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Abstract: 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 metabolic memory. 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. [Copyright &y& Elsevier]

Abstract: As childhood-onset type-1 diabetes increases in incidence worldwide, its onset is shifting towards younger ages. Thus, the relative proportion of adolescents and young adults with a very long duration of type-1 diabetes may gradually increase. Early-onset diabetes may increase the lifetime risk for diabetic vascular complications, although there are other factors – such as long-term glycaemic control, puberty, and familial and genetic factors – which contribute to the overall risk. The focus of this minireview is the natural history of microalbuminuria in children and adolescents with type-1 diabetes. Late complications in type-1 diabetes are almost always subclinical during childhood and adolescence, and advanced vascular complications are rarely seen. Microalbuminuria may appear as the first sign of microvascular complications, and although it may be intermittent or transient in most young patients, screening is important in clinical diabetes care since microalbuminuria is also a strong risk marker for early cardiovascular morbidity. [Copyright &y& Elsevier]