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\rgroup, due to an autoimmune process characterized by a selective destruction of insulin\rproducing pancreatic β-cells progressing over different stages [1]. T1DM develops in ge‐\rnetically susceptible subjects by activation of so far uncharacterized environmental fac‐\rtors that trigger an inflammatory process with infiltration of pancreatic islets and\rsubsequent loss of β-cells. Despite the growing incidence of T1DM, the causative mecha‐\rnisms are not completely defined up to now, and the identification of factors triggering\rthe immune process represents a challenge for clinical immunologists, with practical, di‐\ragnostic and therapeutic implications [2,3]. The clinical onset of T1DM is preceded by an\rasymptomatic period characterized on pathology grounds by insulitis, i.e. an infiltration\rof the pancreatic islet of Langerhans by CD4+, CD8+ T lymphocytes (both Th1 and Th2\rsubsets), B lymphocytes, macrophages and dendritic cells. T lymphocytes can differenti‐\rate into 2 major subsets: Th1, producing IL-2 and IFN-γ, and Th2, secreting mainly IL-4.\rAll these cells produce cytokines which can be directly cytotoxic to β-cells or play an in‐\rdirect role on β-cell destruction influencing some cells of the immune system, then re‐\rsulting in either acceleration or arrest of the immune attack [4]. Worldwide T1DM\rincidence has grown more than two to three fold during the last decades, particularly in\rFinland, where T1DM incidence has increased from 12 to 63 cases per 100,00 [5]. A rais‐\ring incidence has also been reported in Italy, where Sardinia Region shows an incidence\rrate similar to Finland, therefore is called “Hot Spot”