Environmental factors in the etiology of type 1 diabetes

Abstract

Type 1 diabetes is considered to be an autoimmune disease in which T lymphocytes infiltrate the islets of pancreas and destroy the insulin producing beta cell population. Besides antigen specificity, the quality of immune reactivity against islet cell antigen(s) is an important determinant of the beta cell destruction. Much evidence indicates that the function of the gut immune system is central in the pathogenesis, as the regulation of the gut immune system may be aberrant in type 1 diabetes. The role of virus infections in the pathogenesis of type 1 diabetes has been supported by substantial new evidence suggesting that one virus group, enteroviruses, may trigger the beta-cell damaging process in a considerable proportion of patients. The latest evidence comes from studies indicating the presence of viral genome in diabetic patients and from prospective studies confirming epidemiological risk effect. If this association holds still true in ongoing large-scale studies, intervention trials should be considered to confirm causality. Of the dietary putative etiological factors, cow's milk proteins have received the main attention. Many studies indicate an association between early exposure to dietary cow's milk proteins and an increased risk of type 1 diabetes. The question will be answered by a large scale, prospective, randomized, international intervention trial. Another dietary factor in need of more studies is the deficiency of vitamin D. Among toxins, N-nitroso compounds are the main candidates. An interaction of genetic and environmental factors is important in evaluating the possible role of a certain environmental factor in the etiology of type 1 diabetes.

Dietary habits and nutritional biomarkers in Italian type 1 diabetes families: evidence of unhealthy diet and combined-vitamin-deficient intakes

“…Based on our correlation coefficients, present data are within the range observed previously (Kroke et al, 1999), indicating (Harbige, 1996). The deficiency of vitamin D, whose biologically active form is a potent modulator of the immune system, has been suggested among the dietary putative etiological factors in the pathogenesis of T1DM (Akerblom et al, 2002;Zella & DeLuca, 2003). However, vitamin D is rather a hormone.…”

“…It is thought that environmental factors (both protective and inductive) do determine the penetrance of T1DM susceptibility genes (Akerblom et al, 2002). However, whether viral infections, dietary habits, lifestyle, and socioeconomic status may be important in the development of T1DM is debatable (Lipton et al, 1999;Littorin et al, 2001).…”

The effect of birth order and parental age on the risk of type 1 and 2 diabetes among young adults

“…This process, which occurs in genetically susceptible individuals, is triggered by environmental factors [2]. The underlying, mediating environmental factors are not known, although several factors have been proposed, including viral infections [3], dietary factors such as cow's milk protein and gluten [4], environmental toxins [5], increased weight gain in infancy [6] and antenatal factors such as maternal age [7] and birth order [8].…”

Conserved extended haplotypes discriminate HLA-DR3-homozygous Basque patients with type 1 diabetes mellitus and celiac disease

“…3,4 Additionally, it has been proposed that environmental triggering factors may also be implicated in the expression of clinical disease and thus influence its frequency. 5 But, from the genetic viewpoint, there have been a number of observations accumulated during the last few decades that taken together, can help to clarify this issue. First of all, it has been known for a long time that linkage disequilibrium between genes in the MHC region is very strong, reflecting the high frequency of certain haplotypes that are highly conserved, and termed 'conserved extended haplotypes' (CEHs) or 'ancestral haplotypes' (AHs).…”