The association between enteroviruses and type 1 diabetes (original) (raw)
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Enteroviruses and type 1 diabetes: towards a better understanding of the relationship
Reviews in Medical Virology, 2010
Environmental factors, especially viruses, are involved in the initiation or the acceleration of type 1 diabetes (T1D) pathogenesis. Epidemiological data strongly suggest that enteroviruses, such as coxsackievirus B4 (CV-B4), can be associated with T1D. It has been demonstrated that enterovirus infections were significantly more prevalent in at risk individuals, such as siblings of diabetic patients, when they developed anti-β-cell autoantibodies or T1D, and in recently diagnosed diabetic patients, compared with control subjects. The isolation of CV-B4 from the pancreas of diabetic patients strengthened the hypothesis of a relationship between the virus and the disease. Studies performed in vitro and in vivo in animal models helped to discover mechanisms of the infection of pancreas and other tissues, potentially able to play a role in the pathogenesis of T1D. Interestingly, it cannot be excluded that enteroviruses behave as half-devil half-angel since experimental studies suggest that, in certain conditions, these agents would be able to protect individuals against the disease. All of the plausible mechanisms by which enterovirus may be related to T1D will be reviewed here. Copyright © 2010 John Wiley & Sons, Ltd.
Enteroviruses and type 1 diabetes mellitus
Biomedicine & Pharmacotherapy, 2003
Despite decades of research, the etiology of type 1 diabetes mellitus (DM) is unknown. Several risk factors have been associated with type 1 DM, including viral infections, genetic predisposition, nutritional factors, and chemicals. Several investigators hypothesize that the etiologies of type 1 DM result from a complex interaction of genetic and environmental factors. In this paper we review the epidemiologic data linking enteroviruses to type 1 DM and discuss potential mechanisms of pathogenesis.
Enteroviruses and type 1 diabetes
BMJ, 2011
Background Human enteroviruses, which are transmitted via a faecaloral route, have long been associated with type 1 diabetes onset. Increased hygiene in the 20th century may now be responsible for a decreased chance of enterovirus exposure from an early age onward. Infections with enteroviruses may also be more likely to occur at a later age; the recurrent poliomyelitis epidemics in the 20th century were linked to increased hygiene, consistent with this hypothesis. The association of fewer enterovirus exposures and increased diabetes rates may seem at first non-intuitive but may be explained using a combination of human observations and data from experimental coxsackie B virus infections in nonobese diabetic mice.
Clinical & Experimental Immunology, 2012
The hypothesis that under some circumstances enteroviral infections can lead to type 1 diabetes (T1D) was proposed several decades ago, based initially on evidence from animal studies and sero-epidemiology. Subsequently, enterovirus RNA has been detected more frequently in serum of patients than in control subjects, but such studies are susceptible to selection bias and reverse causality. Here, we review critically recent evidence from human studies, focusing on longitudinal studies with potential to demonstrate temporal association. Among seven longitudinal birth cohort studies, the evidence that enterovirus infections predict islet autoimmunity is quite inconsistent in our interpretation, due partially, perhaps, to heterogeneity in study design and a limited number of subjects studied. An association between enterovirus and rapid progression from autoimmunity to T1D was reported by one longitudinal study, but although consistent with evidence from animal models, this novel observation awaits replication. It is possible that a potential association with initiation and/or progression of islet autoimmunity can be ascribed to a subgroup of the many enterovirus serotypes, but this has still not been investigated properly. There is a need for larger studies with frequent sample intervals and collection of specimens of sufficient quality and quantity for detailed characterization of enterovirus. More research into the molecular epidemiology of enteroviruses and enterovirus immunity in human populations is also warranted. Ultimately, this knowledge may be used to devise strategies to reduce the risk of T1D in humans.
Type 1 diabetes mellitus and enterovirus linkage: search for associated etiopathology
The Egyptian Journal of Internal Medicine, 2017
Type 1 diabetes (T1D) is believed to have complex interplay between several enteroviruses (EVs) and host immune system disturbance induced or accelerated by viral pathogenesis. In the past two decades, there has been global upsurge in the incidence of childhood T1D, especially in those less than 5 years. Because of the ubiquity and persistence of EVs in human bowel and their tropism to pancreatic cells, they tend to express certain viral proteins that have propensity for genetic manipulation and activation of autoimmunity that could be potentially linked to T1D. In view of these, we present this review of existing literature in order to analyze the epidemiology and possible association between EV infections, host immune dysfunction, and development of autoimmunity or T1D with the view to encourage the investigation of EV infections and associated virus-induced islet cells autoimmunity and immunopathy in genetically predisposed children.
Virus Infections and Type 1 Diabetes Risk
Current Diabetes Reports, 2010
Common intestinal infections caused by human enteroviruses (HEVs) are considered major environmental factors predisposing to type 1 diabetes (T1D). In spite of the active research of the field, the HEV-induced pathogenetic processes are poorly understood. Recently, after the first documented report on HEV infections in the pancreatic islets of deceased T1D patients, several groups became interested in the issue and studied valuable human material, the autopsy pancreases of diabetic and/or autoantibodypositive patients for HEV infections. In this review, the data on HEV infections in human pancreatic islets are discussed with special reference to the methods used. Likewise, mechanisms that could increase viral access to the pancreas are reviewed and discussed.
Association between enterovirus infection and type 1 diabetes: new findings from Cuban studies
Biotecnología Aplicada, 2009
Enteroviruses have been examined for their possible role in the etiology of type 1 diabetes mellitus (T1DM) for nearly 40 years; however, the evidence remains inconclusive so far. This article provides new findings from Cuban studies suggesting the involvement of enteroviruses, either with the clinical T1DM onset or the pre-clinical stages of the β-cell autoimmunity in populations with low incidence of diabetes and high enteroviral circulation. Potential mechanisms of pathogenesis such as direct β-cell lysis and molecular mimicry are also discussed.
Enteroviruses and causality of type 1 diabetes: how close are we?
Pediatric Diabetes, 2011
General concepts Organ-specific autoimmunity frequently affects the endocrine system, including pancreatic islets. Type 1 diabetes mellitus (T1D) derives from the autoimmune destruction of insulin-secreting β-cells that is triggered by environmental factors (1, 2). Genetic predisposition accounts for 36-50% of disease susceptibility as demonstrated in monozygotic twin studies (3-5). Approximately 90% of new cases lack a family history of T1D indicating a large contribution of exogenous factors to pathogenesis. A variety of associations with viral infections have been reported for human diabetes including rubella, mumps, and cytomegalovirus. However, among investigated agents, human enteroviruses (HEVs) appear to play a prominent role (1). HEVs are extremely common RNA viruses that spread mainly through the fecal-oral route. Overall, these agents cause millions of new infections per year worldwide (6). The enterovirus genus comprises over 100 antigenically different virus types (7). The single-stranded 7.5 kb RNA enteroviral genome encodes for capsid proteins and other proteins involved in viral infectivity and replication. Capsid proteins are highly variable among HEV species and types. Neutralizing antibodies raised against capsid proteins are highly type specific but may also cross-react with related types (8). So far, there are no means for preventing T1D. Sets of well-defined autoantibodies have a strong predictive value (9, 10), but the costbenefit ratio of periodical determinations appears not to justify screening programs at the population level. At the diagnosis of T1D, a small fraction