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https://www.readbyqxmd.com/read/28324484/sodium-glucose-co-transporter-2-sglt2-inhibitor-comparing-trial-data-and-real-world-use
#1
Andrew McGovern, Michael Feher, Neil Munro, Simon de Lusignan
INTRODUCTION: The first cardiovascular safety trial in the sodium-glucose co-transporter-2 (SGLT2) inhibitor drug class, the Empagliflozin Cardiovascular Outcomes and Mortality in Type 2 Diabetes (EMPA-REG OUTCOME) trial, demonstrated significant cardiovascular risk reduction with empagliflozin. It is currently not clear what proportions of people with type 2 diabetes (T2DM) have the same high cardiovascular risk as those included in the trial, and will therefore be likely to experience the same cardiovascular benefit...
March 21, 2017: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/28324037/autotaxin-is-regulated-by-glucose-and-insulin-in-adipocytes
#2
Kenneth D'Souza, Daniel A Kane, Mohamed Touaibia, Erin E Kershaw, Thomas Pulinilkunnil, Petra C Kienesberger
Autotaxin (ATX) is an adipokine that generates the bioactive lipid, lysophosphatidic acid. Despite recent studies implicating adipose-derived ATX in metabolic disorders including obesity and insulin resistance, the nutritional and hormonal regulation of ATX in adipocytes remains unclear. The present study examined the regulation of ATX in adipocytes by glucose and insulin and the role of ATX in adipocyte metabolism. Induction of insulin resistance in adipocytes with high glucose and insulin concentrations increased ATX secretion, whereas co-incubation with the insulin sensitizer, rosiglitazone, prevented this response...
January 16, 2017: Endocrinology
https://www.readbyqxmd.com/read/28324021/endogenous-calcitonin-gene-related-peptide-regulates-lipid-metabolism-and-energy-homeostasis-in-male-mice
#3
Tian Liu, Akiko Kamiyoshi, Takayuki Sakurai, Yuka Ichikawa-Shindo, Hisaka Kawate, Lei Yang, Megumu Tanaka, Xian Xian, Akira Imai, Liuyu Zhai, Kazutaka Hirabayashi, Kun Dai, Keiya Tanimura, Teng Liu, Nanqi Cui, Kyoko Igarashi, Akihiro Yamauchi, Takayuki Shindo
Calcitonin gene-related peptide (CGRP) is a bioactive peptide produced by alternative splicing of the primary transcript of the calcitonin/CGRP gene. CGRP is largely distributed in the cardiovascular and nervous systems, where it acts as a regulatory factor. CGRP is also expressed in organs and tissues involved in metabolic regulation, including white adipose tissue (WAT), where its function is largely unknown. In this study, we examined the effects of endogenous CGRP on metabolic function. When we administered a high-fat diet to CGRP knockout (CGRP-/-) and wild-type (WT) mice for 10 weeks, we observed that food intake did not differ between the two groups, but body weight and visceral fat weight were significantly lower in CGRP-/- mice...
January 20, 2017: Endocrinology
https://www.readbyqxmd.com/read/28324005/insulin-inhibits-nrf2-gene-expression-via-heterogeneous-nuclear-ribonucleoprotein-f-k-in-diabetic-mice
#4
Anindya Ghosh, Shaaban Abdo, Shuiling Zhao, Chin-Han Wu, Yixuan Shi, Chao-Sheng Lo, Isabelle Chenier, Thierry Alquier, Janos G Filep, Julie R Ingelfinger, Shao-Ling Zhang, John S D Chan
Oxidative stress induces endogenous antioxidants via nuclear factor erythroid 2-related factor 2 (Nrf2), potentially preventing tissue injury. We investigated whether insulin affects renal Nrf2 expression in type 1 diabetes (T1D) and studied its underlying mechanism. Insulin normalized hyperglycemia, hypertension, oxidative stress and renal injury, inhibited renal Nrf2 and angiotensinogen (Agt) gene expression and up-regulated heterogeneous nuclear ribonucleoprotein F (hnRNP F) and hnRNP K expression in Akita mice with T1D...
January 23, 2017: Endocrinology
https://www.readbyqxmd.com/read/28323978/assisted-reproductive-technologies-predispose-to-insulin-resistance-and-obesity-in-male-mice-challenged-with-a-high-fat-diet
#5
David Cerny, Claudio Sartori, Stefano F Rimoldi, Théo Meister, Rodrigo Soria, Elisa Bouillet, Urs Scherrer, Emrush Rexhaj
ART alters glucose homeostasis in mice and humans, but the underlying mechanisms are incompletely understood. ART induces endothelial dysfunction and arterial hypertension by epigenetic alteration of the eNOS gene. In eNOS deficient mice, insulin resistance is related to impaired insulin stimulation of muscle blood flow and substrate delivery and defective intrinsic skeletal muscle glucose uptake. We, therefore, assessed glucose tolerance, insulin sensitivity (euglycemic clamp), insulin stimulation of muscle blood flow in vivo and muscle glucose uptake in vitro in male ART and control mice fed a normal chow (NC) or challenged with a high fat diet (HFD) during 8 weeks...
February 8, 2017: Endocrinology
https://www.readbyqxmd.com/read/28323977/short-term-vs-long-term-effects-of-adipocyte-toll-like-receptor-4-activation-on-insulin-resistance-in-male-mice
#6
Caroline Tao, William L Holland, Qiong A Wang, Mengle Shao, Lin Jia, Kai Sun, Xiaoli Lin, Yi-Chun Kuo, Joshua A Johnson, Ruth Gordillo, Joel K Elmquist, Philipp E Scherer
Chronic exposure to diets high in saturated fat (HFD) increases the prevalence of obesity and contributes to the development of low-grade inflammation and insulin resistance. A possible mediator accounting for obesity-associated inflammation and insulin resistance is Toll-like receptor 4 (TLR4). We investigated the role of adipocyte TLR4 in lipid and glucose homeostasis through an inducible, adipocyte-specific deletion of TLR4, the "TADIPO mouse". Consistent with a critical role for inflammation as a positive force for healthy adipose tissue expansion, chronic HFD exposure resulted in exacerbated whole body and muscle insulin resistance in the absence of TLR4 in the adipocyte...
February 24, 2017: Endocrinology
https://www.readbyqxmd.com/read/28323956/hyperhomocysteinemia-promotes-insulin-resistance-and-adipose-tissue-inflammation-in-pcos-mice-through-modulating-m2-macrophage-polarization-via-estrogen-suppression
#7
Xinyu Qi, Bochun Zhang, Yue Zhao, Rong Li, Hsun-Ming Chang, Yanli Pang, Jie Qiao
It has been shown that serum homocycteine (Hcy) levels are higher in women with polycystic ovary syndrome (PCOS). However, the specific role of hyperhomocycteinemia (HHcy) in the development of PCOS has never been reported. Adipose tissue inflammation is featured by the infiltration of macrophages that plays a critical role in the pathogenesis of glucose and insulin intolerance. In this study, C57BL/6 mice were treated with dehydroepiandrosterone (DHEA) and/or high methionine diet to induce PCOS and HHcy mice models...
March 15, 2017: Endocrinology
https://www.readbyqxmd.com/read/28323952/randomized-controlled-trial-of-a-mufa-or-fiber-rich-diet-on-hepatic-fat-in-pre-diabetes
#8
Isabel Errazuriz, Simmi Dube, Michael Slama, Roberto Visentin, Sunita Nayar, Helen O'Connor, Claudio Cobelli, Swapan Kumar Das, Ananda Basu, Walter Karl Kremers, John Port, Rita Basu
Context: Increased prevalence of type 2 diabetes mellitus and prediabetes worldwide has been attributed, at least in part, to a modern lifestyle, in particular, to an unhealthy diet. Objective: To evaluate whether 12 weeks of high MUFA or fiber-rich weight maintenance diet lowers hepatic fat and improves glucose tolerance in people with prediabetes. Design: Subjects underwent a [6, 6-2H2] labeled 75 g oral glucose tolerance test to estimate hepatic insulin sensitivity (Siliver) along with measurement of liver fat fraction (LFF) using magnetic resonance spectroscopy before and after intervention...
March 6, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28323942/incretin-therapies-do-not-expand-%C3%AE-cell-mass-or-alter-pancreatic-histology-in-young-male-mice
#9
Aaron R Cox, Carol J Lam, Matthew M Rankin, Jacqueline S Rios, Julia Chavez, Claire W Bonnyman, Kourtney B King, Roger A Wells, Deepti Anthony, Justin X Tu, Jenny J Kim, Changhong Li, Jake A Kushner
The impact of incretins upon pancreatic β-cell expansion remains extremely controversial. Multiple studies indicate that incretin-based therapies can increase β-cell proliferation, and incretins have been hypothesized to expand β-cell mass. However, considerable disagreement exists on whether incretins actually increase β-cell mass. Moreover, some reports indicate that incretins may cause metaplastic changes in pancreatic histology. To resolve these questions we treated a large cohort of mice with incretin-based therapies and carried out a rigorous analysis of β-cell turnover and pancreatic histology using high-throughput imaging...
March 8, 2017: Endocrinology
https://www.readbyqxmd.com/read/28323940/thyroid-signaling-insulin-resistance-and-type-2-diabetes-mellitus-a-mendelian-randomization-study
#10
Maxime M Bos, Roelof Aj Smit, Stella Trompet, Diana van Heemst, Raymond Noordam
CONTEXT: Increasing evidence suggests an association between thyroid stimulating hormone (TSH), free thyroxine (fT4) and deiodinases with insulin resistance and type 2 diabetes mellitus (T2D). OBJECTIVE: We examined whether TSH and fT4 levels and deiodinases are causally associated with insulin resistance and T2D using Mendelian randomization (MR). METHODS: We selected twenty genetic variants for TSH level and four for fT4 level (identified in a GWAS meta-analysis of European-ancestry cohorts) as instrumental variables for TSH and fT4 level, respectively...
March 9, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28323587/metabolic-syndrome-and-periodontal-disease-among-civilian-pilots
#11
Xi Chen, Lu Xie, Yang Liu, Duanjing Chen, Qing Yu, Xueqi Gan, Haiyang Yu
BACKGROUND: Metabolic syndrome (MetS) is a cluster of metabolic abnormalities that can affect civilian pilots' health. Its prevalence and the correlation with periodontal disease (PD) among pilots had not been previously reported. The aim of the study was to determine MetS and PD status, and to reveal their relationship in a representative sample of Chinese civilian pilots. METHODS: We investigated 303 civilian pilots (mean age 34.92 ± 7.66 yr). General information as well as blood and saliva samples were collected...
December 1, 2016: Aerospace Medicine and Human Performance
https://www.readbyqxmd.com/read/28320081/bariatric-surgery-versus-lifestyle-interventions-for-severe-obesity-5-year-changes-in-body-weight-risk-factors-and-comorbidities
#12
B Øvrebø, M Strømmen, B Kulseng, C Martins
Changes in body weight (BW), risk factors and comorbidities 5 years after Roux-en-Y gastric bypass (RYGB) or different lifestyle interventions are compared. A total of 209 (75% women) severe obese adults were non-randomly allocated to: (A) RYGB (n = 58), (B) weight loss (WL) camp (n = 30), (C) residential intermittent programme (n = 64) or (D) hospital outpatient programme (n = 57). Body weight, risk factors and comorbidities were assessed at baseline, 1 and 5 years. A total of 89 and 54% completed the 1- and 5-year follow-up...
March 20, 2017: Clinical Obesity
https://www.readbyqxmd.com/read/28319810/inhibitors-of-glut-slc2a-enhance-the-action-of-bcnu-and-temozolomide-against-high-grade-gliomas
#13
Alberto Azzalin, Giulia Nato, Elena Parmigiani, Francesca Garello, Annalisa Buffo, Lorenzo Magrassi
Glucose transport across glioblastoma membranes plays a crucial role in maintaining the enhanced glycolysis typical of high-grade gliomas and glioblastoma. We tested the ability of two inhibitors of the glucose transporters GLUT/SLC2A superfamily, indinavir (IDV) and ritonavir (RTV), and of one inhibitor of the Na/glucose antiporter type 2 (SGLT2/SLC5A2) superfamily, phlorizin (PHZ), in decreasing glucose consumption and cell proliferation of human and murine glioblastoma cells. We found in vitro that RTV, active on at least three different GLUT/SLC2A transporters, was more effective than IDV, a specific inhibitor of GLUT4/SLC2A4, both in decreasing glucose consumption and lactate production and in inhibiting growth of U87MG and Hu197 human glioblastoma cell lines and primary cultures of human glioblastoma...
March 17, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28319589/exercise-improves-v-combining-dot-above-o-2max-and-body-composition-in-adt-treated-prostate-cancer-patients
#14
Bradley A Wall, Daniel A Galvão, Naeem Fatehee, Dennis R Taaffe, Nigel Spry, David Joseph, Jeffrey J Hebert, Robert U Newton
INTRODUCTION: Prostate cancer is the most common cancer in men and patients treated with androgen deprivation therapy (ADT) experience unfavourbale changes in body composition and associated metabolic complications, which can increase the risk of cardiovascular disease. We examined the effect of a 6-month program of aerobic and resistance exercise aimed at improving body composition and cardiorespiratory health in this population. METHODS: Ninety-seven men (43-90 years) with localized prostate cancer receiving ADT were randomized to either exercise (EX, n=50) or usual care (CON, n=47)...
March 18, 2017: Medicine and Science in Sports and Exercise
https://www.readbyqxmd.com/read/28319241/alzheimer-disease-signature-neurodegeneration-and-apoe-genotype-in-mild-cognitive-impairment-with-suspected-non-alzheimer-disease-pathophysiology
#15
Stefanie Schreiber, Frank Schreiber, Samuel N Lockhart, Andy Horng, Alexandre Bejanin, Susan M Landau, William J Jagust
Importance: There are conflicting results claiming that Alzheimer disease signature neurodegeneration may be more, less, or similarly advanced in individuals with β-amyloid peptide (Aβ)-negative (Aβ-) suspected non-Alzheimer disease pathophysiology (SNAP) than in Aβ-positive (Aβ+) counterparts. Objective: To examine patterns of neurodegeneration in individuals with SNAP compared with their Aβ+ counterparts. Design, Setting, and Participants: A longitudinal cohort study was conducted among individuals with mild cognitive impairment (MCI) and cognitively normal individuals receiving care at Alzheimer's Disease Neuroimaging Initiative sites in the United States and Canada for a mean follow-up period of 30...
March 20, 2017: JAMA Neurology
https://www.readbyqxmd.com/read/28319117/comparative-genomics-of-clavibacter-michiganensis-subspecies-pathogens-of-important-agricultural-crops
#16
James T Tambong
Subspecies of Clavibacter michiganensis are important phytobacterial pathogens causing devastating diseases in several agricultural crops. The genome organizations of these pathogens are poorly understood. Here, the complete genomes of 5 subspecies (C. michiganensis subsp. michiganensis, Cmi; C. michiganensis subsp. sepedonicus, Cms; C. michiganensis subsp. nebraskensis, Cmn; C. michiganensis subsp. insidiosus, Cmi and C. michiganensis subsp. capsici, Cmc) were analyzed. This study assessed the taxonomic position of the subspecies based on 16S rRNA and genome-based DNA homology and concludes that there is ample evidence to elevate some of the subspecies to species-level...
2017: PloS One
https://www.readbyqxmd.com/read/28319096/hyperglycemia-exacerbates-colon-cancer-malignancy-through-hexosamine-biosynthetic-pathway
#17
A Vasconcelos-Dos-Santos, H F B R Loponte, N R Mantuano, I A Oliveira, I F de Paula, L K Teixeira, J C M de-Freitas-Junior, K C Gondim, N Heise, R Mohana-Borges, J A Morgado-Díaz, W B Dias, A R Todeschini
Hyperglycemia is a common feature of diabetes mellitus, considered as a risk factor for cancer. However, its direct effects in cancer cell behavior are relatively unexplored. Herein we show that high glucose concentration induces aberrant glycosylation, increased cell proliferation, invasion and tumor progression of colon cancer. By modulating the activity of the rate-limiting enzyme, glutamine-fructose-6-phosphate amidotransferase (GFAT), we demonstrate that hexosamine biosynthetic pathway (HBP) is involved in those processes...
March 20, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28319076/clinical-impact-of-hyperglycemia-on-days-0-7-after-allogeneic-stem-cell-transplantation
#18
A Kawajiri, S Fuji, Y Tanaka, C Kono, T Hirakawa, T Tanaka, R Ito, Y Inoue, K Okinaka, S Kurosawa, Y Inamoto, S-W Kim, T Yamashita, T Fukuda
In order to clarify the association between hyperglycemia during the early period after allogeneic stem cell transplantation (allo-SCT) and adverse outcomes, we retrospectively analyzed 563 consecutive patients who underwent allo-SCT at our institute between 2008 and 2015. Patients were categorized into three groups according to mean fasting blood glucose levels on days 0-7 (normoglycemia group<110 mg/dL, n=347; mild hyperglycemia group 110-149 mg/dL, n=192 and moderate/severe hyperglycemia group≥150 mg/dL, n=24)...
March 20, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28319004/updated-risk-factors-should-be-used-to-predict-development-of-diabetes
#19
Mary Angelyn Bethel, Kristen A Hyland, Antonio R Chacra, Prakash Deedwania, Gregory R Fulcher, Rury R Holman, Trond Jenssen, Naomi S Levitt, John J V McMurray, Eleni Boutati, Laine Thomas, Jie-Lena Sun, Steven M Haffner
AIMS: Predicting incident diabetes could inform treatment strategies for diabetes prevention, but the incremental benefit of recalculating risk using updated risk factors is unknown. We used baseline and 1-year data from the Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) Trial to compare diabetes risk prediction using historical or updated clinical information. METHODS: Among non-diabetic participants reaching 1year of follow-up in NAVIGATOR, we compared the performance of the published baseline diabetes risk model with a "landmark" model incorporating risk factors updated at the 1-year time point...
March 2, 2017: Journal of Diabetes and its Complications
https://www.readbyqxmd.com/read/28319002/hba1c-in-relation-to-incident-diabetes-and-diabetes-related-complications-in-non-diabetic-adults-at-baseline
#20
Patricia Anne Metcalf, Cam Kyle, Tim Kenealy, Rod T Jackson
AIMS: We compared the utility of glycated hemoglobin (HbA1c) and oral glucose tolerance (oGTT) in non-diabetic patients for identifying incident diabetes; all-cause mortality; cardiovascular disease (CVD) mortality; CVD, coronary heart disease (CHD), and ischemic stroke events; and diabetes microvascular complications. METHODS: Data from a New Zealand community setting were prospectively linked to hospitalization, mortality, pharmaceutical and laboratory test results data...
February 21, 2017: Journal of Diabetes and its Complications
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