bluuebunny/crossref_metadata_2025 huggingface dataset:
ODP629 A Case of Juvenile Onset Hypophosphatasia Diagnosed In An Elderly Patient With Recurrent Fractures.
Authors: Matos Moises , Peña Ernesto Muñoz , Surya Sowmya K
Published: November 2022

Background

Hypophosphatasia (HPP) is a rare genetic disorder characterized by defective bone mineralization. Here we report a case of juvenile onset HPP in an elderly man. CASE A 77-year-old man presented for management of osteoporosis. He complained of joint pains and trouble walking. He had recurrent non-traumatic fractures since his teenage years and he and his sister were diagnosed with childhood rickets. He sustained fractures of both forearms, right ankle, right hip and left femoral neck, and had undergone right hip replacement and left femoral neck internal fixation. In his 20's, following a MVA he had several tooth extractions and eventually required dentures. He was misdiagnosed with osteogenesis imperfecta, vitamin D deficient osteomalacia and pseudogout, and had been treated with cholecalciferol and alendronate in the past. On exam, we noted a waddling gait, short stature and bowing of his knees. Labs revealed normal vitamin D 25-OH 48 ng/mL (30-100), and PTH 18 pg/mL (14-64), borderline corrected calcium 10.5 mg/dL (8.4-10.6) and elevated phosphorous 4.4 mg/dL (2.2-4.3). ALP was notably low 30 U/L (40-150) and had ranged between 15-46 U/L since 2009. These findings caught our attention and we ordered Vitamin B6 levels which were elevated >250. 0 ng/mL (2.1-21.7). Genetic testing identified two ALPL gene variants, a rare C.340G>A variant and a c.571G>A variant which has been found to be causative of HPP. His DXA scan showed normal L-spine (T-score 3.3) and significantly decreased BMD of the proximal 1/3 of the left forearm (T-score -4.4). Hip and femur were not assessed due to presence of hardware. He is scheduled to start treatment with Asfotase alfa.

Conclusion

HPP is caused by ALPL gene mutations, which lead to loss of function of the enzyme tissue nonspecific alkaline phosphatase (TSNALP). Clinical manifestations such as seizures, recurrent fractures and premature dental loss are observed. Pseudogout may occur due to intraarticular calcium pyrophosphate deposition, as in our patient. Characteristic lab findings are elevated metabolites of TNSALP, including urine inorganic pyrophosphate (PPi) and serum pyridoxal 5'phosphate (PLP) (biologically active metabolite of vitamin B-6). A persistently low ALP is most suggestive and may be a clue for early referral. Genetic testing is confirmatory, but novel mutations may be missed. Delayed diagnosis in our patient led to increased morbidity, potentially avoidable surgeries and inappropriate treatment with bisphosphonate which are contraindicated as they may increase risk for atypical fractures. Asfotase alfa is a TNSALP enzyme replacement therapy designed to address the underlying cause of HPP and studies show improvement in bone mineralization, fracture healing, decreased concentration of PLP and PPi, and improved physical function and quality of life. Cost and availability remain a barrier to many patients.

Presentation: No date and time listed
OR01-2 Increased Fracture Risk in Patients Using Insulin Compared to Metformin, Attenuated in Patients Using Combination of Insulin and Metformin: Based on Common Data Models
Authors: Kim Kwangsoo , Kim Sang Wan , Kimg Jung Hee , Lee Seulbi , Lee Si-Yeon , Shin Chan Soo , Kong Sung Hye
Published: November 2022

Objective

Despite their normal to high bone mineral density, fracture risk was increased in patients with type 2 diabetes. Antidiabetic medications have been suspected to account for the excess risk partly. However, longitudinal comparative studies on the effects of various antidiabetic medications on fractures are limited. We aimed to evaluate the fracture risk of patients using various antidiabetic medications compared to those using metformin.

Methods

We included 6,694 patients aged ≥ 50 years from the common data model (CDM) database between 2008 and 2012, who used the same antidiabetic medications over a year. The patients were grouped as metformin, insulin, sulfonylurea, dipeptidyl-4-inhibitor (DPP4i)+metformin, insulin+metformin, sulfonylurea+insulin, sulfonylurea+metformin, DPP4i+sulfonylurea+insulin, and sulfonylurea+insulin+metformin. The risks of major osteoporotic fractures (MOF) and hip fractures in each group were analyzed using the Cox proportional hazards model compared with the metformin group as a reference.

Results

During a median follow-up duration of 6.1 years, the incidence rates of MOF and hip fracture were 8.36 and 1.53 per 1000 person-year. The mean age was 65.8 years, and 47.7% were women. Compared to metformin users, insulin users showed an increased risk of MOF (hazard ratio [HR] 1.96, 95% confidence interval [CI] 1.28-3.02) and hip fracture (HR 3.06, 95% CI 1.21-7.77) after multivariate adjustments, including age, sex, body mass index (BMI), HbA1c, history of fracture, secondary osteoporosis, rheumatoid arthritis, cardiovascular, cerebrovascular disease, dementia, chronic kidney disease, use of steroid, proton pump inhibitor, and warfarin. Besides, the risk became insignificant in patients using a combination of insulin and metformin in both MOF (HR 1.32, 95% CI 0.77-2.27) and hip fracture risks (HR 2.68, 95% CI 0.56-12.80) after covariates adjustments. In subgroup analysis, insulin users harbored a significantly higher risk for MOF than metformin users only in patients withHbA1c < 7%, or BMI < 25 kg/m2.

Conclusion

From real-world data, we found that insulin users were at elevated risk of MOF and hip fracture compared to metformin users, which might be attenuated in users with a combination of insulin and metformin. The increased fracture risk in insulin users was exaggerated in non-obese and well-controlled diabetic patients, indicating the need for routine fracture risk assessment in these patients.

Presentation: Saturday, June 11, 2022 11:45 a.m. - 12:00 p.m.
PSAT176 Molecular Analysis of AMBRA1 as a Candidate Tumor Suppressor in Sporadic Parathyroid Adenomas
Authors: Arnold Andrew , Costa-Guda Jessica , Chinwo Stephanie , Bellizzi Justin
Published: November 2022

Primary hyperparathyroidism is a common endocrine disorder that is most often caused by a sporadic single-gland parathyroid adenoma. Currently, the only known and experimentally validated oncoprotein for parathyroid adenomas is cyclin D1. The overexpression of cyclin D1 protein has been reported in twenty to forty percent of cases. Eight percent of this overexpression can be explained by DNA rearrangement involving the cyclin D1 locus. The remaining molecular mechanisms behind this overexpression have yet to be identified. In this study, we explored a potential parathyroid tumorigenic mechanism that could increase cyclin D1 stability through a defect in the AMBRA1 E3 ligase adaptor, a molecule responsible for its degradation. Evidence that AMBRA1 may be a tumor suppressor gene includes the accumulation of cyclin D with hyperproliferation in AMBRA1-deficient cells, the context-dependent growth of tumors in Ambra1-deficient mice, and the finding that low levels of AMBRA1 correlated with poor clinical outcomes in The Cancer Genome Atlas (TCGA). We have therefore proceeded examine AMBRA1 for evidence of tumor suppressor-type inactivation within a cohort of parathyroid adenomas. Genomic DNA from twenty-six typical sporadic parathyroid adenomas was subjected to PCR-amplification of all eighteen coding exons of AMBRA1, followed by Sanger sequencing. Sequences were analyzed by comparison to the normal reference sequence, seeking to assess any observed intragenic or splice-site variants as potential or likely loss-of-function mutations. Thus far, with ninety-seven percent of the coding region fully sequenced, no intragenic AMBRA1 inactivating mutations were observed. Three known single nucleotide polymorphisms, considered non-pathogenic, were identified: missense variant c.3028G>T, and 3' UTR variants c.*491T>C and c.*576A>T, each in a single tumor. Future study of increased numbers of parathyroid adenomas is needed to exclude the possibility that AMBRA1 inactivation could play a driver role in a small percentage of cases, and the possibility that AMBRA1 might contribute less directly e.g. via secondarily altered expression also warrants investigation. Nonetheless, our current observations strongly suggest that AMBRA1 does not have a frequent role as a classic 2-hit tumor suppressor gene in sporadic parathyroid adenomas.

Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
PSAT183 Severe Hypocalcemia Precipitated by COVID-19 Infection in a Patient with Albright Hereditary Osteodystrophy and Pseudohypoparathyroidism
Authors: Siddiqui Samrah , Anokwute Akudo , Zahedi Tooraj , Zhang Fan
Published: November 2022

Background

Hypocalcemia is a common endocrine manifestation of COVID 19 infection. We present a rare case of severe hypocalcemia in a patient with a history of Pseudohypoparathyroidism (PHP) type 1A after COVID-19 infection. PHP is a genetic disorder that presents with hypocalcemia, hyperphosphatemia, and secondary hyperparathyroidism due to marked target-organ unresponsiveness to parathyroid hormone (PTH). PHP type 1A also has a characteristic somatic phenotype known as Albright Hereditary Osteodystrophy (AHO), including short stature, brachydactyly, shortened metatarsals, and often reduced intelligence.

Case Presentation

This is a 53-year-old female with PHP type 1A, diabetes mellitus type 2, hypothyroidism, vitamin D deficiency, mild intellectual disability, and hypertension. She presented with new onset of seizures. She was also found to be positive for COVID-19 infection. On Review of systems, she had diarrhea but denied perioral or extremity paresthesia, palpitations, muscle spasms and bone pain. She reported compliance with calcitriol and calcium supplements at home. She had short stature, round face, short neck, obesity, brachydactyly (short digits of right 4th and 5th fingers) and shortened left 4th metacarpal. Labs revealed corrected serum calcium from baseline of 7.8 mg/dL to 4.4 mg/dL, ionized calcium 2.9 mg/dL, vitamin D 12.8ng/ml, PTH 142pg/ml and phosphorus 6.2mg/dl. EKG showed T wave inversions and prolonged QT interval. She did not have tetany, carpopedal spasm, paresthesia, Chvostek's sign, or Trousseau's sign. After receiving a total of 11 grams of elemental calcium, calcitriol, and ergocalciferol, her corrected calcium level improved to 7.4 mg/dL and EKG normalized. She was discharged home with calcium carbonate 1,250 mg twice a day and calcitriol 0.5 mcg daily.

Discussion

PHP type 1A is an autosomal dominant mutation of the stimulatory G protein alpha subunit (G alpha or GNAS) derived from the mother due to genomic imprinting which leads to PTH resistance in the kidneys and parathyroid glands. Our patient had a long-standing history of mild hypocalcemia with calcium and calcitriol supplements. Sudden worsening of hypocalcemia was likely related poor calcium and calcitriol absorption induced by COVID-19 infection. Patient with chronic hypocalcemia may not present with typical hypocalcemia signs or symptoms due to their tolerance.

Conclusion

Clinicians should be aware of the risk of developing severe hypocalcemia in patients who are calcium dependent or vitamin D deficient, malnourished during critical illness, or have COVID-19 infection which may decrease serum albumin and reduce total serum calcium level.

Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
RF06 | PSAT152 Associations between Bone Mass, Hormone Levels and Body Composition in Postmenopausal Women
Authors: Fighera Tayane , dos Santos Betânia Rodrigues , Lima Letícia Kortz Motta , Spritzer Poli Mara
Published: November 2022

Emerging evidence suggests an association between FSH and bone mass in peri- and postmenopausal women. The aim of the present study was to assess body composition parameters and hormone levels as risk factors for low bone mass in women with recent menopause. In this cross-sectional study, we analyzed biorepository samples from 139 postmenopausal women aged 42 to 68 years with no evidence of clinical CVD. Inclusion criteria were as follows: menopause, defined as last menstrual period at least 12 months of amenorrhea and/or 6 months or more of amenorrhea plus FSH levels ≥35 mIU/mL occurring after 40 years of age, and no use of hormone therapy (HT) in the past 3 month. BMD and body composition were assessed by dual-energy X-ray absorptiometry (DXA), SHBG and FSH levels were measured in all patients. Serum estradiol levels were measured by gas chromatography/tandem mass spectrometry assay (GC/MS/MS) in a subset of 57 participants and free estrogen index (FEI) was estimated by dividing estradiol by SHBG × 100. Low bone mass was considered osteoporosis and osteopenia. The mean age was 54.33±5.30 years and median time since menopause was 4 (2 - 9) years. The mean BMI was 26.73±4.38 kg/m2 and 66% of participants were classified as overweight or obese. BMI, BMD and T-sc, lean mass index (LMI) and fat mass index (FMI) were lower, and SHBG was higher in women with FSH levels above the median values (83.6mUI/mL). FSH was inversely correlated with FEI (rho=-0.283, p=0.033) as well as with FMI (rho=-0.288, p=0.001) and LMI (rho=-0.186, p=0.029), but significance was lost after adjustment for estradiol levels (p=0.651). In the univariate linear regression analysis, FSH, FEI, time since menopause, SHBG, FMI and LMI were significant predictors to total femur bone mass, explaining 3.8%, 11.9%, 7.4%, 14.7%, 19.7% and 8.4% of variance in BMD at this site, respectively. In the multivariate model, the association of FSH, time since menopause and FMI with hip bone mass was no longer significant after inclusion of FEI in the respective model. The present results indicate that the negative association between FSH levels and femoral BMD in postmenopausal women are influenced by endogenous estradiol levels, time since menopause and fat mass. Additional studies are needed in order to further analyze whether some direct effect of FSH on bone mass may be additive to the presence of low bone mass in this population.

Presentation: Saturday, June 11, 2022 1:00 p.m. - 1:05 p.m., Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
RF06 | PSAT154 Osteoporosis Likely Increases the Risk of Dementia in Vietnamese Immigrants
Authors: Kim Yu N , Arif Saleena
Published: November 2022

Osteoporosis is a common systemic skeletal disease that predominantly affects people older than 50 years and often co-occurs with dementia. Studies have been conducted to find out the relation between the two, but this is not well studied in the Vietnamese population. This study aimed to analyze the impact of osteoporosis on the risk of dementia in Vietnamese immigrants.

We identified 38(female(F) 26, male(M) 12) community-dwelling Vietnamese patients aged ≥ 55 seen at the cognitive assessment clinic in a community health center 1/2021-8/2021 through chart review. Because either DEXA was not performed or the results were unavailable, 23 patients (F 12, M 11) were excluded. We assigned the patients with normal cognitive tests results or a diagnosis of mild cognitive impairment to the control group and those diagnosed with dementia to the study group.

Among 15 patients, 10(F 9, M 1) patients were diagnosed with dementia. Seven patients (F 6, M 1) had osteoporosis. Five patients (F 5) were assigned to the control group, and two patients had osteoporosis. (OR 3.5000, P = 0.2736)

The odds of developing dementia were 3.5 higher given osteoporosis diagnosis than with no osteoporosis. These results suggested a positive association between osteoporosis and dementia in Vietnamese immigrants. More studies with a larger number of patients in this cohort are needed to investigate this further.

Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m., Saturday, June 11, 2022 1:18 p.m. - 1:23 p.m.
RF30 | PSAT177 A Case of Hypercalcemia Related to Immune Checkpoint Inhibitor-Induced Sarcoidosis-like Granuloma
Authors: Donangelo Ines , Koh Michelle , Lei Lei
Published: November 2022

Background

Immune checkpoint inhibitor (ICI) is an essential part of the treatment of various advanced cancers, but its use can be associated with a number of side effects, including hypercalcemia. The mechanism through which hypercalcemia arises is not well established. One proposed mechanism is through sarcoidosis-like reactions. Here we present an illustrative case.

Clinical Case

A 75-year-old female with past medical history notable for stage IV endometrial adenocarcinoma treated with surgery plus adjuvant chemotherapy, presently on pembrolizumab for 9 months, hypertension, and diabetes was admitted with generalized fatigue, difficulty ambulating, slow movements, and slow speech. Stroke was ruled out with negative neurologic imaging. Blood work revealed elevated calcium 13.8 mg/dL (8.6-10.4 mg/dL) and ionized calcium 1.64 mmol/L (1.09-1.29 mmol/L). Additional workup showed suppressed PTH 7 pg/mL (11-51 pg/mL), 25-OH vitamin D 19 ng/mL (20-50 ng/mL), elevated 1,25(OH)2 vitamin D of 114 pg/mL (19.9-79.3 pg/mL), elevated angiotensin converting enzyme (ACE) level 90 U/L (12-69 U/L), and normal PTHrP, suggestive of PTH-independent hypercalcemia mediated by 1,25(OH)2D as seen in sarcoidosis. Two months prior to admission and seven months after starting pembrolizumab, surveillance CT found improvement in tumor burden but new intrathoracic lymphadenopathy. Lymph node biopsy via bronchoscopy identified non-caseating granulomas suggestive of a sarcoidosis-like reaction. The patient's moderate hypercalcemia was treated with intravenous fluids, calcitonin, and zoledronic acid 4 mg with normalization of calcium levels. Glucocorticoid therapy was initially deferred to avoid counteracting the effect of pembrolizumab, however prednisone 10 mg daily was started 1 month after discharge when calcium rose again to 11.1 mg/dL. Prednisone was tapered off over 8 weeks as her calcium and 1,25(OH)2D levels normalized. She then restarted pembrolizumb, but after the third month she had recurrence of hypercalcemia (calcium 10.8 mg/dL) with elevated 1,25(OH)2D (89.5 pg/mL). She was again treated with prednisone 10 mg daily which was tapered off over 6 weeks with resolution of hypercalcemia. Her calcium levels remained normal off pembrolizumab. The temporal correlation in our case strongly suggests that ICI administration caused sarcoidosis-like granulomas and hypercalcemia.

Conclusion

Immune checkpoint inhibitors are known to occasionally cause hypercalcemia, although the mechanisms are not well established. In our case, moderate hypercalcemia was likely caused by ICI-induced sarcoid-like granulomas that responded promptly to glucocorticoids and interruption of ICI-therapy.

Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m., Monday, June 13, 2022 1:12 p.m. - 1:17 p.m.
ODP147 Free fatty acids stimulate aldosterone secretion in human adrenal carcinoma HAC15 cells
Authors: Ling Guoyu , Bruno Jonathan , Albert Stewart G
Published: November 2022

Primary hyperaldosteronism (PA) accounts for 5-10% of hypertension overall and up to 35% in people with obesity and sleep apnea. It has been postulated that the hyperaldosteronism, in these latter cases, is induced by factors independent of renin/angiotensin activation, but rather through soluble molecules associated with obesity. It has been shown that in obesity, free fatty acids (FFA) are associated with insulin resistance and hypertension. To test the relationship of free fatty acids with aldosterone synthesis, the human adrenal cell line HAC15, which has been extensively studied for adrenal steroidogenesis, was evaluated with regard to both aldosterone (ALDO) synthesis (by ELISA) and the induction of the rate limiting enzyme for aldosterone synthesis (CYP11B2, by quantitative PCR and Western blot). HAC15 responded appropriately to stimulation by angiotensin 2 (AII) with a 2.1-fold rise in ALDO. When this system was challenged with palmitate at 0.8 mM, there was a 1.8-fold increase in ALDO and 8-fold increase in CYP11B2 at mRNA and protein levels. These increases were not associated with the likelihood that the FFA were simply providing metabolic substrate as the effect was not blocked by the carnitine palmitoyltransferase 1 (CPT1) inhibitor etomoxir. However, palmitate treatment when compared to controls, was associated with ER stress, as measured by a four-fold induction of ER stress marker C/-EBP homologous protein mRNA, and with mitochondrial membrane dysfunction, as measured by a 24% decrease of Tetramethylrhodamine, ethyl ester (TMRE) fluorescence. These results suggest that in people with obesity and insulin resistance, FFA may augment or precipitate a state of primary hyperaldosteronism. Further studies are warranted to explore the underlying mechanisms of FFA augmentation of ALDO and its clinical significance.

Presentation: No date and time listed
ODP150 Hypertriglyceridemic Induced Acute Pancreatitis with Diabetic Ketoacidosis Treated with Insulin: A Case Report
Authors: Alam Saima , Khan Areej , Natesan Saikavitha , Oelberg David
Published: November 2022

Introduction

Acute pancreatitis due to hypertriglyceridemia with DKA is a unique entity. The diagnosis of acute pancreatitis in DKA is challenging as most patients present with abdominal pain, and elevated amylase, and lipase are quite common in DKA. Hypertriglyceridemia-induced pancreatitis (HTGP) accounts for 1 to 35 percent of all cases of acute pancreatitis. Pancreatitis may occur in DKA with high anion gap metabolic acidosis. Lack of insulin results in lipolysis with release of free fatty acids. Increased free fatty acids presented to the liver, causes increased VLDL, which inhibits lipoprotein lipase in peripheral tissues and results in elevated triglycerides.

Case presentation

A 29-year-old morbidly obese male with Asperger's syndrome, prediabetes, and hyperlipidemia presented with a 3-day history of sharp, non-radiating, and progressively worsening right upper abdominal pain, associated with nausea, non-bilious vomiting, and shortness of breath. His past medical history was notable for a prior bout of gallstone pancreatitis, for which he underwent a laparoscopic cholecystectomy. On his arrival in the emergency department, he was afebrile, but tachycardic (HR 139), mildly hypertensive (BP 149/98) with a Kussmaul breathing saturating 98% on room air. His lung sounds were clear but diminished and his abdomen was soft but diffusely tender, without peritoneal signs. Initial laboratory tests showed a neutrophilic leukocytosis of 12K, glucose of 867 mg/dL, hyponatremia (corrected 131), ketonuria, with elevated lipase 1,164 U/L. Venous blood gas showed a pH of 7.18 and PCO2 24 mmHg. He also had severe hypertriglyceridemia with a total triglyceride level of > 9,000 mg/dL. His CT abdomen showed peripancreatic inflammation consistent with acute pancreatitis. He was admitted to the ICU, and initially managed with aggressive intravenous fluids and pain control, then was started on an insulin drip for diabetic ketoacidosis and hypertriglyceridemia. His hospital course was notable for the development of acute kidney injury requiring hemodialysis. His triglyceride level gradually decreased and was 396 U/L on hospital day #9. He was discharged on fenofibrate, Lantus 20 units daily and insulin lispro 10 units with meals.

Conclusion

Hypertriglyceridemia is an uncommon but a well-established cause of acute pancreatitis leading to significant morbidity and mortality. In this case, a prediabetic patient presented with DKA and further investigation revealed HTGP. There is currently a paucity of data to support an optimal treatment for this condition; however, both insulin and plasmapheresis have been successfully employed. Plasmapheresis helps remove plasma lipoproteins and reduces triglyceride more rapidly than insulin and has been recommended for severe cases. In our case, insulin infusion alone significantly reduced the triglyceride level.

Presentation: No date and time listed
ODP154 Reduction of Cardiac Adipose Tissue Volume with Short-Term Empagliflozin in Patients with Type 2 Diabetes: Results from the SIMPLE Randomized Clinical Trial
Authors: Brandt-Jacobsen Niels , Jürgens Mikkel , Hasbak Phillip , Gæde Peter , Rossing Peter , Rasmussen Jon , Andersen Camillla Fuchs , Forman Julie , Faber Jens , Inzucchi Silvio , Gustafsson Finn , Schou Morten , Kistorp Caroline
Published: November 2022

Background

Sodium-glucose transporter 2 inhibitors (SGLT2-is) appear to have rapid clinical cardiovascular benefits in type 2 diabetes. Furthermore, SGLT2-is have known effects on fat metabolism. Cardiac adipose tissue (CAT) correlates with known markers of cardiovascular risk and left ventricular function. The effects of SGLT2-i treatment on CAT is largely unknown.

Objective

In this exploratory sub-study from the SIMPLE-trial, we investigated whether empagliflozin affects CAT volume in patients with type 2 diabetes.

Methods

Between April 4, 2017, and May 11, 2020, we randomized 90 patients with type 2 diabetes and established or high risk of cardiovascular disease to either 25 mg empagliflozin or placebo for 13 weeks. The primary focus of this sub-study was change in CAT evaluated by computer-tomography (CT). The analysis included 78 patients who had at least one CT scan. Furthermore, we investigated the effect of empagliflozin on left ventricular mass (LVM), end-diastolic volume (EDV) and end-systolic volume (ESV) evaluated by rest and stress 82Rubidium Positron Emission Tomography CT and changes in whole-body metabolism evaluated by fat mass distribution via dual x-ray absorptiometry and measurements of various parameters of glucose, ketone and lipid metabolism.

Results

Mean ±SD baseline CAT volume was 258.5 mL ±117.9. Empagliflozin reduced CAT after 13 weeks by 12.41 mL (95%CI [-23.83 to -0.99], P=0. 034) as compared with placebo. LVM (-5.16 g, 95%CI [-8.80 to -1.52], P=0. 006), EDV (-7.90 mL, 95%CI [-13.70 to -2.10], P=0. 008) and ESV (-5.46 mL 95%CI [-9.78 to -1.15], P=0. 014) decreased with empagliflozin when comparing groups at week 13. In addition, improvements were observed in whole body metabolic parameters: mean total body weight (-1.48 kg, 95%CI [-2.41 to -0.55], P=0. 002), total fat mass (-0.81 kg, 95%CI [-1.40 to -0.22], P=0. 008), fasting plasma (-1.82 mmol/L, 95%CI [-2.83 to -0.80], P=0. 001), HbA1c (NGSP: -0.76%, 95%CI [-1. 00 to -0.51], P<0. 001; IFCC: -8.28 mmol/mol, 95%CI [-11. 01 to -5.54], P<0. 001), beta-hydroxybutyrate (0. 07 mmol/L, 95%CI [0. 00 to 0.14], P=0. 044), and triglycerides (-16.1%, 95%CI [-27.3 to -3.2], P=0. 017), when comparing groups at week 13. We observed no significant correlation between changes in CAT and changes in LVM, EDV and ESV.

Conclusion

Treatment with empagliflozin provides an early reduction of CAT and improves myocardial structure and function which may explain some of this SGLT2-i's clinical cardiovascular benefits.

Presentation: No date and time listed
OR02-4 Prediabetes is a Risk Factor for Myocardial Infarction-A National Inpatient Sample Study
Authors: Jyotheeswara Pillai Keerthana , Luo Hongxiu , Raj Kavin , Xu Shuang , Thota Geethika
Published: November 2022

Introduction

Prediabetes is defined as Hba1c 5.7% - 6.4%, with an intermediate metabolic state and includes impaired glucose tolerance and impaired fasting glucose due to insulin resistance. While Type 2 Diabetes Mellitus is a well-established risk factor for cardiovascular disease, the possible link between Prediabetes and risk of Myocardial infarction (MI) has become a focus of interest in recent years. We wanted to evaluate if Prediabetes is independently associated with increased risk for MI.

Methods

We included adult patients admitted to teaching hospitals with a primary or secondary diagnosis of "acute myocardial infarction" from the National inpatient sample of 2016, 2017, and 2018. We created three separate multivariate logistic regression models with outcomes as MI, Percutaneous intervention (PCI), and CABG (Coronary artery bypass grafting).

Results

A total of 1,794,149 (95% CI 1,753,742-1,834,556) weighted hospitalizations with MI were included. Out of the 1.79 million patients with MI, 1% had Prediabetes. Prediabetes was greatly associated with increased odds for MI (OR 1.41, 95% CI 1.35-1.47, P=0.000). After adjusting for age, sex, race, family history of MI, dyslipidemia, hypertension, Diabetes, nicotine dependence, and obesity, Prediabetes was significantly associated with increased odds of MI (OR 1.25, 95% CI 1.20-1.31, P=0.000), increased odds of PCI (OR 1.45, 95% CI 1.37-1.53, P=0.000) and increased odds of CABG (OR 1.95, 95% CI 1.77-2.16, P=0.000).

Discussion

Our study shows that Prediabetes may be an independent risk factor for MI despite adjusting for the well-established risk factors. Coronary interventions such as PCI and CABG were highly associated with Prediabetes, suggesting macrovascular CAD. This growing evidence indicates the need to identify patients with Prediabetes and aggressively manage their cardiovascular risk factors to prevent MI. Although Prediabetes is commonly missed during coding and adds a limitation to this study, we would highlight that the association of Prediabetes with Myocardial Infarction, PCI, and CABG is a significant addition to the literature. Our study serves as a wake-up call for clinicians and patients to shift the focus to preventing Prediabetes and not just Diabetes. Our findings reinforce the importance of early recognition by screening and early intervention of Prediabetes by lifestyle changes and/or medications to decrease the risk of cardiovascular events.

Presentation: Saturday, June 11, 2022 12:15 p.m. - 12:30 p.m.
RF32 | PSUN45 Nicotine E-Cigarette Vapors Exposure Disturbs 11β-Hydroxysteroid Dehydrogenase Type 2 Expression in the Kidney May Contribute to E-Cigarette-Induced Blood Pressure Elevation in Mice
Authors: Liu Jenny , Wang Jian , Wang Ying , Shao Xuesi , Lutfy Kabirullah , Friedman Theodore , Jiang Meisheng , Liu Yanjun
Published: November 2022

Inhalation of electronic (e)-cigarettes containing nicotine may elevate blood pressure (BP), but the underlying mechanisms are poorly understood. 11β-HSD2 is crucial for BP regulation by inactivating glucocorticoids in the kidney. Little is known about the effect of e-cigarettes on 11β-HSD2 and their contribution to the process of BP elevation. To examine the possible effects of e-cigarette vapor exposures on renal 11β-HSD2 and BP, four groups of mice were exposed to aerosolized PBS, nicotine-free or nicotine-containing e-cigarettes, with concurrent exposure to either saline or the nicotine antagonist hexamethonium (Hex). Mouse renal M1 CCD cells were used to identify the effects of nicotine on 11β-HSD2 and its transcription factor C/EBPβ. Our results showed that mice exposed to e-cigarettes containing nicotine for 4 weeks markedly decreased the expression and activity of renal 11β-HSD2 and elevated the systolic BP in C57BL/6J mice. Reduction of 11β-HSD2 by nicotine inhalation was accompanied by reduction of renal C/EBPβ and responded to elevated plasma nicotine levels. In contrast, these effects were not observed in mice exposed to e-cigarettes vapor without nicotine compared to PBS controls. Treatment with Hex significantly decreased the elevated ratio of urinary corticosterone to 11-DHC along with stimulation of renal C/EBPβ and prevented the raised BP in mice exposed to e-cigarette vapor containing nicotine. Treating CCD M1 cells with vaporized e-cigarettes containing nicotine extract showed comparable effects with those of pure nicotine for suppression of C/EBPβ and 11β-HSD2, and these effects are blocked by Hex, indicating a mechanistic specificity. Our results indicate that the inhalation of nicotine e-cigarette vapors has potential adverse effects on renal health suggesting that disturbance of renal 11β-HSD2 may contribute to e-cigarette nicotine-induced BP elevation. These findings highlight the potential health risk of e-cigarettes.

Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m., Monday, June 13, 2022 1:00 p.m. - 1:05 p.m.
RF32 | PSUN46 Impact of Hyperparathyroidism on Atrial Fibrillation In-Hospital Outcomes: A Nationwide Perspective
Authors: Chauhan Aditya , Devarakonda Pradeep , Pujari Sai Harika , Gopalakrishnan Akshaya , Karki Monika , Dhulipala Vishal , Reddy Sarath , Warman Jacob , Singh Surbhi , Singh Sohrab , Vigandt Erika
Published: November 2022

Background

Hyperparathyroidism, associated with calcium abnormalities has an increased probability of developing arrhythmias. However, there are very few studies to demonstrate the significance of hyperparathyroidism on Atrial Fibrillation (A-fib).

Methods

This is a retrospective cohort study using the 2017-2018 National Inpatient Sample. Patients with a primary discharge diagnosis of A-fib were extracted with ICD10. Patients with hyperparathyroidism were extracted as a secondary diagnosis. Demographics, clinical complications were compared, and outcomes were assessed using linear and logistic regression models to adjust for confounders.

Results

A total of 649,179 patients (Age >18) were identified with A-fib as the primary diagnosis, and amongst them, 6254 had hyperparathyroidism. Notably, the patients with Hyperparathyroidism and A-fib were more likely to be female and blacks (26.8 vs 8). In-hospital mortality was higher in A-fib patients with hyperparathyroidism (2%) compared to A-fib patients without hyperparathyroidism (0.84%), with a crude odds ratio of 2.4 and adjusted odds ratio of 2.65 (p<0.001). Mean length of stay (LOS) was greater in hyperparathyroidism patients (4.5 vs 3.2 days), with an adjusted odds ratio of 1.26, (p<0.001). Similarly, mean total charges were also significantly higher in hyperparathyroidism patients ($53792 vs $39128).

Conclusions

Among patients with atrial fibrillation, those who have hyperparathyroidism as comorbidity are associated with more in-hospital mortality, LOS, and total charges. Further studies are required to study the causation of this association.

Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m., Monday, June 13, 2022 12:54 p.m. - 12:59 p.m.
RF32 | PSUN50 Hypertriglyceridemia as an Independent Risk Factor on Outcomes of Admissions for SIADH
Authors: Kwei-Nsoro Robert , Awoyomi Moyosoluwa , Khoshbin Katayoun , Ojemolon Pius , Olafimihan Ayobami , Shaka Hafeez
Published: November 2022

Introduction

The syndrome of inappropriate secretion of anti-diuretic hormone (SIADH) is one of the most significant causes of potentially life-threatening hyponatremia. Hypertriglyceridemia (HTG), on the other hand, is one of the few disorders that spuriously reduce sodium levels and should be ruled out in the evaluation of patients with hyponatremia. Very scant literature exists on the coexistence of both conditions, and even less literature compares outcomes in patients with concomitant SIADH and HTG.

Method

We extracted data from the US Nationwide Inpatient Sample (NIS) for 2019. The NIS contains hospital discharge information estimating yearly US hospitalizations. We included hospitalizations with a principal discharge diagnostic code for SIADH using the ICD-10-CM code (E22.2). Hospitalizations of patients less than 18 years were excluded. We then sub-divided the cohort based on the presence/absence of a secondary diagnosis of HTG.

Outcomes compared include inpatient mortality rates, mean length of hospital stay (LOS), mean hospitalization cost (THC), and rates of comorbid septic shock, acute myocardial infarction (AMI), acute respiratory failure (ARF), acute renal failure (AKI), and acute pulmonary edema (PE) between the subgroups. An adjustment was made for age, sex, race, primary payer, median household income by zip code, Charlson Comorbidity Index (CCI), hospital location, bed-size, and teaching status using multivariate regression analysis. Statistical significance was set at a p-value < 0.05.

Results

There were 39,110 hospitalizations involving patients with SIADH as the reason for the admission in 2019. Of these hospitalizations, 41.8% had comorbid HTG. A higher proportion of SIADH hospitalizations involved females, with no significant difference between both cohorts (61 vs 62.7%, p=0.119). Patients with HTG had a higher mean age (75.8±11.1 vs 70.4±14.4 years, p<0.001), a higher proportion of CCI >2, and a higher proportion of ethnic minorities compared to patients without HTG.

Hospitalizations for SIADH with comorbid HTG were associated with lower adjusted odds ratio (aOR) for mortality (0.7 vs 1.4% in patients with HTG, aOR: 0.42, p<0.001), reduced LOS (4.9 vs 5 days, p=0.002), and reduced THC (10,263 vs 11,013 US$, p=0.005). There was no difference in the odds of comorbid septic shock, CVA, AMI, PE, ARF or AKI.

Conclusions

Interestingly, comorbid HTG lowered odds of mortality, LOS, and THC amongst patients hospitalized for SIADH. More studies should be carried out to investigate this rather paradoxical relationship with a view to defining a better understanding and devising more therapeutic strategies for both conditions.

Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m., Monday, June 13, 2022 12:48 p.m. - 12:53 p.m.
LBODP019 Vitamin D Levels In A Population With Type 2 Diabetes
Authors: Elias Natalia Olga , Martinez Adriana Campos , Dicugno Mariana , Souto Julieta , Curria Marina Ines
Published: November 2022

Background

Little is known about the impact of over-the-counter ketone supplementation, used by patients to promote weight loss, on ketosis and serum ketone values. Recent literature suggests that acute ingestion of exogenous ketones leads to increased blood beta-hydroxybutyrate and decreased blood glucose1.

Clinical Case

A 61-year-old man with a history of type 2 diabetes mellitus, atrial fibrillation, hypertension, and hyperlipidemia presented as a transfer to the neurocritical care ICU from an outside hospital for subarachnoid hemorrhage secondary to intracranial saccular aneurysm. His admission hemoglobin A1c was 9.9% (ref 4.4-5.6), blood glucose was 205 mg/dL (ref 70-99), beta-hydroxybutyrate was markedly elevated at 26.2 mg/dL (ref 0-3), and urinalysis showed 80mg/dL ketones (ref 0). Serum toxicology screen was notable for detectable acetone 8mg/dL (ref: none detected). His lactate was 2 mmol/L (ref 0.5-1.9), Cr 0.99mg/dL (0.67-1.17), and HCO3 22 mmol/L (ref 22-27). Arterial blood gas showed pH of 7.37 (ref 7.38-7.47), and an anion gap metabolic acidosis (AGMA) of 15 mmol/L (ref <12). Given the patient's profound ketosis, hyperglycemia, and mild AGMA, the patient was started on an insulin drip for presumed diabetic ketoacidosis (DKA). After 4 hours, the patient's anion gap had decreased to 12mmcol/L. The following day, he was transitioned to basal/bolus insulin, and underwent embolization of his cerebral aneurysm. After further recovery, Endocrinology was consulted for insulin recommendations. The patient denied any prior history of DKA or use of any SGLT2-inhibitors, and denied decreased oral intake or vomiting prior to admission. He did report taking ketone supplements, "Keto Strong: Ketogenic Weight Management – Advanced Formulation," two tabs (700mg "proprietary keto blend") BID for 2-3 years with ingredients listed as: sodium beta-hydroxybutyrate, calcium beta-hydroxybutyrate, magnesium beta-hydroxybutyrate, medium chain triglyceride oil, L-arginine, alpha-ketoglutaric acid, and 7-keto-dehydroepiandrosterone. Given a lack of acidosis, mild hyperglycemia, and mild lactic acidosis without risk factors for euglycemic DKA, it was suspected his profound ketosis out of proportion to clinical picture was secondary to ketone supplementation with a misdiagnosis of DKA.

Conclusion

This is one of the first cases to report profound ketosis in a hospitalized patient likely secondary to exogenous ketone supplementation. Ketosis secondary to nutritional supplementation should be considered once more common etiologies are ruled out. Additional research is needed to determine the role of exogenous ketone use on metabolism and glycemic control. References: Falkenhain, Kaja et al. "Effects of Exogenous Ketone Supplementation on Blood Glucose: A Systematic Review and Meta-Analysis." Advances in nutrition (Bethesda, Md.), nmac036. 5 Apr. 2022

Presentation: No date and time listed
LBODP035 When Is Ketosis Just Ketosis?
Authors: Cannon Sophie M , Angell Trevor E
Published: November 2022

Background

Little is known about the impact of over-the-counter ketone supplementation, used by patients to promote weight loss, on ketosis and serum ketone values. Recent literature suggests that acute ingestion of exogenous ketones leads to increased blood beta-hydroxybutyrate and decreased blood glucose1.

Clinical Case

A 61-year-old man with a history of type 2 diabetes mellitus, atrial fibrillation, hypertension, and hyperlipidemia presented as a transfer to the neurocritical care ICU from an outside hospital for subarachnoid hemorrhage secondary to intracranial saccular aneurysm. His admission hemoglobin A1c was 9.9% (ref 4.4-5.6), blood glucose was 205 mg/dL (ref 70-99), beta-hydroxybutyrate was markedly elevated at 26.2 mg/dL (ref 0-3), and urinalysis showed 80mg/dL ketones (ref 0). Serum toxicology screen was notable for detectable acetone 8mg/dL (ref: none detected). His lactate was 2 mmol/L (ref 0.5-1.9), Cr 0.99mg/dL (0.67-1.17), and HCO3 22 mmol/L (ref 22-27). Arterial blood gas showed pH of 7.37 (ref 7.38-7.47), and an anion gap metabolic acidosis (AGMA) of 15 mmol/L (ref <12). Given the patient's profound ketosis, hyperglycemia, and mild AGMA, the patient was started on an insulin drip for presumed diabetic ketoacidosis (DKA). After 4 hours, the patient's anion gap had decreased to 12mmcol/L. The following day, he was transitioned to basal/bolus insulin, and underwent embolization of his cerebral aneurysm. After further recovery, Endocrinology was consulted for insulin recommendations. The patient denied any prior history of DKA or use of any SGLT2-inhibitors, and denied decreased oral intake or vomiting prior to admission. He did report taking ketone supplements, "Keto Strong: Ketogenic Weight Management – Advanced Formulation," two tabs (700mg "proprietary keto blend") BID for 2-3 years with ingredients listed as: sodium beta-hydroxybutyrate, calcium beta-hydroxybutyrate, magnesium beta-hydroxybutyrate, medium chain triglyceride oil, L-arginine, alpha-ketoglutaric acid, and 7-keto-dehydroepiandrosterone. Given a lack of acidosis, mild hyperglycemia, and mild lactic acidosis without risk factors for euglycemic DKA, it was suspected his profound ketosis out of proportion to clinical picture was secondary to ketone supplementation with a misdiagnosis of DKA.

Conclusion

This is one of the first cases to report profound ketosis in a hospitalized patient likely secondary to exogenous ketone supplementation. Ketosis secondary to nutritional supplementation should be considered once more common etiologies are ruled out. Additional research is needed to determine the role of exogenous ketone use on metabolism and glycemic control. References: Falkenhain, Kaja et al. "Effects of Exogenous Ketone Supplementation on Blood Glucose: A Systematic Review and Meta-Analysis." Advances in nutrition (Bethesda, Md.), nmac036. 5 Apr. 2022

Presentation: No date and time listed
LBODP041 Effects Of Sodium-glucose Co-transporter 2 Inhibitors (sglt-2 Inhibitors) On Adipokines And Inflammatory Biomarkers In Type2 Diabetic Patients
Authors: Kumtree Phonphruet
Published: November 2022

Background

Type 2 diabetes mellitus is a chronic metabolic disease associated with high cardiovascular (CV) risk. SGLT-2 inhibitors reduce HbA1c and show favorable effects on body weight, blood pressure, lipid profile, arterial stiffness, and endothelial function. More importantly, SGLT-2 inhibitors have demonstrated impressive cardioprotective and renoprotective effects. The main mechanisms of cardioprotective effects have been attributed to improvement in cardiac cell metabolism, improvement in ventricular loading conditions, inhibition of the Na+/H+ exchanger in myocardial cells, alteration in adipokines and cytokines production. This exploratory research aimed to observe the effects of Canagliflozin, Dapagliflozin, and Empagliflozin on select inflammatory biomarkers, adiponectin, for instance.

Methods

Comparison of serum adiponectin between baseline with 16-week after SGLT-2 inhibitors therapy were assessed in type 2 diabetic participants. Changes of chosen metabolic and anthropometric variables were discussed.

Results

At 16-week after SGLT-2 inhibitors treatment, a striking increment in mean serum adiponectin by 1.25 mcg/mL (95% CI: 0. 02, 2.48) or 81% was revealed. Furthermore, they showed a reduction of mean BMI 1.12% (95% CI: -1.74%, -0.50%), systolic blood pressure 1 mmHg (95% CI: -1.85, -0.72), diastolic blood pressure 1 mmHg (95% CI: -1.65, -0.52), fasting plasma glucose 34 mg/dL (95% CI: -51.66, -17.10), and HbA1c 0.73% (95% CI: -1.25%, -0.21%). No between-group differences were expressed with the other biomarkers. Serious side effects such as ketoacidosis, hypoglycemic status, genitourinary tract infection, acute kidney injury, or long-term dialysis dependence were not appeared.

Conclusions

SGLT-2 inhibitors can improve changes in serum adiponectin which appreciatively benefit in cardiovascular outcomes among type 2 diabetes. Keywords: SGLT-2 inhibitors, adipokines, inflammatory biomarkers, type 2 diabetes mellitus, adiponectin, cardiovascular outcomes, cardioprotective, renoprotective

Presentation: No date and time listed
LBODP042 Lean Type Two Diabetes: Risk Factors And Outcomes Compared To Typical Presenting Type Two Diabetes
Authors: Singer Alisse , Wilhalme Holly , Cheung Dianne
Published: November 2022

Background

Lean type 2 diabetes (LT2D) is a prevalent manifestation of type 2 diabetes (T2D). However, it has been an understudied subgroup of T2D.

Aim

To compare characteristics and outcomes of patients with LT2D with that of typical presenting T2D.

Methods

A retrospective review of electronic health records was performed between 2013 and 2020. The study included 254 patients with LT2D and 429 patients with typical T2D located in the South Bay of Southern California. LT2D and typical T2D were defined as having a body mass index (BMI) of 18.5 to 24.9 kg/m2 and 25 to 29.9 kg/m2, respectively. Patient-level variables included age, sex, race, ethnicity, educational level, area of deprivation index (ADI), microvascular and macrovascular comorbidities, alcohol use, tobacco use, and diabetes family history. Labs and vital signs obtained included hemoglobin A1c (HbA1c), glomerular filtration rate (GFR), creatinine, albumin, and blood pressure. Student's t-test and Chi-square tests/Fisher's exact tests were performed with SAS version 9.4 to compare differences between the LT2D and typical T2D groups.

Results

Between the diabetes subgroups, there were several statistically significant differences identified. The LT2D population was older, with a mean age of 78.2 years compared with 74.6 years in the typical T2D (p < 0. 001). The LT2D group had a higher percentage of Asians at 40.6% and fewer Caucasians at 35. 0%, while the typical T2D consisted of 22.4% Asians and 46.4% Caucasians (p=0. 0007). Diastolic blood pressure was lower in the LT2D group at 71.6 compared to 73.9 in the typical T2D group (p=0. 0053). There were no differences in sex, HbA1c, systolic blood pressure, hypertension, dyslipidemia, chronic kidney disease, cardiovascular events, peripheral vascular disease, combined microvascular complications, combined macrovascular complications, substance use, education level, ADI, GFR, creatinine, albumin, or number of relatives with diabetes.

Conclusion

We identified several key differences between the LT2D and typical T2D cohort, including age, race, and diastolic blood pressure. Further investigation and large studies are warranted to explore the risk factors and long term outcomes of patients presenting with LT2D. Knowing what the key differences are may help identify appropriate diabetes medical treatments and lifestyle interventions for this particular target population rather than using T2D treatments that are used for a more general population of patients.

Presentation: No date and time listed