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Journal of Clinical Endocrinology and Metabolism

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https://www.readbyqxmd.com/read/28645211/akr1c3-mediated-adipose-androgen-generation-drives-lipotoxicity-in-women-with-polycystic-ovary-syndrome
#1
Michael W O'Reilly, Punith Kempegowda, Mark Walsh, Angela E Taylor, Konstantinos N Manolopoulos, J William Allwood, Robert K Semple, Daniel Hebenstreit, Warwick B Dunn, Jeremy W Tomlinson, Wiebke Arlt
Context: Polycystic ovary syndrome (PCOS) is a prevalent metabolic disorder, occurring in up to 10% of women of reproductive age. PCOS is associated with insulin resistance and cardiovascular risk. Androgen excess is a defining feature of PCOS and has been suggested as causally associated with insulin resistance; however, mechanistic evidence linking both is lacking. We hypothesized that adipose tissue is an important site linking androgen activation and metabolic dysfunction in PCOS...
June 22, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28641384/acute-testosterone-deficiency-alters-adipose-tissue-fatty-acid-storage
#2
Sylvia Santosa, Nikki C Bush, Michael D Jensen
Context: Although the long-term effects of testosterone on adipose tissue lipid metabolism in men have been defined, the short-term regulation of these effects is not well understood. Objective: We examined the effects of acute testosterone withdrawal on subcutaneous abdominal and femoral adipose tissue fatty acid (FA) storage and cellular mechanisms. Design: This was a prospective, randomized trial. Setting: Mayo Clinic Clinical Research Unit...
June 21, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28637222/risk-factors-for-the-development-of-delayed-tsh-elevation-in-neonatal-intensive-care-unit-nicu-newborns
#3
Amnon Zung, Rachel Bier Palmon, Agneta Golan, Mara Troitzky, Smadar Eventov-Friedman, Ronella Marom, Rimona Keidar, Neri Kats, Shlomo Almashanu, Orna Flidel-Rimon
Context: Delayed TSH elevation (dTSH) is defined as elevated TSH in the second neonatal screen (following normal TSH in the initial screen) in premature, low-birth-weight and sick newborns, mostly in the neonatal intensive care unit (NICU) setting. The pathogenesis of dTSH is elusive. Objective: To identify risk factors for dTSH development among newborns in the NICU. Design: setting and patients: A retrospective chart review of neonates with dTSH was conducted in eight university-affiliated NICUs...
June 20, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28633452/threshold-effects-of-circulating-angiopoietin-like-3-levels-on-plasma-lipoproteins
#4
Sergio Fazio, Jessica Minnier, Michael D Shapiro, Sotirios Tsimikas, Patrizia Tarugi, Maurizio R Averna, Marcello Arca, Hagai Tavori
Context: Angiopoietin-like 3 (ANGPTL3) deficiency in plasma due to loss-of-function (LOF) gene mutations causes familial combined hypobetalipoproteinemia (FHBL) type 2 in homozygotes. However, the lipid phenotype in heterozygotes is much milder and does not appear to relate directly to ANGPTL3 levels. Furthermore, the low LDL phenotype in carriers of ANGPTL3 mutations is unexplained. Objective: To determine whether a reduction below a critical threshold in plasma ANGPTL3 levels is a determinant of lipoprotein metabolism in FHBL2, and to study the whether PCSK9 is involved in determining low LDL levels in this condition...
June 19, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28633507/digenic-duox1-and-duox2-mutations-in-cases-with-congenital-hypothyroidism
#5
Zehra Aycan, Hakan Cangul, Marina Muzza, Veysel N Bas, Laura Fugazzola, V Krishna Chatterjee, Luca Persani, Nadia Schoenmakers
Context: The DUOX2 enzyme generates hydrogen peroxide (H2O2), a crucial electron acceptor for the TPO-catalyzed iodination and coupling reactions mediating thyroid hormone biosynthesis. DUOX2 mutations result in dyshormonogenetic Congenital Hypothyroidism (CH) which may be phenotypically heterogeneous, leading to the hypothesis that CH severity may be influenced by environmental factors (eg dietary iodine) and oligogenic modifiers (eg variants in the homologous NADPH-oxidase DUOX1). However, loss of function mutations in DUOX1 have not hitherto been described and its role in thyroid biology remains undefined...
June 16, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28633482/markers-of-adipogenesis-but-not-inflammation-in-adipose-tissue-are-independently-related-to-insulin-sensitivity
#6
Natalia Matulewicz, Magdalena Stefanowicz, Agnieszka Nikolajuk, Monika Karczewska-Kupczewska
Context: In obesity, adipose tissue (AT) undergoes dynamic remodeling, including an alternations in adipogenesis, AT-resident cell content, angiogenesis and turnover of extracellular matrix (ECM) components. Studies on AT in humans have been carried out mostly on people with severe metabolic abnormalities, like type 2 diabetes or morbid obesity. Objective: The purpose of the present study was to investigate subcutaneous AT gene expression of markers of adipogenesis, ECM remodeling and inflammation in young, healthy, overweight or obese subjects...
June 16, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28637297/a-role-for-progesterone-regulated-sfrp4-expression-in-uterine-leiomyomas
#7
Meaghan A Delaney, Ying-Wooi Wan, Gyoung-Eun Kim, Chad J Creighton, Margaret G Taylor, Ramya Masand, Andrew Park, Cecilia Valdes, William Gibbons, Zhandong Liu, Matthew L Anderson
Context: Despite progesterone's key role in uterine smooth muscle tumorigenesis, the mechanisms by which it promotes the growth of uterine leiomyomas remain poorly understood. Objective: The aim of this study was to identify novel gene products mediating progesterone's effects in uterine leiomyomas. Design: Gene expression profiling was used to identify putative progesterone-regulated genes differentially expressed in uterine leiomyomas, which were then studied in vitro...
June 14, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28633420/pancreas-fat-and-beta-cell-mass-in-humans-with-and-without-diabetes-an-analysis-in-the-japanese-population
#8
Rie Murakami, Yoshifumi Saisho, Yuusuke Watanabe, Jun Inaishi, Tami Tsuchiya, Kinsei Kou, Seiji Sato, Minoru Kitago, Yuko Kitagawa, Taketo Yamada, Hiroshi Itoh
Context: The mechanisms by which beta cell mass is reduced in patients with type 2 diabetes (T2DM) remain unclear. It has been postulated that ectopic fat deposits in the pancreas induce beta cell apoptosis, leading to the development of diabetes. Objective: The aim of this study was to clarify the effects of intra-pancreatic fat on beta and alpha cell mass in humans with and without diabetes. Design, Subjects and Methods: Using our tissue database, pancreas sections of 72 Japanese non-diabetic (NDM) autopsy cases and 50 diabetic (DM) and 49 age- and BMI-matched NDM patients who underwent pancreatic surgery were analyzed...
June 14, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28633389/multiple-soluble-tgf-%C3%AE-receptors-in-addition-to-soluble-endoglin-are-elevated-in-preeclamptic-serum-and-they-synergistically-inhibit-tgf-%C3%AE-signalling
#9
Yao Wang, Qi Chen, Min Zhao, Kelly Walton, Craig Harrison, Guiying Nie
Context: Preeclampsia (PE) can be classified into early-onset (<34wk of gestation) and late-onset (>34wk) subtypes. Soluble endoglin, an auxiliary receptor for TGF-β ligands, is increased in PE circulation and believed to inhibit TGF-β action by sequestering the ligands. However, soluble endoglin, with a low affinity to TGF-β ligands, is demonstrated to have little effect by itself on TGF-β action. Objectives: We examined whether multiple soluble TGF-β receptors are elevated in PE circulation and whether they synergistically block TGF-β signalling...
June 14, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28605462/increased-triacylglycerol-lipase-activity-in-adipose-tissue-of-lean-and-obese-men-during-endurance-exercise
#10
Anatoli Petridou, Athanasios Chatzinikolaou, Alexandra Avloniti, Athanasios Jamurtas, Gedeon Loules, Ioannis Papassotiriou, Ioannis Fatouros, Vassilis Mougios
Context: Although there is increasing information on the mechanism of lipolysis in adipose tissue, the effect of exercise on individual factors of lipolysis is less well understood. Objective: We aimed to compare changes in adipose tissue triacylglycerol lipase activity and gene expression of adipose triacylglycerol lipase (ATGL), hormone sensitive lipase (HSL), monoacylglycerol lipase (MGL), perilipin 1, and comparative gene identification 58 (CGI-58) during exercise between lean and obese men...
June 12, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28605459/copy-number-variants-are-enriched-in-individuals-with-early-onset-obesity-and-highlight-novel-pathogenic-pathways
#11
Maria Pettersson, Heli Viljakainen, Petra Loid, Taina Mustila, Minna Pekkinen, Miriam Armenio, Johanna C Andersson-Assarsson, Outi Mäkitie, Anna Lindstrand
Context: Only a handful of genetic causes for childhood obesity have been identified to date. Copy number variants (CNVs) are known to contribute to obesity, both syndromic (15q11.2 deletions, Prader-Willi syndrome) and non-syndromic (16p11.2 deletions) obesity. Objective: To study the contribution of CNVs to early-onset obesity and evaluate the expression of candidate genes in subcutaneous adipose tissue. Design and Setting: A case-control study in a tertiary academic center...
June 12, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28605456/thyroid-function-cardiovascular-risk-factors-and-incident-atherosclerotic-cardiovascular-disease-the-atherosclerosis-risk-in-communities-aric-study
#12
Seth S Martin, Natalie Daya, Pamela L Lutsey, Kunihiro Matsushita, Anna Fretz, John W McEvoy, Roger S Blumenthal, Josef Coresh, Philip Greenland, Anna Kottgen, Elizabeth Selvin
Context: Cardiovascular outcomes in mild thyroid dysfunction (treatment controversial) and moderate or severe dysfunction (treatment standard) remain uncertain. Objective: To examine cross-sectional and prospective associations of thyroid function with cardiovascular risk factors and events. Design: In the Atherosclerosis Risk in Communities (ARIC) Study, we measured concentrations of thyrotropin (TSH), free thyroxine (FT4), and total triiodothyronine (T3) in stored serum samples originally collected in 1990-92...
June 12, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28605453/malignant-pheochromocytoma-and-paraganglioma-272-patients-over-55-years
#13
Oksana Hamidi, William F Young, Nicole M Iñiguez-Ariza, Nana Esi Kittah, Lucinda Gruber, Cristian Bancos, Shrikant Tamhane, Irina Bancos
Context: Malignant pheochromocytoma (PHEO) and paraganglioma (PGL) are rare and knowledge of the natural history is limited. Objective: We aimed to describe baseline characteristics and outcomes of patients with malignant PHEO and PGL (PPGL) and to identify predictors of shorter survival. Design: Retrospective review of patients with malignant PPGL evaluated from 1960 to 2016. Setting: Referral center. Patients: The group comprised 272 patients...
June 12, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28605545/atypical-forms-of-congenital-hyperinsulinism-in-infancy-are-associated-with-mosaic-patterns-of-immature-islet-cells
#14
Bing Han, Zainab Mohamed, Maria Salomon Estebanez, Ross J Craigie, Melanie Newbould, Edmund Cheesman, Raja Padidela, Mars Skae, Matthew Johnson, Sarah Flanagan, Sian Ellard, Karen E Cosgrove, Indraneel Banerjee, Mark J Dunne
Objectives: We aimed to characterise mosaic populations of pancreatic islet cells from patients with atypical CHI (CHI-A) and the expression profile of NKX2.2, a key transcription factor expressed in β-cells but suppressed in δ-cells in the mature pancreas. Patients/Methods: Tissue was isolated from three patients with CHI-A following subtotal pancreatectomy. CHI-A was diagnosed on the basis of islet mosaicism and the absence of histopathological hallmarks of focal- and diffuse CHI (CHI-D)...
June 9, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28605542/alternative-measures-of-hyperglycemia-and-risk-of-alzheimer-s-disease-in-the-community-the-hisayama-study
#15
Naoko Mukai, Tomoyuki Ohara, Jun Hata, Yoichiro Hirakawa, Daigo Yoshida, Hiro Kishimoto, Masafumi Koga, Udai Nakamura, Takanari Kitazono, Yutaka Kiyohara, Toshiharu Ninomiya
Context and Objective: We investigated the associations of hemoglobin A1c (HbA1c), glycated albumin (GA), the GA/HbA1c ratio, and 1,5-anhydroglucitol (1,5-AG) with the development of Alzheimer's disease (AD) in community-dwelling Japanese subjects. Design and Participants: A total of 1,187 subjects aged ≥65 years without dementia were followed up for an average of 4.8 years. Results: During the follow-up, 116 subjects experienced AD. The age- and sex-adjusted incidence of AD increased significantly with higher quartiles of the GA/HbA1c ratio, and a similar tendency was seen for GA, while no such association was observed for HbA1c and 1,5-AG...
June 9, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28605468/attenuation-of-insulin-action-by-an-allosteric-insulin-receptor-antibody-in-healthy-volunteers
#16
Kirk W Johnson, Ann Neale, Allan Gordon, Julie Roessig, Padma Bezwada, Sabine Vukelich, Ira Goldfine, Paul Rubin
Background: X358 (X358) is a fully human monoclonal antibody to the insulin receptor (InsR) that acts as a negative allosteric modulator of insulin signaling. It is being developed as a novel treatment for hyperinsulinemic hypoglycemia. This report describes pharmacokinetic (PK), and pharmacodynamic (PD) data from a first-in-human clinical trial. Methods: A double-blind, placebo-controlled, single ascending dose study was performed with 29 healthy adult males randomized to intravenous infusion of placebo or X358 at 0...
June 9, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28605448/efficacy-of-peptide-receptor-radionuclide-therapy-prrt-for-functional-metastatic-paraganglioma-and-phaeochromocytoma
#17
Grace Kong, Simona Grozinsky-Glasberg, Michael S Hofman, Jason Callahan, Amichay Meirovitz, Ofra Maimon, David A Pattison, David J Gross, Rodney J Hicks
Purpose: Treatment options for unresectable Paraganglioma (PGL)/Phaeochromocytoma (PCC), especially with uncontrolled secondary hypertension (HTN) are limited. Preliminary studies with PRRT suggest efficacy but data on HTN control and survival are lacking. We assessed PRRT outcomes in such patients from 2 referral centres. Methods: 20 consecutive patients (M:F=13:7; 21-77y.o.) with high somatostatin receptor (SSTR) expression treated with 177Lu-DOTA-octreotate, 9 with radiosensitising chemotherapy, were retrospectively reviewed...
June 9, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28595341/obstructive-sleep-apnea-dynamically-increases-nocturnal-plasma-free-fatty-acids-glucose-and-cortisol-during-sleep
#18
Swati Chopra, Aman Rathore, Haris Younas, Luu V Pham, Chenjuan Gu, Aleksandra Beselman, Il-Young Kim, Robert R Wolfe, Jamie Perin, Vsevolod Y Polotsky, Jonathan C Jun
Context: Obstructive sleep apnea (OSA) is associated with diabetes and cardiovascular disease. This association may be related to metabolic changes that transpire during sleep in OSA. Objective: To examine the impact of OSA, elicited by cessation of continuous positive airway pressure (CPAP), on frequently sampled nocturnal metabolic markers including plasma free fatty acids (FFA), glucose, insulin, triglycerides, cortisol, and lactate; as well as glucose production, oral glucose tolerance, blood pressure, endothelial function, cholesterol, and high sensitivity C-reactive protein (hsCRP)...
June 8, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28591831/the-gut-metagenome-changes-in-parallel-to-waist-circumference-brain-iron-deposition-and-cognitive-function
#19
Gerard Blasco, José Maria Moreno-Navarrete, Mireia Rivero, Vicente Pérez-Brocal, Josep Garre-Olmo, Josep Puig, Pepus Daunis-I-Estadella, Carles Biarnés, Jordi Gich, Fernando Fernández-Aranda, Ángel Alberich-Bayarri, Andrés Moya, Salvador Pedraza, Wifredo Ricart, Miguel López, Manuel Portero-Otin, José-Manuel Fernandez-Real
Context: Microbiota perturbations seem to exert modulatory effects on emotional behavior, stress- and pain-modulation systems in adult animals; however, limited information is available in humans. Objective: To study potential relationships among the gut metagenome, brain microstructure and cognitive performance in middle-aged, apparently healthy, obese and nonobese subjects, after weight changes. Design: This is a longitudinal study over a 2-year period...
June 7, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28591820/proton-pump-inhibitors-nephropathy-and-cardiovascular-disease-in-type-2-diabetes-the-fremantle-diabetes-study
#20
Timothy M E Davis, Jocelyn Drinkwater, Wendy A Davis
Context: There is emerging evidence of a range of adverse effects of chronic proton pump inhibitor (PPI) therapy. Objective: To assess the impact of PPI use on albuminuria, renal function and cardiovascular disease (CVD) risk in type 2 diabetes. Design: Longitudinal observational study. Setting: Urban-dwelling community. Patients: Patients with type 2 diabetes from the longitudinal observational Fremantle Diabetes Study Phase II and on stable renin-angiotensin system blocking therapy were divided into those remaining untreated with a PPI (Group 1, n=686), on PPI therapy throughout (Group 2, n=174), and commencing (Group 3, n=109) or discontinuing regular PPI therapy (Group 4, n=67) during the two years between assessments...
June 7, 2017: Journal of Clinical Endocrinology and Metabolism
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