Insulin resistance, lipotoxicity, type 2 diabetes and atherosclerosis: the missing links. The Claude Bernard Lecture 2009

Insulin resistance is a hallmark of type 2 diabetes mellitus and is associated with a metabolic and cardiovascular cluster of disorders (dyslipidaemia, hypertension, obesity [especially visceral], glucose intolerance, endothelial dysfunction), each of which is an independent risk factor for cardiovascular disease (CVD). Multiple prospective studies have documented an association between insulin resistance and accelerated CVD in patients with type 2 diabetes, as well as in non-diabetic individuals. The molecular causes of insulin resistance, i.e. impaired insulin signalling through the phosphoinositol-3 kinase pathway with intact signalling through the mitogen-activated protein kinase pathway, are responsible for the impairment in insulin-stimulated glucose metabolism and contribute to the accelerated rate of CVD in type 2 diabetes patients. The current epidemic of diabetes is being driven by the obesity epidemic, which represents a state of tissue fat overload. Accumulation of toxic lipid metabolites (fatty acyl CoA, diacylglycerol, ceramide) in muscle, liver, adipocytes, beta cells and arterial tissues contributes to insulin resistance, beta cell dysfunction and accelerated atherosclerosis, respectively, in type 2 diabetes. Treatment with thiazolidinediones mobilises fat out of tissues, leading to enhanced insulin sensitivity, improved beta cell function and decreased atherogenesis. Insulin resistance and lipotoxicity represent the missing links (beyond the classical cardiovascular risk factors) that help explain the accelerated rate of CVD in type 2 diabetic patients

SIRGAS core network stability

CAPÍTULO DE LIBRO PUBLICADO POR EDITORIAL EXTERNA. PARTE DE LA SERIE DE LIBROS DEL SIMPOSIO DE LA ASOCIACIÓN INTERNACIONAL DE GEODESIA (IAG SYMPOSIA, volumen 143). The main objective of SIRGAS (Sistema de Referencia Geocéntrico para las Américas) is to provide an accurate spatial and time-referenced infrastructure as a basis for Earth System research and to support scientific and practical applications based on high-precise positioning. Following this purpose, significant achievements related to the extension, analysis, and maintenance of this reference frame have been reached during the last years. However, there are still unresolved problems hindering the attainment of the best possible precision. In particular, the assimilation of seismic-related deformations and non-lineal station movements is very difficult and its omission considerably reduces the reliability of SIRGAS as a high precision reference frame. To advance in the solution of these inconveniences, this paper presents the first kinematic model of the SIRGAS reference frame computed after the strong earthquake occurred in the Chilean region of Maule in February 2010. This model is based on the combination of weekly free normal equations covering the time span from April 18, 2010 to June 15, 2013. Computed station positions and velocities refer to the IGb08 reference frame (the IGS realisation of the ITRF2008), epoch 2012.0. The averaged rms precision is ±1,4 mm horizontally and ±2,5 mm vertically for the station positions at the reference epoch, and ±0,8 mm/yr horizontally and ±1,2 mm/yr vertically for the constant velocities. Comparisons with reference frames based on measurements before the earthquake (like ITRF2008 or former SIRGAS solutions) make evident the strong deformation caused by this earthquake and the necessity of updating accordingly the reference frames in the affected region. Enlace al libro: https://link.springer.com/chapter/10.1007/1345_2015_14