bluuebunny/crossref_metadata_2025 huggingface dataset:
FRI101 Marked Reduction In Severe Resistant Hypertriglyceridemia On PCSK9 Inhibitor
Authors: Kaul Sabrina , Gupta Ankur
Published: October 2023

Disclosure: S. Kaul: None. A. Gupta: None.

Introduction: PCKS9 inhibitors, such as evolocumab, have been shown to lower triglyceride levels by approximately 10-20% (1). However, there have not been any reports of PCSK9 inhibitors lowering triglyceride levels by more than 100%. Clinical Case: A 35-year-old white man presented with hypertriglyceridemia for more than eight years. Past medical history was significant for recurrent pancreatitis and diabetes mellitus type 2 with recent HbA1c of 7.6% (normal range <5.7%) on metformin 1 gram BID and insulin glargine 15 units daily. He had multiple hospitalizations for pancreatitis requiring insulin drip. His triglycerides remained elevated on fenofibrate, atorvastatin, and icosapent ethyl despite alcohol avoidance and changes in diet with progressive elevation to 5000 mg/dL (normal range 0-150 mg/dL) requiring four sessions of plasmapheresis and hospitalization requiring intravenous insulin drip. His family history also included hypertriglyceridemia in his mother. He was started on evolocumab 140 mg subcutaneously every 2 weeks and noted to have drastic improvement of triglycerides down to a normal level of 138 mg/dL. On recent labs, his triglyceride level was noted to be 921 mg/dL with HbA1c at 8.0%. He did admit non-compliance to diet but did not require any more hospitalizations for pancreatitis since starting evolocumab. Conclusions: This is the first reported case of an unexplored potential of evolocumab in patients with severe hypertriglyceridemia. Reference: (1) Warden BA, Fazio S, Shapiro MD. The PCSK9 revolution: Current status, controversies, and future directions. Trends Cardiovasc Med. 2020;30(3):179-185. doi:10.1016/j.tcm.2019.05.007

Presentation: Friday, June 16, 2023
FRI104 A Case Of Nephrotic Syndrome Presenting With Hyperlipidemia
Authors: Romao Isabela J , Taranto Viktoria , Howard Shanik Michael
Published: October 2023

Disclosure: I.J. Romao: None. V. Taranto: None. M.H. Shanik: None.

Introduction: Nephrotic syndrome is associated with increased risk of atherosclerosis, stroke and thromboembolism (1). These complications can be linked to an increase in total cholesterol, LDL and triglycerides levels that are seen in nephrotic syndrome. The aim of this presentation is to highlight the importance of considering nephrotic syndrome in the differential diagnosis of a significantly elevated lipid profile. Case presentation: A 40-year-old woman with a history of anxiety and hypothyroidism presented for evaluation of hyperlipidemia. Blood work revealed a total cholesterol of 636 mg/dL (<200), LDL was 502 mg/dL (<130), triglycerides 325 mg/dL (<150) and HDL 69 mg/dL (>40). She was started on Atorvastatin 80 mg daily. She developed nausea and achiness and was changed to Rosuvastatin 10 mg daily. The lipid profile improved but remained elevated with a total cholesterol of 351 mg/dL and LDL of 215 mg/dL. She was also noted to have elevated blood pressure and leg edema for the past 2 months. She was treated with Hydrochlorothiazide 12.5 mg daily that significantly helped with the leg swelling and weight loss. She was taking levothyroxine 100 mcg and her TSH was 1.95 uIU/mL (0.35-4.9). She did not have a family history of thyroid disease or hyperlipidemia. On exam her blood pressure was 136/100, pulse 108, weight 245 lbs., height 5’7”, respiratory rate 12. She had trace edema of her lower extremities. The significant elevation in cholesterol levels and her history of leg edema were suspicious for protein loss. A urine analysis showed elevated protein in the urine at 87 mg/dL (<15). She completed a 24-hour urine for protein that was markedly high at 16,740 mg/24 hours (<150) consistent with nephrotic syndrome. She was evaluated by a nephrologist who performed a renal biopsy that showed membranous glomerulonephritis and tubular atrophy. No secondary causes were found. Her diuretic was changed to Torsemide 10 mg daily and Lisinopril 10 mg daily was added. After several months her blood pressure normalized to 120/80 and her total cholesterol improved to 202 mg/dL, LDL was 98 mg/dL, triglycerides 229 mg/dL. Albumin level went from 1.8 to 3.8 g/dL (3.5-5.7). She had a marked decrease of protein in the urine from 216 to 35 mg/dL (<15). Conclusion: Nephrotic syndrome should be part of the differential diagnosis of any patient who has a history of significant hyperlipidemia. The abnormalities of serum lipids seen in nephrotic syndrome are largely due to the impaired clearance rather than biosynthesis and can lead to multiple complications. Making the diagnosis of nephrotic syndrome is very important as it is associated with significant cardiovascular and renal disease. 1. Agrawal S, Zaritsky JJ, Fornoni A, Smoyer WE, Dyslipidemia in nephrotic syndrome: mechanism and treatment. Shipra Agrawal, et al. Nature Reviews Nephrology 2018; 14:57.

Presentation: Friday, June 16, 2023
FRI111 Venous Thromboembolism In Cushing Syndrome - A Call For Standardized Anticoagulation Regimen In Hypercortisolism
Authors: Minasyan Mari , Bryk-Wiazania Agata , Rzepka Ewelina , Bogusławska Anna , Hubalewska-Dydejczyk Alicja , Gilis-Januszewska Aleksandra
Published: October 2023

Disclosure: M. Minasyan: None. A. Bryk-Wiazania: None. E. Rzepka: None. A. Bogusławska: None. A. Hubalewska-Dydejczyk: None. A. Gilis-Januszewska: None.

Venous thromboembolism in Cushing Syndrome - a call for standardized anticoagulation regimen in hypercortisolism. Cushing Syndrome (CS) is associated with a 18-fold higher risk of venous thromboembolism (VTE) when compared to the general population with the similar demographic characteristics. Despite numerous studies on hypercoagulability in CS, the unequivocal recommendations regarding timing and dosing of thromboprophylaxis in hypercortisolism are still lacking. We present a case series of patients with CS and VTE, hospitalized in the Endocrinology Department of University Hospital in Krakow. Among 135 patients with CS, we found 7cases of VTE (5.19%), aged 35-65 years, mostly females (n=6). The etiology of CS was predominately pituitary (n=3), the other tissue origins of CS were: adrenal (n=2), ectopic(n=1) and adrenal carcinoma (n=1). Pulmonary embolism (PE) was found in 3 patients, deep venous thrombosis (DVT) in 2 patients, while 2 patients suffered from concomitant DVT and PE. We found that one patient had VTE 5 months before inducing the biochemical remission by a transsphenoidal surgery, while 2 patients within the 30 days after inducing the biochemical remission by either a transsphenoidal surgery in one, or metyrapone treatment in 2nd case. In the remaining 4 patients, VTE episode preceded the diagnosis of CS, ranging from 1 year to 2 months prior to the diagnosis. Among them, 2 PE episodes were associated with other predisposing factors, such as (1) postpartum PE in a 36-year-old women, who was subsequently diagnosed with Cushing disease, and (2) combined oral contraceptive in a 35-year-old woman, who suffered from the peripheral PE, and was eventually diagnosed with adrenal CS. Of note, at the time of VTE episode, 1 patient was treated with warfarin (international normalized ratio at the time of VTE, 1.66), another one took apixaban. One fatal PE occurred on the thromboprophylaxis with low molecular weight heparin, in the hypocortisolemia following metyrapone implementation. To summarize, VTE episode: 1. may be the first, life-threatening presentation of CS; 2. may occur after treatment of hypercortisolism; 3. may happen in patients on thromboprophylaxis or anticoagulant treatment; 4. should be included in the differential diagnosis of a thrombotic event despite coexisting transient factor (e.g. oral contraceptive, delivery). 5. Further multicenter studies are essential to understand the hypercoagulability in CS, and to create the recommendations on this topic.

Presentation: Friday, June 16, 2023
FRI116 Inhibition Of Mitochondrial Fission And Restoration Of Mitochondrial Function Attenuates Vascular Calcification
Authors: Hee Kwon So , Kim Min-Ji , Zerwa Siddique , Kim Seahan , Jueun Byun , Jeon Jae-Han , Lee In-Kyu
Published: October 2023

Disclosure: S. Kwon: None. M. Kim: None. S. Zerwa: None. S. Kim: None. B. Jueun: None. J. Jeon: None. I. Lee: None.

Objectives: Vascular calcification is associated with cardiovascular disease mortality, especially in patients with diabetes mellitus and chronic kidney disease. One of proposed mechanisms for development of vascular calcification suggested mitochondrial dysfunction of vascular smooth muscle cells (VMSCs), especially excessive mitochondrial fission that led to apoptosis and tissue calcium deposit formation. In existing literature, Vitamin B1 inhibited mitochondrial fission and improved mitochondrial function. This study investigated whether inhibiting mitochondrial fission prevents vascular calcification in vitro and in vivo by using inorganic phosphate and cholecalciferol-induced vascular calcification models, respectively. Methods: VMSCs from thoracic aorta of 4-week-old rats were treated by 2.6mM inorganic phosphate and 2mM calcium chloride to induce calcification. 6-week-old male C57BL/6J mice were given vitamin B1 analogue solution or water with daily oral gavage for 13 days, then aortic calcification was induced by subcutaneous injection of 5.5×10-5 IU/kg cholecalciferol for 3 days before sacrifice. Cells and tissues were stained for calcium deposition, (van Kossa stain), apoptosis (TUNEL) and mitochondrial morphology (Mitotracker). Western blotting and quantitative real-time PCR were used to assess calcification pathways and mitochondrial function. Tissue calcium content, normalized with total protein contents, was measured to quantify the extent of calcification. Mitochondrial oxygen consumption ratio (OCR) and mitochondrial membrane potential (JC-1 dye staining) were assessed to analyze quantified mitochondrial function. Results: Calcium deposition in both in vivo and in vitro models were alleviated by vitamin B1 analogue through inhibition of mitochondrial fission and restoration of mitochondrial function. In addition, vitamin B1 analogue downregulated expression of genes related to calcification and osteogenesis, such as bone morphogenic protein 2, osteocalcin, osteopontin, and runt-related transcription factor 2. Conclusion: Prevention of mitochondrial dysfunction in VSMCs may be a viable therapeutic strategy for treatment of vascular calcification.

Presentation: Friday, June 16, 2023
FRI118 3D Reconstruction Of Mitochondria From Human Heart Failure Structures Is Associated With Alterations In CHCHD6 And CHCHD3 Expression
Authors: Gail Marshall Andrea , Vue Zer , Garza-Lopez Edgar , Beasley Heather , Exil Vernat , Actkins Ky'Era , Miller-Fleming Tyne , Othrell Hinton Antentor
Published: October 2023

Disclosure: A.G. Marshall: None. Z. Vue, PhD: None. E. Garza-Lopez: None. H. Beasley, PhD: None. V. Exil: None. K. Actkins: None. T. Miller-Fleming: None. A.O. Hinton: None.

Heart failure (HF) is accompanied by symptoms and signs caused by cardiac dysfunction, resulting in reduced longevity. Critically, HF has been associated with mitochondria dysfunction, causing pathophysiology that might contribute to age-dependent decrease in cardiac function. Thus, we hypothesize that reduced cardiac function in response to HF, affects mitochondrial function and morphology. To test this, we investigated mitochondrial morphological changes using 3D reconstruction from 4 control human hearts and 4 human heart failure patients. Mitochondrial samples were 3D rendered and quantified using serial block facing-scanning electron microscopy and the Amira software. From our HF reconstructions, there are many phenotypes, including fragmentation, nanotunnels, and mitochondrial clustering, compared to controls, which may be associated to mitochondrial dysfunction. Surprisingly, we saw altered expression of CHCHD6 and CHCHD3 in human heart failure samples, based on immunofluorescence. Thus, we knocked out CHCHD6 and CHCHD3 in mouse fibroblasts, myotubes and human-induced pluripotent stem cell-derived cardiomyocytes and saw fragmentation in all three models. Presently, HF represents an unmet need with no approved clinical therapies for damaged myocardium replacement. Here, we suggest that CHCHD3 and CHCHD6 may be a molecular target that functions in the development of HF and possibly develop novel therapeutics for the treatment of HF.

Presentation: Friday, June 16, 2023
FRI122 Determinants Of Primary Aldosteronism Screening In The US: A Nationwide Physician Survey Study
Authors: Turcu Adina F , Salman Zara , Marie Konzen Sonja , Zhang Lei , Liu Haiping , Zhao Lili , Suzer Gurtekin Tuba , Papaleontiou Maria
Published: October 2023

Disclosure: A.F. Turcu: None. Z. Salman: None. S.M. Konzen: None. L. Zhang: None. H. Liu: None. L. Zhao: None. T. Suzer Gurtekin: None. M. Papaleontiou: None.

Background: Primary aldosteronism (PA) is the most common cause of endocrine hypertension, affecting up to 25% of patients with treatment-resistant hypertension. PA contributes to cardiovascular and renal morbidity and mortality, via mechanisms additive to hypertension. Early detection and targeted therapy of PA mitigate the risk of such complications. Despite this, only a minute fraction of patients at risk are ever screened for PA. Objective: To ascertain triggers and barriers for PA screening across US practices. Methods: Physicians treating hypertension, including internists, family practitioners, cardiologists, nephrologists, and endocrinologists, were randomly selected from active members of the American Medical Association. Physicians were surveyed on their practice of PA screening. Multivariable logistic regression was performed to determine factors associated with PA screening. Results: Of 633 response-eligible physicians, 425 (67%) completed the survey, including 32.4% family practitioners, 26.9% internists, 13.2% cardiologists, 12.2% endocrinologists, and 11.8% Nephrologists. Of the respondents, 230 (55.2%) were men; 63% identified as White, 24% Asian, and 6% Black. Most participants reported that resistant hypertension (84.5%), and hypertension and spontaneous hypokalemia (81.4%) prompt them to screen for PA. Conversely, a minority reported diuretic-induced hypokalemia (26%), obstructive sleep apnea (10%), or atrial fibrillation (6.2%) as triggers for PA screening. Compared with internists, endocrinologists and nephrologists were more likely, and family practitioners were less likely to screen for PA in patients with hypertension and hypokalemia, early-onset hypertension, or adrenal nodules. Barriers to PA screening included clinic visit time constraints (37.4%), poor ancillary support (28.1%), testing logistic concerns (26.2%), ability to control hypertension with medications (20.5%), and belief that PA is rare (20.2%). Female physicians and family practitioners were more likely to report not being familiar with results’ interpretation and next steps, and not having time to keep abreast with expert guidelines; private practitioners were most likely to report reimbursement concerns. Conclusions: Heterogeneity in screening for PA exists among physicians at the frontline of hypertension care. Increasing awareness and developing tools to facilitate PA screening are crucial for the recognition and adequate care of millions of patients with hypertension.

Presentation: Friday, June 16, 2023
FRI125 Recurrence Of Primary Aldosteronism Long-Term After Adrenalectomy For Aldosterone-Producing Adenoma With KCNJ5 Gene Mutation: A Two-Cases Report
Authors: Aiga Ko , Kometani Mitsuhiro , Aono Daisuke , Karashima Shigehiro , Yoneda Takashi
Published: October 2023

Disclosure: K. Aiga: None. M. Kometani: None. D. Aono: None. S. Karashima: None. T. Yoneda: None.

Primary aldosteronism (PA) is a major cause of secondary hypertension. PA is known to have higher prevalence of cerebral or cardiovascular complications, indicating the importance of early detection and treatment for PA. PA is caused by autonomous secretion of aldosterone in the adrenal glands. PA is characterized by high plasma aldosterone concentration, low plasma renin activity and hypokalemia. PA is classified into unilateral PA (aldosterone-producing adenoma [APA] or unilateral hyperplasia) and bilateral PA (bilateral adrenal hyperplasia). PA with aldosterone excess in bilateral adrenal glands is defined as bilateral PA. On the other hand, PA with aldosterone excess in unilateral adrenal gland is defined as unilateral PA. Strategies for PA treatment depends on the subtype of PA. Medication by mineralocorticoid receptor antagonists is a common treatment for bilateral PA. Adrenalectomy is the most efficient treatment for unilateral PA. In general, patients tend to maintain normal serum potassium level and blood pressure after adrenalectomy, and recurrence of PA is extremely rare. Recently, mutation in the gene named KCNJ5 was found to derive APA. Herein, we report two cases of PA recurrence more than 10 years after surgical treatment for APA. Somatic mutation in KCNJ5 was detected in the first occurrence of PA in both cases. First case, a 52-year-old woman was examined for hypertension 22 years after total adrenalectomy of the right adrenal gland. Recurrent PA was diagnosed based on high aldosterone-renin-ratio (ARR), identification of left adrenal gland tumor by computed tomography (CT), and a confirmatory test. Second case, a 65-year-old man was examined for hypertension 17 years after total adrenalectomy of the left adrenal gland. He had maintained his blood pressure using medication since the onset of hypertension 4 years after the surgery. A year later, a high ARR was observed. PA recurrence was determined by a right adrenal gland tumor noted on CT and a confirmatory test. Tissues of the adrenal gland were obtained from adrenalectomy in both cases. Histopathological analysis revealed presence of one adenoma in the first case, while two adenomas were confirmed in the second case. Somatic mutation in KCNJ5 gene was detected in both cases. To date, there are no specific guidelines established for the management of recurrent PA. Early detection is crucial for the prevention of severe cardiovascular diseases. Long-term follow-up is recommended after the treatment of PA.

Presentation: Friday, June 16, 2023
THU253 The Hemoglobin Wayne Variant And Association With Falsely Elevated HbA1c
Authors: Mulpuri Neha , Bryant Ananda , Shahin Daryoush , Soe Kyaw
Published: October 2023

Disclosure: N. Mulpuri: None. A. Bryant: None. D. Shahin: None. K. Soe: None.

Background: Hemoglobin Wayne (Hb Wayne) is a rare, silent alpha chain variant caused by a frameshift mutation in the HbA2 gene. Although clinically silent, this mutation falsely elevates HbA1c values. Clinical cases: We are presenting three cases of Hb Wayne patients referred to our diabetes clinic within the last 5 years. All three cases were Caucasian-American males diagnosed with uncontrolled diabetes based on high HbA1c values of ranging from 10.1-10.6 %. One of the patients was initially started on metformin while the other patients’ treatment plan included dietary and lifestyle modifications. Review of the labs showed that renal function, complete blood count and fasting plasma glucose were within the normal range. High HbA1c value was noted by routine screening lab without having any symptoms related to DM or features of insulin resistance. The discrepancy between high HbA1c values and other glycemic index parameters (serum glucose and FSBG values) was noted. Subsequently, further work up was done (repeat HbA1c with different assay and fructosamine) to verify the diagnosis of uncontrolled DM. Fructosamine levels and repeat HbA1c with a different assay (enzymatic assay at Quest lab) were normal. Hemoglobin electrophoresis confirmed presence of an abnormal alpha variant consistent with Hb Wayne. The patients were reassured and educated about this Hb variant, and no further treatment for DM was pursued. Conclusion: Rare hemolgobinopathies may be more common than previously expected as they can be clinically silent and easily overlooked. While HbA1c has been an important clinical tool for diagnosis and management of diabetes, clinicians should look for underlying reasons which can affect HbA1c assay if there is any discrepancy between HbA1c, FSBG and plasma glucose values. The laboratory at our institution uses cation- exchange High Performance Liquid Chromatography method (Bio-Rad D-100 instrument) resulting in falsely high HbA1c values. Some hemoglobinopathies can affect the widely used HbA1c testing method such as CE-HPLC. The impact on HbA1c values will differ depending on hemoglobin variant and specific method and assay used. Given the limitations of HbA1c testing, clinicians should avoid relying heavily on HbA1c values in management and diagnosis of diabetes. It is vital that clinicians use their clinical judgment to correlate HbA1c with other clinical parameters such as continuous glucose monitoring data, glycated albumin,1,5 anhydroglucitrol (1,5 –AG), fingerstick blood glucose, plasma glucose and fructosamine values.

Presentation: Thursday, June 15, 2023
THU262 Improvement Of Pharmacokinetic Properties Of Vasoactive Intestinal Peptide Through Backbone Modifications
Authors: Al Najar Mathew S , Lipchik Andrew M
Published: October 2023

Disclosure: M.S. Al Najar: None. A.M. Lipchik: None.

Vasoactive Intestinal Peptide (VIP) is a 28 amino acid neuropeptide hormone that is a part of the glucagon/secretin family. VIP has myriad physiological functions, including incretin effects, immune modulation, corneal wound repairing, and lacrimal secretion. VIP executes these functions through activation of two B1 family of G-protein-coupled receptors, VPAC1 and VPAC2, leading to cAMP production. Previous research has demonstrated that VIP has immense therapeutic potential in treating many diseases including type 2 diabetes, cardiovascular disease, and autoimmune diseases such as rheumatoid arthritis, type 1 diabetes, and Crohn's disease. Although VIP has proven to be pharmacologically active in these diseases, its utility as a therapeutic is limited due to its short half-life in circulation (less than one minute) caused by proteolytic degradation. Previous efforts have been made to improve serum stability through peptide stapling using lactamization and olefin-metathesis. However, both strategies failed to increase the stability of VIP. Additional strategies are needed to improve serum stability of VIP. A potential alterative approach is the utilization of peptide backbone modifications to prevent proteolytic recognition and degradation. The introduction of unnatural amino acids and analogs such as N-methyl amino acids and peptoids into the VIP sequence alters the peptide bond by placement of a methyl group or a side chain on the amine. Here, we present a library of VIP analogs containing N-methyl amino acids and peptoid substitutions. The serum stability, structural conformation, and pharmacological activity of the VIP analog library was compared and tested against wild-type VIP. The incorporation of N-methyl amino acids or peptoid residues demonstrated significant improvement in stability in human serum. In addition, the VIP analogs maintained alpha-helical confirmation similar to wild-type VIP. Finally, the VIP analogs were shown to maintain pharmacological activity as VPAC1 agonist as measured by cAMP production and glucose-dependent insulin secretion. Together, these results display the incorporation of unnatural amino acids with modified backbones can improve pharmacokinetics while maintaining pharmacodynamics of VIP, allowing for the potential use of VIP as a therapeutic.

Presentation: Thursday, June 15, 2023
THU270 Efficacy Of Patient Support Program On Management Of Cardiovascular Risk Factors For Adults With Type 2 Diabetes Mellitus
Authors: Shah Abhishek , Damse Sneha , Thiyagarajah Premalatha , Soulat karine , Ahadome Theo
Published: October 2023

Disclosure: A. Shah: None. S. Damse: None. P. Thiyagarajah: None. K. Soulat: None. T. Ahadome: None.

Efficacy Of Patient Support Program On Management Of Cardiovascular Risk Factors For Adults With Type 2 Diabetes Mellitus.

Type 2 diabetes mellitus (T2DM) is a major risk factor for cardiovascular disease. Patients with T2DM have 2 to 3 times the risk of cardiovascular mortality and morbidity.1 This study aimed to assess the efficacy of an intensive intervention strategy in improving cardiovascular risk factors, HbA1C level in high-risk patients with T2DM. Methods: An interventional program with a multi component strategy was delivered by Wellthy therapeutics over a period of 40 weeks. The program had interventions including customized dietary plans, behavioral interventions, including stress management and coping skills training, lifestyle counseling, disease awareness and self-management training of symptoms at home. Interventions were initiated by certified health coaches via chats and calls. A high-risk diabetic cohort whose HbA1C greater than 10% were recruited by convenience sampling method. Intervention Statistical analysis was done using SPSS version 21. Results: The mean age of patients was 48.49±14.46. The mean of HbA1C, Total Cholesterol, LDL, Triglycerides, BMI at baseline was 11.4, 195.42, 125.9, 247.26, 26.77 respectively. The mean of HbA1C, Total Cholesterol, LDL, Triglycerides, BMI at the endline was 9.70, 181.98, 119.82, 195.34, 25.95 respectively. The effect of the Paired Ttest witnessed that intensive intervention strategy had a statistically significant improvement in effect on the cardiovascular risk factors from baseline to follow up p<0.05.(HbA1C p=.001, Total cholesterol p=.019, Triglycerides p=.002, BMI p=.007). Conclusion: This program played a highly significant role in managing cardiovascular risk factors by training patients in self-monitoring, medication adherence, and knowledge on disease awareness. There is increasing evidence that these interventions can support modification of lifestyle risk factors among people with coronary T2DM; however, existing interventions are disparate. These types of interventions play a potential role in meeting the individual needs and preferences to optimize self-management of their disease.

Presentation: Thursday, June 15, 2023
THU279 Long duration Of CFTR Modulators Consistently Improve Glucose Metabolism Parameters In Patients With Cystic Fibrosis
Authors: Cohen Amitay , Mass Alon , Zangen David , Cohen-Cymberknoh Malena
Published: October 2023

Disclosure: A. Cohen: None. A. Mass: None. D. Zangen: None. M. Cohen-Cymberknoh: None.

Background: Impaired glycemic control and consequently Cystic fibrosis Related Diabetes (CFRD) due to gradual pancreatic β-cell dysfunction is a common complication (upto 50% in adults) in patients with cystic fibrosis (CF.) The novel use of CFTR modulators (CFTRm), improve pulmonary function and reduce disease exacerbations. Data regarding the long-term effect of CFTRm on glycemic control is limited. In this observational-retrospective study, we evaluate the effect of CFTRm on the classical pathophysiological deterioration in glucose tolerance in patients with CF. Methods and Results: 15 patients with CF (ages 13-37) treated with CFTRm were followed by routine Oral Glucose Tolerance Test (OGTT). OGTT Results of Pre and 3-81 months (mean 28) post initiation of CFTRm therapy were compared and also classified to 4 classic categories: normal glucose tolerance (NGT), indeterminate (INDET), impaired glucose tolerance (IGT) and diabetes (CFRD). The end point of OGTT at 120 minutes significantly improved post CFTRm therapy being 159.7 (80-419.4) compared to 130.4 (54-286) pre-CFTRm (p = 0.047). Regarding the categories sub-classification of patients: Two patients with CFRD improved after CFTRm therapy to NGT or INDET. 2 with INDET pre-therapy improved to NGT post therapy.Of 3 patients with IGT, 2 improved to NGT or INDET and 1 worsened to CFRD. Out of the 6 patients who had NGT pre CFTRm therapy, 4 remained NGT, one worsened to INDET, and one became CFRD. Conclusions: This is the first and largest study so far demonstrating consistent significant improvement in glycemic control in CFRD after CFTRm treatment of at least 3 months duration. Treatment seems to delay and possibly reverse the deterioration in glycemic control that is typical to the natural history of patients with cystic fibrosis. Larger studies are indicated but awareness to the current findings may prevent hypoglycemic events while staying on a fixed insulin dose while on CFTRm therapy.

Presentation: Thursday, June 15, 2023
THU281 Real-World Survey Of Adherence To Guidelines Regarding Type 1 Diabetes And Aerobic Exercise
Authors: Anthony Henske Joseph , Beach Gavin , Albashaireh Arwa
Published: October 2023

Disclosure: J.A. Henske: None. G. Beach: None. A. Albashaireh: None.

Background: Managing hyperglycemia and hypoglycemia before, during, and after aerobic exercise remains one of the greatest challenges for those living with type 1 diabetes. Several publications offer guidelines and recommendations but it is not well established to what extent these are followed by those living with diabetes. In order to assess the implementation and awareness of these guidelines and in particular guidelines around risk of hypoglycemia and safety recommendations, we created an online survey which was posted to focused social media groups limited to adults with type 1 diabetes who run, jog, or walk for exercise. Results: The entire 96-question survey was completed by 102 adults with a mean age of 42 and a mean duration of diabetes of 20 years. The self-reported average HbA1c of respondents was 7.1%. 68% of respondents reported exercise 4 or more days per week. Average mileage was 23 miles per week. The respondents were predominantly female (69%), Caucasian (94%), and from the United States (78%). There was a high rate of technology use as 97% of respondents report using CGM and 75% are using insulin pumps. 80% reported learning about diabetes and exercise mostly from trial and error, 46% from social media, 32% from their medical team, 28% from online searches, some using multiple methods. 27% of respondents reported fear of hypoglycemia as a significant barrier to exercise and 36% reported increased glucose variability as a result of exercise. 19% of respondents reported having hypoglycemia unawareness. 3% reported never having symptoms of hypoglycemia at any glucose level, 21% feel first symptoms with BG <50mg/dL, 26% at 50-60 mg/dL, and 40% at 60-70mg/dL. Despite published guidelines, 73% reported that they exercise even if severe hypoglycemia <50mg/dL in the last 24 hours, 74% do not check for ketones even if unexplained hyperglycemia >250mg/dL prior to exercise. 11% reported exercising with ketones present in blood or urine. 10% reported developing DKA after exercise. 86% experienced the need to stop exercise due to hypoglycemia and 18% reported a severe hypoglycemic event during exercise. 49% report not wearing diabetes identification during exercise. 41% reported difficulty with overnight hypoglycemia after exercise. Conclusion: In a real-world survey of 102 individuals with relatively well-controlled type 1 diabetes (mean A1c 7.1%) who walk, run, or jog extensively for exercise (23 miles per week), hypoglycemia awareness and management is a significant concern and barrier for them. Implementation science efforts and increased awareness of current guidelines and development of an educational curriculum surrounding type 1 diabetes and exercise may prove helpful to improve outcomes.

Presentation: Thursday, June 15, 2023
THU285 Predictive Factors Of Response To Liraglutide In Long-standing Type 2 Diabetes: A Real-life Study
Authors: Romero Fabiola , Ferreira Dahiana , Galiana Rodriguez Maria , Escurra Clara , Muller Alejandra , Rodriguez Roque , Valinotti Elizabeth
Published: October 2023

Disclosure: F. Romero: None. D. Ferreira: None. M. Rodriguez: None. C. Escurra: None. A. Muller: None. R. Rodriguez: None. E. Valinotti: None.

Introduction: Liraglutide demonstrated efficacy, safety and cardioprotective effects in DM2 in RCT and real-life studies. Benefits across diverse spectrum of patients, but the degree of HbA1c improvement differs within groups with different demographics and clinical characteristics.Objectives: To evaluate the effect of the addition of liraglutide on metabolic control and weight in patients with DM2 treated with oral antidiabetics (OADS) and/or insulin, who do not achieve good control and to identify predictive factors for a greater decrease in HbA1c.Materials and methods: Prospective study, at the Endocrinology Service of the Social Security Institute in 2019, which included patients with DM2 and HbA1c greater than 7%, on treatment with OADS, basal insulin ± OADS or basal/bolus insulin ± OADS, in who were added liraglutide 1.8 mg/day SC. At 6 months, the reduction in HbA1c and body weight was evaluated.Results: 103 patients with DM2 of 59.6 ± 10 years old, 66.3% women and 12.5 ± 6 years of duration of DM2 were included. 18.3% treated only with OADS and 81.7% with insulin (47.1% basal insulin ± OADS and 34.6% basal/bolus insulin ± OADS) initial weight 99.1 ± 23.5 kg, BMI 37.4 ± 8.2 kg/m2, basal glycemia 182.7 ± 65 mg/dl and HbA1C 9.2 ± 1.6%. At 6 months of addition of liraglutide, weight loss of 3.2 ± 3.8 kg, 23.12% decreased > 5%, and 5.8% > 10%. The decrease in HbA1c was 1.1 ± 1.3%, 58.7% decreased > 1%, and 21.2% > 2%, the final glycemia was 145.7 ± 52.3 mg/dl. 38% managed to suspend insulin (basal 8.3%, rapid 10.9%) or reduce the dose of basal insulin (10%). The initial mean values were compared: age, years of DM duration, weight, BMI, glycemia and HbA1c among the patients who achieved a reduction of 1 or more % of HbA1c, finding significant differences for initial BMI (p 0.02), basal glycemia (p 0.010), initial HbA1c (p 0.022). In addition, the proportions of patients in terms of sex, different initial treatment groups and weight reduction were compared, and a significant difference was observed only in the latter (p 0.036). Conclusion: In this study of patients with long-standing diabetes, mostly treated with insulin and poor metabolic control, the addition of liraglutide achieved a reduction in HbA1C of 1% or more in almost two thirds, especially in those with higher initial values of BMI, glycemia and HbA1c and in those who achieved weight reduction. An important group achieved the suspension or reduction of the insulin dose.

Presentation: Thursday, June 15, 2023
THU287 Comparison Of Renal Protective Effects Between SGLT2 Inhibitors And DPP4 Inhibitors In Real-World Clinical Practice
Authors: Park Hyeong-Kyu , Park Sang-Joon , Kwon Soon-Hyo , Kim Hye-Jung , Byun Dong-Won
Published: October 2023

Disclosure: H. Park: None. S. Park: None. S. Kwon: None. H. Kim: None. D. Byun: None.

Recent prospective randomized studies have shown that sodium-glucose cotransporter 2 (SGLT2) inhibitors had renal protective effects compared to placebo. In this study, we compared the renal composite outcomes between patients with diabetes treated with SGLT2 inhibitors and those treated with dipeptidyl peptidase 4 (DPP4) inhibitors using real-world clinical data. This retrospective observational study used the Observational Medical Outcomes Partnership Common Data Model (OMOP-CDM) database at four different university hospitals (Soonchunhyang university hospitals in Seoul, Bucheon, Chunan, and Gumi) in Korea. Subjects prescribed SGLT2 inhibitors or DPP4 inhibitors for at least 90 days were included in the SGLT2 inhibitor or DPP4 inhibitor group, respectively. Subjects prescribed GLP-1 receptor agonist or insulin were excluded in both groups. Renal composite outcomes included a 30% decline in estimated glomerular filtration rate (eGFR) compared to baseline or creatinine doubling or dialysis or death from any cause. After propensity score matching, clinical characteristics in each group at each hospital were well balanced at baseline. Our results from hospitals in Seoul, Bucheon, and Gumi have shown that SGLT2 inhibitor decreased renal composite outcomes compared to DPP4 inhibitor (hazard ratio (HR) 0.644, p=0.020; HR 0.560, p<0.001; HR 0.657, p=0.010, respectively). Furthermore, when all the data were combined, renal composite outcomes were significantly lower in the SGLT2 inhibitor group compared to the DPP4 inhibitor group (HR 0.659, p<0.001). In conclusion, SGLT2 inhibitors effectively reduce renal composite outcomes compared to DPP4 inhibitors in real-world clinical practice.

Presentation: Thursday, June 15, 2023
THU304 Diabetic Ketoacidosis In Pregnancy: A Nationwide Analysis Of Trend In Hospitalizations, Comorbidities And Outcomes
Authors: Master Vidisha , Faisaluddin Mohammed , Fatima Samia , Parekh Dhruv , Charatz Seth
Published: October 2023

Disclosure: V. Master: None. M. Faisaluddin: None. S. Fatima: None. D. Parekh: None. S. Charatz: None.

Introduction: Diabetic Ketoacidosis (DKA) is an obstetric emergency associated with high materno-fetal morbidity and mortality. Aim: To analyse the trend of DKA hospitalizations among pregnant women, and to evaluate the comorbidities and in hospital outcomes associated with DKA events in United States. Methods: A national population- based study was conducted in the US. Hospitalizations during pregnancy from 2015 - 2020 were identified using ICD- 10 codes (E101) from Healthcare Cost and Utilization Project (HCUP), National Inpatient Sample (NIS) database. Pregnant women with DKA and without DKA formed the two comparison cohorts. Demographic characteristics, baseline comorbidities, and outcomes such as maternal mortality, fetal mortality, length of stay (LOS), and cost of hospitalization were compared. A two- tailed p-value of p< 0.05 was used to determine the statistical significance. Results: 11,215 out of 14,613,248 hospitalizations during pregnancy were identified with DKA from 2015 - 2020. An increasing trend in DKA hospitalizations per 100,000 pregnancy related hospitalizations was noted, highest in 2017 and 2020. Demographic distribution was similar in both groups. Comorbidities such as pre-eclampsia, eclampsia, gestational hypertension, tobacco and alcohol use were more common in the DKA group (p<0.0001). DKA was associated with higher maternal (0.18% vs 0.01%) and fetal mortality rates (2.9% vs 0.7%) compared to non-DKA group (p<0.0001). The median length of hospital stay was higher (3 days vs 2 days), along with the median cost of hospitalization ($25,248 vs $18,306) among pregnant DKA patients. Other in hospital outcomes such as need for mechanical ventilation, cardiac arrest, cardiac arrhythmias, acute kidney injury, need for dialysis, and septic shock, were all higher in DKA patients (p<0.0001). Conclusion: DKA in pregnancy is associated with high maternal and fetal mortality, longer LOS, higher cost of hospitalizations, and other maternal morbidities, as compared to non-DKA hospitalizations during pregnancy. A high index of suspicion for DKA should be maintained in all pregnant women, along with prompt evaluation and treatment.

Presentation: Thursday, June 15, 2023
THU316 Relatively Rare And Increasingly Fatal; A Case Of Euglycemic DKA In A Patient With Gestational Diabetes
Authors: Dimech Christina , Rabiei-Flori Elham , Lynn Bononi Patricia
Published: October 2023

Disclosure: C. Dimech: None. E. Rabiei-Flori: None. P.L. Bononi: None.

Diabetic ketoacidosis (DKA) is an endocrine emergency and can be a catastrophic event during pregnancy, increasing both maternal and fetal mortality. Euglycemic DKA (EDKA) during pregnancy is a rare, acute, life-threatening emergency characterized by euglycemia, metabolic acidosis and ketosis. EDKA has been reported in pregnancies complicated by Type 1 diabetes, Type 2 diabetes and gestational diabetes. Unlike DKA, the diagnosis of EDKA is often overlooked because of the absence of hyperglycemia. The incidence of DKA and EDKA are higher during pregnancy due to physiologic changes of increasing insulin resistance from human placental lactogen, placental insulinase, and progesterone which result in a relative insulin deficiency as the pregnancy progresses. Additionally, tocolytic therapy to delay preterm labor and antenatal corticosteroids given to promote fetal lung development, pose unique triggering factors in pregnancy which can further precipitate DKA. We report a case of EDKA in a 37-year-old G2P0010 Caucasian female at 29 week 6 day gestation with recently diagnosed gestational diabetes on diet therapy (HbA1c 6.3%), who was admitted for atypical preeclampsia. Initial laboratory studies revealed an anion gap metabolic acidosis (anion gap=24, arterial pH 7.242) with euglycemia (blood glucose 123mg/dL). She underwent emergent C-section 24 hours after admission due to development of pre-eclampsia with severe features. Despite delivery, she had persistent and worsening high anion gap metabolic acidosis (HAGMA). The Endocrinology service was consulted and ordered a beta hydroxybutyrate level which was elevated at 6.18mmol/L (0.02-0.30mmol/L) with 3+ ketonuria. Intravenous insulin and dextrose were instituted with gradual improvement in acidosis. EDKA is an easily missed diagnosis that should always be considered during pregnancy in a patient with high anion gap metabolic acidosis. Prompt recognition and treatment is essential to minimize complications to mother and fetus.

Presentation: Thursday, June 15, 2023
THU324 Euglycemic Diabetic Ketoacidosis Coinciding With COVID-19 Infection During Pregnancy
Authors: Alkhathlan Mujahed , Siddiqui Ayesha
Published: October 2023

Disclosure: M. Alkhathlan: None. A. Siddiqui: None.

Background: Pregnancy is well known to be a diabetogenic and ketogenic state. When coinciding with an acute illness like COVID-19 infection, it can lead to full-blown DKA requiring intervention to reverse ketoacidosis. Complete restoration of normal glycemic status can be achieved after treatment of COVID-19 infection. Clinical case: A 34-year-old, G3 P2 woman who was at 26 weeks gestation with triplet pregnancy presented to the ED with fever, shortness of breath, nausea and vomiting for 3 days. She had gestational hypertension and impaired glucose tolerance during her previous pregnancy, but none during her current pregnancy. She had tested positive for COVID-19 infection at an outpatient evaluation for mild upper respiratory symptoms, two days prior to her presentation. Vital signs in the ER were T 35.3 °C, RR 22, HR 103, BP 121/70, and O2 sat 95% on 4 L/min nasal cannula. Initial laboratory testing showed sodium 132 (135-145), potassium 4.4 (3.5-5.5), bicarb 9 mmol/L (22-29), anion gap 18 mmol/L (5-14), BUN 3 mg/dL (6-23), creatinine 0.43, eGFR > 60, glucose 113 mg/dL (74-109), serum ketones 3.13 mmol/L (0.02-0.27) and lactate 1.6 mmol/L (0.5-2.5). ABG confirmed acidosis with pH of 7.29, and PCO2 was 22. She was diagnosed with euglycemic DKA after ruling out other possible etiologies of high anion gap metabolic acidosis. She received betamethasone by the Obstetrics team and fetal monitoring was initiated. DKA treatment was started with IV insulin, dextrose and close glucose monitoring. She had complete resolution of metabolic acidosis after 34 hours and did not require subcutaneous insulin treatment post-DKA resolution. She was able to tolerate oral diet with significant improvement of all her symptoms. She required only supportive treatment for COVID-19 infection and tested negative on the third day of hospitalization. Conclusion: Pregnancy is a ketogenic state and when superimposed with a significant acute illness of COVID-19, can lead to euglycemic DKA even in the absence of gestational diabetes. Early detection and treatment of ketoacidosis with COVID-19 is critical to avoid fetal and maternal complications or premature delivery.

Presentation: Thursday, June 15, 2023
THU325 Covid-19 Outcomes In Cancer Patients With Diabetes
Authors: Tan Ngo Emmeline Monique , Thosani Sonali
Published: October 2023

Disclosure: E.T. Ngo: None. S. Thosani: None.

Diabetes mellitus and cancer are risk factors for poor outcomes in patients with Covid-19 (Covid). In this study, we compare Covid outcomes in patients with diabetes and cancer in relation to their inpatient glucose control.

We conducted a retrospective review of cancer patients with diabetes hospitalized at our institution from 12/1/2020-7/31/2021 for Covid (n=117). Readmissions were excluded (n=13). Apart from demographic data, other variables reviewed included cancer type, stage, treatment, comorbidities, laboratory data for glucose and inflammatory markers, and Covid-related management. Utilizing average daily glucose for each patient, we calculated percentage of inpatient days with glucose values with euglycemia (average daily glucose within target range of 70-180 mg/dL) and hyperglycemia (average daily glucose values above target of 180 mg/dL). Wilcoxon rank-sum test for contiguous variables and Fisher’s exact test for categorical variables were done to compare the distribution of variables between groups. Kaplan-Meier curve was generated for survival analysis.

Of the 104 patients, 73% were age ≥60, 54.8% were male, 49% had BMI >30, and majority (88.5%) were not vaccinated for Covid. 81.7% had type 2 diabetes, 14.4% had drug-induced (i.e. steroid) diabetes, and the remaining had type 1 diabetes. The most common comorbidities were hypertension (56.7%) and heart failure (8.65%). Hematologic malignancies (40.4%) were the prevailing cancer diagnosis. Of patients with cancer staging available (n=50), 33.7% were stage 4, and 66.3% were on active cancer treatment at the time of hospitalization. 49% of the entire cohort had severe Covid on presentation; 21% (n=22) died during hospital stay. Comparison of Covid-related variables and inflammatory markers between euglycemic (n-18) vs. hyperglycemic (n=86) group noted significant differences in LDH, Hba1c and use of steroids which was significantly higher in hyperglycemic group. There was no difference in overall survival (p=0.46) and non-ICU length of stay (p=0.06) noted between groups.

Our study confirms high mortality rate from Covid in hospitalized patients with diabetes and cancer. As noted, inpatient glycemic control to achieve targets in this patient population was not associated with reduction in mortality or improvement in Covid-related outcomes, which is in alignment with previously published studies.

Presentation: Thursday, June 15, 2023
THU326 Subcutaneous Insulin Aspart Every 4 Hours In the Treatment Of COVID-19 Patients With Diabetic Ketoacidosis: A Retrospective Study
Authors: Chiewchalermsri Dararat , Wanittansirichok Chayanin , Sriphrapradang Chutintorn
Published: October 2023

Disclosure: D. Chiewchalermsri: None. C. Wanittansirichok: None. C. Sriphrapradang: None.

SUBCUTANEOUS INSULIN ASPART EVERY 4 HOURS IN THE TREATMENT OF COVID-19 PATIENTS WITH DIABETIC KETOACIDOSIS: A RETROSPECTIVE STUDY

Introduction: COVID-19 infection increases the risk of diabetic ketoacidosis (DKA). To limit the healthcare workers’ exposure when taking care of the COVID-19 patients, treatment of DKA with subcutaneous (SC) rapid-acting insulin analogs every 4 hours was suggested in many professional recommendations. However, the evidence to support this strategy is lacking. We aimed to report the efficacy and safety of SC insulin aspart every 4 hours in the management of DKA in COVID-19 patients. Methods: We retrospectively reviewed all confirmed COVID-19 patients aged >15 years who developed mild-moderate DKA between July 2020 and October 2021 in our institution. Insulin aspart was delivered 0.4 units/kg SC every 4 hours. When blood glucose (BG) decreased to <250 mg/dL, the dose of insulin aspart was reduced to 0.2 units/kg every 4 hours until resolution of DKA. SC Basal insulin 0.15-0.2 units/kg was also initiated at the time of DKA diagnosis. Result: A total of 7 patients had mean age of 67.43±13.19 years with body mass index of 25.49±3.42 kg/m2. Most was 71.4% of female and all had pre-existing type 2 diabetes mellitus. All patients received high-dose steroid for COVID-19 treatment. Initial biochemical parameters were BG of 449±157.3 mg/dL, hemoglobin A1c of 10.58±2.81%, pH of 7.34±0.07, beta-hydroxybutyrate of 4.0±1.51 mmol/L, and HCO3 of 15.5±2.17 mmol/L. Time to resolution of DKA were 12.7±5.82 hours. Conclusion: From our cohort, SC rapid-acting insulin administered every 4 hours could be applied in the selected COVID-19 patients with mild-moderate DKA.

Presentation: Thursday, June 15, 2023