bluuebunny/crossref_metadata_2025_split huggingface dataset:
490-P: Gallbladder Function in Diabetes Assessed by Ultrasound
Authors: JOULEH TARANEH , NORDAAS INGRID K. , TJORA ERLING , MELING SONDRE , DIMCEVSKI GEORG , GILJA ODD H. , SØFTELAND EIRIK 
Published: June 2023

Background: Gastrointestinal complaints are common in diabetes mellitus (DM), and may be associated with gastrointestinal autonomic neuropathy. However, reliable methods for investigating gastrointestinal autonomic function are lacking. Could gallbladder dysfunction indicate gastrointestinal autonomic neuropathy as a complication of DM?
Aim: To compare stimulated gallbladder emptying in people with long-standing type 2 DM, early diabetes (early DM), and healthy controls (HC). Methods: This study included 62 subjects (19 with DM, 15 with early DM, and 28 HCs) who underwent 3D ultrasound imaging before and after intake of a high-fat meal. Gallbladder volumes, ejection volumes (EV), and ejection fractions (EF) were calculated.
Results: Maximum preprandial volume was significantly different between the three groups (p=0.04) and higher in the DM group compared to HCs (33.8 mL vs. 23.0 mL, p=0.01). The DM group had significantly higher EV than the HCs (19.4 mL vs. 13.6 mL, p=0.05). Median EF did not differ significantly between the groups.
Conclusion: Higher preprandial gallbladder volume and altered gallbladder function, expressed through higher EV in patients with DM may indicate gastrointestinal neuropathy. Ultrasonographic assessment of gallbladder emptying may prove a useful biomarker for this condition.

Disclosure
T.Jouleh: None. I.K.Nordaas: None. E.Tjora: None. S.Meling: Consultant; Novo Nordisk, Lilly, AstraZeneca, Boehringer-Ingelheim, Sanofi. G.Dimcevski: None. O.H.Gilja: None. E.Søfteland: None.
493-P: SCS for the Treatment of Painful DPN—Consistent Outcomes from Multiple RCTs
Authors: BODE BRUCE W. , GRUNBERGER GEORGE , FISHMAN MICHAEL , MURPHY MELISSA , VIGERSKY ROBERT A. , JOHANEK LISA , LARUE MADDIE 
Published: June 2023

Pain associated with diabetic peripheral neuropathy (DPN) is treated medically with gabapentin/pregabalin, tricyclic antidepressants, and serotonin-norepinephrine reuptake inhibitors1 which are often not satisfactory long-term. Spinal Cord Stimulation (SCS) is an effective alternative per 3 randomized controlled trials (RCTs)2,3,4. We reviewed and compared 3 published RCTs2,3,4 comparing SCS to conventional treatments for painful DPN in subjects with mostly type 2 diabetes (Table 1). Study outcome measures included a composite primary endpoint where patients could be identified as treatment responders by reduction in pain diary scores or Patient Global Impression of Change, ≥50% reduction in VAS measurement for pain, and a compound primary endpoint of ≥50% reduction in pain score and no neurologic decline. EQ5D questionnaires were used to assess Quality of Life. The difference in treatment success between SCS and control for the primary endpoint in the Intention-to-Treat populations ranged from 52 - 58%. Improvement in EQ5D index scores at 6 months ranged from 0.124 - 0.380. The similarity of outcomes in 3 RCTs2,3,4 demonstrate that SCS is an effective treatment modality for DPN pain compared with conventional medical approaches. Patients from 1 study4 have been followed-up to 18 months8 and patients in another2 up to 10 years9 with similar outcomes, demonstrating long-term benefits of SCS for patients with painful DPN.

Disclosure
B.W.Bode: Advisory Panel; Ascensia Diabetes Care, MannKind Corporation, Medtronic, Novo Nordisk, Zealand Pharma A/S, Research Support; Abbott Diabetes, Abvance Therapeutics, Better Therapeutics, Inc, Dexcom, Inc., Diasome, Dompé, Insulet Corporation, Lilly Diabetes, Medtronic, Novo Nordisk, Sanvita Medical, Senseonics, Provention Bio, Inc., REMD Biotherapeutics, ViaCyte, Inc., Xeris Pharmaceuticals, Inc., vTv Therapeutics, Speaker's Bureau; Abbott Diabetes, American Diabetes Association, Boehringer Ingelheim and Eli Lilly Alliance, Insulet Corporation, Lilly Diabetes, MannKind Corporation, Novo Nordisk, Sanofi, Xeris Pharmaceuticals, Inc., Stock/Shareholder; Glytec, LLC. G.Grunberger: Advisory Panel; CeQur SA, Nevro Corp., LifeScan Diabetes Institute, Speaker's Bureau; Eli Lilly and Company, Novo Nordisk. M.Fishman: Consultant; Abbott, Biotronik, Medtronic, Nevro Corp., Other Relationship; Medtronic, Abbott, Research Support; Abbott, Boston Scientific Corporation, Medtronic, Nalu, SGX Medical, Thermaquil, Biotronik, Stock/Shareholder; Celeri Health, Thermaquil. M.Murphy: Consultant; Medtronic, Relievant. R.A.Vigersky: Employee; Medtronic. L.Johanek: Employee; Medtronic. M.Larue: Employee; Medtronic.

Funding
Medtronic
494-P: The Role of Serum 25-Hydroxyvitamin D in Diabetes-Associated Cognitive Impairment
Authors: ZHU WEN , WANG SHAOHUA , NIU TONG , LIU KUNYU 
Published: June 2023

Objective: 25-hydroxyvitamin D (25[OH]D) has received attention being involved in exerting effects in diabetes-associated mild cognitive impairment (MCI). We aimed to examine the relationship between 25(OH)D and the risk of incident MCI, and the exact mechanism to regulate MCI in diabetes.
Methods: This cross-sectional study was conducted from 103 patients with type 2 diabetes (aged 40-75years), focusing on cognitive function. After adjustment for age, gender and education level, the partial correlation analysis were used to estimate the relationship of 25(OH)D level with multiple neuropsychological tests and metabolism profile, including glucose and lipid metabolism, blood pressure, coagulation and thyroid function. The mediating effects of metabolism profile on the relationship 25(OH)D with cognitive function were were performed by the simple mediating effect model of Model 4.
Results: These participants were finally divided into two groups basing on MoCA: MCI group (n=31) and healthy group (n=72). MCI group showed a lower 25(OH)D level and unfavorable metabolic profiles characterized by higher levels of HbA1c and LPa, but lower levels of INR and FT3 (all p&lt;0.05). The partial correlation analysis found there were positive correlation between 25(OH)D and MoCA, VFT, CDT, LMT, AVLT-IR and AVLT-DR (respectively, r=0.023, p=0.0; 02; r=0.272, p=0.006; r=0.280, p=0.005; r=0.241, p=0.016; r=0.319, p=0.001; r=0.242 p=0.015), primarily reflecting memory, execution and attention. Decreased 25(OH)D level was also correlated with lower FT3 and higher HbAc1 and LPa (respectively, r=0.361, p&lt;0.001; r=-0.223, p=0.026; r=-0.260, p=0.009). In addition, the association between 25(OH)D and MoCA was found to be mediated by FT3 and LPa, with the mediation effect calculated to be 25.57% and 16.69%.
Conclusion: Decreased 25(OH)D increased the risk of incident MCI, especially memory, execution and attention dysfunction in diabetes, and their relationship were may mediated by FT3 and LPa.

Disclosure
W.Zhu: None. S.Wang: None. T.Niu: None. K.Liu: None.
499-P: Leveraging the Technological Advances of Virtual Reality (VR) to Foster Engaging and Interactive Learning, Ultimately Impacting Patient Quality of Care
Authors: ALLEN RUSSIE , WELCH LAUREN K. 
Published: June 2023

Leveraging the technological advances of virtual reality (VR) to foster engaging and interactive learning, ultimately impacting patient quality of care.
With continual information evolution, staying current with relevant updates and guideline recommendations can be challenging. Innovative approaches, such as the VR Experience - a cylindrical room showcasing 360-degree wrap around animated content - enlivens education through concise, yet memorable subject matter immersion, transforming the intangible to tangible.
VISION RELIEF is an educational initiative focused on the timely diagnosis and appropriate application of guideline-based treatment for retinal diseases, including diabetic retinopathy (DR). Available in live and digitized formats, learners engage with visual illustrations of retinopathy essentials in screening, detection, and multidisciplinary management, guided by expert faculty dialogue and holographic elements to enhance the 10-minute encounter.
Results: A total of 1040 learners from the 2022 American Diabetes Association Conference engaged with both the live (n=712) and virtual (n=328) educational formats. Of learners that completed pre-/post-testing (n=644), there was a mean 21% competence gain in ability to recognize the importance of early detection and referral of diabetic eye disease, potential visual benefit from early initiation of DR treatment and value of multidisciplinary management. Additionally, 99% of respondents (n=573) reported that VR enhanced their learning experience, with increased likelihood for retinopathy screening referral (82%) and multidisciplinary care of DR patients (80%) (N=527).
Conclusions: Use of innovative technologies can enhance continued learning, advancing the ability to provide high-quality, integrated care.

Disclosure
R.Allen: None. L.K.Welch: None.

Funding
Regeneron Pharmaceuticals Inc.
5-LB: Rescuing Alpha-Cell Function in Type 1 Diabetes
Authors: PANZER JULIA , PUGLIESE ALBERTO 
Published: June 2023

Increased glucagon secretion from the pancreatic alpha cell is the first and most important defense against hypoglycemia. In T1D this defense mechanism is lost. We propose that the loss of the neighboring beta cells causes, and in turn the loss of inhibitory signals they generated, is a key factor in the inability of alpha cells to respond appropriately to blood sugar levels. The sudden cessation of this inhibitory input during hypoglycemia is a necessary signal for the glucagon response. We hypothesize that reactivation of endogenous paracrine and autocrine signaling might restore the alpha cell’s ability to respond to hypoglycemia in T1D. We used isolated islets and tissue slices from non-diabetic organ donors and donors with T1D and measured dynamic hormone secretion and calcium recordings. We found that alpha cell responses are briefer than the sustained beta cell responses. If not reset by inhibitory input, the alpha cell is not able to respond again. Glucagon secretion can be recovered by activation of paracrine signals to inhibit the alpha cell. We found full glucagon recovery if reset for 15 min or longer using high glucose in healthy islets (no reset 0.51 +/- 0.09 vs. 5 min reset 0.99 +/- 0.12 vs. 15 min 1.63 +/- 0.31, fold change to baseline +/- SEM). In tissues from T1D donors, alpha cells failed to respond to decreases in glucose concentration despite normal glucagon content and responses to KCl depolarization. Baseline glucagon secretion was significantly elevated compared to healthy individuals (mean 25.93 +/- SEM 8.55 pM in T1D vs 7.49 +/- 2.21, p&lt;0.05). Furthermore, we found severely diminished Ca2+ responses to both lowering glucose concentration and glutamate receptor stimulation. We demonstrate that alpha cells from T1D donors cannot mount an efficient glucagon response due to deficient glutamate receptor signaling and loss of paracrine inhibitory input. Our results suggest that restoring both signals rescues glucagon secretion.

Disclosure
J. Panzer: None. A. Pugliese: Consultant; Provention Bio, Inc.

Funding
American Diabetes Association (4-22-PDFPM-12 to J.P.); The Leona M. and Harry B. Helmsley Charitable Trust (2018PG-T1D053, G-2108-04793)
50-OR: First-Trimester Dietary Phenolic Compounds and Lipids Are Associated with Hyperinsulinism at Birth in Type 1 Diabetes Pregnancy
Authors: MEEK CLAIRE L. , STEWART ZOE A. , FEIG DENICE , KOULMAN ALBERT , MURPHY HELEN R. 
Published: June 2023

Objective: Type 1 diabetes in pregnancy is associated with perinatal complications attributed to offspring hyperinsulinism. Conventional management prioritises glycaemia in mid/late pregnancy to reduce hyperinsulinism, but the timing and pathophysiology of hyperinsulinism remains unclear. We assessed if hyperinsulinism, quantified by cord C-peptide at birth, was associated with early pregnancy metabolism.
Methods and Outcomes: 111 women in the Continuous Glucose Monitoring (CGM) in Pregnant women with Type 1 diabetes Trial (CONCEPTT) had a livebirth with measurement of cord C-peptide. Liquid chromatography-mass spectrometry of maternal serum (12, 24, 34 wks; n=101) and cord blood (n=93) measured 2105 metabolites. Statistical analysis: linear regression of Cord C-peptide and metabolites with adjustment for maternal age, BMI, parity, ethnicity, education, intervention and glycemia (and birth gestation for offspring metabolites). Significance limit was p=0.001.
Results: In maternal blood at 12 weeks, positive associations were noted between nine metabolites and cord C-peptide, including lipids (monoglycerides, triglycerides and phospholipids), saccharin and three other dietary phenolic compounds. At 24 weeks, two dietary phenols and several lipids maintained positive associations. At 34 weeks, 124 species in maternal blood showed positive associations with cord C-peptide, including saccharin, free fatty acids, monoglycerides, diglycerides, triglycerides, phospholipids. The profile was distinct from that of large-for-gestational age and neonatal hypoglycemia, despite the perceived pathophysiological overlap in these conditions. In cord blood, carnitines and betonicine were associated with C-peptide.
Conclusions: Lipids, saccharin and other dietary phenols in early pregnancy warrant further investigation as potentially modifiable contributors to offspring hyperinsulinism in type 1 diabetes pregnancy.

Disclosure
C.L.Meek: Research Support; Dexcom, Inc. Z.A.Stewart: None. D.Feig: Advisory Panel; Novo Nordisk Canada Inc., Speaker's Bureau; Sanofi, Novo Nordisk Canada Inc. A.Koulman: None. H.R.Murphy: Advisory Panel; Medtronic, Research Support; Dexcom, Inc.

Funding
Diabetes UK; JDRF
510-P: Tissue Nanotransfection–Based Endothelial-Targeted Epigenetic Gene Editing In Vivo to Rescue Diabetic Ischemic Wounds
Authors: VERMA SUMIT S. , KACAR SEDAT , GNYAWALI SURYA C. , FEHME LEILA S. , SEN CHANDAN K. , SINGH KANHAIYA 
Published: June 2023

Our previous work (PMID: 35192691) has identified that genetically silenced phospholipase Cγ2 (PLCγ2) hinders VEGF therapy of the diabetic ischemic limb. Hyperglycemia caused hypermethylation of endothelial specific gene promoter. Given that epigenetic changes are reversible, this work tests the significance of gene-targeted therapeutic DNA demethylation in improving blood flow to diabetic ischemic wounds. Bipedicle ischemic wounds were placed in streptozotocin (STZ) induced acute diabetic C57BL6 mice. Diabetic VWF+ dermal endothelial cells were isolated using flow sorting. In wound tissue, PLCγ2 promoter CpG methylation levels were analyzed using bisulfite sequencing. Next, to specifically demethylate PLCγ2 promoter in endothelial cells, a demethylation cocktail was designed: (i) (scFv)-TET1 catalytic domain (TET1CD) system capable of inducing targeted DNA methylation, and (ii) endothelial promoter driven gene specific guide RNAs. This demethylation cocktail was delivered at the diabetic ischemic wound-edge employing non-viral topical tissue nano-transfection (TNT) technology. PLCγ2 protein expression outcomes were assessed using flow cytometry. Functional outcome of such demethylation was assessed using Laser Speckle Perfusion imaging (Perimed Inc.) and ultrasonography (Vevo 2100) at days 3, 7&10. Overall DNA hyper methylation was prominent in murine ischemic flaps as demonstrated by the increased ratio of 5-methylcytosine (methylation mark) to 5-hydroxymethylcytosine (demethylation mark) (n=5). Specifically, the PLCγ2 promoter was hypermethylated (n=5). TNT mediated endothelial-targeted demethylation of the PLCγ2 promoter increased its expression (n=4). Such demethylation-based upregulation of PLCγ2 improved wound tissue blood flow with increased abundance of VWF+/PLCG2+ vascular elements (n=4). TNT-based endothelial demethylation of the PLCγ2 gene promoter improved perfusion of cutaneous diabetic wounds.

Disclosure
S.S.Verma: None. S.Kacar: None. S.C.Gnyawali: None. L.S.Fehme: None. C.K.Sen: n/a. K.Singh: None.

Funding
U.S. Department of Defense (W81XWH-22-1-0146)
516-P: Lineage Tracing of Vasculogenic Fibroblasts In Vivo and Their Significance in the Rescue of Diabetic Ischemic Tissue
Authors: KACAR SEDAT , SINGH KANHAIYA , VERMA SUMIT S. , REESE DIAMOND , KUMAR MANISHEKHAR , ROY SASHWATI , SEN CHANDAN K. 
Published: June 2023

Our recent work reported on the identification of the vasculogenic fibroblast (VF) that is capable of generating new blood vessels during tissue repair (Pal et al. Nat Com, 2023). While these cells are physiologic and injury-inducible, the generation of VF is blunted under conditions of diabetes. Such barrier may be overcome by the inhibition of fibroblast miR-200b using tissue nanotransfection technology (PMIDs: 28785092, 34837085, 35819852, 36380587). To understand the mechanisms underlying VF function and significance, in this work we developed miR-200b-429fl/fl COL1A2creER GT(ROSA)mT/mG mice. In these mice, miR-200b regions in fibroblasts (COL1A2+ cells) are knocked out in response to tamoxifen. To gain insight into the significance of VF in vivo, ischemic hind limb studies were performed. Tamoxifen treatment not only led to Cre excision of miR-200b-429 in these mice, but also induced the constitutive expression of ROSA driven tdTomato in fibroblasts with onset of permanent GFP expression. Significant lowering of miR-200b was noted in laser capture dissected dermal fibroblast tissue elements from the wound-edge of tamoxifen treated mice (n=4). Tamoxifen treatment led to significantly enhanced perfusion in animals subjected to ischemic injury as determined by laser speckle perfusion imaging (Perimed Inc.) (n=8). This rescue was associated with increased abundance of GFP+CD31+ VF (n=5) which accounted for 26% of all CD31+ vascular cells in the laser captured blood vessels (n=9). Thus, targeted lowering of miR-200b abundance within fibroblasts resulted in substantial augmentation of VF in vivo which was associated with improved blood flow.

Disclosure
S.Kacar: None. K.Singh: None. S.S.Verma: None. D.Reese: None. M.Kumar: None. S.Roy: None. C.K.Sen: n/a.
518-P: Prior to Development of Neuropathy, People with Diabetes Have Altered Morphological and Mechanical Properties of the Ankle Joint, Tendons, and Muscles
Authors: HOVEIZAVI ROYA , GAO FAN , FISHER SIMON 
Published: June 2023

Diabetes-related anatomical changes to the foot that foment ulcer formation are attributed to diabetic neuropathy. We hypothesized that prior to development of neuropathy, diabetes is associated with biomechanical changes in the ankle joint. To test this hypothesis, morphological properties of Achilles tendon, soleus, medial and lateral gastrocnemius muscles were evaluated by a LOGIQ ultrasound device at preset ankle (−30, −15,0,10) and knee (90,180) positions in both subjects with diabetes without neuropathy (DM; n=11, age 53±11, 3M, 8F, 87±16 kg, HbA1c 7.37±1.80, disease duration 75±79 months) and nondiabetic controls (CON; n=12, age 45±17, 5M, 7F, 75±14 kg). Monofilament (5.07/10 g) testing confirmed absence of neuropathy. As compared to CON, DM demonstrated significantly shorter Achilles length (p=0.002), smaller cross section area (p=0.018), higher Achilles stiffness (p=0.006), shorter muscle fascicles across the soleus muscle (p=0.03), higher stiffness in the soleus (p=0.001) and lateral gastrocnemius (p=0.002), and higher pennation angles for all three muscles (p&lt;0.05). The current study demonstrates altered muscle-tendon unit mechanical properties in subjects with diabetes without neuropathy. These changes indicate a pathological process that may contribute to plantar ulcer formation even in absence of diabetic neuropathy.

Disclosure
R. Hoveizavi: None. F. Gao: None. S. Fisher: None.
520-P: Bedside Amputation Surgery for Isolated Toe(s) Necrosis in a Diabetes Department—Prognostic after One-Year Follow-up
Authors: FÉRON FLORINE , RIVELINE JEAN-PIERRE , GAUTIER JEAN-FRANÇOIS , KEVORKIAN JEAN-PHILIPPE 
Published: June 2023

For isolated toe(s) necrosis complicating diabetic foot ulcers (DFU), level of amputation is a frequent topic of disagreement between diabetologists and surgeons. Bedside Amputation Surgery (BAS) performed by a diabetologist might be an option to get rid of a major surgery (complete transmetatarsal amputation [TMA] or transtibial amputation [TTA]) usually and initially recommended by the surgeon in this case. Indications of this practice need to be specified. This monocentric, retrospective, observational study assessed the outcome at 1 year of patients with diabetes mellitus (DM) after an accessible BAS performed by the diabetologist for isolated and delimited toe(s) necrosis consisting of transphalangeal amputation, metatarsophalangeal disarticulation or TMA of one axis. The primary endpoint is the one-year healing rate without secondary surgery performed by a surgeon in the operating room. Out of 783 patients admitted for DFU (05/2016-10/2021), 66 underwent BAS (8.5%). One-year follow-up was achieved for 55 patients (5 deaths from other causes and 6 lost of follow-up): males 82%, type 2 DM 96%, DM median duration 18 years, median HbA1C 9%. One-year healing rate was 62% (34/55). Among 21/55 patients with no healing at 1 year, 19 received secondary surgery in the operating room (TTA 32% (6/19), complete TMA 37% (7/19) and revision surgery gesture 31% (6/19), median delay: 41 days). Failure was observed in patients with more severe leg arteriopathy (1 vs 2 vascular leg axes, p=0.03) with no significant difference in foot vascularization. Soft tissue infection at the time of BAS was significantly more present in the unhealed group (80% vs 47%, p=0.02) with a higher CRP level (84 vs 23mg/L, p= 0.001). BAS allows optimal care in about 2 out of 3 cases, avoiding the need to perform major surgeries. The number of vascular leg axes (&lt;1) as well as degree of soft tissue infection need to be assessed before suggesting the indication.

Disclosure
F.Féron: None. J.Riveline: Board Member; Abbott Diabetes, Medtronic, Dexcom, Inc., Novo Nordisk, Eli Lilly and Company, Sanofi. J.Gautier: Advisory Panel; Bayer Inc., Eli Lilly and Company, Sanofi, Other Relationship; Novo Nordisk. J.Kevorkian: None.
523-P: Identifying Risk Factors Associated with Diabetic Foot Wounds Outcomes within a Safety-Net Hospital System
Authors: GUNAWAN FELONA , JOHNNY BLESSING , GUNASEKARAN UMA 
Published: June 2023

Dallas county has a high prevalence of diabetes and increasing rates of diabetic foot wound related lower extremity amputations in the past few years. The healthcare spending associated with diabetic foot wounds and its complications is significant, with an average cost of hospitalization for lower extremity amputation of $91,000 at Parkland Health. To better understand the risk factors for developing diabetic foot wounds and its complications, we performed an electronic medical record review of patients with diabetic foot wounds who had a visit at the Parkland Diabetes Clinic between 2019-2022. We identified 78 patients (average age 51 years, 81% male, 68% Hispanic, 21% Black, 10% Caucasian, 68% receiving charity care) with type 2 diabetes and diabetic foot wounds. The average diabetes duration was 13 years, and the average A1c was 11.1% at diagnosis and improved to 8.5% within 3-6 months. The wounds completely healed in 42% (33/78) of the patients by 4 months, with an average time to healing of 72 days. Patients with healed wounds had lower average final A1c (8.3 vs 8.7%), shorter duration of diabetes (12 vs 14 years), and lower rate of peripheral vascular disease (52 vs 60%) compared to those with non-healed wounds. In conclusion, diabetic foot wounds were particularly prevalent among uninsured male Hispanic population within our safety-net health system. Better glycemic control and earlier detection of diabetes may lead to improved diabetic foot wound outcomes. Identifying these risk factors will help us better tailor educational and clinical interventions to prevent the development of diabetic foot wounds and improve clinical outcomes for patients with diabetic foot wounds.

Disclosure
F.Gunawan: None. B.Johnny: None. U.Gunasekaran: None.