title: [Insulin resistance and evolution].
abstract: Both infections and injuries activate the immunity system, leading to a series of metabolic changes which place the organism at a disadvantage and contribute to its elimination, thus facilitating the repair of the injured tissue. The study of the actions of tumour necrosing factor alpha (TNF-alpha) and interleukin-6 (IL-6), classically implicated in inflammatory processes and in fighting infection, has revealed numerous metabolic effects. Some gene polymorphisms of TNF-alpha and IL-6 (associated with a different TNF-alpha or IL-6 transcription rate) and the plasma concentrations of the soluble TNF-alpha receptor are found to be simultaneously associated with resistance to insulin, the proportion of body fat and with the mortality linked with different chronic infections. Therefore, it seems that the immune system is designed to fight infections effectively and to provide certain survival advantages during periods of intermittent fasting so frequent in the past. By inducing a resistance to insulin in the muscles, the energy substrates would thus be reserved for neuronal metabolism. In the presence of an insulin-resistance genotype and a westernization of the environment (carbohydrate-rich diet, an increase in saturated fat, low fibre and sedentary lifestyle), a genotype with a high cytokine response will contribute to a worsening of the resistance to insulin and, finally, to type 2 diabetes mellitus and atherosclerosis. The advantages for our ancestors of a large cytokine response (eradication of the lesion) or moderate resistance to insulin (protection against food shortage) have led in the present day to the development of atherosclerosis now that the characteristics of the environment have changed. It is contended that these changes constitute examples of good adaptation to the environment or poor concordance between our current lifestyle and our genome.
authors.affiliation: Unidad de Diabetes, Endocrinología y Nutrición (UDEN), Hospital Universitario de Girona Dr. Josep Trueta, Girona, España. endocrino@htrueta.scs.es
authors.forename: J M
authors.initials: JM
authors.lastname: Fernández-Real Lemos
mesh_terms: D005075:Biological Evolution; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D015850:Interleukin-6 / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
chemical_list: D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha
vernacular_title: Resistencia a la insulina y evolución.