bluuebunny/crossref_metadata_2025_split huggingface dataset:
6524 Sex-Specific Single Cell Genetic Architecture Of Human Islets With And Without Type 2 Diabetes
Authors: Qadir M , Elgamal R M , Kudtarkar P , Gaulton K J , Mauvais-Jarvis F 
Published: October 2024

Abstract
Disclosure: M. Qadir: None. R.M. Elgamal: None. P. Kudtarkar: None. K.J. Gaulton: None. F. Mauvais-Jarvis: None.
Type 2 diabetes (T2D) is a heterogeneous disease and biological sex affects its pathogenesis including the development of adiposity, insulin resistance, and β cell failure. For example, ketosis-prone diabetes is a phenotypically-defined form of T2D with acute β cell failure and severe insulin deficiency, predominantly observed in men. However, what mechanisms drive male predominance in β cell failure is unknown. To fully understand the sex-based pathogenesis of islet failure in diabetes, the study of sex differences in human islet biology and dysfunction is essential. To decipher sex differences in human islets genetic architecture and function, we performed an orthogonal series of experiments from 15 islets of non-diabetic (ND) donors, using single cell RNAseq (scRNAseq) and single nucleus assay for transposase-accessible chromatin sequencing (snATACseq). We also leveraged 37 ND and T2D donors for scRNAseq data from the human pancreas analysis program (HPAP) dataset. We studied over 200,000 single cells spanning the accessible genome and transcriptome. It is the largest study of sex-based single-cell genomics and transcriptomics of human islets to date. We observe that in cultured human ND islets, in the absence of the in vivo hormonal environment, islet cell transcriptome, and genome accessibility across coding regions are predominantly limited to sex chromosome genes. Of particular interest are sex differences in gene accessibility and expression of the X-linked KDM6A and Y-linked KDM5D demethylase genes in female (F) and male (M) islet cells respectively. Furthermore, analysis of T2D islets revealed a greater number of autosomal differentially expressed genes (DEGs) in F (721 upregulated and 1164 downregulated, FDR &lt; 0.01) compared to M β cells (111 upregulated and 99 downregulated, FDR &lt; 0.01). M β cell DEGs over-representation analysis revealed suppressed insulin secretion and processing pathways, while F β cell DEGs exhibited suppression of oxidative phosphorylation and electron transport chain pathways. Thus, although, sex differences in gene expression and accessibility of cultured ND human islets are restricted to sex chromosome genes, during the transition from ND to T2D, major sex differences in autosomal DEGs appear, with a greater number of autosomal DEGs in F compared to M T2D islets.
Presentation: 6/3/2024
7578 SGLT2 Inhibitor Is Associated With A Decreased Risk Of Cerebrovascular Events And Dementia Compared To Thiazolidinedione In Subjects With Type 2 Diabetes
Authors: Park Hyeong-Kyu , Park Sang Joon , Kim Hye Jung , Byun Dong Won 
Published: October 2024

Abstract
Disclosure: H. Park: None. S. Park: None. H. Kim: None. D. Byun: None.
Subjects with type 2 diabetes (T2D) are at higher risk of developing cerebrovascular disease, cognitive decline, and dementia. Hyperinsulinemia and insulin resistance in the brain have been linked to amyloid beta metabolism, raising the risk of Alzheimer's dementia. Recently, several clinical studies have shown potential beneficial effects of sodium glucose co-transporter-2 (SGLT2) inhibitors, and thiazolidinediones, in the risk of cerebrovascular events and dementia in T2D. This study was aimed to investigate the comparative efficacy of SGLT2 inhibitors and thiazolidinediones in modifying the risk of cerebrovascular events, dementia, and Alzheimer's dementia. Using the common data model, we analyzed patients from December 31, 2011 to December 30, 2022 from 15 hospitals in South Korea. Clinical outcomes between SGLT2 inhibitors and thiazolidinediones were compared using hazard ratios (HRs), with large-scale propensity score matching and a random-effects model applied. Our analyses showed that subjects on SGLT2 inhibitors had a significantly reduced rate of cerebrovascular events (HR 0.2787, 95% CI 0.1882-0.4127, p&lt;0.00001), dementia (HR 0.5395, 95% CI 0.3824-0.7614, p=0.0004), and Alzheimer's dementia (HR 0.586, 95% CI 0.4634-0.7411, p&lt;0.00001), compared to those on thiazolidinediones. In summary, these results suggest that SGLT2 inhibitor administration is associated with a lower risk of cerebrovascular events, dementia, and Alzheimer's dementia compared to thiazolidinedione in subjects with T2D. Further studies are warranted to confirm our findings and elucidate the underlying mechanisms.
Presentation: 6/3/2024
7568 Sickle Cell Variant Promotes Glycemic Dysregulation In A Mouse Model Of Human Sickle Cell Trait And Sickle Cell Disease
Authors: Zapater Joseph L , Layden Brian T 
Published: October 2024

Abstract
Disclosure: J.L. Zapater: None. B.T. Layden: None.
Since cases of type 2 diabetes mellitus (T2DM) are rising due to environmental and societal factors, it is estimated that in the coming decades that T2DM will affect twenty percent of the United States population and that mortality from diabetic complications will continue to rise. It is therefore critical to accurately diagnose and treat T2DM early, however this proves difficult in certain populations. Sickle cell anemia is a common hemoglobinopathy in which changes in red blood cell turnover lead to inaccurate measurement of hemoglobin A1c and incongruencies between this and other glucose measures, making it difficult to establish a diagnosis of T2DM. The sickle cell variant has been linked to higher hemoglobin A1c, and with 1-in-10 African Americans having the sickle cell trait (SCT), an increasing prevalence of sickle cell disease (SCD), and a higher risk of diabetic complications in those with SCT or SCD, it is critical that we elucidate the precise mechanisms by which the sickle cell variant affects glycemic homeostasis. In this work, we utilized a mouse model of human sickle cell anemia to begin to determine the biochemical mechanisms governing glucose handling in the presence of the sickle cell variant by examining glycemic homeostasis under normal and obesogenic conditions. Townes sickle cell mice containing human hemoglobin with either two normal β-globin chains (littermate controls) or one normal and one sickle β-globin chain (SCT) were placed on either a normal chow diet or on a high fat diet (HFD) until 20 weeks of age to induce an obesogenic state. Although no overt glycemic phenotype was noted, 20-week-old HFD-fed SCT mice exhibited an increased glucose excursion following an oral glucose load compared to littermate controls. Though serum insulin levels were comparable, HFD-fed SCT mice also exhibited a reduced whole-body insulin sensitivity during insulin tolerance testing compared to controls, correlating with the noted increased glycemic excursion. With these findings, we have initiated work with Townes mice containing two normal α-chains and two sickle β-chains (SCD), which is found in human sickle cell anemia. Early results show that chow-fed SCD mice exhibit greater random and fasting glucose levels at 8 and 12 weeks of age, despite similar fasting insulin levels. These findings suggest that the presence of one sickle β-globin chain, as in SCT, promotes hyperglycemia in the obesogenic state through reduction of whole-body insulin sensitivity. Furthermore, the presence of two sickle β-globin chains, as in SCD, is sufficient to dysregulate glycemic control under normal conditions. In total, these findings demonstrate that the presence of the sickle cell variant promotes glucose dysregulation and hyperglycemia, meaning that it is essential to understand the glycemic regulation in patients with sickle cell trait and sickle cell anemia.
Presentation: 6/1/2024
8413 Skeletal Muscle Mass, Insulin Sensitivity, And Beta-Cell Function In The Development Of Type 2 Diabetes: A 16-Year Prospective Cohort Study
Authors: Mun H , Lee S , Kim S , Yoo S J , Son J 
Published: October 2024

Abstract
Disclosure: H. Mun: None. S. Lee: None. S. Kim: None. S. Yoo: None. J. Son: None.
Background: The relationship of relative muscle mass with beta-cell dysfunction and insulin resistance in the development of type 2 diabetes is unclear. We therefore aimed to evaluate longitudinal changes in glycemia, insulin sensitivity, and beta-cell function according to muscle mass. Methods: We prospectively evaluated 7090 middle-aged and older participants without diabetes at baseline every 2 years with oral glucose tolerance tests for 16 years in the Korean Genome Epidemiology Study. Weight-adjusted appendicular skeletal muscle mass was used to derive the muscle mass index (MMI). Using linear mixed-effect models, we assessed trajectories of fasting and 2-hour post-load glucose (2hPG), the composite insulin sensitivity index (ISIcomp), the 60-minute insulinogenic index (IGI60), and the disposition index (DI) according to sex-specific MMI tertiles before diagnosis with type 2 diabetes or the completion of follow-up. Results: During a median follow-up of 13.9 years, 1742 (24.5%) participants were diagnosed with type 2 diabetes. The risk of developing type 2 diabetes gradually increased as MMI decreased (multivariable-adjusted hazard ratio 1.36; 95% CI 1.29; 1.44 per SD decline in MMI). After age- and sex adjustment, significant differences were found in fasting and 2hPG trajectories between low and high MMI tertiles during follow-up (p &lt; 0.001 for group-by-time interaction). The low MMI tertile showed significantly lower ISIcomp and DI at baseline compared to the high MMI tertile. The rate of increase in IGI60 was significantly lower in the low MMI tertile than in the high MMI tertile (0.0021 vs. 0.0191; p &lt; 0.001) despite a progressive decline in ISIcomp during follow-up. The rate of decrease in DI was significantly greater in the low MMI tertile than in the high MMI tertile (-0.0228 vs. -0.006; p &lt; 0.001). Conclusion: Sufficient muscle mass in middle-aged and older adults could protect against incident type 2 diabetes by preserving beta-cell function to compensate for aging-induced reductions in insulin action, independent of obesity.
Presentation: 6/1/2024
6765 Surveillance For Side Effects Of Glycemic Control: Von Gierke Disease And Recurrent Diarrhea With Hospitalized Approach
Authors: Gone Jayanthraj , Fegahli Elie , Thompson Trevor 
Published: October 2024

Abstract
Disclosure: J. Gone: None. E. Fegahli: None. T. Thompson: None.
Background: Von Gierke disease is an autosomal recessive disorder leading to the inability to break down glycogen. Clinical features manifest at 3-6 months including symptoms of hypoglycemia, short stature, thin legs, round face, protruding abdomen, muscular hypotonia, and psychomotor retardation. Workup shows hypoglycemia, lactic acidosis, hyperuricemia, hyperlipidemia, anemia, hepatomegaly, and renomegaly. Patients may develop inflammatory bowel disease, osteopenia, renal failure, hepatic tumors, and pulmonary hypertension. Molecular sequencing confirms the diagnosis. Feeding glucose at regular intervals prevents hypoglycemia. One should avoid fructose, lactose, sucrose, and galactose. Oral citrate or bicarbonate is used to treat lactic acidosis. Gout, hyperlipidemia, anemia, IBD and osteoporosis are managed accordingly. Regular screening for osteoporosis, renal failure, hepatic tumors, and pulmonary hypertension is recommended. Liver transplantation results in optimal management. Gene therapy clinical trials are underway. Clinical Case: We present a case of von Gierke disease in a 20-year-old male presenting to the Emergency Department for recurrent nausea, emesis, poor oral intake, water diarrhea and subjective fever. Inpatient workup showed lactic acidosis, hyperuricemia, hypertriglyceridemia, transaminitis, and fibrofatty hepatomegaly. Intravenous fluids, antiemetics and cornstarch were given. Symptoms including nausea, emesis, and diarrhea improved, most notably after adjustments made to cornstarch dosage and frequency. The patient was discharged with an antiemetic and an antidiarrheal and with recommendations to continue scheduled cornstarch. Patient was educated about the importance of proper diet compliance and close outpatient follow up. Hence, management of von Gierke disease should include not only strict glycemic control but also close surveillance for possible side effects, such as diarrhea. Moreover, future studies are necessary to support empiric modifications in management despite a basis of a hypothetical rationale. Conclusion: An essential goal of managing GSD-1 is not only strict glycemic control but also close surveillance for possible side effects, such as diarrhea. Adjustments to maintaining normoglycemia may be mandatory by manipulating factors including dosage and frequency of oral carbohydrates, such as cornstarch, to reduce the recurrence of side effects as much as possible. Treatment regimens should be individualized to each case because the initial presentation and response to treatment in every patient can be different, whether it is minor or major. Future studies about the mechanisms regarding possible side effects of treatment, such as diarrhea, are warranted to corroborate empiric changes in management, like adjusting dosage and frequency or medications, despite having a hypothetical rationale.
Presentation: 6/1/2024
7501 The Effect Of Liraglutide On Postprandial Hypoglycemia In Non-Bariatric Surgery Patients; A Case Series And Review Of Literature
Authors: Almistehi Wael Mohammad , Alatawi Jamilah Atallah , AlJalal Wesam Abdullah 
Published: October 2024

Abstract
Disclosure: W.M. Almistehi: None. J.A. Alatawi: None. W.A. AlJalal: None.
Background: Postprandial hypoglycemia is not an uncommon symptom with various causes and pathophysiology, including exaggerated insulin response related to rapid glucose absorption like in patients with dumping syndrome post-bariatric, Impaired glucagon sensitivity, Insulin resistant-related hyperinsulinemia, Alcohol, and idiopathic. It affects the patient's quality of life, causing autonomic and neuroglycopenic symptoms. In extreme cases, it might be fatal as well. To our knowledge, there are no published studies on using Liraglutide in patients with postprandial hypoglycemia without a history of bariatric surgery. Methods: This case series involved six patients who share a similar presentation to the endocrine clinic in the Obesity, Endocrine and Metabolism Center in King Fahad Medical City-Riyadh, Saudi Arabia. All patients with adrenergic symptoms and hypoglycemia documented less than 65 mg/dl, mainly post-meal, within 3-4 hours. We prescribed Liraglutide and other medical treatment regimens to improve their symptoms and follow them up for up to two years. Results: There are six patients, five females and one male, aged between 22 and 55 years old. They presented with adrenergic symptoms such as sweating, dizziness, hunger, shivering and blurring of vision with documented hypoglycemia less than 65 mg/dl that improved with meal. Of the six patients, four had symptoms triggered by eating, one reported symptoms mainly after stress, and the last had no specific trigger factor. Two patients were started on Acarbose and Diazoxide at doses of 50 mg twice daily and 100 mg Three times daily, respectively, with persistent adrenergic symptoms; those two patients started on Liraglutide 0.6 mg with titration up for a dose of 3 mg daily. Both had significant improvement in symptoms with decreased frequency and severity of hypoglycemia during the two-year follow-up. Another two patients had persistent symptoms while treated only with Acarbose 50 mg thrice daily. The first patient started on Liraglutide 0.6 mg daily and titrated to a dose of 1.8 mg daily for two years with no improvement of symptoms, but the patient was not compliant with the medication. The other patient reached 3 mg daily with partial improvement of symptoms at two years of follow-up. The last two patients started immediately on Liraglutide. The first one takes 1.8 mg daily and has significantly improved his symptoms since starting the medication until eight months follow up (up to date). The last case received 3 mg daily and showed improvement of his hypoglycemia up to two years follow up. Conclusion: Liraglutide might be a good option for treating postprandial hypoglycemic patients with good clinical outcomes. However, more publications are needed to evaluate the efficacy and long-term follow-up in treating this group of patients.
Presentation: 6/3/2024
7347 The Efficacy And Safety Of Oral Semaglutide In Asian Patients With Type 2 Diabetes:A Systematic Review And Meta-Analysis
Authors: Wang T , Liao L 
Published: October 2024

Abstract
Disclosure: T. Wang: None. L. Liao: None.
Objectives: To evaluate the efficacy and safety outcomes of oral semaglutide in Asian and non-Asian patients with type 2 diabetes mellitus(T2DM). Methods: Search several databases for randomized controlled trials (RCTs) of oral semaglutide in patients with T2DM. The primary outcomes included Participants who achieved HbA1c &lt;7.0% (53 millimoles per mole [mmol/mol]), Participants losing 5% or more of baseline body weight, adverse events (AE), serious adverse events (SAE). Risk ratios (RR) and 95% confidence intervals (CI) were calculated to evaluate the outcomes. Results: This meta-analysis included 8 RCTs with a total of 5662 patients. Using a placebo as a control group, semaglutide was effective in controlling blood sugar and reducing body weight in both Asian and non-Asian subgroups. meanwhile, compared to non-Asians, semaglutide 3mg(Chi2 4.54, P=0.03, I2=78%, 2 subgroup), 7mg (Chi2 7.79, P=0.005, I2=87.2%, 2 subgroup), 14mg (Chi2 7.97, P=0.005, I2=87.4%, 2 subgroup) oral preparation can make the level of HBA1c in Asian race more reach the therapeutic target. In Asian or non-Asian subgroups, semaglutide significantly reduced patient weight compared to active medicine. And semaglutide did not increase the risk of adverse reactions, whether Asian or not. Conclusion: Oral semaglutide is more effective in Asians, and semaglutide 7mg or 14mg is preferred over other active medicines.
Presentation: 6/3/2024
12624 The Efficacy Of Glp1 Receptor Agonists As Adjunct Therapy To Insulin In Patients With Type 1 Diabetes: A Meta-analysis
Authors: Azar Maria Abi , Harb Frederic , Nakhoul Laurette B , Nakhoul Nancy Fawzy 
Published: October 2024

Abstract
Disclosure: M. Abi Azar: None. F. Harb: None. L.B. Nakhoul: None. N.F. Nakhoul: None.
Rationale GLP1 receptor agonists are a class of antidiabetic that are well established in type 2 diabetes. While their efficacy in type 1 diabetes remains uncertain, this meta-analysis aims at evaluating the benefits of adding GLP1-RAs to insulin in patients with type 1 diabetes. The goal is to summarize advantages and drawbacks from updated existing literature. Objectives This study aims to evaluate the effects of adding GLP-1 receptor agonists to insulin therapy for type 1 diabetes, focusing on blood sugar control, body weight, insulin needs, and cardiovascular safety. It will analyze updated existing literature to assess the benefits and risks of this dual treatment approach. Search methods We searched PubMed, Medline, Scopus and Cochrane Library for relevant studies using keywords related to GLP-1 agonists, insulin, and type 1 diabetes. Eligibility criteria The study necessitates randomized controlled trials (RCTs) that compare GLP-1 RAs receptor agonists plus insulin versus insulin plus placebo in patients with type 1 diabetes, regardless of age or gender. Primary outcomes focus on HbA1c, with secondary outcomes evaluating changes in body weight, insulin requirements, systolic blood pressure, and Heart rate. Synthesis methods All statistical analyses were conducted using the Revman web software developed by Cochrane, and a p-value &lt;0.05 will be considered statistically significant. Synthesis of results The analysis of 12 studies (1570 patients) showed GLP-1 RAs added to insulin reduced HbA1C significantly -0.3 % [-0.43--0.17], suggesting efficacy in type 1 diabetes. However, moderate to significant heterogeneity and bias were observed. GLP-1 RAs also led to a -4.6 Kg [-4.64, -4.57] greater weight reduction and lower insulin needs -4.32 IU[-4.38,-4.24], with a consistent reduction in SBP but an increase in heart rate. Conclusion: This meta-analysis of 12 studies with 1567 participants shows significant benefits of GLP-1 RA therapy in type 1 diabetes management but highlights the need to tailor treatments and explore further due to identified heterogeneity.
Presentation: 6/2/2024
9353 The Impact Of Artificially Sweetened Drinks On Metformin Efficacy
Authors: Ismail Esraa , Bernier Angelina Valladares 
Published: October 2024

Abstract
Disclosure: E. Ismail: None. A.V. Bernier: None.
Title: The Impact of Artificially Sweetened Drinks on Metformin EfficacyBackground: Consumption of artificially sweetened beverages (ASB) as a recommended alternative to sugar sweetened beverages (SSB) may have a negative effect on metformin therapy for adolescents with prediabetes and obesity. A recent preclinical study showed that ASB impair release of growth differentiation factor 15 (GDF15), a hormone secreted in response to metformin therapy with an important role in glucose homeostasis and energy balance. Objectives: This translational pilot study evaluated the effect of ASB on metformin glycemic and energy balance outcomes, and metformin induced rise in GDF15.Design: Forty-six children 10-21 years with obesity and prediabetes started on metformin (500 mg twice daily), received dietary counseling to discontinue SSB and then randomized to restrict beverage intake to ASB or unsweetened beverages (USB). A beverage frequency questionnaire was collected biweekly. Anthropometric measurements, 24-hour dietary recall, hunger assessment, and lab work were obtained at baseline and 12 week follow up. Results: Of 46 participants, the mean age was 13.5 ± 2.2 years, and 54.3% were female with 54.3% Black, 10.9% Hispanic/Latino. The baseline BMI was 40.5 ± 8.5 kg/m², percent of the 95th percentile (%95th%ile) was 152.5 ± 29, and BMI z score was 3.2 ± 1.0. Thirty-six participants completed the study, with 44% in the USB group. A greater decrease in BMI [-0.55 ± 1.49 vs -0.23 ± 1.6 (p=0.6558)], %95th%ile [-3.94 ± 5.78 vs -2.28 ± 5.91 (p=0.4628)], and BMI z score [-0.12 ± 0.19 vs -0.09 ± 0.21 (p=0.7024)] was seen in the USB arm vs ASB arm though not statistically significant. A greater increase in GDF-15 was observed in the USB arm, with a mean change of 33.4 ± 58.34 vs 19.77 ± 85.87 in the ASB arm though not statistically significant (p=0.3272). A1c and dietary intake, remained similar from baseline to postintervention. There was no significant difference between groups for metformin intake.Conclusions: Initial findings of this pilot demonstrate a potential effect of dietary beverage intake on efficacy of metformin therapy on weight parameters. Although the USB arm showed small to medium decreases in BMI, %95th%ile, and BMI z score, along with an increase in GDF15 levels, no changes reached statistical significance (p &lt; 0.05) due to the study's limited sample size and short intervention period. The recruitment of participants from a pediatric obesity clinic is not a representative sample of entire population limiting the generalizability of research findings however these results convey important need for larger studies in varied populations to clarify this salient dietary recommendation.
Presentation: 6/1/2024