvement of Cardiovascular Autonomic Neuropathy after Metabolic Bariatric Surgery in Korean Subjects with Obesity
Authors: JANG HAN NA , MOON SEOIL , MOON JOON HO , PARK YOUNG SUK , CHOI SUNGHEE , JANG HAK CHUL , OH TAE JUNG 
Published: May 2022

Object: Cardiovascular autonomic neuropathy (CAN) is one of chronic vascular complications of diabetes, and obesity is a major risk factor for CAN. Metabolic bariatric surgery (MBS) dramatically improved both diabetes and obesity. In this study we investigated the influence of MBS on CAN in Korean subjects with obesity.
Method: We recruited patients who underwent bariatric surgery from October 20to February 2021 prospectively. CAN was evaluated before and 6 months after surgery by Ewing method including change in heart rate (HR) and blood pressure (BP) according to deep breathing, Valsalva maneuver, and postural change by AFT-800 (MEDICORE, Gyeonggi-do, Republic of Korea) . Standard deviation of NN interval (SDNN) , root mean square of successive RR interval difference (RMSSD) , total power, and very low, low, and high frequency were compared before and after surgery.
Result: A total of 22 patients were evaluated. Patients' mean age was 42.1 ± 9.1 years, and 8 patients (36.4%) were male, and the mean follow-up duration was 189.0 days. Among them, 15 (68.2%) subjects had diabetes, and none had cardiovascular disease. The resting HR before surgery was 79.2 ± 13.7 bpm, and it decreased significantly to 67.4 ± 8.2 bpm after surgery (P&lt;0.001) . Changes in HR and BP according to Valsalva maneuver, posture change, and handgrip were not significantly different before and after surgery. However, SDNN significantly increased from 25.3 [13.7-41.8] ms to 35.2 [22.6-40.4] ms (P=0.046) , and RMSSD also tended to increase. In addition, the high frequency significantly increased from 36.1 [16.8-180.3] ms2 to 117.8 [34.6-357.7] ms2 (P=0.042) after surgery.
Conclusion: MBS significantly improved indicators of parasympathetic denervation, an early manifestation of CAN.

Disclosure
H.Jang: None. S.Moon: None. J.Moon: None. Y.Park: None. S.Choi: None. H.Jang: None. T.Oh: None.
473-P: Correlation between Serum Elabela and Type 2 Diabetic Retinopathy
Authors: GU WENSHA , SHI MIN , CHEN YANNA , LIU YUTING , SONG JING , ZHANG HONG 
Published: May 2022

Aim: To analyze the relationship between serum Elabela (ELA) levels and type 2 diabetic retinopathy (DR) .
Methods: A total of 81 patients with type 2 diabetes were collected. According to the stages of diabetic retinopathy, the patients were divided into three groups: group 1: no diabetic retinopathy stage, group 2: non-proliferative diabetic retinopathy (NPDR) and group 3: proliferative diabetic retinopathy (PDR) , with 27 patients in each group. Serum ELA levels were detected by ELISA. Relevant clinical datas were recorded and analyzed.
Results: There were no statistical significance in age, BMI, FPG, HbA1c, t-chol, TG, LDL-C, HDL-C among 3 groups (all P&gt; 0.05) . The duration of diabetes in group 1 was significantly shorter than that in groups 2 and 3 (all P&lt;0.05) , and there were significant differences in SBP, DBP, eGFR and Cre in groups 3 compared with those in groups 1 and 2 (P&lt;0.05) . From group 1 to group 3, the levels of ELA decreased gradually, with statistical significance among the three groups (P&lt;0.05) . Correlation analysis showed that serum ELA levels were negatively correlated with the course of diabetes, DR, SBP, Cre (P&lt;0.05) , and positively correlated with eGFR (P&lt;0.05) . Stepwise multiple linear regression analysis showed that the most relevant variables for ELA were age, BMI and DR (P=0.005; P = 0.000; P = 0.001) . According to ROC curve analysis, the sensitivity and specificity of ELA in the diagnosis of diabetic retinopathy were 59.3%, 83.3%, and the area under the curve was 0.753 (95%CI: 0.638, 0.869, P=0.000) .
Conclusions: With the progressive of diabetic retinopathy, the level of serum ELA decreases gradually. ELA may be a potential clinical predictor and therapeutic target of diabetic retinopathy.

Disclosure
W.Gu: None. M.Shi: None. Y.Chen: None. Y.Liu: None. J.Song: None. H.Zhang: None.

Funding
National Natural Science Foundation of China Grant Award (81200595/81400807/81700723) , Six High-peak Talents Project of Jiangsu Province (WSN-101) , Research Project of Jiangsu 333 engineering (BRA2016232) and Research Project of Jiangsu Provincial Commission of Health and Family Planning (F201549/H201667) , and International Science and Technology Cooperation Project of Huaian (HAC201707) .
478-P: GALNT2 Variant Associates with Increased ANGPTL3 Circulation Level and Obesity
Authors: THANGAVEL ALPHONSE T. , ABU-FARHA MOHAMED , HEBBAR PRASHANTHA , QADDOUMI MOHAMMAD G. , ALMULLA FAHD , ABUBAKER JEHAD 
Published: May 2022

Background: Polypeptide N-Acetylgalactosaminyltransferase 2 (GALNT2) gene has been associated with serum lipid levels, insulin resistance, and adipogenesis. One of its variants, rs4846914 has been shown to associate with Triglycerides and HDL levels in global genome-wide association studies. ANGPTL proteins have emerged as important regulators of lipid metabolism through its regulation of lipoprotein lipase activity. In this study we aimed to evaluate the association between GALNT2 variant with plasma level of ANGPTL3, 8 and apolipoproteins in individuals of Arab ethnicity.
Methods: GALNT2 rs4846914 variant was genotyped in a cohort of 278 Arab individuals from Kuwait. Plasma levels of ANGPTL3 and 8 were measured by ELISA. Apolipoproteins were measured by Luminex multiplexing assay. Significance of association signals was assessed using Bonferroni-corrected P-values.
Results: The GALNT2 rs4846914_G allele was associated with increased ANGPTL3 but not ANGPTL8 plasma levels. It was associated with obesity status with an odds ratio of 1.45 (CI:1.024-2.055) (P-value =0.036) . It also associated with increased levels of ApoC1 (P-values ≤0.006) and lower levels of HDL (P-values ≤0.05) . Levels of HDL were found to be mediated by interactions between genotypes (AG+GG) at rs4846914 and measures of percentage body fat (PBF) , apolipoproteins A1a, C1 and B48.
Conclusions: Association between GALNT2 variant and lipid metabolism could be mediated through the increased ANGPTL3 protein level.

Disclosure
A.T.Thangavel: None. M.Abu-farha: None. P.Hebbar: None. M.G.Qaddoumi: None. F.Almulla: None. J.Abubaker: None.
479-P: Lipid Pattern in Men with Hypogonadism and Type 2 Diabetes Receiving Long-Term Testosterone Treatment Compared with an Untreated Control Group: Update of a Real-World Registry
Authors: SAAD FARID , HAIDER KARIM S. , HAIDER AHMAD 
Published: May 2022

Background: Previous studies reported inconsistent effects of testosterone therapy on the lipid profile in men with hypogonadism.
Methods: Of 370 men with hypogonadism and T2DM, 190 received testosterone undecanoate 1000 mg/12 weeks (T-group) , 180 opted against treatment (CTRL) . Means and standard deviations of absolute measures over 13 years of treatment are reported.
Results: Mean baseline age: 62.0±5.2, mean (median) follow-up: 9.3±3.1 (10) years. Total cholesterol (TC) (mmol/L for all lipids) decreased from 8.3±1.1 to 5.1±0.3 in T-group and increased from 7.1±1.2 to 8.4±1.4 in CTRL (p&lt;0.00for both) . HDL increased from 1.0±0.4 to 1.6±0.3 in T-group and decreased from 1.1±0.5 to 0.8±0.4 in CTRL (p&lt;0.00for both) . The TC:HDL ratio decreased from 9.8±4.2 to 3.2±0.6 in T-group and increased from 8.0±3.9 to 13.8±6.8 in CTRL (p&lt;0.00for both) .LDL decreased from 4.7±0.8 to 2.6±0.2 in T-group and increased from 4.1±1.4 to 5.2±1.6 in CTRL (p&lt;0.00for both) . Triglycerides decreased from 3.5±0.6 to 2.2±0.1 in T-group and increased from 3.1±0.6 to 3.8±0.8 in CTRL (p&lt;0.00for both) . Non-HDL decreased from 7.3±1.1 to 3.5±0.3 in T-group and increased from 6.0±1.4 to 7.7±1.5 in CTRL (p&lt;0.00for both) . Remnant cholesterol decreased from 2.7±0.9 to 0.9±0.3 in T-group and increased from 2.0±1.0 to 2.5±0.7 in CTRL (p&lt;0.00for both) . The triglyceride:HDL ratio decreased from 9.4±4.4 to 3.1±0.7 in T-group and increased from 8.0±4.0 to 14.1±6.9 in CTRL (p&lt;0.00for both) .
Conclusions: Long-term treatment with TU in men with hypogonadism and T2DM improved the lipid profile, which worsened in controls.

Disclosure
F.Saad: Consultant; Bayer AG, Stock/Shareholder; AbbVie Inc., Bayer AG, GlaxoSmithKline plc. K.S.Haider: Other Relationship; Bayer AG. A.Haider: Other Relationship; Bayer AG.

Funding
Bayer AG
491-P: Ten Years of the National Diabetes Prevention Program: Scaling the Lifestyle Change Program across the United States
Authors: CHAPPELL ASHLEY , ELY ELIZABETH 
Published: May 2022

The National Diabetes Prevention Program (National DPP) is a public-private partnership to build a nationwide delivery system for an evidence-based lifestyle change program (LCP) proven to prevent or delay the onset of type 2 diabetes in adults with prediabetes. Using data collected through the Diabetes Prevention Recognition Program (DPRP) , which certifies programs as official National DPP sites since 2012, this study shows how programmatic milestones have impacted enrollment trends over the past years. At the end of 2012, only 13 states had enrolled participants, with the highest number reported by MT (269) . By 2013, the number of states with programs increased to 41, with the highest number of enrollees reported by OH (931) and FL (840) . In 2015, online delivery modes were introduced, this allowed participants to enroll in programs located outside of their current states of residence and led, to an increase in enrollment across 50 states and DC. Notable increases were then seen in IL (13 to 670) , KS (9 to 786) , and LA (59 to 1362) . In January 2018, the Medicare Diabetes Prevention Program (MDPP) was launched, which allowed eligible Medicare beneficiaries to enroll in the LCP as a covered service. By the end of 2018, in-person (IP) enrollment sharply increased in organizations approved as MDPP suppliers, and large increases in IP enrollment from 2017 to 2018 were seen in AL, MO, NJ, and NV. The ongoing COVID-pandemic significantly impacted National DPP enrollment trends. Most states’ online enrollment increased by at least 20% from March 2020 to March 2021, with NC, CO, and NY showing large increases of 176%, 243%, and 590%, respectively. In contrast, CA, DE, and MS had decreases in online enrollment of 7%, 8%, and 26%, respectively. Enrollment trends have proven to be important reflections of milestones in the evolution of the National DPP. Expanding the number of organizations offering the MDPP, as well as those offering virtual delivery, allows the Program to continue to scale.

Disclosure
A.Chappell: None. E.Ely: None.
495-P: Fully Immersive Virtual Reality Improves Empathy towards People with Diabetes
Authors: BEVERLY ELIZABETH A. , LOVE MATTHEW , LOVE CARRIE 
Published: May 2022

Background: Virtual reality (VR) is a major driving factor in the growth of the medical education market. VR simulates objects, places, and interactions in a 3D multimedia sensory environment. Research shows its effectiveness in surgical training, anatomy, and role-playing in clinical encounters. However, minimal research has compared the effectiveness of different delivery modes. The purpose of this study was to compare fully-immersive and semi-immersive VR in diabetes training.
Methods: In this quasi-experimental study, healthcare trainees participated in either a fully-immersive 360-degree VR training with head-mounted displays (prior to SARS-CoV-2 pandemic) or a semi-immersive online VR training (during pandemic) . Participants completed the Diabetes Attitude Scale-3, Jefferson Scale of Empathy, and Transcultural Self-Efficacy Tool pre- and post-training. We conducted paired t-tests and independent t-tests with mean change scores for each measure to examine differences between study arms.
Results: A total of 115 trainees participated (22.0±3.7 years, 82.6% women, 79.1% White, 24.3% medical students) . Participants in the fully-immersive VR arm (n=69) showed improvements in all diabetes attitude subscales, empathy, and all cultural self-efficacy subscales. Participants in the semi-immersive arm (n=46) showed improvements in all diabetes attitude subscales and two of the three cultural self-efficacy subscales, but not empathy (t=1.360, p=.182) or affective cultural self-efficacy (t= -1.798, p=.081) . Comparisons between fully-immersive and semi-immersive VR revealed no differences in diabetes attitudes or cultural self-efficacy; however, the fully-immersive VR showed greater improvements in empathy (t= -4.325, p&lt;.001) .
Conclusion: Our findings suggest fully-immersive VR is more effective in improving empathy than semi-immersive VR training. Future research should use a randomized-control design to compare the two delivery modes and examine the measures over time.

Disclosure
E.A.Beverly: None. M.Love: None. C.Love: None.