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Journal of Clinical Endocrinology and Metabolism

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https://www.readbyqxmd.com/read/28673045/the-effect-of-pcsk9-loss-of-function-variants-on-the-postprandial-lipid-and-apob-lipoprotein-response
#1
Teik Chye Ooi, Jacqueline A Krysa, Seham Chaker, Hussein Abujrad, Janice Mayne, Kathy Henry, Marion Cousins, Angela Raymond, Colette Favreau, Monica Taljaard, Michel Chrétien, Majambu Mbikay, Spencer D Proctor, Donna F Vine
CONTEXT: PCSK9 mediates the degradation of the low-density lipoprotein receptor (LDLR) thereby increasing plasma low density lipoprotein cholesterol (LDL-C). Variations in the PCSK9 gene that are associated with loss-of-function (LOF) of PCSK9 result in a greater expression of hepatic LDLR, lower concentrations of LDL-C, and protection from cardiovascular disease (CVD). Apolipoprotein-B (apo) remnants also contribute to CVD risk and are similarly cleared by the LDLR. We hypothesized that PCSK9-LOF carriers would have significantly lower fasting and postprandial remnant lipoproteins on top of lower LDL-C...
June 30, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28666360/overnight-closed-loop-control-improves-glycemic-control-in-a-multicenter-study-of-adults-with-type-1-diabetes
#2
Sue A Brown, Marc D Breton, Stacey M Anderson, Laura Kollar, Patrick Keith-Hynes, Carol J Levy, David W Lam, Camilla Levister, Nihat Baysal, Yogish C Kudva, Ananda Basu, Vikash Dadlani, Ling Hinshaw, Shelly McCrady-Spitzer, Daniela Bruttomesso, Roberto Visentin, Silvia Galasso, Simone Del Favero, Yenny Leal, Federico Boscari, Angelo Avogaro, Claudio Cobelli, Boris P Kovatchev
Context: Closed-loop control (CLC) for the management of T1D is a novel method for optimizing glucose control and strategies for individualized implementation are being developed. Objective: Analyze glycemic control in an Overnight CLC system designed to "reset" the patient to near normal glycemic targets every morning. Design: Randomized cross-over multicenter clinical trial. Participants: 44 subjects with T1D on insulin pump therapy...
June 28, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28666346/insulin-secretion-and-insulin-sensitivity-before-and-after-surgical-treatment-of-pheochromocytoma-or-paraganglioma
#3
Hisako Komada, Yushi Hirota, Anna So, Tomoaki Nakamura, Yoko Okuno, Hidenori Fukuoka, Genzo Iguchi, Yutaka Takahashi, Kazuhiko Sakaguchi, Wataru Ogawa
Context: Pheochromocytoma and paraganglioma are catecholamine-producing tumors that often impair glucose tolerance. The effects of these tumors on insulin sensitivity and insulin secretion in patients have remained unclear, however. Objective: To characterize the influence of pheochromocytoma or paraganglioma on glucose tolerance, we comprehensively analyzed various parameters related to insulin secretion or insulin sensitivity in patients with these tumors. Design: Hyperglycemic and hyperinsulinemic-euglycemic clamps as well as an oral glucose tolerance test (OGTT) were performed in subjects before and after tumor excision...
June 28, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28666345/thyroid-hemiagenesis-incidence-clinical-significance-and-genetic-background
#4
Ewelina Szczepanek-Parulska, Ariadna Zybek-Kocik, Leonard Wartofsky, Marek Ruchala
Context: Thyroid hemiagenesis (THA) constitutes a rare, congenital disorder that is characterized by an absence of one thyroid lobe. Because the pathogenesis and clinical significance of this malformation remain undefined, specific clinical recommendations are lacking, especially for asymptomatic cases. Evidence Acquisition: The PubMed Database was searched (years 1970-2017) and the following terms were used to retrieve the results: "thyroid hemiagenesis", "thyroid hemiaplasia", "one thyroid lobe agenesis" and "one thyroid lobe aplasia"...
June 28, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28666341/duox2-mutations-are-associated-with-congenital-hypothyroidism-with-ectopic-thyroid-gland
#5
Marina M L Kizys, Ruy A Louzada, Miguel Mitne-Neto, Jessica R Jara, Gilberto K Furuzawa, Denise P de Carvalho, Magnus R Dias-da-Silva, Suzana Nesi-França, Corinne Dupuy, Rui M B Maciel
Context: Thyroid dysgenesis (TD) is the leading cause of congenital hypothyroidism (CH). The etiology of TD remains unknown in about approximately 90% of cases, the most frequent form being thyroid ectopia (TE; 48-61%). Objective: To search for new candidate genes in hypothyroid children with TE. Design/Setting/Participants: We followed a cohort of 268 TD children and performed whole-exome sequencing (WES) in three children with CH with TE (CHTE) and compared them with 18 thyroid-healthy controls...
June 28, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28666334/targeting-adrenomedullin-to-improve-lipid-homeostasis-in-diabetic-pregnancies
#6
Yuanlin Dong, Ancizar Betancourt, Michael Belfort, Chandra Yallampalli
Context: Gestational diabetes mellitus (GDM) is associated with disturbances in maternal lipid metabolism. Hypertriacylglycerolemia in GDM is associated with an increased risk of large for gestational age neonates, but the pathogenesis of disrupted lipid homeostasis remains unclear. Objectives: To determine the role of adrenomedullin (AM), a multifunctional peptide, in lipid metabolism in GDM. Design: Omental adipose biopsies were collected in term pregnancy from women with normal glucose tolerence (NGT, n=10) and GDM (n=10)...
June 28, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28655174/diagnosis-and-management-of-osteopetrosis-consensus-guidelines-from-the-osteopetrosis-working-group
#7
Calvin C Wu, Michael J Econs, Linda A DiMeglio, Karl L Insogna, Michael A Levine, Paul J Orchard, Weston P Miller, Anna Petryk, Eric T Rush, Dolores M Shoback, Leanne M Ward, Lynda E Polgreen
Background: Osteopetrosis encompasses a group of rare metabolic bone diseases characterized by impaired osteoclast activity or development, resulting in high bone mineral density. Existing guidelines focus on treatment of the severe infantile forms with hematopoietic cell transplantation (HCT), but do not address the management of patients with less severe forms for whom HCT is not the standard of care. Therefore, our objective was to develop expert consensus guidelines that would address the management of these patients...
June 26, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28651370/changes-in-visceral-adiposity-subcutaneous-adiposity-and-sex-hormones-in-the-diabetes-prevention-program
#8
Catherine Kim, Dana Dabelea, Rita R Kalyani, Costas A Christophi, George A Bray, Xavier Pi-Sunyer, Christine H Darwin, Swaytha Yalamanchi, Elizabeth Barrett-Connor, Sherita Hill Golden, Edward J Boyko
Context: The degree to which changes in visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) relate to corresponding changes in plasma sex steroids is not known. Objective: We examined whether changes in VAT and SAT areas assessed by computed tomography were associated with changes in sex hormones (dehydroepiandrosterone [DHEAS], testosterone, estradiol, estrone, and sex hormone binding globulin [SHBG]) among Diabetes Prevention Program participants...
June 23, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28651368/risk-of-recurrence-in-pituitary-neuroendocrine-tumors-a-prospective-study-using-a-five-tiered-classification
#9
Gérald Raverot, Emmanuelle Dantony, Julie Beauvy, Alexandre Vasiljevic, Sara Mikolasek, Françoise Borson-Chazot, Emmanuel Jouanneau, Pascal Roy, Jacqueline Trouillas
Background: Most pituitary neuroendocrine tumors (PitNET) show benign behavior, but a significant number are invasive, recur or resist to medical treatment. Based on a retrospective case-control study we recently proposed a classification of PitNETs of prognostic relevance. This prospective study aims to test the value of this classification in an independent patient cohort. Methods: The cohort included patients of a single center operated upon a PitNET. Using a grading system based on invasion on MRI, immunocytochemical profile (ICC), Ki-67, mitotic index, and p53 positivity, tumors were classified...
June 23, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28651346/effect-of-apoe-%C3%AE%C2%B5-genotype-on-lipoprotein-a-and-the-associated-risk-of-myocardial-infarction-and-aortic-valve-stenosis
#10
Leonard Kritharides, Børge G Nordestgaard, Anne Tybjærg-Hansen, Pia R Kamstrup, Shoaib Afzal
Context: Lipoprotein(a) is a genetic risk factor for myocardial infarction and aortic valve stenosis. APOE ε2/3/4 genotypes affect plasma lipoprotein(a); however, the effects of APOE genotypes on the prediction of myocardial infarction and aortic valve stenosis by lipoprotein(a) are unknown. Objective: We tested the hypothesis that APOE ε2/3/4 genotype affects plasma lipoprotein(a), the contribution of plasma apoE levels this effect, and the associated risk of myocardial infarction and aortic valve stenosis...
June 23, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28651343/does-a-first-degree-family-history-of-diabetes-impact-placental-maternal-and-fetal-vascular-circulation-and-inflammatory-response
#11
Marina Shargorodsky, Michal Kovo, Letizia Schraiber, Jacob Bar
Context: Heritability of diabetes is associated with hyperinsulinemia, impaired endothelial function, and inflammatory up-regulation. However, no studies have examined whether a family history of diabetes effects placental vascular circulation. Objective: The present study was designed to investigate the impact of a first-degree family history of type 2 diabetes (FHD) on placental vascular circulation and inflammatory lesions. Design: Observational cohort study...
June 23, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28645211/akr1c3-mediated-adipose-androgen-generation-drives-lipotoxicity-in-women-with-polycystic-ovary-syndrome
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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