bluuebunny/crossref_metadata_2025 huggingface dataset:
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

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 <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

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 <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

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 < 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
8114 The Need For Autoantibody Screening And Diagnostic Criteria For Immune-Checkpoint Inhibitor-Induced Type 1 Diabetes
Authors: Gupta Ashna , Sanekommu Harshavardhan , Ravin Andrew B , Akula Monica , Cheng Jennifer
Published: October 2024

Disclosure: A. Gupta: None. H. Sanekommu: None. A.B. Ravin: None. M. Akula: None. J. Cheng: None.

Background: Immune-checkpoint inhibitors (ICIs) such as Nivolumab have been extensively studied, especially in relation to their side-effect profiles. Patients on Nivolumab are prone to immune-related adverse events (irAEs) including type 1 diabetes mellitus, thyroiditis, and hypopituitarism. Prior studies have indicated that ICIs can unmask existing diabetic autoimmunities, but currently no specific guidelines exist for autoantibody screening prior to initiating treatment. We report a unique case of a young patient with newly diagnosed immune-checkpoint inhibitor-induced type 1 diabetes (ICI-T1DM) who was found to have mixed autoantibody results. Clinical Case: This is a 31-year-old male who was diagnosed with fibrolamellar hepatocellular carcinoma (pT23N0) and underwent partial hepatic resection later that year. Repeat imaging showed new hepatic lesions, thus Nivolumab was initiated. He received a total of three cycles, after which he presented to the hospital with symptoms of fever and nausea; labs were consistent with diabetic ketoacidosis (DKA) for which he was treated with IV insulin and aggressive hydration with successful resolution. Nivolumab was stopped and the patient was discharged on a basal-bolus insulin regimen. Further outpatient workup was significant for A1c 5.9% (n<5.7%), C-peptide (with glucose 220mg/dL) 0.7 (n=0.8-3.9ng/mL), glutamic acid decarboxylase autoantibody (GAD Ab) 11 (n<5.0U/mL). Insulin antibody and islet cell antibody IgG were negative. Due to the acute onset in the presentation and the recent use of Nivolumab, the patient was diagnosed with ICI-T1DM. He remained insulin-dependent after discharge. Unfortunately, soon after, he began showing signs of liver failure and ultimately underwent liver transplantation. Conclusion: This case highlights two crucial aspects - the importance of screening for autoantibodies prior to initiating an ICI and the necessity for guidelines in diagnosing ICI-T1DM. Given the evidence linking positive GAD Ab to a higher risk of developing DKA and earlier onset ICI-T1DM, it is beneficial to screen patients for these autoantibodies prior to ICI initiation to identify those more susceptible to developing ICIDM1. It may also be beneficial to obtain a C-peptide level prior to initiation to evaluate for endogenous insulin production. Additionally, while several factors support the diagnosis of ICI-T1DM such as recent ICI use, acute DKA presentation, low C-peptide levels, and the need for exogenous insulin, there is currently no specific criteria for the formal diagnosis of ICI-T1DM. Consequently, the decision to continue an ICI remains uncertain until specific diagnostic criteria are established for healthcare providers.

Presentation: 6/2/2024
7971 The Role of PDX1 In Beta Cell Response To GLP1
Authors: Bheeman Chandni , Vann Kenji , Astapova Olga
Published: October 2024

Disclosure: C. Bheeman: None. K. Vann: None. O. Astapova: None.

Mature Onset of Diabetes of the Young Type 4 is a rare form of diabetes mellitus caused by a defect in the Pancreatic and Duodenal homeobox 1 (PDX-1) gene, which is predominantly expressed in β-cells and is an important factor in insulin gene transcription. We aim to study the impact that a PDX1 mutation (modeled after a patient) has on the beta cell response to GLP1. This was a 33-year-old nonobese man who presented to the clinic with new onset diabetes without ketosis. He was treated with insulin and metformin and his hemoglobin A1c decreased from 16% to 6.1% in six months. Other labs showed c-peptide of 8.9 ng/mL in setting of a blood glucose of 231 mg/dL, negative islet cell antibodies and glutamic acid antibodies. Of note, patient also had significant family history of diabetes. Due to high probability of MODY, genetic testing was obtained. He was found to have a heterozygous frameshift mutation in codons 228 -233 leading to a 17 base pair deletion in the PDX1 gene causing replacement of the 56 C- terminal amino acids with a shorter, missense C-terminal tail. Patient was started on dulaglutide 0.75 mg weekly but was hypoglycemic on the smallest dose so he was then switched to Semaglutide and has been maintained on less than 0.25 mg weekly. The clinical question we aim to answer was why was this patient so sensitive to GLP1 agonist activity. To study how the mutation affects response to GLP1 we are using mouse beta-TC-6 cell as they are insulin secreting, and regulated by glucose. The PDX-1 gene is highly conserved among species and the mouse PDX gene is comparable to the human gene. We used CRISPR-Cas9 to introduce the same 17 base-pair deletion into the mouse PDX-1 gene in beta-TC-6 cells. We first measured the glucose stimulated insulin secretion in control cells to examine first and second phases of insulin secretion, determining that the first phase of insulin occurs in twenty minutes and the second phase starts at about two hours. We also evaluated if these cells responded GLP-1 by increasing insulin secretion. We found that these cells respond to glucose and GLP1 in an additive manner. Insulin was measured by enzyme-linked immunosorbent assay (ELIZA). In the next phase of the experiment we aim to determine the effect of the GLP-1 in cell lines with the PDX1 deletion mutation as compared to control cell line. We will measure insulin secretion by ELISA in both mutant and the control cells treated with and without glucose and GLP1. We will measure insulin at 0 minutes and 30 minutes and insulin mRNA at 0 minutes and 6 hours to determine the first and second phases of insulin production. Our results will help guide personalized treatment for patients with MODY type 4 and improve our understanding of beta cell response to GLP1.

Presentation: 6/2/2024
8527 The Role Of SGLT2 Inhibitors In Outcomes After LVAD Implantation
Authors: Carafone Lindsay , McNitt Scott , Goldenberg Ilan , Alexis Jeffrey
Published: October 2024

Disclosure: L. Carafone: None. S. McNitt: None. I. Goldenberg: None. J. Alexis: None.

Introduction: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are important medications in the treatment of diabetes mellitus, however they offer several additional benefits, including improved heart failure outcomes in patients with and without diabetes. The role of SGLT2i in heart failure outcomes for patients who receive left ventricular assist device (LVAD) implantation is not known. Right heart failure, in particular, is a frequent complication and major contributor to morbidity and mortality after LVAD implantation. SGLT2i have been increasingly used in patients who undergo LVAD implantation, however it is unknown whether right heart failure events post-LVAD implantation are meaningfully impacted by SGLT2i use. Objective: The purpose of this study was to evaluate the role of SGLT2i in outcomes after LVAD implantation. The primary endpoint was the onset of a first right heart failure (RHF) event following LVAD implantation. Secondary endpoints included recurrent RHF, first and recurrent hospitalization for RHF, and all-cause mortality. Methods: The study population comprised all consecutive patients who received a HeartMate 3 LVAD implantation at the medical center from 9/25/2015 through 9/1/2023 who are included in the institution’s LVAD Database. Both patients who received and did not receive a SGLT2i were included. A time-dependent model was used to evaluate treatment with SGLT2i as a time-dependent variable. Multivariable propensity score matching was used in the analysis of outcomes. Results: A total of 399 patients were analyzed, which included 175 patients who received SGLT2i and 224 patients who did not receive SGLT2i. Cox proportional hazards regression, employing propensity score stratification, demonstrated SGLT2i use was not associated with a statistical significant effect in the primary endpoint of a first occurrence of RHF event (HR = 1.41, 95% CI = 0.77-2.61, p = 0.268). Similarly, SGLT2i use was not associated with secondary outcomes, including recurrent RHF (HR = 1.28, 95% CI = 0.76-2.16, p = 0.360), first or recurrent hospitalization for RHF (HR = 0.38, 95% CI = 0.11-1.33, p = 0.131 and HR = 0.63, 95% CI = 0.27-1.46, p = 0.285, respectively), and all-cause mortality (HR = 0.90, 95% CI = 0.44-1.83, p = 0.771). Presence or absence of diabetes diagnosis did not significantly impact outcomes. Conclusions: The observational data in this study suggest no incremental benefit of SGLT2i for right heart failure or mortality outcomes after LVAD implantation, however large-scale prospective studies are needed to evaluate the role of SGLT2i in this setting. Further elucidating the role of these medications in LVAD outcomes will be critical in clinical decision-making regarding use of SGLT2i in this population.

Presentation: 6/1/2024
12443 Thioredoxin Interacting Protein (Txnip) Regulates Cellular Senescence And Lifespan
Authors: Abubaker Mohammed , Xia Ling , George Fantus I
Published: October 2024

Disclosure: M. Abubaker: None. L. Xia: None. I.G. Fantus: None.

Thioredoxin-interacting protein (Txnip) is a ubiquitously expressed protein that belongs to the α-arrestin family. It is unique among α-arrestin proteins in its ability to bind and inhibit thioredoxin (Trx), a major endogenous antioxidant. In the context of diabetes, hyperglycemia upregulates Txnip, which in turn promotes oxidative stress and apoptosis, and has been associated with progression of diabetes and its microvascular complications. Paradoxically, TXNIP also acts as a tumor suppressor, as evidenced by the development of hepatocellular carcinoma in Txnip knockout (KO) mice. Loss of Txnip is associated with enhanced glucose uptake but a shift in cellular metabolism towards glycolysis and lactate accumulation reminiscent of the Warburg effect seen in cancer cells. In our studies of glomerular mesangial cells (MC) we observed that late-passage cells (25 passages) exhibited significantly reduced Txnip expression (p<0.05) coinciding with the development of senescence, consistent with “replicative” senescence. To explore the role of Txnip, we compared primary mouse MC obtained from wild-type (WT) and Txnip KO mice at early passages (5-7). Txnip KO MCs displayed significantly increased expression of senescence markers P53 and P16, as well as enhanced senescence-associated beta-galactosidase staining (p<0.05), confirmed in kidney cortex of KO mice. Txnip KO MCs exhibited higher activation of Akt associated with lower PTEN activity compared to WT. Activation of Akt is known to stimulate the generation of reactive oxygen species (ROS). ROS (DCF fluorescence) were significantly elevated in Txnip KO MCs (p<0.05). While mitochondrial ROS generation (mitosox) was not altered, there was an increase in the expression of NADPH oxidase 4 (NOX4). Additionally, Txnip KO MCs showed increased activation of the oncogene RAS and reduced apoptosis. Inhibition of Akt rescued the senescence phenotype in Txnip KO MCs, accompanied by reduced total ROS and NOX4 expression. Accumulation of senescent cells is a hallmark of organismal aging. Using a Y-maze apparatus, we assessed spatial memory in 21-month-old mice. KO mice exhibited compromised memory function compared to their WT counterparts. Significantly, Txnip KO mice, male and female, showed a shortened lifespan (median WT 28 m; KO 20.3 m; and Maximum WT 38 m; KO 29.5 m; Kaplan-Meier p<0.001) and increased susceptibility to tumor growth at later ages. Our findings demonstrate for the first time that loss of Txnip contributes to cellular senescence through mechanisms consistent with oncogene-induced senescence, including increased Akt and RAS activation. These findings highlight the potential importance of Txnip in age-related diseases and tumorigenesis. Considering Txnip as a potential therapeutic target in diabetes, our data emphasize caution since overexpression and under-expression of TXNIP can both have adverse health consequences.

Presentation: 6/3/2024
8591 Tight Blood Glucose Control In Patients With Diabetes In The Icu Does Not Decrease Mortality: A Systematic Review And Meta-Analysis
Authors: Defante M L , Ximenes B X , Morais B A , Martins O C , Prizão V M , Correa T L , de Souza M M
Published: October 2024

Disclosure: M.L. Defante: None. B.X. Ximenes: None. B.A. Morais: None. O.C. Martins: None. V.M. Prizão: None. T.L. Correa: None. M.M. de Souza: None.

Tight Blood Glucose Control in Patients with Diabetes in the ICU Does Not Decrease Mortality: A Systematic Review and Meta-Analysis Background: Dysglycemia is a common complication in critically ill patients admitted to the Intensive Care Unit (ICU). However, there is controversy among clinical trials and a lack of evidence for patients with diabetes on this matter. Therefore, we aimed to perform a meta-analysis comparing tight with liberal blood glucose control among patients with diabetes in the ICU. Hypothesis: Among patients with diabetes, tight blood glucose control is a safe option in the ICU to avoid hyperglycemia episodes. Methods: We searched PubMed, Cochrane Central, and EMBASE for studies comparing tight with liberal blood glucose control in critically ill patients with diabetes in the intensive care unit. The main outcome was mortality. Statistical analysis was performed using Review Manager 5.17 (Cochrane Collaboration) and RStudio 2023.12.0. Heterogeneity was assessed with I² statistics and Cochran's Q test. Quality assessment was performed with the Cochrane tool for assessing the risk of bias in randomized trials. Results: 6 randomized clinical trials with 3,775 patients were included. The frequency of mortality showed no statistically significant difference between patients under tight blood glucose control (385/1872; 20.56%) compared to those under liberal blood glucose control (345/1903; 18.12%) (OR 1.16; 95% CI 0.98-1.37; p= 0.09; I²= 0%). No further analysis was conducted due to a lack of outcome data for patients with diabetes in the trials. All studies were considered at low risk of bias. The funnel-plot showed no evidence of publication bias despite the small number of studies. Conclusion: The mortality outcome showed no statistically significant difference between the intervention and control groups. Observational studies suggest that hyperglycemia and hypoglycemia may have different physiological implications in patients with diabetes, making them poor markers of physiologic stress and risk of mortality. More randomized clinical trials are needed to make it possible to run more robust meta-analyses and clarify this clinical question.

Presentation: 6/2/2024
7700 Two Years Of Testosterone Therapy Reduces Glycemia In Males At High Risk Of Type 2 Diabetes Without Affecting Beta Cell Function: Results From A Randomised Controlled Trial And Cellular Model
Authors: Umapathysivam M , Nawaz S , Robledo K , Allan C A , Bracken K , Grossmann M , Handelsman D J , Inder W J , Jesudason D , Stuckey B , Yeap B , Januszewski A , Jenkins A , Conway A , Hastoy B , Wittert G A
Published: October 2024

Disclosure: M. Umapathysivam: None. S. Nawaz: None. K. Robledo: None. C.A. Allan: None. K. Bracken: None. M. Grossmann: None. D.J. Handelsman: None. W.J. Inder: None. D. Jesudason: None. B. Stuckey: None. B. Yeap: None. A. Januszewski: None. A. Jenkins: None. A. Conway: None. B. Hastoy: None. G.A. Wittert: Consulting Fee; Self; I-Nova. Grant Recipient; Self; Lawley pharmaceuticals, Bayer, Weight Watchers, Eli Lilly & Company. Speaker; Self; Bayer, Inc., Amgen Inc, Besin Health Care.

Background: In the Testosterone for the prevention of type 2 diabetes (T4DM) Study, treatment with testosterone (T)-undecanoate (1000 mg IM 3 monthly) vs placebo decreased fat mass and reduced the risk of T2D by 40% after 2 years. However, the mechanism(s) by which T therapy prevents or reverts T2D remain unclear. Aim: To assess (1) the impact of T treatment on insulin resistance (IR) and beta-cell function in the T4DM study and (2) the in-vitro effect of graded T exposure on glucose stimulated insulin secretion (GSIS) from the human beta-cell line EndoC-βH1. Methods: (1) T4DM study: Men (n= 1007) from the T4DM study aged, 50-74 years, waist circumference (WC) >95cm, with prediabetes, or newly diagnosed T2D (by OGTT) and serum testosterone (T) ≤ 14 nmol/L (chemiluminescent assay) treated with T-undecanoate (1000 mg IM 3 monthly) or placebo for 2 years. Men were included if they had fasting bloods at baseline, weeks 18, 66, and 102 (N=743). We compared the change in glycated albumin, and derived measures of beta-cell function (HOMA2-B) and insulin resistance (HOMA-IR) using fasting glucose and c-peptide in T and placebo treated men using linear regression models.(2) EndoC-βH1 were incubated with T 5nM, 10nM and 15nM for 20 min and 15nM T for 2-days. Insulin secretion and content were measured at baseline (1mM glucose) and after 20 min exposure 20mM glucose. Results: Treatment with T compared to placebo reduced glycated albumin (-3.4 umol/L; 95%CI:1.4-5.4, p<0.001) maximally at week 66, along with C-peptide (corrected for baseline C-peptide and change in fasting glucose) (-0.12 nmol/L;-0.22,-0.02; p=0.01), HOMA2-B (-6.1; 95%CI: -16, 3.7; p=0.2) and HOMA-IR (-0.20; 95%CI: -0.59,0.20; p=0.3). In-vitro, acute exposure of EndoC-βH1 to 5nM and 10nM of T had no effect on GSIS, and 15nM T reduced GSIS (<20%, p=0.002). T, at 15nM for 2 days was without effect on GSIS. EndoC-βH1 insulin content was not altered at any concentration or timeframe of T exposure. Conclusion: In men with pre-diabetes or early T2D, T treatment reduces glycemia without evidence either in vivo or in-vitro of an affect to increase insulin secretion.

Presentation: 6/1/2024
7184 Type 2 Diabetes As An Independent Risk Factor For Increased Incidence Of Cardiovascular Events In Patient With Nonalcoholic Fatty Liver Disease
Authors: Roh E , Son K , Jung H , Huh J , Lee S , Ihm S H , Han K D , Kang J
Published: October 2024

Disclosure: E. Roh: None. K. Son: None. H. Jung: None. J. Huh: None. S. Lee: None. S. Ihm: None. K. Han: None. J. Kang: None.

Background: Although coexistence of type 2 diabetes (T2DM) and non-alcoholic fatty liver disease (NAFLD) has been linked to unfavorable metabolic profile and an increasing cardiovascular risk, the impact of T2DM on the risk of developing CVD within the context of NAFLD remains unclear. This study aimed to investigate long-term CVD outcomes in patients with NAFLD according to glycemic status using nationwide cohort of Korean adults. Methods: This retrospective, longitudinal study included 1,057,775 patients with NAFLD, who had participated in the national health screening in 2009 and were followed up until 2020. The baseline glycemic status was divided into three categories [normal fasting glucose (NFG), impaired fasting glucose (IFG) and T2DM]. Cox proportional hazards models were used to assess the association of glycemic status with incident CVD. Results: During a median follow-up period of 10.3 years, 26,491 cases of MI, 55,791 cases of stroke, and 11,147 cases of CV death were identified. After adjusting for possible covariates, participants with T2DM had a higher risk of CVD, with hazard ratios of 1.394 (95% CI 1.351−1.439) for MI and 1.391 (95% CI 1.362−1.420) for stroke, and 1.457 (95% CI 1.392−1.524) for CV mortality, compared to those with NFG. The increased risk of CVD attributable to T2DM was more profound among individuals with fewer conventional CVD risk factos, including younger age, not obese, and the absence of hypertension. Conclusions: These results suggest that the identification of T2DM in individuals of NAFLD may help the prediction of future progression of CVD.

Presentation: 6/3/2024
8145 Type 2 Diabetes In A Patient With IMAGe Syndrome
Authors: Mulpuri Neha , Mirfakhraee Sasan , Abramowitz Jessica
Published: October 2024

Disclosure: N. Mulpuri: None. S. Mirfakhraee: None. J. Abramowitz: None.

Background: Individuals with mutations that lead to deficiency of POLE1 (a catalytic subunit of polymerase epsilon) may have clinical features of IMAGe syndrome (intrauterine growth restriction, metaphyseal dysplasia, adrenal hypoplasia congenital, and genitourinary anomalies) in addition to distinctive facial features and variable immunodeficiency. Of 15 reported cases in the literature, none were previously characterized with type 2 diabetes mellitus (T2DM). Clinical case: This is a 25-year-old woman with a history of IMAGe syndrome (confirmed mutation in the POLE gene). With regards to IMAGe syndrome history, during the prenatal period, she had growth restriction in the third trimester with delivery at 38 weeks. At 4 years-old, she presented with adrenal crisis and was started on glucocorticoid and mineralocorticoid therapy, now taking hydrocortisone 2.5mg three times daily (8.6 mg/m2/day) and fludrocortisone 0.05mg daily. Initial labs in the adult endocrine clinic were notable for serum glucose 339 mg/dL (65-99 mg/dL), undetectable estradiol (< 15 pg/ml) with FSH 6.8 mIU[JA1] /mL and LH 2.0 mIU/mL, TSH 1.25 mIU/L (0.40-4.50 mIU/dL), FT4 0.7 ng/dL (0.8-1.8 ng/dL). The patient denied any history of T2DM. She also denied polyuria, polydipsia, or weight loss. There was no stigmata of peripheral insulin resistance on exam. Subsequent labs included HbA1c 8.9%, fructosamine 417 mcmol/L (200-285 mcmol/L), insulin 18.4 mcIU/mL (2.6-24.9 mcIU/mL), and C-peptide 3.9 ng/dL (1.1-4.4 ng/dL) with serum glucose 164 mg/dL. Islet cell, insulin, and GAD-65 antibodies were undetectable. CT abdomen/pelvis did not show any pancreatic mass or anomalies. Initially, prandial insulin (lispro 3 units prior to each meal) was initiated given post-prandial hyperglycemia noted on continuous glucose monitoring. Low-dose levothyroxine, 25 mcg daily, was initiated given concern for secondary hypothyroidism, with subsequent normalization of serum thyroxine. HbA1c improved to 7.4% six months later. Ultimately, she transitioned to sitagliptin 25 mg daily and her latest HbA1c was 6.2% three years after initial diagnosis of T2DM. Conclusion: Of the 15 cases of IMAGe syndrome with mutations in POLE described in Logan et al, none were noted to have diabetes. The patient described above was diagnosed with new-onset diabetes at age 21, presumably T2DM in the context of undetectable antibodies and high-normal C-peptide. Interestingly, she did not have any typical stigmata of peripheral insulin resistance. Glucocorticoids used for the treatment of adrenal insufficiency in patients with IMAGe syndrome can contribute to development of T2DM. Patients with IMAGe syndrome on chronic glucocorticoids should be monitored for hyperglycemia and diabetes. Additionally, glucocorticoid doses should be optimized to balance mitigating side effects such as hyperglycemia and osteoporosis while preventing adrenal crisis.

Presentation: 6/3/2024
8178 Uncontrolled Diabetes Mellitus Presenting As Chronic Diarrhea
Authors: Nguyen Huong D
Published: October 2024

Disclosure: H.D. Nguyen: None.

Introduction: Majority of patients with newly diagnosed diabetes mellitus present with well-known symptoms and signs of hyperglycemia, including polydipsia, polyuria, visual disturbances, fatigue, weight loss. Fewer than one percent of patients present with chronic diarrhea (1). We hereby present a case of uncontrolled DM presenting as chronic diarrhea. Case: A 44-year-old male with history of post-ablative hypothyroidism, class I obesity, vitamin D deficiency reported 4 to 5 months history of increased stool frequency 4-5 times a day and intermittent watery, non-bloody, non-tarry diarrhea 2 times a week. No fever, chills, weight loss, or recent travel. Diarrhea had not improved with a 2-month trial of low FODMAP diet. On the physical exam, height 177cm, weight (wt) 97kg, BMI 30.56 in 11/2023 (wt 98 kg in 4/2023). Laboratory work-up showed wbc 7.4K (4.2-9.2), CRP 0.4 mg/dl, ESR 15mm/hr, TSH 0.943 mcIU/ml (.45-4.5), tTG IgA <2U/ml, deamidated gliadin IgA 6 units (0-19), IgA 159 mcg/dl (90-386), fecal calprotectin 74 mcg/g (0-120), HIV negative, stool H pylori negative. BG 287 mg/dl, A1c 10.2% 11/29/23 (was 5.6% 2020). He was started on insulin glargine and aspart. At the 6-week follow-up, blood glucose improved to 70s to low 100s, and stool frequency improved to 2 times/day and diarrhea had resolved. Discussion: Chronic diarrhea, defined as having 3 or more stools a day for more than 4 weeks, can affect about 10% of patients with diabetes mellitus. Many of these patients have associated conditions such as celiac disease, food intolerance, chronic pancreatitis with pancreatic exocrine insufficiency, bacterial overgrowth, inflammatory bowel disease, bacterial or parasitic infections, or medication adverse side effects. Some studies have attributed diarrhea of unknown causes in patients with DM to autonomic dysfunction (2). Other studies have shown diarrhea may be due to increased colonic transit time and altered intestinal pH rather than autonomic dysfunction (3). Since the underlying cause of diabetic diarrhea is not always clear, empiric symptom treatment may be indicated. Transdermal clonidine may be helpful in controlling diarrhea without causing orthostatic hypotension. In this case, as the stool frequency and diarrhea improved without any other treatment after diabetes control improved, we believe the underlying cause was uncontrolled DM. Conclusion: Uncontrolled DM should be on the differential diagnosis for chronic diarrhea of unclear etiology. References: 1. Miller, LJ. Small intestinal manifestations of diabetes mellitus. The Yale Journal of Biology and Medicine.1983; 56:189-193,1983. 2. Ogbonnaya, KI et al. Diabetic diarrhea. Pathophysiology, diagnosis, and management. Arch Intern Med. 1990; 150:262-267. 3. Sangnes DA et al. Diabetic diarrhea: a study on gastrointestinal motility, pH levels and autonomic function. Journal of Internal Medicine. 2021; 290:1206-1218.

Presentation: 6/3/2024
6562 Understanding The Role Of The Novel Hexokinase HKDC1 In Alzheimer’s Disease
Authors: Farooq Zeenat , Jorgensen Julianne , Layden Brian T
Published: October 2024

Disclosure: Z. Farooq: None. B.T. Layden: None.

Alzheimer’s disease (AD) is a chronic neurodegenerative condition, clinically characterized by loss of neurons. AD is responsible for causing 70% of global cases of dementia and constitutes and huge health and socio-economic burden, with limited availability of therapeutic options. While loss of neuronal integrity in AD is known, studies thus far have focused only on the deposition of amyloid plaques, leaving a huge gap in our understanding of the role of metabolic regulation and inflammation associated with AD. Studies in the literature suggest a link between accumulation of amyloid beta plaques, altered insulin action, and perturbed hypothalamic glucoregulation in AD pathology leading to increased hepatic glucose production and hyperglycemia. However, the complex mechanisms underlying the deleterious impact of metabolic derangements and insulin resistance on AD pathogenesis are poorly characterized. HKDC1, the fifth hexokinase, is highly expressed in the normal brain, with decline in expression observed in aging and Alzheimer’s disease mice models, but its function remains entirely unexplored. However, it is known to be involved in gestational diabetes mellitus (GDM), type 2 diabetes (T2D), and fatty liver disease. In this study, we explored the role of brain specific HKDC1 in pathogenesis of AD with our brain specific HKDC1 knock out (KO) and other mice models. We have observed that loss of HKDC1 in the brain is accompanied by dysregulation of glucose metabolism, decline in memory and learning, and an increase in senescence and neuroinflammation in mice. Interestingly, we have also observed that HKDC1 is exclusively localized to mitochondria in the brain and its absence leads to a reduction in the expression of markers of mitochondrial biogenesis, while causing an increase in tau-phosphorylation and ER stress. Through RNA sequencing, we have also identified novel targets of HKDC1 in the brain related to metabolic networks, triggering the pathogenesis of AD downstream of HKDC1. These findings uncover a novel role for HKDC1 as a key metabolic gene involved in the pathogenesis of AD in a mitochondrial-dependent manner in mice. Further studies on dissecting the molecular mechanism of HKDC1 involvement in AD could define a novel strategy for timely intervention of Alzheimer’s disease and possibly other forms of dementia.

Presentation: 6/1/2024
12322 Unraveling The Complexity Of Stiff-Person Syndrome: A Case Of Ozempic-Induced Gastric Paralysis In A Patient With Comorbid Type 2 Diabetes Mellitus
Authors: Igburuke Loveth Eseoghene , Tawde Poonam , Oparaocha Victory , Horani Mohamad Hosam , Salim Yusuf , Salim Muhammad , Salim Omar
Published: October 2024

Disclosure: L.E. Igburuke: None. P. Tawde: None. V. Oparaocha: None. M.H. Horani: None. Y. Salim: None. M. Salim: None. O. Salim: None.

Stiff-Person Syndrome (SPS) is a rare neurological disorder characterized by persistent muscle stiffness and spasms, often triggered by emotional or physical stress. The condition, predominantly affecting adults with a slight female preponderance, is believed to result from autoimmune mechanisms targeting glutamic acid decarboxylase (GAD). Treatment usually involves symptomatic relief with medications like benzodiazepines, while immunomodulatory therapies are considered for refractory cases. Despite its low prevalence, SPS is noteworthy due to its association with autoimmune conditions. The clinical landscape of SPS is complicated by its link to gastrointestinal dysmotility, stemming from dysregulation in GABAergic pathways. Patients with SPS are predisposed to gastrointestinal issues, which can be exacerbated by certain medications, such as glucagon-like peptide-1 (GLP-1) receptor agonists like Ozempic (semaglutide). GLP-1 receptor agonists, although effective for managing type 2 diabetes, can rarely cause severe gastrointestinal complications, including gastric paralysis. This report details a case of a 55-year-old male with SPS and type 2 diabetes mellitus who developed gastric paralysis following Ozempic therapy. The patient presented with progressive muscle stiffness and spasms over six months, with a history of type 2 diabetes and hypertension. Despite treatment with diazepam and gabapentin, his symptoms persisted, leading to the addition of Ozempic. Shortly after starting Ozempic, he experienced severe gastrointestinal symptoms, including nausea, vomiting, and abdominal distension. Gastric paralysis was confirmed through gastric emptying studies and esophagogastroduodenoscopy. Despite stopping Ozempic and supportive care, the patient required prolonged hospitalization. Gradual improvement in gastric motility was observed, and the patient was eventually discharged with ongoing management of SPS and diabetes. This case highlights the diagnostic and therapeutic challenges in managing SPS, particularly with comorbidities like type 2 diabetes. While GLP-1 receptor agonists are beneficial for diabetes management, they can lead to severe gastrointestinal issues, especially in patients with underlying neurological conditions. Clinicians should carefully consider the risk of gastrointestinal complications when prescribing GLP-1 receptor agonists and monitor patients closely to optimize outcome.

Presentation: 6/1/2024
6992 Unveiling Factitious Hypoglycemia
Authors: Patel T A , Chlebek S , Porter T
Published: October 2024

Disclosure: T.A. Patel: None. S. Chlebek: None. T. Porter: None.

Background: Factitious disorder causing hypoglycemia is a condition in which a patient intentionally uses a glucose-lowering agent without any apparent external gains. This is a rare and challenging clinical diagnosis, which often results in the use of unnecessary medical resources. Clinical Case: A 31-year-old woman, with a history of Type 1 Diabetes and Hypothyroidism, was admitted to the Intensive Care Unit (ICU) for persistent severe hypoglycemia. The patient reported an increase in the frequency and severity of hypoglycemic episodes despite a progressive reduction in her total daily insulin use; most recently, with complete cessation of insulin use for 2 months. A review of outside medical records revealed multiple emergency room visits and hospitalizations due to hypoglycemia. Notably, the patient was an emergency department registered nurse (RN). On admission, the patient was placed on a dextrose infusion with as needed dextrose boluses. Despite these interventions, she continued to become intermittently hypoglycemic. Initial tests were consistent with exogenous insulin use: critically low serum glucose (31 mg/dL, normal 60-99 mg/dL), undetectable C-peptide (<0.1 ng/mL, normal 1.1-4.4 ng/mL), and elevated insulin (32.3 uIU/mL, normal 2.6-24.9 uIU/mL). The patient denied recently self-administering insulin and she was not treated with insulin in the hospital prior to obtaining these labs. Additionally, there was a significant rise in the glucose level (58 mg/dL, positive >30 mg/dL) after intramuscular administration of 1 mg glucagon, which confirmed insulin mediated hypoglycemia. The remainder of the biochemical work-up was unremarkable. GAD65 and IA-2 autoantibodies were positive, confirming the patient’s history of type 1 diabetes. It was recommended that the patient have a one-to-one sitter for continuous direct observation. The patient, thereafter, became hyperglycemic with no further episodes of hypoglycemia for the remainder of the hospitalization. Psychiatry was placed on consult and diagnosed the patient with factitious disorder. Conclusion: Factitious disorder is a rare but important condition to be included in the differential diagnosis of recurrent hypoglycemia. Biochemical findings will include a low serum glucose, undetectable C-peptide, and an inappropriately elevated insulin. Psychiatric evaluation can, thereafter, support the diagnosis and clinical management. Establishing the diagnosis of factitious hypoglycemia is critical for appropriately treating these patients, minimizing unnecessary testing, and avoiding multiple hospitalizations.

Presentation: 6/3/2024
Iteratively Reweighted Least Squares-based Generalized Linear Model for Assessing the Impact of Macroeconomic Indicators on Property Investment
Authors: Abubakar Hamza , Misiran Masnita , Karaye Abubakar Balarabe , Gambo Nura
Published: October 2024

This study explores the impact of macroeconomic indicators on Net Present Value (NPV) in the Malaysian property sector from 2010 to 2022. Using data from Sharia-compliant property firms, Generalized Linear Models (GLMs) and logistic regression analyze Consumer Price Index (CPI), Gross Domestic Product (GDP), interest rate (IR), and exchange rate (ER) effects on NPV. Significant positive associations are found for CPI (coefficient = 0.028, p = 0.001) and GDP (coefficient = 0.004, p = 0.045), indicating higher inflation and economic growth enhance NPV. Conversely, ER (coefficient = −0.015, p = 0.003) and IR (coefficient = −0.042, p < 0.001) negatively impact NPV, reflecting currency volatility and borrowing costs. GLM-IRLS models show robust predictive power (Deviance = 235.67, R-squared = 0.30), informing strategic decision-making for property investments amid economic fluctuations.
Recurrent Anterior Shoulder Dislocation with Coracoid Fracture in an Old Age Male: A Rare Case Report
Authors:   Department of Orthopaedics, Pt. Madan Mohan Malviya Hospital, Mumbai, Maharashtra, India., Sawant Kaustubh , Bansal Sagar ,   Department of Orthopaedics, Pt. Madan Mohan Malviya Hospital, Mumbai, Maharashtra, India.
Published: October 2024

Introduction:Anterior shoulder dislocation is a common pathology in young males with less prevalence in other age groups. Anterior shoulder dislocation being the most common variety of dislocation among the shoulder dislocation can be managed both conservatively and surgically. Recurrent anterior dislocation in middle-aged males with a coracoid fracture is a rare entity and should be managed with proper pre-operative planning including computed tomography (CT) scan, magnetic resonance imaging (MRI), and surgery. Case Report: A 65-year-old male is a known case of recurrent anterior dislocation presented with anterior shoulder dislocation 1½ years back. Closed reduction was done. Radiological evaluations such as CT scan and MRI were done which were suggestive of bony Bankart and coracoid fracture which was managed with open Latarjet procedure. Conclusion: Recurrent anterior shoulder dislocation with a concomitant coracoid fracture is a rare entity in old age, which can be managed with a Latarjet procedure and has a good post-operative outcome. Keywords: Recurrent anterior shoulder dislocation, coracoid fracture, Latarjet procedure.
Synovial Hemangioma: An Overlooked Cause of Chronic Knee Pain in Children
Authors:   Department of Orthopaedics, Indira Gandhi Institute of Medical Science, Patna, Bihar, India,, Kumar Indrajeet , Sanchay Vaibhav ,   Department of Orthopaedics, Indira Gandhi Institute of Medical Science, Patna, Bihar, India,, Ahmed Wasim ,   Department of Orthopaedics, Indira Gandhi Institute of Medical Science, Patna, Bihar, India,, Kumar Santosh ,   Department of Orthopaedics, Indira Gandhi Institute of Medical Science, Patna, Bihar, India,, Bhadani Janki Sharan ,   Department of Orthopaedics, Paras HMRI Hospital, Patna, Bihar, India.
Published: October 2024

Introduction: Synovial hemangioma of the knee is a benign vascular malformation that is often misdiagnosed due to its non-specific symptoms. Case Report: We present a case involving a 7-year-old male child with chronic knee pain and swelling in the left knee, which remained undiagnosed for over 3 years. Magnetic reso-nance imaging revealed a synovial vascular malformation. Surgical excision of the lesion and partial synovectomy were performed, and histopathological analysis confirmed the di-agnosis of synovial hemangioma. After 18 months of follow-up, there were no signs of re-currence or recurrent joint effusion. Conclusion: Synovial hemangioma of the knee, although uncommon, should be considered as a differential diagnosis in cases of chronic knee pain and swelling. En-bloc excision is the treatment of choice to prevent recurrence, yielding good clinical outcomes. Keywords: Synovial hemangioma, chronic knee pain, pediatric knee swelling, synovial vascular malformation, atraumatic knee pain.
Arthroscopic Reconstruction of Injured Anterior Cruciate Ligament Using Peroneus Longus Graft With Fixed Loop Endobutton – A Prospective Study
Authors:   Department of Orthopaedic Surgery, J.J.M. Medical College, Davangere, Karnataka, India., Shetty Subodh B , Prabhakar Powdhan H ,   Department of Orthopaedic Surgery, J.J.M. Medical College, Davangere, Karnataka, India., Kajava Vachan ,   Department of Orthopaedic Surgery, J.J.M. Medical College, Davangere, Karnataka, India., Rao Harsh Kirthi ,   Department of Orthopaedic Surgery, J.J.M. Medical College, Davangere, Karnataka, India., M. K. Lokesh Sarma ,   Department of Orthopaedic Surgery, J.J.M. Medical College, Davangere, Karnataka, India.
Published: October 2024

Introduction: ACL injuries are more common amongst active young people where RTA and sports injuries predominate as the most common methods of injury ACL reconstruction with peroneus longus graft method have been used more frequently nowadays. The advantages of peroneus longus graft are, Adequate graft length of minimum of 25 to 30 cm. Adequate thickness of minimum 8.5 to 9mm,Less incidence of graft thinning, Lesser hamstring and quadriceps weakness, Minimal donor site morbidity. Minimal restriction of ankle movements. Materials and Methods: A prospective study of 25 patients with injured anterior cruciate ligament without meniscal injury within the age group of 18-55 years managed with arthroscopic reconstruction of anterior cruciate ligament with peroneus longus graft and fixed loop endobutton at femoral side and interference screw at tibial side. Functional outcome was assessed using clinical examination, International Knee Documentation committee and Lysholm knee scoring scale, FADI score (foot and ankle disability index score). Patients were followed up at 2, 4, 8, 12weeks and 6, 8 months post-operatively. Results: This study consists of 25 cases of Anterior Cruciate Ligament injury. ACL rupture was common in second and third decade of life. In our study, 18(63.34%) were sports related injuries, 5(26.66%) were due to road traffic accidents and 2(10%) were atraumatic degenerations. 22(80%) showed excellent results and 3(20%) showed good results. Conclusions: Arthroscopic ACL reconstruction using peroneus longus graft and Fixed-loop Endobutton and interference screws provided excellent post-operative clinical outcome in terms of knee stability, subjective knee and ankle function and range of movements of the knee and ankle in our study. Keywords: Arthroscopic surgery, Anterior cruciate ligament, Fixed-loop Endobutton, interference screws peroneus longus graft