bluuebunny/crossref_metadata_2025_split huggingface dataset:
6491 Macrophage Depletion Does Not Affect Beta Cell Dedifferentiation in Islets of Prediabetic NOD Mice
Authors: Laybutt R , Chan J , Liang C , Lee K 
Published: October 2024

Abstract
Disclosure: R. Laybutt: None. J. Chan: None. C. Liang: None. K. Lee: None.
Background: Pancreatic beta cell dedifferentiation may be an important contributing factor to beta cell dysfunction in type 1 and type 2 diabetes, but the triggering stimuli are poorly understood. We previously demonstrated that islet macrophages are critically important for the disruption of beta cell identity gene expression in the db/db mouse model of type 2 diabetes. However, the effects of islet macrophages on beta cell identity in type 1 diabetes are not clear. Our goal was to examine the gene expression pattern of islet-associated macrophages in non-obese diabetic (NOD) mice and to assess their potential influence on beta cell identity and function. Methods: Islets were isolated from 12-week-old female prediabetic NOD mice and control BALB/c mice. Macrophages were sorted using flow cytometry. Islets were treated ex vivo with clodronate-containing liposomes to deplete macrophages. Gene expression was assessed by real-time RT-PCR. Insulin and proinsulin secretion was assessed. Results: Macrophages from NOD islets showed a distinct gene expression pattern compared to BALB/c islet macrophages, suggesting a different functional state. Macrophages from NOD islets displayed a less inflammatory gene expression pattern with reduced interleukin 1 beta (IL1b) and tumor necrosis factor alpha (Tnfα) and elevated IL-1 receptor antagonist (Il1rn). Islet cells from NOD mice displayed reduced expression of genes related to beta cell identity. The mRNA levels of islet-associated transcription factors (Pdx1, NeuroD1 and Nkx6.1), glucose transporter (Glut2), the rate-limiting enzyme of the glycerol-phosphate shuttle, mitochondrial glycerol phosphate dehydrogenase 2 (Gpd2), ATP-sensitive potassium channel (kcnj11), incretin GIP and GLP-1 receptors (Gipr and glp1r) and adaptive unfolded protein response genes (Xbp1, Hspa5, Grp94 and Fkbp11) were reduced. Clodronate-liposome treatment of islets depleted macrophages, as evidenced by reduced mRNA expression of CD11b and F4/80. However, the depletion of macrophages in islets of NOD mice did not affect beta cell identity gene expression. Beta cell dysfunction in NOD islets was evidenced by increased proinsulin secretion. Proinsulin secretion remained elevated following macrophage depletion in NOD islets. Conclusion: These novel findings suggest that islet macrophages of prediabetic NOD mice are in a reduced inflammatory state. In contrast to previous findings from our group in a mouse model of type 2 diabetes, we found that depleting macrophages in islets from NOD mice did not improve beta cell dedifferentiation. Depleting islet macrophages may not be beneficial for restoring beta cell identity gene expression in type 1 diabetes.
Presentation: 6/2/2024
9358 Maternal Blood Glucose And Hypothalamus Volume: Novel Insights For Intergenerational Transmission Of Endocrine Traits
Authors: Marchildon Cédrik , Arguin Mélina , Doyon Myriam , Cote Samantha , Michaud Andreanne , Huck Julia , Gingras Véronique , Perron Patrice , Hivert Marie-France , Bouchard Luigi , Whittingstall Kevin 
Published: October 2024

Abstract
Disclosure: C. Marchildon: None. M. Arguin: None. M. Doyon: None. S. Cote: None. A. Michaud: None. J. Huck: None. V. Gingras: None. P. Perron: None. M. Hivert: None. L. Bouchard: None. K. Whittingstall: None.
Objective: Several studies have linked maternal hyperglycaemia to diabetes-prone phenotype in the offspring, yet the mechanisms underlying these associations remain unclear. In adults, the hypothalamus is known to play a crucial role in the progression of obesity and diabetes. In utero exposure to maternal hyperglycaemia may thus selectively target the developing hypothalamus. To test this hypothesis, we explored the link between maternal glycemia and offspring brain volumes at 10-12-year-old. Methods: This study was conducted in a subgroup of 48 mother-child pairs from the Gen3G prospective pre-birth cohort. Pregnant women completed a 75g oral glucose tolerance test (OGTT) at 24-30 weeks of pregnancy. Maternal glucose was measured at fasting, 1h, and 2h during the OGTT and area-under-the curve of glucose (AUCgluc) was calculated using the trapezoid method. When participating offspring reached 12 years of age, they were invited back to the clinical research centre to complete a high-resolution structural MRI from which regional brain volumes and hypothalamic subvolumes were quantified using FreeSurfer (Fisch, 2012). Results: Participating mothers were 28.6 (± 4.4) years old at enrolment, their mean BMI was 25.3 (± 6.3) kg/m2, and 6 women had gestational diabetes diagnosed from the IADPSG criteria. At follow-up, offspring were 10.9 (± 0.4) years old, and mean BMI was 18.3 (± 3.3) kg/m2. Our investigation revealed a significant and positive correlation between maternal AUCgluc and total offspring hypothalamic volume (r = 0.41, p = 0.004, n = 48). No significant correlations were observed in other cortical and sub-cortical regions (all p&gt;=0.05). The link between maternal AUCgluc and hypothalamic volume was considerably stronger in female offspring (r = 0.54, p = 0.008, n = 23) than in males (r = 0.26, p = 0.22, n = 25). Conclusions: We found an association between higher maternal glycemia and greater offspring hypothalamic volumes, particularly among females. These results suggest that prenatal exposure to hyperglycaemia may lead to hypothalamic programming in a sex-dependent manner. Considering that recent studies have linked the hypothalamic disturbances to endocrine dysregulation, our findings may lead to a new understanding of obesity and the intergenerational transmission of endocrine traits. Ref:Fischl B. Freesurfer. NeuroImage. 2012 Aug 10;62(2): 774-81. doi:10.1016/j.neuroimage.2012.01.021
Presentation: 6/2/2024
7393 Measuring Diabetes Outcomes of Telemedicine Versus In-Office Visits at an Endocrinology Practice in Rural West Virginia
Authors: Muojieje Chukwudi , Driscoll Henry Keane , Thiab Ghadah , Nayiri Derian , crow Samuel , Saurborn Emily , Boustany Heba 
Published: October 2024

Abstract
Disclosure: C. Muojieje: None. H.K. Driscoll: None.
Background: West Virginia has limited specialty access despite high diabetes rates. Telemedicine expanded during COVID-19 as an alternative for care delivery while encouraging social distancing. Objective: Compare diabetes outcomes between telemedicine and in-office visits at the Marshall Health Endocrinology practice in Huntington, West Virginia Methods: Retrospective cohort study using records from Marshall Health Endocrinology from March 2019-March 2023. Adults aged 18-65 with type 1/type 2 diabetes with baseline HbA1c &gt;7% on medications were included with clinic follow-up every 6 months. Primary outcome was HbA1c change. Secondary outcomes were changes in LDL cholesterol, triglycerides, microalbumin/creatinine ratio and diabetes hospitalizations. Change scores were calculated by subtracting values from the visit from values at 3-6 month follow up. Wilcoxon Signed Rank test compared outcomes within each patient. The study was approved by the Marshall IRB. Results: Of 72 patients, 8 had complete data allowing comparison between visit types for HbA1c. HbA1c increased after telemedicine (mean=-1.2; SD=2.08) but stayed the same after in-office (mean=0.03; SD= 0.19; p=0.039). Insufficient data precluded analysis of secondary outcomes. Conclusion: Results suggest potentially worse glycemic control with telemedicine versus in-office visits, unlike prior studies finding equivalence between telemedicine and in-office care for diabetes outcomes. This study’s findings were similar to previous study that have found telemedicine had slightly worse outcomes. This contrasts with other previous studies that generally found telemedicine to be equally efficacious for diabetes management. The small sample size precludes definitively establishing worse outcomes for telemedicine. Larger randomized studies are needed to definitively compare outcomes between visit types for rural diabetes populations and determine if telemedicine truly delivers subpar diabetes outcomes compared to in-office care.
Presentation: 6/3/2024
5036 Metformin-associated vitamin B12 deficiency as a potential cause of recurrent chronic subdural hematoma
Authors: Thewjitcharoen Yotsapon , Chongvoranond Peachaphol , Nakasatien Soontaree , Krittiyawong Sirinate , Himathongkam Thep 
Published: October 2024

Abstract
Disclosure: Y. Thewjitcharoen: None. P. Chongvoranond: None. S. Nakasatien: None. S. Krittiyawong: None. T. Himathongkam: None.
Background: Metformin-associated vitamin B12 deficiency is now considered a common side effect especially in those receiving a higher dose and those with existing risk factors. Many cases of vitamin B12 deficiency are overlooked or sometimes even misdiagnosed especially in patients with non-classical manifestations such as mild anemia without macrocytosis, neuropsychiatric manifestations, and symptoms of frailty. Among elderly individuals, the spectrum of symptoms and signs suggestive of vitamin B12 deficiency might be nonspecific and may occur because of other diseases. Due to the aging population, the incidence of chronic subdural hematoma has been on the rise. Here, we present a case of metformin-associated vitamin B12 deficiency as a potential underlying cause of gait instability leading to a recurrent chronic subdural hematoma. Clinical case: An 84-year-old man with well-controlled type 2 diabetes mellitus presented to the outpatient department with dizziness and fatigue for 2 weeks. The patient did not report any recent trauma. He had been in his usual state of health until 10 months ago when he began to have frequent fallings and fatigue. Acute-on-chronic subdural hematoma was found from computed tomography of the head. The patient’s history was significant for type 2 diabetes mellitus with metformin treatment 1,700 mg/day for more than 25 years, post-transcatheter aortic valve implantation for aortic stenosis, and coronary artery disease. He had been on dual antiplatelet therapy and proton pump inhibitor. Subsequent evaluations demonstrated mild normocytic anemia, mild thrombocytopenia, undetectable plasma vitamin B12 level, elevated plasma homocysteine, and normal folate level. Improvement in neurological symptoms occurred within one week of vitamin B12 replacement and surgical hematoma evacuation. Conclusions: Our case highlights the importance of assessing vitamin B12 status among elderly patients taking metformin and it is essential for clinicians to maintain a high index of suspicion in elderly patients with prolonged use of metformin presented with gait instability and frequent fallings. With the ageing of society and the continuing growth of the older population, metformin-associated vitamin B12 deficiency is expected to have an emerging complication in the future. Routine measurement of vitamin B12 level for metformin-treated individuals should be considered.
Presentation: 6/1/2024
6909 Mortality and Readmission Rates for Inpatients with Diabetic Foot Ulcer in a Tertiary, Urban Medical Center: A Five-Year Retrospective Review
Authors: Chancay Azucena Herrera , Fanas Raul Lopez , Tabassum Humera , Daily Johanna , Myers Alyson 
Published: October 2024

Abstract
Disclosure: A. Herrera Chancay: None. R. Lopez Fanas: None. H. Tabassum: None. J. Daily: None. A. Myers: None.
Background: Diabetic Foot Ulcer (DFU) is a severe complication of diabetes mellitus and is associated with high rates of morbidity and mortality. The incidence of DFUs and amputation disproportionately impact Black and Hispanic populations. DFU is also associated with a high rate of hospital readmissions and prolonged length of stay (LOS). The goal of this study was to examine 1-year mortality data, LOS and readmission rate. Methods: This study was a retrospective chart review of 1348 patients admitted to three hospitals in our system in the Bronx from 6/1/16 to 5/31/21. Data was extracted from the EPIC® electronic health records, based on the diagnoses ICD 10 codes, E10.621 and E11.622. Inclusion criteria was patients admitted with an active DFU regardless of other admission diagnosis, age 18 years or above. The index admission was defined as the first admission in our medical records within the date range. Patients were excluded if their index admission was not accessible through our EMR. Simple logistic regression and multiple logistic regression were used to analyze the association between variables of interest and mortality at index admission and at 1-year, LOS and re admissions. Results: Of the 650 eligible patients, the mean age was 59 + 13 years, 70% of patients were male, and majority were non-White (88%). Mortality was 1% during the index admission and the risk increased to 6% at 1 year after the index admission. Readmission with an active DFU from the index admission occurred in 15% of patients within 30-days, 32% of patients within 90 days, and 55% of patients within 1 year. The mean length of stay was 9 +7.5 days. Discussion: Our study in an urban region has identified high rates of mortality and costs associated with DFU, which has been reported in many settings. This patient population is high risk for poor outcomes and targeted programs are needed to reduce mortality and provide care to reduce readmissions. Future studies that explore the challenges of DFU health care and that test interventions are needed to improve DFU related health outcomes.
Presentation: 6/2/2024
12328 Multimodal Imaging Reveals Changes In Beta Cell Metabolism And Heterogeneity Throughout Pregnancy
Authors: Cuala Janielle M , Singh Tvisha , Deng Chris , Jayapalan Kavya , Dhawan Sangeeta , White Kate , Georgia Senta 
Published: October 2024

Abstract
Disclosure: J.M. Cuala: None. T. Singh: None. C. Deng: None. K. Jayapalan: None. S. Dhawan: None. K. White: None. S. Georgia: None.
During pregnancy, a unique, transient metabolic stressor, pancreatic islets adapt by balancing hormone production to maintain tight glucose homeostasis. Maternal insulin demand increases as systemic insulin resistance increases. To keep up with the increase in demand, beta cell functional dynamics change throughout pregnancy, including increasing insulin synthesis and lowering the threshold for glucose-stimulated insulin secretion (GSIS). Failure to adapt can lead to gestational diabetes (GD), a complication in 14% of pregnancies worldwide, feeding into a vicious cycle of impaired function and, eventually, hyperglycemia. Fundamentally, beta cell function is dictated by its metabolism, calcium signaling, and insulin content upon glucose stimulation. To better understand how beta cell maladaptation during pregnancy leads to gestational diabetes, we propose to apply a multidisciplinary approach to integrate novel tools to assess function and metabolism fluctuations throughout normal pregnancy. Using live isolated islets from wild-type C57BL/6 (BL6) and InsCre-gCAMP6f fl/fl (INS-gCAMP) mice, we will measure GSIS and take 4D images using metabolic fluorescence lifetime imaging (FLIM) and confocal microscopy to visualize and quantify metabolic and functional changes at different time points at cellular resolution. We expect functional and metabolic capacity levels to increase during the onset of beta cell remodeling (∼Day 8) and continue to peak throughout pregnancy. In contrast, changes in beta cell heterogeneity become more evident at the peaks of beta cell proliferation and expansion (∼Day 11-14). The proposed study will implement novel techniques to establish beta cell functional and metabolic information within a 3D pancreatic islet context throughout different time points of pregnancy. With this, we will provide greater insight into beta cell biology and its adaptation to metabolic stress to better understand the progression of gestational diabetes, which can then be applied to investigate other cellular adaptive dynamics that affect health and disease.
Presentation: 6/2/2024
7636 Once-weekly Insulin Icodec versus Once-daily Long-acting Insulins for Type 2 Diabetes Mellitus: Systematic Review and Meta-analysis
Authors: Ribeiro S G , Chavez M P , Hespanhol L C , Neto A B , Gauza M d , Paqualotto E , Balieiro C A , Padovese C C , Sa J R 
Published: October 2024

Abstract
Disclosure: S.G. Ribeiro: None. M.P. Chavez: None. L.C. Hespanhol: None. A.B. Neto: None. M.D. Gauza: None. E. Paqualotto: None. C.A. Balieiro: None. C.C. Padovese: None. J.R. Sa: None.
Background: Insulin icodec is a novel, long-acting, once-weekly basal insulin analog. Its comparative efficacy and safety with basal once-daily insulins in type 2 diabetes mellittus is uncertain. Objective: Evaluate potential efficacy, benefits and risks associated with icodec compared to once-daily basal insulin analogs (degludec or glargine). Methods: We systematically searched PubMed, Cochrane, and Embase for randomized controlled trials (RCTs) published until June 2023 comparing icodec versus long-acting insulin analogs (degludec and glargine) in type 2 diabetes mellitus (T2DM) with at least 12 weeks of follow-up. Binary endpoints were assessed with risk ratios (RRs) and continuous endpoints were compared using weighted mean differences (WMDs), with 95% confidence intervals (CIs). The protocol was registered in PROSPERO (CRD42023452468). Results: A total of seven RCTs and 3,286 patients with T2DM were included, of whom 1,509 (60.6%) received icodec treatment. The follow-up period ranged from 16 to 78 weeks. Compared with once-daily basal insulin analogs, icodec led to a greater improvement in HbA1c (WMD -0.15%; 95% CI -0.21, -0.10; p&lt;0.0001; I²=0%) and time in range (TIR) (WMD 2.83%; 95%CI 0.94; 4.71; p=0.003; I2=22%). Body weight was increased with icodec treatment (WMD 0.78 Kg; 95%CI 0.42, 1.15; p&lt;0.01; I2=86%). There was also a higher rate of injection site reactions (RR 1.89; 95%CI 1.12, 3.18; p=0.016; I²=0%) and nasopharyngitis (RR 1.94; 95%CI 1.11, 3.38; p=0.020; I²=0%) in the icodec group, compared with once-daily regimens. There was no significant difference between groups in fasting plasma glucose. Conclusions: In this meta-analysis of RCTs, insulin icodec led to better control of HbA1c and TIR as compared with once-daily insulin regimens, albeit with increased weight gain and a higher rate of injection site reaction in the Icodec group.
Presentation: 6/3/2024
12331 Overcoming Limitations Of Identifying Proliferating β-cells In Dispersed Primary Islets Culture For Drug Discovery
Authors: Xu Haixia , Rebecca Schugar , Lee Sooyeon , Annes Justin P 
Published: October 2024

Abstract
Disclosure: H. Xu: None. S. Rebecca: None. S. Lee: None. J.P. Annes: None.
Tremendous efforts have been made with screening platforms to identify islet β-cell mitogens that may be used to treat diabetes. However, promising compounds induce profound proliferation of islet non-β-cells in available screening platforms, calling for both β-cell targeted drug discovery and rigorous identification of β-cell identity to reduce false positivity. First, we used an established drug discovery dispersed islet cell-based platform(2D) to test the replication-promoting activity of GNF2133, a selective DYRK1A inhibitor that promotes β-cell proliferation, in isolated islets from human, rat and mouse. After 72 h in vitro culture, replication of non-β cells (PDX/Insulin negative) contributed to over 60% of the total replicating cells (Ki67+) in all species (human: 64%, rat: 71%, mouse: 67%). Mouse islets, which exhibit the greatest non-β-cell replication response upon GNF2133 treatment (4-fold above baseline, [50 nM]), were selected for subsequent studies. Next, we evaluated identification efficiency of β cell markers in this image-based platform. β cells, selected by the quantification value of insulin intensity, comprised 60-70% of total cell population at 48 h, 50-60% at 72 h and 20-30% at 96 h (p&lt; 0.0001 for both comparisons: 48 h vs 72 h, 72 h vs 96 h). Basal replication of β-cells (Insulin+Ki67+) was 2.80%, 2.32%, 0.85% at 48 h, 72 h and 96 h, respectively. By comparison, the proportion of non-β cells showed an increasing trend as 2.48%, 6.49%, 8.68%, correspondingly. Identification with PDX1, another β cell marker, exhibited the same findings. Prolonged culture of dispersed islet cells, as these results indicate, favors growth of non-β-cells over β-cells. In addition, proliferating β-cells express lower levels of differentiation markers makes their discernment from replicating non-β cells more challenging. 窗体顶端 To minimize the duration of monolayer culture, replication induction was measured using intact islets with addition of BrdU during the last 24 h of culture. Then, islets were either directly fixed (3D) or dispersed and cultured for an additional 36 hour before being fixed (3D+2D). Immunostaining showed 70-80% PDX1 positive cells from both methods, which resembles in vivo β cell distribution within primary mouse islets. Basal β-cell replication in 3D+2D method was 0.30%, similar to in vivo BrdU labelling level. Upon mitogen treatment, PDX1+BrdU+ cells increased to 6.57% in 3D+2D method, slightly lower than 10.02% in 3D assay (p&lt;0.05) yet significantly higher than 1.15% in 2D assay (&lt;0.01). In summary, we developed a 3D+2D assay that enhances β-cell survival and the β-cell replication-induction response. This platform, while offering reduced throughput, provides a robust platform for discovery of β-cell replication-promoting compounds. Further validation with human islets is needed.
Presentation: 6/2/2024