Environmental Factors Associated With Childhood-Onset Type 1 Diabetes Mellitus

D’Angeli, Marisa A; Merzon, Eugene; Valbuena, Luisa F.; Tirschwell, David; Paris, Carolyn A.; Mueller, Beth A.

doi:10.1001/archpediatrics.2010.115

Cited by 69 publications

(83 citation statements)

References 48 publications

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“…In accordance to hygiene hypothesis, several studies report the lowest incidence of T1DM in areas with poorest hygiene condition [50,31]. These data are supported by the experiments in non-obese diabetic (NOD) mice (mice that spontaneously develop a condition resembling T1DM) and in BB rats, in which caesarean delivery and isolated living conditions increased the incidence of diabetes from 40% to 80%.…”

Section: Hygiene Hypothesismentioning

confidence: 64%

“…It is been observed an increased incidence of disease in children born to older mother [25,34,38,39]. These data are confirmed by a population-based case-control study in [31]. Another widely discussed topic is tobacco exposure, as influencing immune system, and represents a risk factors for T1DM.…”

Section: Social Factorsmentioning

confidence: 69%

“…It is also been reported a correlation between a high intake of nitrosamines, nitrites and nitrates and T1DM [25,28] [29]. Several studies support this link [30], while others did not find any association with T1DM [31].…”

Section: In Utero and Postnatal Dietary Exposurementioning

confidence: 98%

“…In humans, several studies reported a significant inverse correlation between the incidence of T1DM and certain socioeconomic index (unemployment, lack of a car, crowded housing conditions, and living in rental housing rather than purchased property) [50,51]. In the people living in Washington state from 1987 to 2005, D'Angeli and colleagues found a negative association between T1DM and some indicators of lower economic status or care access, such as an unmarried mother (OR 0.79%; 95% CI 0.69-0.91), inadequate prenatal care (OR 0.53%; 95% CI 0.40-0.71), or Medical insurance (OR, 0.67; 95% CI 0.58-0.77) [31]. Young children with older brothers and sisters and sharing the bedroom, as well as those who attended a day-care centre during the first six months of life showed a lower incidence of T1DM later in life than children who did not attend a day-care centre and who had no older siblings [52].…”

Section: Hygiene Hypothesismentioning

confidence: 99%

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Environmental Factors and Type 1 Diabetes Mellitus in Pediatric Age Group

d’Annunzio¹,

Accogli²,

Tallone³

et al. 2013

Genes and Autoimmunity - Intracellular Signaling and Microbiome Contribution

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Section: Hygiene Hypothesismentioning

confidence: 64%

Section: Social Factorsmentioning

confidence: 69%

Section: In Utero and Postnatal Dietary Exposurementioning

confidence: 98%

Section: Hygiene Hypothesismentioning

confidence: 99%

See 2 more Smart Citations

Environmental Factors and Type 1 Diabetes Mellitus in Pediatric Age Group

d’Annunzio¹,

Accogli²,

Tallone³

et al. 2013

Genes and Autoimmunity - Intracellular Signaling and Microbiome Contribution

View full text Add to dashboard Cite

“…Genetic predisposition and environmental factors are involved in T1D development, with the incidence increasing dramatically over the last twenty years, especially in younger children (Harjutsalo et al, 2008), highlighting the influence of environmental factors in disease progression. Some environmental factors proposed to influence T1D development include lack of Vitamin D from decreased sun exposure (Takiishi et al, 2010), reduced exposure to microbes leading to dysregulation of immune responses (D'Angeli et al, 2010), viral infections such as Coxsackievirus-B (Hober et al, 2012) and infant nutrition (Knip et al, 2010). In terms of genetic susceptibility, certain loci within the human MHC, known as the human leukocyte antigen (HLA), region confer the greatest genetic risk for T1D including DRB1 0401 and DQA1 0301 alleles (Erlich et al, 2008).…”

Section: Type 1 Diabetesmentioning

confidence: 99%

Transgenic expression of proinsulin to inactivate insulin-specific CD8+ T-cell responses in autoimmune diabetes

Reeves¹

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Type 1 diabetes (T1D) results from autoimmune destruction of pancreatic β cells. The current treatment for the fatal insulin-deficiency in T1D is injection of exogenous insulin. Despite the dramatic increase in survival from the use of exogenous insulin, complications develop from imperfect glycemic control and exogenous insulin does not rectify the underlying cause of disease, the diabetogenic autoimmune response. Hence, there is a need for an effective therapy that impedes the progress of the pathogenic autoimmune response. β cell-reactive CD8 + In the NOD mouse model of T1D, insulin is the primary β-cell antigen that elicits disease. As such, I have investigated T-cell tolerance to insulin in an adoptive transfer setting in which TCR transgenic (G9) CD8 + T cells specific for insulin B15-23 (InsB15-23) were transferred to transgenic mice over-expressing proinsulin in APC. Subsequently, I examined the effect of introducing transgenic proinsulin expression on diabetes development in wild type NOD mice.When transferred to mice transgenically expressing proinsulin, naïve G9 T cells proliferated extensively prior to undergoing rapid deletion. In proinsulin transgenic recipients, the remaining population of G9 T cells displayed reduced T-cell receptor (TCR) expression and bound less InsB15-23-loaded, H2-K d -tetramer compared to G9 T cells that had been transferred to non-transgenic NOD recipients. Interestingly, TCR down-regulation represented that which occurred for OVA-specific CD8 + T cells transferred to mice expressing OVA in APC in a non-autoimmune prone strain.Importantly, naïve G9 T cells did not expand or produce the important effector cytokine, interferon (IFN)-γ, in response to InsB15-23 immunisation after transfer to proinsulin transgenic mice. These data confirm naïve G9 T cells undergo rapid deletion and inactivation after transfer to mice transgenically-expressing proinsulin, despite genetic tolerance defects in NOD mice. Memory CD8 + T cells (Tmem) perpetuate β-cell autoimmunity and pose a distinct barrier to immunotherapy. It was pertinent to determine whether inactivation of insulin-specific CD8 + Tmem also occurs after transfer to mice expressing proinsulin in APC. To test inactivation of insulin-specific CD8 + Tmem, G9 Tmem were generated using an in vitro culture method. Cultured G9 Tmem were validated by assessing phenotypic markers and cytokine production. Similarly to naïve G9 T cells, G9 Tmem proliferated extensively and most G9 Tmem were rapidly deleted after transfer to mice overexpressing proinsulin in APC. The remaining, non-deleted population of G9 Tmem was infrequent ii and exhibited reduced TCR expression. Furthermore, G9 Tmem did not expand or produce IFN-γ in response to InsB15-23 immunisation, consistent with functional inactivation. These results demonstrate transgenic proinsulin expression in APC overcomes genetic defects in NOD mice to induce tolerance in insulin-specific CD8 + Tmem.From the data described above, transgenic proinsulin expression is tolerogenic for in...

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