Influence of environment on insulin sensitivity

Genetic and environmental factors influence insulin sensitivity (IS) during one's lifetime. Actually, uterine environment may affect IS at birth and later in life. In particular, various exogenous toxic substances, coupled to a genetic predisposition, may remarkably influence the regulation of the hypothalamus–hypophysis–adrenal gland axis, and the production or the activity of insulin, cerebral incretins, pro-inflammatory cytokines, and placental hormones. Owing to this reaction against environmental injuries, fetal growth and endocrine system development may be impaired, leading to low or large birth weight, or prematurity. Reduced growth in early life has been related to insulin resistance, which can be silent for years and evident in predisposed adults. The incidence of type 2 diabetes mellitus and obesity associated with sedentary lifestyle patterns and inadequate dieting behaviors in children and adolescents has rapidly increased during the last decade.Recent evidences suggest that the Pro12Ala polymorphism of the peroxisome proliferator-activated receptor- (PPAR-) gene and the angiotensin converting enzyme (ACE) I/D gene polymorphism combined with environmental factors, such as phthalates interfering with the post receptorial action of insulin, alter insulin-sensible tissues. Therefore, IS, deriving from a complex interaction between genotype and environment, may change during life and depends on previous metabolic control, which is a sort of metabolicmemory. The goal for the future is preventing the complications associated with impaired IS through the control of exogenous factors and the use of drugs selectively effective on its pathogenesis.