bluuebunny/crossref_metadata_2025_split huggingface dataset:
7358 Profile of Circulating miRNAs Associated with Body Weight Reduction in Type 2 Diabetes Patients Treated with GLP-1 Receptor Agonist Dulaglutide: Secondary Analysis of AWARD-7 Trial
Authors: Satake Eiichiro , McFarlin Brandon E , Cin Tye Sok , Ricca Joseph , Matthew Wilson Jonathan , Duffin Kevin L , Krolewski Andrzej S 
Published: October 2024

Abstract
Disclosure: E. Satake: None. B.E. McFarlin: Employee; Self; Eli Lilly & Company. S.C. Tye: None. J. Ricca: None. J.M. Wilson: Employee; Self; Eli Lilly & Company. K.L. Duffin: Employee; Self; Eli Lilly & Company. A.S. Krolewski: Grant Recipient; Self; Novo Nordisk, NNF14OC0013659.
Background: Glucagon-like peptide-1 (GLP-1) receptor agonists have been shown to have beneficial effects on reducing body weight, such as appetite control, reducing fat accumulation, and improving metabolic parameters. However, the underlying mechanism remains unclear, and no biomarker has been established to predict or monitor the effects of GLP-1 receptor agonists. Circulating microRNAs (miRNAs) are short, non-coding RNA molecules known to regulate proteins. In this study, we investigated the effect of the GLP-1 receptor agonist Dulaglutide (DULA) treatment on longitudinal changes in plasma concentrations of circulating miRNAs. We analyzed the correlation with body weight change in patients enrolled in the AWARD-7 trial. Methods: Plasma samples were obtained from patients with type 2 diabetes (T2D) and chronic kidney disease (CKD) stages 3-4 who were treated with Dulaglutide 1.5 mg (n=29) or insulin Glargine (n=31) for 52 weeks. Using the HTG edgeSeq platform, we measured 2,079 miRNAs at baseline, 26 weeks, and 52 weeks. As a sub-cohort of the study, we divided patients receiving DULA treatment into two categories: patients who lost 3 kg of weight during the first 26 weeks of treatment (n=11) and those who did not (n=18). Fold change (FC) values were calculated for each patient and each miRNA by dividing the concentration of miRNA at 26 weeks by its concentration at baseline. Results: Body weight at 26 weeks in the DULA treatment group was significantly reduced compared to the placebo group (p=7.6x 10-4). Among the patients who received DULA treatment and lost 3 kg of body weight during this period, 31 miRNAs were found to be significantly up/downregulated at baseline compared to those who did not lose weight. Out of these miRNAs, 18 showed a significant correlation with the change in body weight between baseline and 26 weeks. Further analysis of the changes in miRNAs from baseline to 26 weeks (delta) revealed that 102 miRNAs differed significantly between the patients who lost body weight and those who did not. Among these miRNAs, 47 were found to be correlated with delta body weight at 26 weeks. Conclusion: This study demonstrated circulating miRNAs associated with body weight reduction in T2D patients treated with a GLP-1 agonist. These miRNAs have the potential to serve as biomarkers to predict or monitor the effect of DULA on body weight in T2D patients and may provide a mechanistic understanding of physiological processes associated with weight reduction.
Presentation: 6/3/2024
8515 Role of Insulin Receptor in Trpv1-positive Adipocyte Progenitor Cellsin Adipocyte Differentiation and Metabolic Function
Authors: Sahin C , Camara H , Shamsi F , Lynes M , Tseng Y H 
Published: October 2024

Abstract
Disclosure: C. Sahin: None. H. Camara: None. F. Shamsi: None. M. Lynes: None. Y. Tseng: None.
Brown adipose tissue (BAT), a specialized fat that dissipates energy to produce heat, is an important endocrine organ in the regulation of energy balance. Stimulating BAT activation and beiging of white adipose tissue (WAT) are new strategies to combat metabolic diseases, such as obesity and diabetes. Traditionally, thermogenic adipocytes are known to originate from mesenchymal Pdgfrα-expressing adipocyte progenitor cells (APCs). A previous study conducted by our lab identified vascular smooth muscle cells as a novel cellular origin of APCs. These cells are characterized by the expression of transient receptor potential cation channel subfamily V member 1 (Trpv1+). With cold exposure, the Trpv1+ APC-derived adipocytes are increased in BAT and WAT and differentiated into highly thermogenic adipocytes. These findings indicate that the Trpv1+-APCs may play an important role in the development of brown and beige adipocytes in response to cold. This study was designed to explore the function of the Trpv1+ APC-derived adipocytes in thermogenic adipocyte differentiation and metabolic regulation. We generated a mouse model in which insulin receptor (IR), a well-known player in adipocyte differentiation, was deleted in the Trpv1+ APCs to impair their adipogenic potential. Trpv1-Cre::mTmG::IRflox transgenic and IRwt control mice were housed at cold temperature (5°C) for 7 days. Because the lineage tracing mTmG system was included, we were able to trace the fate of Trpv1+ APCs in the presence or absence of IR. We first examined the adipogenic capacity of the IR-deficient Trpv1+ cells in BAT and WAT tissues using whole-mounted adipose tissue imaging. In control mice, approximately 30% of all mature adipocytes were derived from Trpv1+ APCs in adipose tissue in response to cold. With ablation of IR in Trpv1+ APCs, this contribution was significantly reduced in BAT (by 11.7 % in females; 6.1% in males), inguinal WAT (by 16.8% in females; 19.3% males), and perigonadal WAT (by 11.4% in females; 14.8% in males) in transgenic mice compared to control mice. These results showed that IR-deficiency in the Trpv1-expressing cells impaired their adipogenesis in both male and female mice. In contrast, thermogenic genes (e.g., Ucp1, Pparγc1a, Cox7a1) were not significantly altered in BAT and inguinal WAT of the IR-deficient Trpv1+ APCs mice. Despite the changes in the adipocyte populations, we observed that deletion of IR in Trpv1+ APCs has no impact on body weight, food intake, fat mass, glucose tolerance, and insulin sensitivity relative to control mice. Taken together, blocking the contribution of Trpv1+ APCs to the mature adipocyte population results in no metabolic changes in mice, suggesting that the other APCs, such as PdgfRα+ APCs, may potentially compensate for impaired adipogenesis in different adipose tissues.
Presentation: 6/1/2024
8729 Role of PARP1 in Macrophage-dependent Regulation of Adipose Tissue Inflammation, Adipogenesis, and Diet-induced Obesity
Authors: Zhu J , Gupte R , Nandu T S , Kraus W L , Huang D 
Published: October 2024

Abstract
Disclosure: J. Zhu: None. R. Gupte: None. T.S. Nandu: None. W.L. Kraus: None. D. Huang: None.
Adipose tissue macrophages play a significant role in maintaining adipose tissue homeostasis, as well as promoting chronic low-grade inflammation during the development of obesity and metabolic dysfunction. However, the crosstalk between macrophages and adipocytes, especially how macrophages affect adipogenesis in obese adipose tissue, are still poorly understood. We have investigated the function of PARP1 in the control of adipogenesis by using an adipocyte precursor-specific Parp1 knockout mouse model. Here, to investigate the role of macrophage PARP1 in regulating adipogenesis, we deleted Parp1 in the myeloid lineage by crossing Parp1loxp/loxp mice with LysMCre mice (Parp1 cKOLysMCre). Macrophages-specific knockout of Parp1 dramatically reduced LPS-induced pro-inflammatory gene expression in bone marrow-derived macrophages (BMDMs). To explore whether macrophage-specific Parp1 knockout affects adipocyte differentiation, we treated the primary preadipocytes from stromal vascular fraction (SVF) of white adipose tissue with the conditioned medium from LPS-stimulated control or Parp1 cKOLysMCre BMDMs throughout a 6-day period of differentiation. We observed that exposure of preadipocytes to the conditioned medium of Parp1 cKOLysMCre macrophages promoted adipogenesis by Oil Red O staining, as well as by monitoring the expression of key proadipogenic marker genes (e.g., Adipoq and Fabp4) by RT-qPCR. To further investigate the role of macrophage-specific deletion of Parp1 in metabolic outcomes, we fed the Parp1 cKOLysMCre mice with a high fat diet for 12 weeks. The knockout mice exhibited a significant increase in body weight compared to the control mice. Interestingly, we observed a reduction of the total number of macrophages resident in the adipose tissue from macrophage-specific Parp1 knockout mice. To explore the underlying mechanism, we performed single cell RNA-seq for adipose tissue macrophages using sorted SVF cells collected from HFD-fed mice. The results demonstrated dramatic reductions in macrophage M1 marker genes and pro-inflammatory transcription factors in Parp1 cKOLysMCre mice. Taken together, our study suggests that Parp1 knockout in macrophages selectively affects the recruitment and pro-inflammatory activation of macrophages, as well as adipocyte differentiation in adipose tissue. Importantly, despite the decreased adipose tissue inflammation, macrophage-specific Parp1 knockout enhanced adipogenesis, which leads to obesity in mice.This work was supported by a grant from the NIH/NIDDK (R01 DK069710) and funds from the Cecil H. and Ida Green Center for Reproductive Biology Sciences Endowment, to W.L.K., and a grant from NSFC (82270929) to D.H.
Presentation: 6/1/2024
12394 "Sugar And Tumors: A Case Report On New-onset Diabetes In Metastatic Pheochromocytoma With Elevated Dopamine Levels"
Authors: Agrawal Bhavika , mehta vidhi , naseem rabia , Renzu Mahvish , rashid rakin 
Published: October 2024

Abstract
Disclosure: B. Agrawal: None. V. mehta: None. R. naseem: None. M. Renzu: None. R. rashid: None.
Introduction: Metastatic pheochromocytoma is a rare neuroendocrine tumor with potential complication of new-onset diabetes mellitus (DM). We present a case highlighting the challenges in managing a patient with metastatic pheochromocytoma and concurrent DM. Case presentation: A 66-year-old male with a history of hypertension and gout initially presented in 2010 with an adrenal mass, later identified as pheochromocytoma and resected. In 2018, he presented with bilateral leg pain, revealing metastatic disease-causing spinal cord compression along with metastatic lung nodules and metastasis in adrenalectomy bed. Despite interventions including T6,7,8 laminectomy in 2020 and radiation therapy, metastases persisted. In 2024, he presented with polyuria, polydipsia, and hyperglycemia (blood glucose &gt;500 mg/dL). Laboratory findings showed elevated a1c of 15 in addition to elevated normetanephrines, metanephrines, and dopamine with levels of 3880, 48 and 488 respectively. He was diagnosed with new-onset DM and started on insulin therapy in addition to metformin and jardiance. Discussion: Secondary diabetes mellitus (DM) in secretory pheochromocytoma occurs in approximately 50% of cases, manifesting from mild insulin resistance to severe presentation like DKA. Epinephrine-secreting tumors contribute to glucose intolerance by activating beta receptors, thereby stimulating gluconeogenesis. Patients with higher levels of epinephrine and preoperative glucose intolerance were more prone to developing postoperative hypoglycemia, requiring close monitoring during the postoperative period. Additionally, research by DiSalvo et al. Epinephrine-secreting tumors have a more significant impact on hyperglycemia by impairing insulin secretion and stimulation GLP-1. Tumor resection has been found to be more effective effective in restoring normal glucose homeostasis in these patients. Dopamine-secreting pheochromocytomas are rare neoplasms characterized by the presence of immature catecholamine vesicles that inhibit dopamine conversio owing to localized dopamine beta hydroxylase. Typically presenting around the age of 48, these tumors often lack excess catecholamines, leading to atypical symptoms such as local discomfort or pain from tumor compression. These neoplasms are less detectable on metaiodobenzylguanidine (MIBG) scans, necessitating positron emission tomography (PET) for accurate diagnosis. Surgical resection is the treatment, with preoperative management involving metyrosine instead of alpha blockers. These tumors are frequently diagnosed late, often in a malignant stage, contributing to poor prognosis Conclusion: Overall, understanding the complex interplay between catecholamines and glucose metabolism is crucial for the comprehensive management of patients with pheochromocytoma and secondary DM.
Presentation: 6/1/2024
7328 A case of Adrenal Calcifications in a Patient with Familial Cerebral Cavernous Malformations
Authors: Dorin Richard I , Aguirre Lina E , Bomgardner Magdalena 
Published: October 2024

Abstract
Disclosure: R.I. Dorin: None. L.E. Aguirre: None. M. Bomgardner: None.
Background: Familial syndromes of cerebral cavernous malformation (fCCM) having autosomal dominant inheritance and variable penetrance and expression have been linked to loss of function mutations at three genetic loci. The association of small focal adrenal calcifications with fCCM was only recently recognized in a New Mexican cohort of subjects predominately carrying the founder common Hispanic mutation in the CCM1 locus (stop codon Q455X in the Krev1 interaction trapped gene 1 [KRIT1]). We report a case of bilateral, focal adrenal calcifications in a patient affected by fCCM. Clinical Case: A 72-year-old Hispanic male with past medical history of intracranial CCM was referred for osteoporosis and hyperthyroidism due to multinodular goiter. Small focal calcifications of the adrenal glands were incidentally noted on prior imaging studies. There was no history of anticoagulant use, adrenal hemorrhage, or systemic/adrenal infection. The patient was without clinical manifestations of adrenal insufficiency, morning cortisol and plasma ACTH concentrations were normal, and exam was negative for hyperpigmentation or cutaneous vascular malformations. Brain MRI revealed the presence of over 100 parenchymal CCM lesions. A family history of CCM was reported in multiple family members, including 7/10 siblings. Conclusion: In addition to cutaneous malformations, small focal adrenal calcifications are now recognized as one of the extra-neurological manifestations of fCCM, particularly in patients harboring the common Hispanic CCM1/KRIT1 mutation. Whether adrenal calcifications are observed in fCCM patients having other mutations of KRIT1 or other genetic loci of fCCM (CCM2 or PDCD10) remains to be determined. The focal adrenal calcifications are believed to be result of dyssynchronous, subclinical hemorrhagic events related to vascular malformations in the adrenal gland. These findings implicate a role for KRIT1 in endothelial development in the adrenal gland in addition to established role in CNS, spinal cord, and skin. Our patient appeared had normal adrenocortical function, as expected for the focal nature of the adrenal lesions. Though adrenal function has not been evaluated in fCCM patients, there are no reports of primary adrenal insufficiency in fCCM in the literature. Adrenal calcifications may be considered to represent an imaging biomarker for fCCM, and fCCM should be included in the differential diagnosis of adrenal calcifications. The incidental recognition of characteristic small, focal adrenal calcifications in either bilateral or unilateral adrenal glands should prompt evaluation for fCCM. References: Strickland CD, Eberhardt SC, et al. Familial Cerebral Cavernous Malformations Are Associated with Adrenal Calcifications on CT Scans: An Imaging Biomarker for a Hereditary Cerebrovascular Condition. Radiology. 2017; 284(2):443-450.
Presentation: 6/2/2024
7412 A Case of Exogenous Cushing Syndrome in a Patient with History of Acromegaly Status Post Transsphenoidal Resection Complicated by Panhypopituitarism Requiring Glucocorticoid Replacement
Authors: Capozza Alexandria , Heluey Camila , Chaidarun Sushela S 
Published: October 2024

Abstract
Disclosure: A. Capozza: None. C. Heluey: None. S.S. Chaidarun: None.
Introduction: Exogenous Cushing syndrome is a complication of long-term glucocorticoid therapy. Frequency of Cushingoid features such as truncal obesity, buffalo hump, moon faces, weight gain, striae, ecchymosis, and skin thinning increases as the glucocorticoid dose increases. Here we present a case of exogenous Cushing syndrome in a patient with history of acromegaly status post transsphenoidal resection of adenoma complicated by panhypopituitarism requiring glucocorticoid replacement. Clinical Case: A 37-year-old female with history of acromegaly status post transsphenoidal resection of somatotroph/thyrotroph adenoma in 2019 complicated by panhypopituitarism, diabetes insipidus, and type 2 diabetes was admitted after presenting with diarrhea and electrolyte derangements. At home, the patient was on desmopressin 0.1 mg nightly, dexamethasone 1.5 mg daily, levothyroxine 175 mcg nightly, and estradiol 1 mg daily. Her dexamethasone dose had been increased from 0.75 mg-1 mg daily to 1.5 mg daily over the years due to hypoglycemia. At time of admission, labs were significant for free T4 of 2.20 (0.93-1.70 ng/dL), free T3 1.7 (2-4.4 pg/mL), sodium 130 (135-145 mmol/L), potassium 2.8 (3.5-5 mmol/L), calcium 7.4 (8.5-10.5 mg/dL), phosphorous 1.0 (2.5-4.5 mg/dL), PTH 237 (15-65 pg/mL), 25-OH vitamin D 39 (21-100), 1,25 vitamin D 31 (18-78 pg/mL), and glucose 207 (65-199 mg/dL). On physical exam, she had signs of acromegaly including large tongue, thick lips, large nose, prognathism, frontal bossing, and deep voice. She also appeared Cushingoid with rounded face, thin skin, multiple areas of ecchymosis, wide purple striae over the abdomen and upper arms, posterior cervical hump, supraclavicular fullness, and trunk obesity. Long-term, supra-physiologic dose glucocorticoids were thought to be the cause of her Cushingoid appearance. Glucocorticoids were also contributing to hyperglycemia and reduced conversion of free T4 to free T3. Conclusion: Glucocorticoids have numerous adverse effects such as hyperglycemia, exogenous Cushing syndrome, osteoporosis to name a few. Higher doses and longer duration of glucocorticoids carry a higher risk of adverse effects. This case illustrates the importance of thorough physical exam and frequent assessment for adverse effects in patients on glucocorticoids. Both acromegaly and Cushing syndrome render poor health outcomes, so optimal treatment and long-term care of post-surgical hypopituitarism is important.
Presentation: 6/3/2024
7469 A Case of Severe Transient Hypercortisolism In a Patient With Bacterial Meningitis
Authors: Harxhi Rea , Valentin Mihailescu Dan , Pilati Stamatoula 
Published: October 2024

Abstract
Disclosure: R. Harxhi: None. D.V. Mihailescu: None.
Background: Increased cortisol levels are known to occur in states of significant stress caused by acute illness. This may be attributed to stress leading to a rise in the corticotrophin releasing hormone thereby increasing adrenocorticotrophic hormone levels. This may consequently result in severe transient hypercortisolism and bilateral adrenal structural changes.Clinical case:A 55-year-old female with a past medical history of HTN and pre-diabetes presented to the hospital with a headache and altered mental status starting the day prior to admission. On arrival, she was found to be hypertensive, confused and was diagnosed with acute bacterial meningitis caused by streptococcus pneumoniae. Initial labs were notable for a potassium level of 2.5 mEq/L (normal 3.5-5 mEq/L). Work-up of persistent hypokalemia revealed a cortisol of 54.83 ug/dL (normal 6.7-22.6 ug/dL), ACTH 166 pg/mL (normal 9-50 pg/mL), aldosterone &lt; 1 ng/dL (normal 3-16 ng/dL), and renin 0.57 (normal 0.25-5.82). CT of the abdomen showed bilateral periadrenal fat stranding, larger on the left with no adrenal nodules. On physical exam, patient did not exhibit any cushingoid features. Significantly elevated AM cortisol levels persisted despite treatment with high dose dexamethasone as part of the meningitis regimen (20 mg) resulting in unsuppressed AM cortisol of 9.22 ug/dL. An MRI of the brain showed a partially empty sella rendering a pituitary adenoma unlikely. Patient’s clinical status improved rapidly, and hypokalemia resolved. A low dose dexamethasone suppression test performed 9 days post admission produced an appropriately suppressed cortisol (1.0 ug/dL) and ACTH (14 pg/mL) levels, thus confirming a functional response to acute illness. Conclusion: This is a rare case of severe transient hypercortisolism with periadrenal congestion (“fat stranding”) resulting in hypokalemia (likely due inappropriate activation of mineralocorticoid receptors) in the setting of acute illness. There have been a very limited number of similar cases reported in literature, particularly with respect to CNS infections. It is important to recognize the response to acute stress could produce significant elevation of cortisol levels leading to the activation of mineralocorticoid receptors, therefore mimicking primary hyperaldosteronism.
Presentation: 6/1/2024
8045 A Case Report of Primary Adrenal Insufficiency Due to a Novel Pathogenic Variant in NR0B1 (Dax 1) Gene
Authors: de Lemos Manuela Nascimento , de Oliveira Martins Graziela , Richter Cicogna Julia Isabel , Scalissi Nilza Maria , Lima-Jr Jose Viana 
Published: October 2024

Abstract
Disclosure: M.N. Lemos: None. G.D. Martins: None. J.R. Cicogna: None. N.M. Scalissi: None. J.V. Lima-Jr: None.
Background: X-linked adrenal hypoplasia congenita caused by a pathogenic variant in NR0B1/DAX-1 is a rare inherited disorder. Patients with adrenal hypoplasia congenita are usually diagnosed with primary adrenal insufficiency in infancy or early childhood and usually present hypogonadotropic hypogonadism during adolescence. Clinical Case: Our male patient first presented with adrenal crisis at the age of 11 years, managed with glucocorticoids (prednisolone) and mineralocorticoids (fludrocortisone) in a local hospital at Bahia state, Brazil. He was referred to our reference service in Sao Paulo at the age of 14, in regular use of those medications. In this time, he brought some laboratorial analysis from the time of diagnosis, and it showed hyponatremia (sodium 99 mEq/L; NR 135 - 150) and hyperkalemia (potassium 6,7 mEq/L; NR 3,5 - 5), ACTH 23,2 pg/mL (NR &lt; 45) and basal cortisol 6,6 mcg/dL (NR 5 - 18). In addition, we had from this time some additional laboratorial data from our admissional analysis, that found S-DHEA 10,1 mcg/dL (NR: 23,8 - 267,7), total testosterone 472 ng/dL (NR: 240 - 816), FSH 3,05 mUI/L (NR: &lt; 10), LH 2,63 mUI/L (NR: &lt;10), aldosterone 1,9 ng/dL (NR: 5 - 23) and renin &gt; 500µIU/mL (NR: 2,8 - 39,9). Over the years, he started to present hyperpigmented skin lesions, due to primary adrenal insufficiency, resulting in great psychological suffering. We have screened hypogonadism many times during follow-up, but it was never found. The Genetics analysis by next generation sequence (NGS) identified in homozygosity, in gene NR0B1 (DAX1) on X chromosome, a variant of normality (chrX:30.309.248 C&gt;T) were amino acid tryptophan was replaced by a stop codon. The patient does not have any brother, no other similar cases in the family and their parents deny consanguinity. Our case differs from others previously described because of the absence of associated hypogonadism, which is very common in NR0B1 variants. Clinical lesson/Conclusion: This case report shows that the absence of hypogonadism does not exclude the possibility of primary adrenal insufficiency caused by NR0B1(DAX 1) gene variants, and encourages genetic testing to patients living with this disease.
Presentation: 6/2/2024