Comparative incidence of Type I diabetes in children aged under 15 years from South Asian and White or Other ethnic backgrounds in Leicestershire, UK, 1989 to 1998

Raymond, Neil T.; Jones, Jaes; Swift, Peter; Davies, Melanie J.; Lawrence, Ian; McNally, PG; Burden, Mary; Gregory, Robert; Botha, J. L.; Burden, A C

doi:10.1007/pl00002951

Cited by 53 publications

(28 citation statements)

References 11 publications

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“…Similar as other complex diseases such SLE, genetic factors are implicated in the modulation of disease susceptibility [36e38]. However, the dramatic increase of T1D incidence worldwide in genetically stable populations, the significant international discrepancies for disease incidence particularly for the incomplete concordance of disease susceptibility in monozygotic twins, and reports of increased incidence when individuals migrate from low-incidence to highincidence areas [38,39] cannot be accounted by the genetic factors alone, demonstrating that other non-genetic components such as environmental trigger related epigenetic factors, also play a major role in determining disease risk [40e45]. Indeed, the environmental triggers often used for the explanation of differences of disease frequency across many populations and the rapid rise in disease frequency in the last few decades [34].…”

Section: Discussionmentioning

confidence: 99%

DNA methylation impairs TLR9 induced Foxp3 expression by attenuating IRF-7 binding activity in fulminant type 1 diabetes

Wang

Zheng

Hou

et al. 2013

Journal of Autoimmunity

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Section: Discussionmentioning

confidence: 99%

DNA methylation impairs TLR9 induced Foxp3 expression by attenuating IRF-7 binding activity in fulminant type 1 diabetes

Wang

Zheng

Hou

et al. 2013

Journal of Autoimmunity

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“…Reports of epidemic outbreaks of T1D further implicate environmental factors in the etiology of T1D [79][80][81]. Third, migration studies show that the incidence of diabetes in offspring of individuals who had moved from a low-incidence to a high-incidence country is increased compared with the incidence recorded in the country of origin [82,83]. Fourth, viruses [84,85] and virus-specific antibodies [86][87][88][89] can be detected in newly diagnosed patients with T1D.…”

Section: Viruses and T1dmentioning

confidence: 93%

The Role of Toll-Like Receptor Pathways in the Mechanism of Type 1 Diabetes

Lien¹,

Zipris²

2009

CMM

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Toll-like receptors (TLRs) and the innate immune system play a key role in sensing and eliminating microbial infections. Interactions between TLRs and their ligands expressed by microbial pathogens induce a cascade of intracellular signaling events, culminating in the upregulation of proinflammatory pathways. Over the past two decades, numerous studies have established the role of the acquired immune system in the mechanism triggering type 1 diabetes (T1D). The recent discovery of TLRs has led to the recognition that the innate immune system may act, under some circumstances, as a double-edged sword. In addition to its beneficial role in host defense, it may lead to upregulation of proinflammatory autoimmune responses, islet destruction and diabetes. Indeed, recent observations are consistent with the hypothesis that altered innate functions exist in patients with T1D and could be part of the mechanism leading to disease onset, but the underlying mechanisms and the relevance of these alterations to early events triggering disease remain to be identified. Data obtained from mouse and rat models of T1D implicated TLR pathways in both disease induction and prevention. In both the NOD mouse and diabetes-prone BB (BBDP) rat, TLR upregulation can suppress disease. In the BioBreeding Diabetes Resistant (BBDR) rat, however, diabetes induced by virus infection involves the upregulation of TLR9 pathways, and generic TLR upregulation synergizes with virus infection on diabetes induction. Studies performed in mouse models of T1D with spontaneous or induced T1D implicate TLR1, TLR2, TLR3, and TLR7 in disease mechanisms. The finding that TLR pathways are involved in mediating islet inflammation holds great promise for identifying new molecules that could potentially be targeted to specifically suppress the autoimmune process in individuals at high risk for disease development. The potential link between TLR upregulation and autoimmunity emphasizes the need for caution in using new therapies involving TLR agonists as vaccine adjuvants.

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“…First, different ethnic groups' secondgeneration migrants, exhibit incidence rates nearing those of the host European population rather than those in their native countries [54]. Thus, disclosing the 'wearing-off' of genetic differences over generations, plausibly due to the environmental modulating aspect of geographical residence.…”

Section: Type-1 Diabetes Mellitus (T1d)mentioning

confidence: 99%