Environmental Factors and Type 1 Diabetes Mellitus in Pediatric Age Group

Abstract

Type 1 diabetes mellitus (T1DM) is the most common endocrinopathy in pediatric age group, due to an autoimmune process characterized by a selective destruction of insulin producing pancreatic β-cells progressing over different stages [1]. T1DM develops in ge‐ netically susceptible subjects by activation of so far uncharacterized environmental fac‐ tors that trigger an inflammatory process with infiltration of pancreatic islets and subsequent loss of β-cells. Despite the growing incidence of T1DM, the causative mecha‐ nisms are not completely defined up to now, and the identification of factors triggering the immune process represents a challenge for clinical immunologists, with practical, di‐ agnostic and therapeutic implications [2,3]. The clinical onset of T1DM is preceded by an asymptomatic period characterized on pathology grounds by insulitis, i.e. an infiltration of the pancreatic islet of Langerhans by CD4+, CD8+ T lymphocytes (both Th1 and Th2 subsets), B lymphocytes, macrophages and dendritic cells. T lymphocytes can differenti‐ ate into 2 major subsets: Th1, producing IL-2 and IFN-γ, and Th2, secreting mainly IL-4. All these cells produce cytokines which can be directly cytotoxic to β-cells or play an in‐ direct role on β-cell destruction influencing some cells of the immune system, then re‐ sulting in either acceleration or arrest of the immune attack [4]. Worldwide T1DM incidence has grown more than two to three fold during the last decades, particularly in Finland, where T1DM incidence has increased from 12 to 63 cases per 100,00 [5]. A rais‐ ing incidence has also been reported in Italy, where Sardinia Region shows an incidence rate similar to Finland, therefore is called “Hot Spot” [6,7]. Interestingly, this rise of inci‐ dence was not followed by a parallel increased frequency of the major risk genes [8]. T1DM can be defined as a polygenic disease, and the genes mainly involved include