bluuebunny/crossref_metadata_2025_split huggingface dataset:
8202 Retrospective Analysis of Mixed-Meal Testing in People with Suspected Spontaneous Post-Prandial Hypoglycemia
Authors: Sankaran Naveena , Jalleh Ryan , Bischoff Carmen , Marathe Chinmay 
Published: October 2024

Abstract
Disclosure: N. Sankaran: None. R. Jalleh: None. C. Bischoff: None. C. Marathe: None.
Introduction: While there is no consensus on the optimal confirmatory test for postprandial hypoglycemia, guidelines suggest evaluation with a mixed meal test that is most likely to provoke symptoms of hypoglycemia as nominated by the patient. However, studies evaluating post-bariatric surgery hypoglycemia indicate that meals with a lower carbohydrate content are less likely to be associated with postprandial hypoglycemia. It is hypothesized that a greater carbohydrate load may result in an excessive second-phase insulin response resulting in hypoglycemia. We evaluated the outcomes of consecutive mixed meal tests in individuals with suspected spontaneous postprandial hypoglycemia and the relationship with the percentage carbohydrate content of the test meal. Methods: We retrospectively analysed the data of 103 unselected patients who were referred to undergo a 5-hour mixed meal test following an overnight fast, between the years 2010 - 2023 at the Royal Adelaide Hospital. Correlations were determined using a linear regression model and Student’s t-test was used to compare the mean carbohydrate meal content in those with and without postprandial hypoglycemia. Outcomes: Outcomes that were measured included post-meal blood glucose, plasma insulin, plasma C-peptide levels and the macronutrient composition of the meal. Subjective reporting of symptoms during the test were also noted and correlated with the symptoms included in the Edinburgh Hypoglycemia Score. Results: 33/103 participants were excluded as they had previously undergone islet cell transplant or bariatric surgery. Out of the remaining 70 participants referred for confirmatory MMT testing, 51 were female and 19 were male. The ages of the participants ranged from 16 to 74, with the median age of 40 years. 9 participants (6 females and 3 males) had abnormal results with glucose below 3.0mmol/L. 34 participants experienced hypoglycemia with glucose levels recorded below 4.0mmol/L during the test. There was no difference in carbohydrate content consumed (61.1g, P=0.30) or percentage carbohydrate (64.5%, P=0.17) in the group without postprandial hypoglycemia compared with those with postprandial hypoglycemia (carbohydrate content 67.9 g, 69.6% carbohydrate). No correlation could be identified between the percentage of carbohydrate content of the meal with the glucose nadir (P=0.75), peak insulin concentration (P=0.99) or peak C-peptide concentration (P=0.40). The percentage of carbohydrate content of the meal was neither associated with hypoglycemia (P=0.17) or symptoms (P=0.41). Conclusion: On mixed meal testing, postprandial symptoms and hypoglycemia does not correlate with either carbohydrate load or the percentage carbohydrate content of the nominated meal.
Presentation: 6/1/2024
6769 Rhabdomyolysis In Diabetic Emergencies Highlighting The Necessity Of Prompt Creatine Kinase Monitoring
Authors: Tiwari Apoorv , Corsten Melanie , Salari Wajiha , Malik Nikhale , Dabaja Abed , Saad Chadi 
Published: October 2024

Abstract
Disclosure: A. Tiwari: None. M. Corsten: None. W. salari: None. N. Malik: None. A. Dabaja: None. C. Saad: None.
Rhabdomyolysis results from skeletal muscle necrosis, causing the release of intracellular contents into the bloodstream. While its association with life-threatening diabetic emergencies is rare, it remains a significant complication. We detail the case of a 37-year-old male admitted with acute pancreatitis who subsequently developed a hyperosmolar hyperglycemic state accompanied by significant electrolyte imbalances. Upon arrival at our emergency department, he displayed severe dehydration, stupor, a blood glucose level surpassing 2,000 mg/dl, and high anion gap metabolic acidosis. His condition worsened when his creatine kinase levels surged from 210 U/L to 39,000 U/L, leading to oliguric renal failure and the need for hemodialysis. His thyroid profile was unremarkable and was not on any medication. Comprehensive treatment included crystalloids, parenteral insulin, and rigorous ICU monitoring with mechanical ventilation. Following this, the patient showed rapid improvement and was discharged without requiring further dialysis. A thorough history and observation established a rare but strong link between rhabdomyolysis and hyperosmolar hyperglycemic states. These situations can intensify nephrotoxic events, especially in patients already facing severe dehydration and prerenal factors. This case emphasizes the critical need for consistent monitoring of creatine kinase levels in diabetic emergencies. Such monitoring ensures early detection and facilitates effective management of rhabdomyolysis-induced acute kidney injury, reducing potential complications and improving patient outcomes.
Presentation: 6/3/2024
12560 RIMOC1, A Novel Regulator Of Mitochondrial Function, And Its Role In Pancreatic Beta-cell Survival, Mitophagy, And Diabetogenesis
Authors: Filingeri D , Liu R , Negi V , Lee J , Kumar A , Mandi V , Moulik M , Yechoor V 
Published: October 2024

Abstract
Disclosure: D. Filingeri: None. R. Liu: None. V. Negi: None. J. Lee: None. A. Kumar: None. V. Mandi: None. M. Moulik: None. V. Yechoor: None.
Background: Literature supports preserving beta-cell function as an approach to slowing diabetes progression. Mitochondria emerge as an interesting area of focus, driving cellular respiration and glucose-stimulated insulin secretion (GSIS) within beta-cells in physiologic conditions, and leading to increased intracellular ROS generation when damaged. Damaged mitochondria are recycled via lysosomes by mitophagy, and defects in mitophagy have been linked to numerous disease states, with more recent data implicating impaired mitophagy with beta-cell death. Our previous work on the Hippo-TEAD pathway and beta-cell survival led to the isolation of the TEAD binding partner RIMOC1 (RAB7A-Interacting MON1-CCZ1 Complex Subunit 1), a protein highly expressed in pancreatic beta-cells, though its role in beta-cells remains unknown. The overarching hypothesis is that RIMOC1 is protective against the development of diabetes by preserving beta-cell mitophagy and mitochondrial function, and that impaired RIMOC1 function would lead to beta-cell failure and diabetes.Methods: We have generated both a stable INS2 RIMOC1 KO (knockout) cell line and an INS1-Cre RIMOC1 KO mouse model, that are beta-cell specific knockouts of RIMOC1. Mitochondrial membrane potentials were measured using TMRE and JC1 stains, and mitophagy was quantified using the mtKeima probe via flow cytometry. Protein expression was quantified via western blotting. Ongoing studies involving our mouse model include in vivo GTTs (glucose tolerance testing), ex vitro GSIS experiments to assess beta-cell function from mouse islets, and seahorse assays to quantify mitochondrial function. Results: Published GEO datasets show RIMOC1 expression is positively correlated with beta-cell maturity and negatively correlated with glucose load and HgbA1c. Our in vitro data demonstrates RIMOC1 knockout leads to decreased insulin mRNA expression, decreased insulin content, and increased beta-cell cycle inhibition. Early in vivo data shows worsened hyperglycemia with oral refeeding after fasting. In vitro mitophagy experiments demonstrate significantly diminished mitochondrial membrane potential in RIMOC1 KO INS2 cells. Conclusions: RIMOC1 is highly expressed in beta-cells and has a significant role in maintaining euglycemia through mitochondrial functioning, insulin processing, and altered mitophagy. This research highlights RIMOC1 as a promising target of further diabetes research.
Presentation: 6/2/2024
8297 Risk Of Pancreatic Cancer In Patients With Diabetes Mellitus And Pancreatitis: A Nationwide Nested Case-Control Study
Authors: Kim Young-eun , Kim Hae Kyung , Yu Min Heui , Nam Chung Mo , Kang Eun Seok 
Published: October 2024

Abstract
Disclosure: Y. Kim: None. H. Kim: None. M. Yu: None. C. Nam: None. E. Kang: None.
Background: Despite diabetes mellitus and pancreatitis being known risk factors for pancreatic cancer, but because of their low incidence, patients with these conditions are not included in pancreatic cancer screening. This study aimed to determine the high-risk subgroup of patients with diabetes and pancreatitis that would benefit from pancreatic cancer screening. Methods: A nested case-control study was conducted using data from the national health information database of the Korean National Health Insurance Service. Patients were categorized into the following groups: type 2 diabetes only (T2D-only), pancreatitis only (PAN-only), type 2 diabetes followed by pancreatitis (T2D-PAN), post-pancreatitis DM (PPDM), and no diabetes and no pancreatitis (NDNP). Conditional logistic regression was used to determine significant associations of each group with pancreatic cancer development risk. Results: The risk of pancreatic cancer was significantly higher in the T2D-PAN (adjusted odds ratio [AOR], 4.96; 95% confidence interval [CI], 4.48-5.49) and PPDM (AOR, 4.71; 95% CI, 4.12-5.37) groups than in the NDNP group. Furthermore, the T2D-PAN and PPDM groups had a significantly higher risk of pancreatic cancer than the T2D-only and PAN-only groups. Compared to patients in the NDNP group, patients with PPDM using insulin had a 9-fold increased risk (AOR, 9.84; 95% CI, 6.77-14.29), and patients with T2D-PAN using insulin had a 6-fold increased risk (AOR, 6.62; 95% CI, 5.33-8.20). Conclusion: Patients with both diabetes and pancreatitis had a higher risk of pancreatic cancer than those with either alone, regardless of the order of occurrence, and insulin use was associated with an additional increase in pancreatic cancer risk. These results suggest that these subgroups of patients could be considered to benefit from pancreatic cancer screening.
Presentation: 6/2/2024
12338 Risk Of Retinopathy In Patients With Type 2 Diabetes On Semaglutide
Authors: Gupta A , Nassar M , Ghanim H 
Published: October 2024

Abstract
Disclosure: A. Gupta: None. M. Nassar: None. H. Ghanim: None.
Title: Risk of Retinopathy in Patients with Type 2 Diabetes on SemaglutideBackground: The use of semaglutide in patients with diabetic retinopathy (DR) has raised safety concerns. While previous studies, including a meta-analysis and the SUSTAIN trial, suggested an association between rapid HbA1c reduction and retinopathy progression, recent data question the increased risk with semaglutide. Our study investigates this risk of intensive therapy benefits for the prevention of DR. Methods: This retrospective cohort study utilized TriNetX electronic health records, analyzing 117,693,426 patients with type 2 diabetes mellitus (T2DM) on anti-hyperglycemic drugs. We divided patients into those with and without a history of retinopathy, further subdividing them by treatment (Semaglutide, Sitagliptin, and Empagliflozin). After matching for confounders, we analyzed the incidence and progression of retinopathy among 336,338 Semaglutide, 578,117 Sitagliptin, and 434,552 Empagliflozin patients without a history of DR, as well as a cohort with history. Results: In patients without a prior history of DR, semaglutide showed a significant reduction in DR incidence over three years compared to sitagliptin and empagliflozin (p&lt;0.0001). However, in those with a history, the reduction was not statistically significant (p &gt; 0.05). Patients with mild DR on Semaglutide experienced fewer progressions to severe stages (p&lt;0.0001), while outcomes in severe cases were inconclusive.Discussion: Semaglutide may lower the risk of developing DR in patients with T2DM without a prior history of DR and potentially stabilize or improve mild conditions without worsening severe retinopathy. The observed effects could influence treatment choices, emphasizing the need for individualized patient management. Conclusion: Semaglutide appears safe regarding retinopathy risk in patients with T2DM, offering protective benefits in those without history and not exacerbating conditions in those with prior DR. This underscores the drug's potential for comprehensive diabetes management without compromising ocular health.
Presentation: 6/3/2024
8030 Sexually Dimorphic Metabolic Consequences Of CCN5/WISP2 Gene Deletion Revealed A Male-Specific Pattern Of Gene Expression
Authors: Yang M , Xega V , Zakikhani M , Liu J L 
Published: October 2024

Abstract
Disclosure: M. Yang: None. V. Xega: None. M. Zakikhani: None. J. Liu: None.
Matricellular protein CCN5/WISP2 is a novel target of IGF-1 and WNT signaling within the pancreatic islets. Our previous research suggests CCN5 promotes β-cell proliferation and survival through Akt/PKB and focal adhesion kinase signaling pathways. More recently, we have reported sexual dimorphic features of CCN5 gene deletion and overexpression. Specifically, male knockout mice demonstrated improved insulin sensitivity and glucose tolerance upon high-fat diet (HFD)-induced obesity, while females were unaffected (ENDO 2022). On the other hand, male aP2-CCN5 transgenic mice that overexpress CCN5 in adipose tissues were partially protected from HFD-streptozotocin induced diabetes, with improved glucose tolerance; females exhibited impaired glucose tolerance and exacerbated diabetes (ENDO 2023). Our findings indicate that an increased level of CCN5 protects β-cells, but only in male mice. This protection cannot be solely attributed to the pro-islet effect and suggests the involvement of extra-pancreatic and sex-specific roles. This study indirectly screened normal CCN5 gene expression by detecting β-galactosidase activity, measured in X-gal-stained tissues before fixation and sectioning. In order to create the gene deletion through homologous recombination, LacZ was inserted between exons 2 and 5 of the CCN5 gene. As a result, male knockout mice exhibited a distinct blue staining in the pseudostratified columnar epithelium with stereocilia of the epididymis and vas deferens. This type of epithelium comprises a single layer of cells but appears to have multiple layers due to the nuclei being at different levels. The epithelium possesses long projections made of actin filaments and plays a crucial role in absorbing, transporting, and maturing sperm cells. The staining was also clear in Leydig cells of the testis, which produce testosterone, which was confirmed using immunohistochemistry and authentic CCN5 antibody. In female mice, however, only a few cells in the ovary and scattered staining was observed in the endometrial glands of the uterus. Since androgens promote energy expenditure, lipolysis, and insulin sensitivity, knockout or overexpression of CCN5 may potentially affect androgen and/or sperm production, leading to metabolic consequences in males. Our results from in vitro, knockout, and overexpression models support the notion that CCN5 promotes β-cell growth and survival against diabetes and further suggest that it possesses sex-specific, metabolic effects.
Presentation: 6/2/2024
7657 Single Cell RNAseq And Omics Revealed Novel Role Of Liver Group 2 Innate Lymphocytes In Regulation Of Hepatic Gluconeogenesis
Authors: Fujimoto Masanori , Tanaka Tomoaki 
Published: October 2024

Abstract
Disclosure: M. Fujimoto: None. T. Tanaka: None.
Background: The liver is an important organ that maintains homeostasis of glucose metabolism in the body through gluconeogenesis. It is considered that gluconeogenesis in hepatocytes is particularly active around the portal vein. However, since excessive gluconeogenesis aggravates the pathogenesis of diabetes, it is necessary to elucidate the regulatory mechanism of gluconeogenesis. Although several studies revealed that group 2 innate lymphocytes (ILC2) contribute to blood glucose maintenance in adipose and pancreatic tissues, the contribution of liver ILC2s to glucose metabolism is unknown. This study aims to elucidate the contribution of liver ILC2s to glucose metabolism and its molecular mechanism. Methods: We administered IL-33, an endogenous ILC2 activator, to BALB/c and NSG mice, and measured fasting blood glucose levels and blood glucose elevation by gluconeogenic substrate pyruvate, and blood glucose levels in liver ILC2s transplanted NSG mice. Molecular mechanisms were analyzed by single cell-RNAseq (scRNA-seq) of liver ILC2s, lung ILC2s and hepatocytes, GATA3 transcription complex, ATAC-seq, GATA3-ChIP-seq, and Metabolomics of primary hepatocytes. Results: IL-33 strongly induced IL-13 production by liver ILC2s, lowered fasting blood glucose, and suppressed pyruvate-induced glucose elevation; these effects were not observed in NSG mice lacking immune cells including ILC2s. A hypoglycemic effect of IL-33 was observed in liver ILC2-transplanted NSG mice, but not in mice transplanted with IL-13-deficient ILC2s, suggesting the effect is IL-13-dependent. scRNA-seq results showed that liver ILC2s showed higher IL-13 expression than lung ILC2s, and IL-33 treatment suppressed the expression of gluconeogenic enzymes in the G6pc-high hepatocyte population. The interaction between liver ILC2s and G6pc-high hepatocytes via IL-13/IL-13 receptors was also demonstrated; co-culture of ILC2s with primary cultured hepatocytes resulted in decreased expression of hepatocyte gluconeogenic enzymes and accumulation of multiple gluconeogenic substrates. In addition, IL-13 neutralizing antibody treatment attenuated the effect of the decreased expression of gluconeogenic enzymes in hepatocytes. Transcription factor GATA3 complex analysis and GATA3-ChIPseq suggested binding of GATA3 of the AP-1 family (JunB) in liver ILC2s. Overexpression, knockdown, and scRNA-seq results suggest that AP1 may act in a GATA3-repressive manner in liver ILC2s. Discussion The functional characteristics of liver ILC2s, hepatocyte heterogeneity and subcluster were demonstrated by scRNA-seq, suggesting that liver ILC2s may directly suppress hepatocyte gluconeogenesis via IL-13. This may play a novel role in the homeostasis of hepatic glucose metabolism.
Presentation: 6/1/2024
8722 Sodium-Glucose Cotransporter 2 Inhibitors And The Risk Of Kidney Cancer Among Patients With Type 2 Diabetes: A Population-Based Cohort Study
Authors: Lee M , Kim H , Kim R H , Yang Y , Lee S , Kang E 
Published: October 2024

Abstract
Disclosure: M. Lee: None. H. Kim: None. R. Kim: None. Y. Yang: None. S. Lee: None. E. Kang: None.
There is an important need to develop clinical strategies to reduce the risk of incident kidney cancer, especially in patients with type 2 diabetes (T2D) and concomitant chronic kidney disease. Here, we investigated kidney cancer risk associated with sodium-glucose cotransporter 2 (SGLT2) inhibitor use in patients with T2D, using a nationwide cohort of the Korean National Health Insurance claims and health examination database. After 1:1 propensity score matching, 83,531 SGLT2 inhibitor users and 83,531 non-users on other oral glucose-lowering drugs were selected from 814,685 cancer-free participants, aged 20 to 79 years, who started oral glucose-lowering drugs for T2D from 2014 to 2018. During 559,738 person-years of follow-up, 143 (25.5 per 100,000 person-years) new kidney cancer events occurred. SGLT2 inhibitor use was associated with a 37% reduced risk of kidney cancer compared with other oral glucose-lowering drug use (18.1 vs. 29.9 per 100,000 person-years; hazard ratio [HR], 0.63; 95% CI, 0.43 to 0.92). The reduced kidney cancer risk by SGLT2 inhibitor use was consistent even after additional adjustment for all variables composing the propensity scores (HR, 0.64; 95% CI, 0.43 to 0.93) and regardless of age, sex, BMI, comorbidities, or diabetic complications including nephropathy (all p &gt; 0.1 for interaction). SGLT2 inhibitor use may be a preferable option for patients with T2D at high risk of kidney cancer.
Presentation: 6/3/2024
6810 Successful Insulin Allergy Desensitization To Humalog During The Second Trimester Of Pregnancy
Authors: Noreña Jairo , Seav Susan , Jiang Shirley , McGhee Sean , Tan Marilyn , Basina Marina 
Published: October 2024

Abstract
Disclosure: J. Noreña: None. S. Seav: None. S. Jiang: None. S. McGhee: None. M. Tan: None. M. Basina: None.
Background: Insulin allergy is rare, occurring in only 0.1 to 3% of people with insulin-treated diabetes. During pregnancy, this incidence is even lower due to a relative immunosuppressive state. Currently, there are no standardized insulin allergy desensitization protocols for this specific patient population. Clinical Case: A 39-year-old female (G4P3003) with T2DM and multiple prior medication allergies presented to the antepartum unit in her 17th week of pregnancy due to hyperglycemia and reported insulin allergy to NPH insulin.Patient was initially diagnosed with gestational diabetes during her third pregnancy, requiring NPH insulin which she seemed to tolerate well at the time. She remained medication-free for two years post-delivery but later developed T2DM with an A1c of 6.8%. Metformin and Jardiance, previously prescribed, were discontinued upon confirmation of her current pregnancy. She opted to manage her diabetes through diet and exercise alone, but her A1c rose to 7.0%, prompting the initiation of NPH.Following the first dose of NPH at home, she experienced a localized burning sensation at the injection site associated with facial flushing, followed by a diffuse, pruritic, erythematous rash on her face, chest, abdomen, and bilateral arms. Due to her history of anaphylaxis to other drugs (mainly antibiotics), she was admitted to the hospital for monitoring. Inpatient attempts with lower doses of NPH and then a trial of glargine triggered new rash episodes. Work-up revealed negative insulin antibodies, low IgG, and a normal CBC. She was started on Humalog to cover basal dose administered every 6 hours and additional prandial injections, which she tolerated prior to discharge. One week later, she developed a new local erythematous reaction at the Humalog injection site followed by a generalized rash which led to her readmission.Allergy was consulted and facilitated a successful desensitization protocol to Humalog. The protocol included escalating doses of insulin administered every 30 minutes (0.1u, 0.2u, 0.4u, 0.8u, 1u, 2u, 3u, 3u) to achieve a pre-determined cumulative dose of 10.5 units. Patient tolerated the protocol well and was discharged with q6h Humalog for basal coverage in addition to prandial doses with plan to transition to insulin pump therapy with Humalog soon. Conclusion: This unique case demonstrates how insulin desensitization can be a safe and successful strategy to help achieve insulin tolerance and glycemic control during pregnancy. Election of an insulin, such as Humalog, that can achieve the one-hour post-prandial glucose target during pregnancy and also provide effective basal coverage should be considered as desensitization can only be done with one insulin type at a time.
Presentation: 6/2/2024