bluuebunny/crossref_metadata_2025 huggingface dataset:
7725 Could COVID-19 Be the Trigger for Type 1 Diabetes?
Authors: Ahsan E , Foo F F , Ravin A , Akula M , Hu k , Ong R , Holland S , Hossain M , Cheng J
Published: October 2024

Disclosure: E. Ahsan: None. F.F. Foo: None. A. Ravin: None. M. Akula: None. K. Hu: None. R. Ong: None. S. Holland: None. M. Hossain: None. J. Cheng: None.

Introduction: COVID-19 disrupts glucose homeostasis, which may result in hyperglycemia and new-onset diabetes mellitus. It has been hypothesized to be caused by an increased inflammatory response, increased insulin resistance, and a degree of acute viral pancreatic damage. A meta-analysis showed that the incidence of new-onset diabetes was found to be as high as 14.4% (95% CI: [5.9%-25.8%]). Here, we report a case of COVID-19-induced diabetes to spread awareness among healthcare providers and encourage early detection to prevent long-term complications. Clinical Case: A 54-year-old African American female with a past medical history of hyperlipidemia, obesity, and hypothyroidism presented to our endocrinology office for evaluation and management of diabetes mellitus (DM). She presented with symptoms of 66-pound weight loss, polydipsia, polyphagia, and polyuria. Her labs on diagnosis were significant for blood glucose of 550 mg/dl (70-100 mg/dl), hemoglobin A1c >15.5% (<5.7%), and bicarbonate 23 mmol/L (20-31 mmol/L). She started on insulin and then switched to semaglutide after six months. Her fasting glucose on the follow-up visit was 103 mg/dl, the anti-glutamic acid decarboxylase 65 (GAD-65) antibody was 8,558.9 units/ml (<5 units/ml), C peptide was 1.9 ng/ml (0.5-2ng/ml), and Islet Antigen-2 (IA-2) autoantibody was <7.5 U/ml (0-7.49 U/ml). Despite positive antibodies, her C-peptide suggested enough beta-cell function, and she was switched from insulin to semaglutide. The patient was diagnosed with autoimmune diabetes, which may be from the COVID-19 infection, and was educated about regular follow-up and new medications like teplizumab that may help prevent the progression to needing insulin. Clinical Lesson: The exact mechanism of new-onset COVID-19-induced diabetes is still unknown. However, multiple risk factors are theorized to play a role in COVID-induced DM. These include defects in insulin production and glucose clearance, obesity, stress hyperglycemia, insulin resistance, and steroid therapy. Our patient had a history of obesity but no history of diabetes, steroid use, or any personal or family history of autoimmune processes. Compared to COVID-19 patients with normoglycemia or hyperglycemia, patients with preexisting diabetes and newly diagnosed diabetes experienced more severe complications, such as shock, ARDS, acute kidney injury, hypoalbuminemia, and severe COVID-19 complications. Additional research is required to investigate the various pathophysiologies and treatment options, including new medications that may prevent the disease's further progression. Diabetes caused by COVID-19 should be treated cautiously, and prompt diagnosis and care are essential to preventing further complications.

Presentation: 6/3/2024
8613 Diabetes remission: experience from a randomized control trial conducted in a tertiary care hospital in India
Authors: Chakraborty Ananda Mohan , Waila Rama , Bhansali Shobhit , Bhujade Harish , Sachdeva Naresh , Bhadada Sanjay
Published: October 2024

Disclosure: A.M. Chakraborty: None. R. Waila: None. S. Bhansali: None. H. Bhujade: None. N. Sachdeva: None. S. Bhadada: None.

Introduction: The usual perception and interpretation of diabetes mellitus is that of an irreversible and chronic persistent disease with little scope for remission. Following the success of metabolic surgery and intensive lifestyle modification, it is time for pharmacotherapy to sept in. Methodology: It was a single-center, randomized controlled trial conducted in patients having HbA1c below 9 % at randomization and having a duration of diabetes less than 2 years. Patients with organ-threatening chronic diseases and severe diabetes-related complications have been excluded. Study populations have been randomized to 1:1 to receive pharmacotherapy with oral semaglutide, dapagliflozin, and metformin in one arm and vildagliptin, metformin, and titrated glimepiride in the control arm. Duration of therapy was 6 months including 2 months of up titration of semaglutide. Patients have been followed up for 3 months after stopping all therapy following 6 months of therapy. The primary outcome was to find out the remission rates in patients with Type 2 diabetes mellitus treated with a combination of oral Semaglutide and dapagliflozin on top of metformin monotherapy and to compare with the standard diabetes practice. The secondary outcome was to assess the anthropometric change and change in beta cell function parameters with a mixed meal tolerance test. Results: A total of 38 patients have completed therapy, 17 were in the trial arm and 21 in the control arm. Among 17 patients in the trial arm, all the patients were in remission as per the prespecified criteria. Among the patients who completed 6 months of follow-up (n-13), 11 patients (84%) maintained remission in the trial arm. The remission rate was 100% in the trial arm and 48% in the conventional arm (p<0.001) after 3 months and 84% and 27.7% in the trial arm and conventional arm respectively after 6 months of follow-up (p<0.05). Reduction in BMI (p <0.001) and percent body fat (p<0.01) and increase in disposition index after mixed meal tolerance test (p<0.01) was statistically related to remission. Conclusion: Remission of diabetes as defined by ADA in the consensus statement (HbA1c < 6.5 % without glucose-lowering therapy for at least 3 months) is a reality. It can be achieved by pharmacotherapy targeting body weight and adiposity. The main predictors of remission were a reduction of BMI and body fat and an increased disposition Index. Since it is an ongoing study, further follow-up is planned to determine the continuation of the remission phase among those who achieved remission with pharmacotherapy.

Presentation: 6/3/2024
9317 Diabetogenic Stress-Mediated Beta Cell Extracellular Vesicle:Autophagy Pathway Crosstalk
Authors: Roy A , Ariyaratne G , Matveyenko A , Javeed N
Published: October 2024

Disclosure: A. Roy: None. G. Ariyaratne: None. A. Matveyenko: None. N. Javeed: None.

Diabetogenic stressors including elevated free fatty acids (lipotoxicity), low-grade systemic inflammation, and proteotoxicity are central to the development of Type 2 Diabetes (T2D). Due to their high protein synthetic burden, β-cells employ autophagy and endo/lysosomal pathways to reduce protein aggregates, and protect β-cell mass and function. Recently, extracellular vesicles (EVs; 30-150 nm sized nanoparticles) have been shown to work in tandem with autophagy to facilitate cellular adaptation and intercellular communication. As diabetogenic stressors have been shown to perturb autophagy via lysosomal defects, our group has noted enhanced EV secretion. Thus, we hypothesize that diabetogenic factors enhance EV secretion through activation of an EV-based secretory autophagy pathway and that re-balancing of both pathways could improve β-cell function in T2D. To test this, MIN6 cells were exposed to free fatty acid palmitate (PAL; 24h), or pro-inflammatory cytokines IL-1β, TNFα, and IFNγ (CYTO; 48h). Expression of autophagic markers, LC3 and p62 were increased in CYTO and PAL conditions suggesting defects in auto/lysosomal function. Upon PAL/CYTO treatment in MIN6 cells, conditioned media EVs were isolated using differential ultracentrifugation. We noted enhanced protein expression of LC3-II and p62 in PAL- and cytoEVs, suggesting a diversion of immature autophagosome components into EVs due to lysosomal inhibition. To restore balance between autophagy:EV flux, we used EV biogenesis inhibitor, GW4869 (GW; 24h) or autophagy inducer, rapamycin (Rapa; 24h) on MIN6 cells exposed to PAL or CYTO. Isolated EVs were subjected to Nanoparticle Tracking Analysis (NTA) which showed a significant reduction in EV concentration with GW or Rapa addition (p<.05). Isolated mouse islet exposed to CYTO+GW/Rapa or PAL+GW/Rapa showed significant improvements in glucose stimulated insulin secretion (vs. CYTO or PAL; p<.05). Taken together, these data implicate activation of EV-based secretory autophagy in response to diabetogenic stressors and thus, potential targets to improve functional β-cell mass.

Presentation: 6/2/2024
8809 Digital Twin Technology for Remission of T2DM and Normalization of Glycemic and Extraglycemic Parameters: 18 Months Intent to Treat Analysis of the Prospective Randomized Controlled Clinical Trial
Authors: Joshi Shashank Rameshchandra , Dharmalingam Mala , Vadavi Arun , Keshavamurthy Ashok , Bhonsley Suchitra , Mohamed Thajudeen , Balasubramanian Akshaya , Shamanna Dr Paramesh
Published: October 2024

Disclosure: S.R. Joshi: None. M. Dharmalingam: None. A. Vadavi: None. A. Keshavamurthy: None. S. Bhonsley: None. T. Mohamed: None. A. Balasubramanian: None. D. Shamanna: None.

Objective: This study aims to evaluate the effectiveness of a comprehensive metabolic health intervention in normalizing various metabolic parameters associated with Type 2 Diabetes Mellitus (T2DM), hypertension, and Non-Alcoholic Fatty Liver Disease (NAFLD). The intervention's impact was measured by assessing changes in several key health metrics over a period of 540 days. Methods: Patients were monitored at baseline and after 540 days (D540) of the intervention. The study focused on the percentage of patients achieving normalization in various metabolic parameters at D540 compared to the baseline values. Results: Notable improvements were observed across multiple parameters. The percentage of patients with HOMA2IR within the normal range increased from 21.6% (47 patients) to 39.4% (86 patients). Similarly, the proportion of patients with HOMA2B above the normal threshold rose from 36.7% (80 patients) to 67.0% (146 patients). HbA1c normalization showed a significant increase from 7.3% (16 patients) to 65.6% (143 patients). Other parameters also showed considerable improvement: BMI normalization from 32.6% (71 patients) to 52.3% (114 patients) Waist Circumference normalization increased in males (90 cm) and females (80 cm) from 23.4% (51 patients) to 56.9% (124 patients) Fasting Plasma Glucose normalization from 24.8% (54 patients) to 64.2% (140 patients) TG/HDL ratio normalization from 27.1% (59 patients) to 56.4% (123 patients) HDL normalization in males (>40) and females (>50) from 17.4% (38 patients) to 49.5% (108 patients) LDL normalization (<100) from 23.4% (51 patients) to 23.9% (52 patients) hsCRP normalization (<3 mg/L) from 11.9% (26 patients) to 44.5% (97 patients) NAFLD Liver Fat Score normalization (>-0.64) from 11.9% (26 patients) to 56.0% (122 patients) NAFLD Fibrosis Score normalization (>-1.455) from 77.5% (169 patients) to 92.7% (202 patients) Urine Microalbumin to Creatinine ratio normalization (<30 mg/g) from 78.4% (171 patients) to 93.1% (203 patients) SBP normalization (<140) from 85.8% (187 patients) to 91.3% (199 patients) DBP normalization (<90) from 76.1% (166 patients) to 84.4% (184 patients)Discussion: The significant shift towards normalization in these parameters suggests the effectiveness of the treatment protocol in managing and potentially reversing chronic metabolic diseases, including T2DM, hypertension, and NAFLD.

Presentation: 6/1/2024
8378 Disparities In Telemedicine Use In Latinx Patients With Diabetes: Real Life Observations
Authors: Kim S , Qu J , Thedki P , Wright L A
Published: October 2024

Disclosure: S. Kim: Consulting Fee; Self; Signos, Inc.. Grant Recipient; Self; The Diabetes Link. P. Thedki: None. L.A. Wright: None.

Background and Aims The Latinx population is disproportionately affected by diabetes and related complications and face greater challenges to accessing medical care than white patients. Telemedicine, a novel strategy for addressing such lack of access has not been evaluated in the Latinx population affected by diabetes.We aimed to assess telemedicine use in Latinx patients with diabetes compared to non-Latinx, within the same diabetes clinic (same care team and access to same digital platform). Secondary aims: HbA1c and use of CGM. Methods: All patients were offered telemedicine services and were considered users if they completed =/>1 telemedicine visit during the 3-month study period. Demographics, race/ethnicity, telemedicine use, language, type of diabetes: type 1(T1D), type 2(T2D) or other; HbA1c(+/- 3 months from visit) and use of CGM at the time of visit were extracted. Results: Latinx patients: n=61, 42 Spanish speaking only; mean age 52.4; 32 female; 46 with T2D. Non-Latinx: n=81, mean age 53.2; 43 female; 43 had T1D. Telemedicine use was 22% in Latinx vs 39% in non-Latinx patients, p=0.007. Mean A1c was 7.4% in Latinx vs 7.1% in non-Latinx, p=0.04 CGM use was more common in non-Latinx patients, p=0.01. Conclusions T2D was more common and telemedicine use was lower in Latinx compared to non-Latinx patients, most were Spanish speaking only, they had higher HbA1c and less CGM use. While telemedicine has the potential to increase access to care, social determinants of health, such as digital literacy, access to device and/or reliable internet are likely barriers that contribute to health inequalities in this population.

Presentation: 6/2/2024
7049 DUNNIGAN LIPODYSTROPHY AND SUCCESSFUL USE OF AID WITH U200
Authors: Kader T , Seltzer S , Williams A
Published: October 2024

Disclosure: T. Kader: None. S. Seltzer: None. A. williams: None.

Our patient is a 60 year old female with dunnigans partiallipodystrophy diagnosed after her niece was diagnosed and was sent to genetics; She was found to have a mutation in LMNA geneand had a heterozygous sequence variant.She was diagnosed with partial lipodystrophy and had macrovascular complications including carotid stenosis requiring surgical intervention.She was treated originally with insulin pump therapy that was sensor augmented along with glp1 agonist and sglt2 inhibitor but she developed recurrent pancreatitis and glp1 agonist was stopped. The pancreatitis was not induced by hypertriglycidemia as her levels were normal.Since then she had poorly controlled diabetes with a1c 8.7 percent and was having some hypoglycemia.;After consultation with the patient about off□ label use of AID pump technology for type 2 diabetes and off□ label use of u200 in AID pump she was willing to try and results were quite impressive with a1c falling close to 7 and time in range up to 70 percent with no lows. Her total insulin dosages were approximately 200 units q day but with u 200 she was changing every 2 days .Despite insulin resistance and dunnigan lipodystrophy this case exemplifies safety of u200 in AID pump in a patient with dunnigans lipodystrophy. It is the first of such report and more studies should be done using this technology in this rare group of patients with insulin resistance and poorly controlled diabetes.

Presentation: 6/1/2024
12314 Effectiveness Of Continuous Glucose Monitors In Patients With Type 2 Diabetes On Washington Medicaid Or Financial Assistance
Authors: Deng Alexandra , Thirumalai Arthi , Lin Jenny , Weber Marianne , Zuo Silu
Published: October 2024

Disclosure: A. Deng: None. A. Thirumalai: None. J. Lin: None. M. Weber: None. S. Zuo: None.

Continuous glucose monitors (CGMs) have become more accessible for patients with type 2 diabetes mellitus (T2DM) on one insulin injection per day who have either commercial or Medicare plans. However, there are still strict requirements for patients with Washington State Medicaid, creating disparities in diabetes care for vulnerable populations. The aim of this study is to assess the effectiveness and adherence of CGMs in patients with T2DM on Washington State Medicaid plans or institutional financial assistance who are prescribed at least one insulin injection daily, similar to Medicare requirements. This ongoing prospective cohort study enrolled 40 adult patients with T2DM, baseline A1C greater than 7%, and prescribed at least one insulin injection per day from three Harborview Medical Center clinics. Through grant funding, patients were provided with Freestyle Libre 2 CGMs for 6 months. Since this is an ongoing study, we present preliminary results of patients who completed 3 months of CGM use. Effectiveness was measured by the change in A1C from baseline to 3 months after initiation of the CGM (primary outcome) and change in CGM glycemic metrics on ambulatory glucose profile (AGP) from baseline to 3 months after initiation of CGM (secondary outcomes). Assessment of adherence to the CGMs involved tracking the percentage of CGM data captured from the AGP reports recorded at each visit and monitoring dispense history. Twenty patients reached the 3-month follow-up with a median age of 59 years; 60% female, 70% non-English speaking; 45% with Medicaid, and 55% with Harborview Financial Assistance as insurance coverage. Median baseline A1C was 9.2%, duration of diabetes was 10 years, number of diabetes medications was 3, daily insulin injections of 2, and number of blood glucose checks per day was 1. At first CGM download (2 weeks), the median time in range (TIR, glucose 70-180 mg/dL) was 53.5%, coefficient of variation was 35.3% and percent of data captured was 80%. At 3-month follow-up, the median reduction in A1c was –1.2% (IQR -1.8, -0.5). On CGM, the median TIR had increased to 60.5%, coefficient of variation had improved to 31.5% and percent of data captured was 79%. In this ongoing study, preliminary findings show encouraging early evidence of improved glycemic control after CGMs were initiated and patients sustained greater than 70% CGM data captured at 3 months. These results should be interpreted with caution given the small number of participants with results at 3 months. Nonetheless, once the study is complete, the outcomes may be used to inform eligibility requirements for continuous glucose monitors in patients with Washington Medicaid or Harborview Financial Assistance.

Presentation: 6/3/2024
8753 Efficacy and safety of bempedoic acid for patients with type 2 diabetes and hypercholesterolemia: a meta-analysis of randomized trials and post-hoc studies
Authors: Godoi A , Silva C H , Hespanhol L C , Romeiro P , Silva C , Balieiro C A , Texeira T
Published: October 2024

Disclosure: A. Godoi: None. C.H. Silva: None. L.C. Hespanhol: None. P. Romeiro: None. C. Silva: None. C.A. Balieiro: None. T. Texeira: None.

Background: Statins, the primary treatment for lowering LDL cholesterol and cardiovascular risk, have been associated with a worsened glycemic control. Moreover, several patients with hypercholesterolemia, including those with type 2 diabetes mellitus (T2DM), are unable to meet treatment goals with statins. Bempedoic acid (BA) has shown promising results in trials with patients with high cholesterol and cardiovascular disease, however, its efficacy in a population restricted to patients with T2DM remains unclear. Purpose: To perform a systematic review and meta-analysis comparing the therapeutic efficacy and safety of BA versus placebo in patients with T2DM and hypercholesterolemia. Methods: PubMed, Cochrane Central and Embase were systematically searched up to January 2024 include randomized controlled studies (RCTs) and post-hoc studies assessing the use of BA in a population of patients with T2DM on prior lipid-lowering therapy. Efficacy outcomes assessed were mean change in low-density lipoprotein C (LDL-C), high-density lipoprotein C (HDL-C), and non-HDL, as well as an increase in HbA1c. Safety outcomes included incidence of hyperglycemia, gout, myalgia and treatment discontinuation due to adverse events. Outcomes were pooled using risk ratios (RR) and mean differences (MD) with 95% confidence intervals (CI). Statistical analysis was performed with RevMan 5.4.1 and R Studio software. Heterogeneity was assessed with I² statistics. The protocol was registered in PROSPERO. Results: A total of seven RCTs with 7475 patients with T2DM were included, of whom 3842 (51.4%) were allocated to use BA and 3633 (48.6%) were allocated to placebo. Follow-up time ranged from 2 to 52 weeks. The use of BA was associated with a significantly lower LDL-C (MD -30.19mg/dL; -37.56 to -22.82 95% CI; p<0.001), and non-HDL (MD -20.05mg/dL; -20.15 to -19.95 95% CI; p<0.001), although with a lower HDL-C (MD -5.00mg/dL; -5.01 to -4.99 95% CI; p<0.001) compared to placebo. Furthermore, BA use results in significantly lower rates of myalgia (RR 0.74; 0.60 to 0.91 95%CI; p=0.004). There were no differences regarding HbA1c increase (p=0.13), treatment discontinuation (p=0.51), hyperglycemia (p-0.57), or gout (p=0.05) between groups. Conclusion: In this meta-analysis of randomized trials and post-hoc studies, the use of BA was associated with an improved lipid profile without worsening glycemic control or causing significant adverse events, although at the cost of a lower HDL-C.

Presentation: 6/1/2024
12582 Electronic-cigarette Exposure Induces Hyperglycemia With A Fibrotic Phenotype In Skeletal Muscle In Mice Subjected To A High-fat Diet
Authors: Rivera Juan Carlos , Chavez Jennifer , Espinoza-Derout Jorge , Hasan Kamrul M , Shao Xuesi M , Sinha-Hikim Amiya P , Friedman Theodore C
Published: October 2024

Disclosure: J. Rivera: None. J. Chavez: None. J. Espinoza-Derout: None. K.M. Hasan: None. X.M. Shao: None. A.P. Sinha-Hikim: None. T.C. Friedman: None.

Obesity and electronic cigarette (e-cigarette) use are highly prevalent among youth in the USA. Indeed, young e-cigarette users report less physical activity, leading to a decline in quality of life. Recent studies show e-cigarettes reduce skeletal muscle (SkM) performance in mice; however, the underlying metabolic and SkM cellular effects are unclear. E-cigarettes plus a high-fat diet (HFD) increase mice lipolysis and plasma-free fatty acids. These harmful changes in the liver and heart are prevented by the lipolysis inhibitor Acipimox (Acip). As SkM plays a crucial role in metabolic and chronic disease prevention, understanding the impact of e-cigarettes and HFD on SkM is essential.We exposed C57BL6 mice to e-cigarette inhalation in a free-moving system to deliver 2.4% nicotine in a similar way to humans. Mice were fed with an HFD and divided into 3 groups: Saline (control), e-cigarette (bluCig), and e-cigarette plus Acip (rescue group) for 12 weeks. SkM uptakes 70-80% of the postprandial glucose, so we performed a glucose tolerance test. We found higher glycemia in the e-cigarette compared to the Saline group, while the e-cigarette plus Acip group showed improved glycemia. Histological analysis of SkM with Hematoxylin and eosin (HE) staining revealed large extracellular fibrotic structures in the group with e-cigarettes, suggesting fibrosis. Sirius Red (SR) stain identified collagen deposition. The SR quantification showed an increase in the collagen in the e-cigarette to the saline-exposed group without recovery in the e-cigarette plus Acip group. Fibrosis restricts the SkM hypertrophy. So we analyzed the insulin-like growth factor-1 (IGF-1) (a key anabolic factor) by RT-qPCR. The mRNA levels of IGF-1 were reduced in the SkM of e-cigarettes compared to the Saline group, without recovery of the Acip group. In SkM hypertrophy, Satellite cells (SCs) are stimulated by IGF-1 and SkM fibrosis can affect SCs by restricting them. So we analyzed by western blot the SCs through the transcriptional factor PAX7 (SC marker). We found PAX7 levels were lower in the e-cigarette compared with the Saline group without recovery in the Acip group. These findings suggest the detrimental effects of e-cigarettes on glycemia and SkM health in mice, with implications for long-term health outcomes, particularly among obese individuals and e-cigarette users. Further research is necessary for understanding these adverse effects and promoting youth health. GRANT SUPPORT: U54MD007598, SC2GM135127, U54MD007598-14S2, PR190942, DA050723, and R25DA050723 grants.

Presentation: 6/3/2024
6366 Elevated Baseline Triglycerides As an Independent Risk Factor For Coronary Artery Disease
Authors: Askar Esraa , Moran Heberth , Yuksel Simge , Bleich David
Published: October 2024

Disclosure: E. Askar: None. H. Moran: None. D. Bleich: None.

Introduction: Diabetes is considered a coronary artery disease (CAD) risk equivalent. Studies have shown that the baseline level of triglycerides plays a role in cardiovascular risk independent of LDL levels lowered with statins. Numerous studies demonstrate that, in the general population, coronary artery calcium (CAC) scoring predicts and reclassifies cardiovascular disease (CVD) events, even in the absence of other risk factors. Here, we present a case of a 65 -year-old Caucasian male with elevated baseline triglycerides and a high CAC score, increasing his CVD risk despite the normalization of his triglycerides with statin therapy.Case presentation: A 65-year-old Caucasian male with a history of hypertension, hyperlipidemia, and diabetes presented to our endocrinology clinic for the management of hyperlipidemia and diabetes. His medications included empagliflozin 10 mg daily, repaglinide 1 mg three times a day, atorvastatin 20 mg daily, and amlodipine 10 mg daily. He had no complaints, and the physical examination was unremarkable. His recent HbA1c was 7.4%. Six months prior to presentation, he was found to have elevated triglycerides of 253 mg/dL (normal range: 10-149 mg/dL), low HDL of 34 mg/dL (normal range: >39 mg/dL), LDL of 84 mg/dL (normal range: 0-99 mg/dL), and total cholesterol of 167 mg/dL (normal range: 100-200 mg/dL). At that time, he was started on atorvastatin, and his recent triglycerides and HDL levels normalized. He was referred for CAC scoring, and the result was 2733 , which is above the 90th percentile for men between the ages of 65 and 69. As a result, he was further referred to a coronary angiogram. Conclusion: McGarry at the University of Texas Southwestern Medical Center was the first to describe the elevated triglyceride along with low HDL phenotype associated with insulin resistance. They explained this phenotype as a result of hepatic insulin resistance. Elevated insulin levels reduce the activity of lipoprotein lipase (LPL). As a result of that, the VLDL triglycerides rise, forming small dense LDL with a strong atherogenic potential.In the 2010 published ACCORD study, the effects of simvastatin alone versus simvastatin and fenofibrate were compared in 5500 Patients with type 2 diabetes. The experimental group did not exhibit any significant adverse cardiovascular events after eight years. However, the mean triglyceride was only 162 mg/dL. Consequently, no assumptions about the impact of the treatment on cardiovascular events in a more pertinent subset of people with greater baseline triglycerides could be made.While there has been controversy on the role of triglycerides in CVD, the idea of lowering triglycerides in diabetes patients with high triglycerides and low HDL to lower the risk of CVD is well supported.

Presentation: 6/2/2024
8433 Elucidation of the Molecular Basis of Human and Mouse Pancreatic β-Cell Senescence Induced by Hyperglycemia
Authors: Iwasaki Kanako , Carapeto Priscila , Aguayo-Mazzucato Cristina
Published: October 2024

Disclosure: K. Iwasaki: None. P. Carapeto: None. C. Aguayo-Mazzucato: None.

Background and AIM: Senescent cells accumulate with age and contribute to the development of chronic diseases, including Type 2 Diabetes (T2D). Whereas senescence is an important pathogenic mechanism in diabetes, the role of hyperglycemia as a metabolic driver of pancreatic β-cells has not been clarified. The aim of this study is to elucidate the molecular basis of hyperglycemia-induced pancreatic β-cell senescence using human and rodent islets. Methods: 1) Human islets were cultured for 2 weeks in 20.2 mM high (HG) or 2.8mM low glucose (LG), and analyzed by qPCR and glucose-responsive insulin secretion (GSIS) to explore the molecular basis of senescence in ex vivo. To test the effects of senescent cell removal, senolytics Dasatinib (1μM) and Quercetin (20μM) (DQ) were used. 2) To evaluate the effects of hyperglycemia in vivo, we transplanted mouse and human islets under the kidney capsule of normoglycemic (NG) or streptozocin-induced hyperglycemic (Stz-Db) immunodeficient mice for two weeks. Graft function was evaluated by intraperitoneal glucose tolerance test and cellular identity using qPCR or immunohistochemistry. DQ (5mg/kg/day + 50mg/kg/day) was used to evaluate the effects of removing senescent cells in transplantation (Tx). To investigate the effect of specific removal of p16-positive senescent β-cells in transplanted islets, INK-ATTAC mice islets (p16Ink4a-mediated apoptosis by targeted activation of caspases) were transplanted into Stz-Db and treated with BB homodimer (BB) to remove p16+ cells or vehicle. Results: (1) Human islets from 5 healthy donors cultured in HG had an increased senescence index (mean of senescence markers p16, p21 and HMGB1 mRNA) when compared to LG islets (p<0.05) and lost glucose responsiveness as evaluated by ex vivo GSIS compared to LG (p<0.05). 2) Human islets (1000IEQ) were transplanted to Stz-Db or NG mice. In Stz-Db graft, P21 mRNA significantly increased with decreased expression of β-cell genes when compared to NG. Stz-Db mice treated with DQ (Db-DQ) for 5 days after Tx, significantly decreased expression of senescence index (p<0.05) and increased in β-cell index (mean of β-cell hallmark genes) (p<0.05) at mRNA levels. Stz-Db mice transplanted with INK-ATTAC mice islets had lower fed glucose levels, decreased p16 mRNA, increased expression β-cell hallmark genes and improved insulin secretion ex vivo after removal of p16+ cells. Conclusion: Sustained exposure of human islets to hyperglycemia induced cellular senescence, leading to pancreatic β-cell dysfunction and loss of cellular identity. Furthermore, elimination of senescent cells may protect pancreatic β-cells from hyperglycemia-induced functional decline, which may have potential clinical application in both Type 1 Diabetes and T2D.

Presentation: 6/2/2024
8469 Endocrinologists Underutilize Virtual Care Services Resulting in Suboptimal Clinical and Financial Outcomes
Authors: Terry David
Published: October 2024

Disclosure: D. Terry: Employee; Self; Valendo Health.

Less than 150,000 Medicare patients with diabetes (PWD) receive billable telehealth and remote monitoring services, even though over 12 million PWDs are eligible for these services. This is a missed quality opportunity, as studies show that PWDs who receive these services experience reductions in A1C levels and improvements in TIR. It is also a missed financial opportunity for Endocrinologists, who are among the lowest paid specialists in the US. The economics of Endocrinology are important, because inadequate compensation is leading to access constraints when the diabetes population is growing, and care complexity is increasing. We analyzed billed virtual health claims for every Medicare PWD in 2022. The types of services we examined included: Chronic Care Management (CCM & PCM), Continuous Glucose Monitoring (CGM & RPM), Medical Nutrition Therapy (MNT), and Diabetes Self-Management Training (DSMT). When we looked by Endocrinologist by virtual care service type, we found the following levels of service delivery for Endocrinologists at the median levels of utilization:4.8% of eligible PWDs received remote Continuous Glucose Monitoring support.4.2% received virtual Chronic Care Management services.6.2% received virtual Diabetes Self-Management Support.<1% received Medical Nutrition Therapy This is clearly a missed clinical quality opportunity as a study published in JAMA in October 2023, Comprehensive Telehealth Model to Support Diabetes Self-Management, reported the following improvements for PWDs who received virtual care for 6 months:Mean change in A1C levels: Type 1: -0.6%; Type 2: -1.0%Mean TIR Improvement: Type 1: 16%; Type 2: 18% It is also a missed financial opportunity for Endocrinology practices. Each patient with diabetes is potentially eligible for $100 or more of virtual care services per month. We’ve looked at every Endocrinology practice in the US and many are missing out on over a million dollars of annual revenue opportunity. This is important as Endocrinology organizations everywhere, independent and hospital based, are struggling to retain the doctors & staff necessary to provide adequate access to care - leading to months of wait time to see an Endocrinologist. The prevalence of diabetes is growing significantly, while Endocrinologist capacity is shrinking. Value added and billable virtual care services create new opportunities for Endocrinologist to generate the revenue necessary to increase clinical capacity and improve access by creating diverse clinical teams led by Endocrinologists and supported by Diabetes Educators, Dietitians, and others with expertise in diabetes who can care for many more PWDs. Creating virtual care capabilities is also an early step in moving Endocrinology into Value-Based Care arrangements that reward providers for improving care and reducing costs rather than for generating more visits.

Presentation: 6/1/2024
7311 Endoplasmic reticulum (ER) stress and its associated signaling modulate incretin receptor signaling in pancreatic β cells
Authors: Lee J
Published: October 2024

Disclosure: J. Lee: None.

Pancreatic β-cell dysfunction and eventual loss are key steps in the progression of type 2 diabetes (T2D), and endoplasmic reticulum (ER) stress and its associated signaling have been implicated in these β-cell pathologies. However, the precise molecular events surrounding ER stress and its signaling responses in β-cell dysfunction remain unknown. A notable β-cell dysfunction during obesity and T2D progression is an impaired β-cell response to incretin hormones such as glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). Despite the fact that GIP loses most of its insulinotropic efficacy, GLP-1 receptor (GLP-1R) agonists remain effective owing to GLP-1R’s signaling switch from Gs to Gq. Here, we discovered that ATF4, an ER stress-associated signaling factor, promotes the expression of PDE4D, which disrupts β-cell function, including incretin action, via a downregulation of cAMP signaling. We found that β-cell-specific transgenic expression of ATF4 led to early β-cell dysfunction and loss, a phenotype similar to accelerated T2D. Also, we revealed that nuclear localization of ATF4 and PDE4D expression was increased β cells of obese and diabetic (db/db) mice. Accordingly, pharmacological inhibition of the ATF4 or PDE4 activity in the islets alleviated β-cell dysfunction and promoted incretin-simulated insulin secretion in db/db mice. ER stress also induced GLP-1R’s signaling transition from Gs to Gq in mouse islets. Intriguingly, chemical chaperones known to alleviate ER stress, such as 4-PBA and TUDCA, enforced GLP-1R’s Gq utilization rather than reversing GLP-1R’s signaling switch induced by ER stress or obesity. In addition, the activation of XBP1 or ATF6, two other key ER stress-associated signaling factors, promoted Gs utilization in GLP-1R signaling, whereas they had no effect on Gq employment under ER stress conditions. Our findings show that ER stress and its associated signaling events alter incretin receptor signaling, which could be a therapeutic target for protecting β-cell function during the progression of T2D.

Presentation: 6/3/2024
8075 Euglycemic Diabetic Ketoacidosis Associated With Cocaine Use
Authors: Solanki Naisargee Nilesh , Kiani Amna Nadeem , Feldman Marc
Published: October 2024

Disclosure: N.N. Solanki: None. A.N. Kiani: None. M. Feldman: None.

Euglycemic diabetic ketoacidosis (EDKA) is characterized by increased anion gap metabolic acidosis, ketonemia or ketonuria, and normal blood glucose levels (<200 mg/dL). Due to the absence of hyperglycemia, it commonly presents as a diagnostic and therapeutic dilemma. EDKA is commonly associated with decreased caloric intake, sodium-glucose cotransporter-2 (SGLT-2) inhibitors, recent use of insulin, heavy alcohol consumption, chronic liver disease, glycogen storage disorders, and drug-induced intoxication. Cocaine use is a lesser-known etiology for EDKA. We present a case of a 64-year-old female with a history of type 2 diabetes mellitus who presented with complaints of decreased oral intake for two days secondary to nausea and vomiting and productive cough for one week, along with cocaine use. Despite an extensive history of diabetes and no recent SGLT-2 inhibitor use, her labs were consistent with euglycemic DKA. Her imaging and further investigations revealed respiratory syncytial virus pneumonia. The patient was initially managed for starvation ketoacidosis with fluid resuscitation with no improvement in acidosis and later treated with DKA protocol with rapid correction of her anion gap metabolic acidosis. This case highlights the challenges associated with diagnosing and treating EDKA. Early initiation of DKA protocol should be considered in diabetic patients presenting with euglycemia with high anion gap metabolic acidosis with a clinical picture of starvation and cocaine use.

Presentation: 6/3/2024
8269 Euglycemic Diabetic Ketoacidosis Secondary to Rapid Weight Loss in a Patient on Dapagliflozin
Authors: Sridhar Archana , Iqbal Aimen , Kaur Ravleen , Kumar Arathi Prabha , Haider Faryal , Babic Milos
Published: October 2024

Disclosure: A. Sridhar: None. A. Iqbal: None. A. Prabha Kumar: None. F. Haider: None. M. Babic: None.

Background: Euglycemic DKA (eDKA) is a potentially life-threatening complication in patients taking SGLT 2 inhibitors (SGLT2i). Common precipitating factors include strenuous exercise, carbohydrate restriction, starvation, and alcohol use. Clinical case: The patient is a 71-year-old female with past medical history of Type 2 diabetes mellitus (DM), gastro-esophageal reflux disease, hypertension, hyperlipidemia, coronary artery disease and chronic pain syndrome. She presented with complaints of nausea, vomiting, reduced appetite and generalized weakness for the past 4 days. She also reported an intentional weight loss of 35 pounds in the last 6 weeks achieved with daily exercise and a carbohydrate restricted diet. She had been taking Dapagliflozin-Metformin 5-1000 mg twice daily and pioglitazone 30 mg once daily for 2 years and Ozempic subcutaneous injection 1 mg weekly for 6 months. Physical examination in the ED showed normal vital signs, dry mucous membranes, and trace bilateral lower extremity edema. Blood work was significant for venous blood gas pH 7.24, bicarbonate 9 mmol/L, anion gap 30 mmol/L, blood glucose 94 mg/dL, HbA1c 5.8 % and WBC 13.2 K/uL. Urinalysis was positive for glucose and ketones. The patient was admitted for management of eDKA and was started on intravenous 10% dextrose infusion and insulin infusion. Endocrinology was consulted and they recommended following DKA protocol and stopping Dapagliflozin at discharge. She was maintained on insulin infusion for 48 hours after which her anion gap normalized, and she was transitioned to subcutaneous insulin with Lantus 8 units and sliding scale insulin. During this time the patient’s symptoms resolved, and she was able to tolerate oral diet. She eventually resumed her home medications with oral Metformin 1000 mg twice daily and pioglitazone 30 mg once daily. Dapagliflozin and Ozempic were discontinued at discharge. Strenuous exercise and carbohydrate restriction which caused rapid weight loss, were likely the triggers for eDKA in our patient. A diabetes educator was involved at discharge and the patient was counseled to avoid possible triggers and identify warning signs and symptoms in the future. The patient was discharged with a follow up appointment with her Endocrinologist. Conclusion: High index of clinical suspicion is important to promptly diagnose eDKA in patients taking SGLT2i. Patient education on avoiding precipitating factors and early recognition of signs and symptoms is necessary to reduce mortality.

Presentation: 6/3/2024
6660 Euglycemic DKA Induced by SGLT-2 Inhibitor Following Administration ofTirzepatide
Authors: Gurel Kursat , Mathew Shannon , Zeidan Mahmoud , Al Barznji Saman , Alkhankan Fadi
Published: October 2024

Disclosure: K. Gurel: None. S. Mathew: None. M. Zeidan: None. S. Al Barznji: None. F. Alkhankan: None.

Introduction Tirzepatide has side effects of diarrhea, nausea, vomiting, and loss of appetite(2). SGLT-2 inhibitors may cause Euglycemic Diabetic ketoacidosis(EDKA) by inducing carbohydrate starvation and volume depletion(1). Clinical Case A 72-year-old male with a past medical history of T2DM(Hg A1c 8.4[≤ 6%]) on empagliflozin, metformin, hyperlipidemia, obesity on tirzepatide who presents with complaining of nausea, vomiting, and abdominal pain. The patient noted that he started experiencing symptoms two days before admission following receiving tirzepatide dose. He takes Tirzepatide every 10 days and he was started on empagliflozin 1 month ago. The patient started to have a loss of appetite, nausea, and vomiting on the day he received his tirzepatide injection. Over the next two days, the patient’s nausea and vomiting worsened and the patient was not able to tolerate food. On admission, ABG demonstrated pure metabolic acidosis (pH of 7.24[7.30-7.40], bicarb of 11.8 [21 - 28 mmol/L] PCO2 of 27.4[ 41 - 51 mmHg]). BMP showed anion gap of 20(3-15 mmol/L) with glucose level of 145(74-106 mg/dl) . Beta-Hydroxybutyrate level was 6.3(0.0 -0.27 mmol/L). UA was only significant for glucose level of >1000(negative) and ketone level of 40(negative). Lipase level was 539(73-393 U/L). CT abdomen ruled out acute pancreatitis. No infection source was identified. Upon admission to the ICU unit, the patient was started on D5 with KCL 20 mEq and Insulin drip. The patient was followed up with a glucose check every hour and BMP every 4 hours. On day 2 of admission, the Anion gap was normalized and the insulin regimen was transitioned to subcutaneous insulin. The patient was placed on carbohydrate consistent diet. On discharge, the patient was advised to avoid taking SGLT-2 inhibitors including empagliflozin. Conclusion Tirzepatide's potential side effects, including diarrhea, vomiting, and appetite loss, may contribute to volume depletion and carbohydrate starvation(2). Individuals using both SGLT-2 inhibitors and Tirzepatide should be closely monitored for these symptoms. Reference 1-)Baggio LL, Drucker DJ. Glucagon-like peptide-1 receptor co-agonists for treating metabolic disease. Mol Metab. 2021 Apr;46:101090. doi: 10.1016/j.molmet.2020.101090. Epub 2020 Sep 25. PMID: 32987188; PMCID: PMC8085566. 2-)Plewa MC, Bryant M, King-Thiele R. Euglycemic Diabetic Ketoacidosis. [Updated 2023 Jan 29]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK554570/

Presentation: 6/2/2024
7604 Examining Disparities in Diabetes Control and Complications: A Comparative Study of Type 2 Diabetes Mellitus Patients in Rural and Urban Saudi Arabia
Authors: Alqifari Saleh F , Alkomi Omar , Amirthalingam Palanisamy , Alrasheed Tariq , Muqresh Mohamad Ayham , Hamad Heba , Khojah Abdullah , Alshehri Nada , Alhunayhani Budur , AbuAlhasan Bothainah , Alajlan Noura , Alatawi Shahad , Alsabeelah Norah , Wasel Afaf , Alqifari Abdulrahman
Published: October 2024

Disclosure: S.F. Alqifari: None. O. Alkomi: None. P. Amirthalingam: None. T. Alrasheed: None. M. Muqresh: None. H. Hamad: None. A. Khojah: None. N. Alshehri: None. B. Alhunayhani: None. B. AbuAlhasan: None. N. Alajlan: None. S. Alatawi: None. N. Alsabeelah: None. A. Wasel: None. A. Alqifari: None.

Background: The escalating global prevalence of diabetes is also mirrored in Saudi Arabia. Approximately one in four individuals in the country is diagnosed with diabetes, as reported by the World Health Organization (WHO). The Ministry of Health has taken steps to address the needs of patients with diabetes by creating more than 20 specialized diabetes care centers in various regions throughout Saudi Arabia. However, disparities in access and utilization of primary healthcare facilities persist between rural and urban provinces within the country. Highlighting these disparities would bridge healthcare gaps between rural and urban areas to enhance diabetes management, ensure better access to specialized care, and improve the overall well-being of individuals living with Type 2 Diabetes Mellitus (T2DM) in Saudi Arabia. Objectives: This study aims to examine disparities in diabetes control and complications in patients with T2DM in rural and urban Saudi Arabia. Methods: This is an observational retrospective study conducted from November 2022 until May 2023, we collected data from 13 diabetes care centers across Saudi Arabia to assess diabetes control and complications of T2DM among patients who received their care in rural and urban Saudi Arabia. Results: Among 709 patients residing in rural and urban areas, rural area patients' recent HbA1c readings were generally within the range of 7-8%. Among these patients, around 2.6% had a history of heart disease, and 6.08% had experienced cerebrovascular events. Limb numbness was reported by 44.34% of subjects, 47.82% experienced vision complications, and renal impairment was observed in 10.43% of the participants. Additionally, among male patients, 26.41% suffered from erectile dysfunction. Remarkably, 21% of the rural patients reported having been hospitalized due to diabetes complications at least once in the past 12 months. Conclusion: The study findings emphasize the importance of considering regional disparities and socio-environmental factors when managing diabetes and its complications. Additional research is needed to understand the underlying causes and develop targeted interventions for improved diabetes care in rural and urban populations in Saudi Arabia.

Presentation: 6/2/2024