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By Miguel Angel Garcia Médico de familia . España
Stephen D Wiviott, Itamar Raz, Marc P Bonaca, Ofri Mosenzon, Eri T Kato, Avivit Cahn, Michael G Silverman, Thomas A Zelniker, Julia F Kuder, Sabina A Murphy, Deepak L Bhatt, Lawrence A Leiter, Darren K McGuire, John P H Wilding, Christian T Ruff, Ingrid A M Gause-Nilsson, Martin Fredriksson, Peter A Johansson, Anna-Maria Langkilde, Marc S Sabatine
BACKGROUND: The cardiovascular safety profile of dapagliflozin, a selective inhibitor of sodium-glucose cotransporter 2 that promotes glucosuria in patients with type 2 diabetes, is undefined. METHODS: We randomly assigned patients with type 2 diabetes who had or were at risk for atherosclerotic cardiovascular disease to receive either dapagliflozin or placebo. The primary safety outcome was a composite of major adverse cardiovascular events (MACE), defined as cardiovascular death, myocardial infarction, or ischemic stroke...
November 10, 2018: New England Journal of Medicine
Ekaterina A Khramtsova, Lea K Davis, Barbara E Stranger
Nearly all human complex traits and disease phenotypes exhibit some degree of sex differences, including differences in prevalence, age of onset, severity or disease progression. Until recently, the underlying genetic mechanisms of such sex differences have been largely unexplored. Advances in genomic technologies and analytical approaches are now enabling a deeper investigation into the effect of sex on human health traits. In this Review, we discuss recent insights into the genetic models and mechanisms that lead to sex differences in complex traits...
December 23, 2018: Nature Reviews. Genetics
Jerry W Shay, Woodring E Wright
Many recent advances have emerged in the telomere and telomerase fields. This Timeline article highlights the key advances that have expanded our views on the mechanistic underpinnings of telomeres and telomerase and their roles in ageing and disease. Three decades ago, the classic view was that telomeres protected the natural ends of linear chromosomes and that telomerase was a specific telomere-terminal transferase necessary for the replication of chromosome ends in single-celled organisms. While this concept is still correct, many diverse fields associated with telomeres and telomerase have substantially matured...
February 13, 2019: Nature Reviews. Genetics
(no author information available yet)
The American Diabetes Association (ADA) "Standards of Medical Care in Diabetes" includes ADA's current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, a multidisciplinary expert committee, are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA's clinical practice recommendations, please refer to the Standards of Care Introduction Readers who wish to comment on the Standards of Care are invited to do so at professional...
January 2019: Diabetes Care
Francis J Alenghat, Andrew M Davis
No abstract text is available yet for this article.
February 4, 2019: JAMA: the Journal of the American Medical Association
P J Larkin, N I Cherny, D La Carpia, M Guglielmo, C Ostgathe, F Scotté, C I Ripamonti
No abstract text is available yet for this article.
October 1, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
Sleiman Razzouk
Modern genetic therapy incorporates genomic testing and genome editing. It is the finest approach for precision medicine. Genome editing is a state-of-the-art technology to manipulate gene expression thus generating a particular genotype. It encompasses multiple programmable nuclease-based approaches leading to genetic changes. Not surprisingly, this method triggered internationally a wide array of controversies in the scientific community and in the public since it transforms the human genome. Given its importance, the pace of this technology is exceptionally fast...
November 2018: Annals of Human Genetics
Anthony H V Schapira
Mitochondria have a crucial role in cellular bioenergetics and apoptosis, and thus are important to support cell function and in determination of cell death pathways. Inherited mitochondrial diseases can be caused by mutations of mitochondrial DNA or of nuclear genes that encode mitochondrial proteins. Although many mitochondrial disorders are multisystemic, some are tissue specific--eg, optic neuropathy, sensorineural deafness, and type 2 diabetes mellitus. In the past few years, several disorders have been associated with mutations of nuclear genes responsible for mitochondrial DNA maintenance and function, and the potential contribution of mitochondrial abnormalities to progressive neurodegenerative diseases such as Parkinson's disease and Alzheimer's disease has been recognised...
May 12, 2012: Lancet
Gabriel M Pagnotti, Maya Styner
Despite association with low bone density and skeletal fractures, marrow adipose tissue (MAT) remains poorly understood. The marrow adipocyte originates from the mesenchymal stem cell (MSC) pool that also gives rise to osteoblasts, chondrocytes, and myocytes, among other cell types. To date, the presence of MAT has been attributed to preferential biasing of MSC into the adipocyte rather than osteoblast lineage, thus negatively impacting bone formation. Here, we focus on understanding the physiology of MAT in the setting of exercise, dietary interventions, and pharmacologic agents that alter fat metabolism...
2016: Frontiers in Endocrinology
Ele Ferrannini
New England Journal of Medicine, Volume 371, Issue 16, Page 1547-1548, October 2014.
October 16, 2014: New England Journal of Medicine
Erin E Mulvihill, Daniel J Drucker
Dipeptidyl peptidase-4 (DPP4) is a widely expressed enzyme transducing actions through an anchored transmembrane molecule and a soluble circulating protein. Both membrane-associated and soluble DPP4 exert catalytic activity, cleaving proteins containing a position 2 alanine or proline. DPP4-mediated enzymatic cleavage alternatively inactivates peptides or generates new bioactive moieties that may exert competing or novel activities. The widespread use of selective DPP4 inhibitors for the treatment of type 2 diabetes has heightened interest in the molecular mechanisms through which DPP4 inhibitors exert their pleiotropic actions...
December 2014: Endocrine Reviews
Bernard Man Yung Cheung, Tommy Tsang Cheung, Nithushi Rajitha Samaranayake
Obesity is a major health problem worldwide. Although diet and physical activity are crucial in the management of obesity, the long-term success rate is low. Therefore antiobesity drugs are of great interest, especially when lifestyle modification has failed. As obesity is not an immediate life-threatening disease, these drugs are required to be safe. Antiobesity drugs that have been developed so far have limited efficacies and considerable adverse effects affecting tolerability and safety. Therefore, most antiobesity drugs have been withdrawn...
August 2013: Therapeutic Advances in Drug Safety
Guntram Schernthaner, Carl Erik Mogensen, Gerit-Holger Schernthaner
Diabetic nephropathy (DN) affects an estimated 20%-40% of patients with type 2 diabetes mellitus (T2DM). Key modifiable risk factors for DN are albuminuria, anaemia, dyslipidaemia, hyperglycaemia and hypertension, together with lifestyle factors, such as smoking and obesity. Early detection and treatment of these risk factors can prevent DN or slow its progression, and may even induce remission in some patients. DN is generally preceded by albuminuria, which frequently remains elevated despite treatment in patients with T2DM...
September 2014: Diabetes & Vascular Disease Research
Howard Leong-Poi
No abstract text is available yet for this article.
September 23, 2014: Circulation
Javier Delgado-Lista, Pablo Perez-Martinez, Antonio Garcia-Rios, Ana I Perez-Caballero, Francisco Perez-Jimenez, Jose Lopez-Miranda
A strict adherence to the Mediterranean Diet (MedDiet) has repeatedly been linked to a low risk of cardiovascular disease in several situations. Initially, the mechanisms considered as possible causes of this were based on the effects of this dietary pattern on the so-called traditional risk factors (especially lipids and blood pressure). However, the high relative reduction in the prevalence of cardiovascular morbidity and mortality were not proportional to the limited findings about regulation of those traditional risk factors...
2016: Critical Reviews in Food Science and Nutrition
Valentin S Bruttel, Jörg Wischhusen
Cancer stem cell (CSC) biology and tumor immunology have shaped our understanding of tumorigenesis. However, we still do not fully understand why tumors can be contained but not eliminated by the immune system and whether rare CSCs are required for tumor propagation. Long latency or recurrence periods have been described for most tumors. Conceptually, this requires a subset of malignant cells which is capable of initiating tumors, but is neither eliminated by immune cells nor able to grow straight into overt tumors...
2014: Frontiers in Immunology
Jeffrey Friedman
Historically, adipose tissue was considered to be a passive storage vessel discharging nutrients in times of famine and accumulating fat in times of surfeit. This view changed with the identification of leptin as an adipocyte hormone. Leptin functions as an afferent signal in a negative feedback loop that regulates food intake and metabolism to maintain homeostatic control of adipose tissue mass. Before this, the existence of a system maintaining homeostatic control of energy balance was unclear. The identification of leptin has thus uncovered a new endocrine system that also links changes in nutrition to adaptive responses in most if not all other physiologic systems...
October 2014: Journal of Endocrinology
Sandra Milić, Davorka Lulić, Davor Štimac
Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in the world. Presentation of the disease ranges from simple steatosis to non-alcoholic steatohepatitis (NASH). NAFLD is a hepatic manifestation of metabolic syndrome that includes central abdominal obesity along with other components. Up to 80% of patients with NAFLD are obese, defined as a body mass index (BMI) > 30 kg/m(2). However, the distribution of fat tissue plays a greater role in insulin resistance than the BMI. The large amount of visceral adipose tissue (VAT) in morbidly obese (BMI > 40 kg/m(2)) individuals contributes to a high prevalence of NAFLD...
July 28, 2014: World Journal of Gastroenterology: WJG
Tara C Mueller, Marc A Burmeister, Jeannine Bachmann, Marc E Martignoni
Cachexia is frequently described in patients with pancreatic ductal adenocarcinoma (PDAC) and is associated with reduced survival and quality of life. Unfortunately, the therapeutic options of this multi-factorial and complex syndrome are limited. This is due to the fact that, despite extensive preclinical and clinical research, the underlying pathological mechanisms leading to PDAC-associated cachexia are still not fully understood. Furthermore, there is still a lack of consensus on the definition of cachexia, which complicates the standardization of diagnosis and treatment as well as the analysis of the current literature...
July 28, 2014: World Journal of Gastroenterology: WJG
Michael Rosenbaum, Rudolph L Leibel
The hyperphagia, low sympathetic nervous system tone, and decreased circulating concentrations of bioactive thyroid hormones that are common to states of congenital leptin deficiency and hypoleptinemia following and during weight loss suggest that the major physiological function of leptin is to signal states of negative energy balance and decreased energy stores. In weight-reduced humans, these phenotypes together with pronounced hypometabolism and increased parasympathetic nervous system tone create the optimal circumstance for weight regain...
October 2014: Journal of Endocrinology
2014-07-28 22:20:08
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