Coxsackievirus B infections have been associated with clinical manifestation of insulin-dependent diabetes mellitus (IDDM) in several studies, but their initiating role in the slowly progressing beta-cell damage is not known. This is the first prospective study designed to assess the role of coxsackie B and other enterovirus infections in the induction and acceleration of this process. Three separate series were studied: 1) an intrauterine exposure series comprising 96 pregnant mothers whose children subsequently manifested IDDM and 96 control mothers whose children remained nondiabetic; 2) a cohort of 22 initially unaffected siblings of diabetic children who were followed until they developed clinical IDDM (mean observation time, 29 months) and 110 control siblings who remained nondiabetic; 3) a case-control series comprising 90 children with newly diagnosed IDDM and 90 control subjects. Enterovirus infections were identified on the basis of significant increases in serum IgG, IgM, or IgA class antibodies against a panel of enterovirus antigens (capture radioimmunoassay). Enterovirus antibodies were significantly elevated in pregnant mothers whose children subsequently manifested IDDM, particularly in cases in which IDDM appeared at a very young age, before the age of 3 years (P < 0.005). Serologically verified enterovirus infections were almost two times more frequent in siblings who developed clinical IDDM than in siblings who remained nondiabetic (mean, 1.0 vs. 0.6 infections/follow-up year; P < 0.001). This difference was seen both close to the diagnosis of IDDM and several years before diagnosis.(ABSTRACT TRUNCATED AT 250 WORDS)
"Coxsackie virus B (CVB) or LCMV does not cause diabetes RIP-IL6 mice Viral infections, especially with human enterovirus (HEV), have received much attention as potential environmental trigger of human T1D . CVB has been shown to bear both enhancing and protective capacity in the NOD mouse model of T1D, depending on the context. "
[Show abstract][Hide abstract] ABSTRACT: Inflammatory mechanisms play a key role in the pathogenesis of type 1 and type 2 diabetes. IL6, a pleiotropic cytokine with impact on immune and non-immune cell types, has been proposed to be involved in the events causing both forms of diabetes and to play a key role in experimental insulin-dependent diabetes development. The aim of this study was to investigate how beta-cell specific overexpression of IL-6 influences diabetes development. We developed two lines of rat insulin promoter (RIP)-lymphocytic choriomeningitis virus (LCMV) mice that also co-express IL6 in their beta-cells. Expression of the viral nucleoprotein (NP), which has a predominantly intracellular localization, together with IL6 led to hyperglycemia, which was associated with a loss of GLUT-2 expression in the pancreatic beta-cells and infiltration of CD11b+ cells, but not T cells, in the pancreas. In contrast, overexpression of the LCMV glycoprotein (GP), which can localize to the surface, with IL-6 did not lead to spontaneous diabetes, but accelerated virus-induced diabetes by increasing autoantigen-specific CD8+ T cell responses and reducing the regulatory T cell fraction, leading to increased pancreatic infiltration by CD4+ and CD8+ T cells as well as CD11b+ and CD11c+ cells. The production of IL-6 in beta-cells acts prodiabetic, underscoring the potential benefit of targeting IL6 in diabetes.
Journal of Autoimmunity 12/2014; 55(1). DOI:10.1016/j.jaut.2014.02.002 · 8.41 Impact Factor
"These environmental risk factors may initiate autoimmunity or accelerate and precipitate an already ongoing beta cell destruction . Potential risk factors, such as early foetal events , viral infections during pregnancy and postnatally  , and early exposure to cow's milk components and other nutritional factors  may initiate the autoimmune process. Since type 1 diabetes in childhood is associated with estimates of general wealth such as gross domestic product  it has been suggested that lifestyle habits related to wealth might be responsible for the changes in trend. "
[Show abstract][Hide abstract] ABSTRACT: This paper describes the methodology, results and limitations of the 2013 International Diabetes Federation (IDF) Atlas (6th edition) estimates of the worldwide numbers of prevalent cases of type 1 diabetes in children (<15 years). The majority of relevant information in the published literature is in the form of incidence rates derived from registers of newly diagnosed cases. Studies were graded on quality criteria and, if no information was available in the published literature, extrapolation was used to assign a country the rate from an adjacent country with similar characteristics. Prevalence rates were then derived from these incidence rates and applied to United Nations 2012 Revision population estimates for 2013 for each country to obtain estimates of the number of prevalent cases. Data availability was highest for the countries in Europe (76%) and lowest for the countries in sub-Saharan Africa (8%). The prevalence estimates indicate that there are almost 500,000 children aged under 15 years with type 1 diabetes worldwide, the largest numbers being in Europe (129,000) and North America (108,700). Countries with the highest estimated numbers of new cases annually were the United States (13,000), India (10,900) and Brazil (5000). Compared with the prevalence estimates made in previous editions of the IDF Diabetes Atlas, the numbers have increased in most of the IDF Regions, often reflecting the incidence rate increases that have been well-documented in many countries. Monogenic diabetes is increasingly being recognised among those with clinical features of type 1 or type 2 diabetes as genetic studies become available, but population-based data on incidence and prevalence show wide variation due to lack of standardisation in the studies. Similarly, studies on type 2 diabetes in childhood suggest increased incidence and prevalence in many countries, especially in Indigenous peoples and ethnic minorities, but detailed population-based studies remain limited.
Diabetes research and clinical practice 12/2013; 103(2). DOI:10.1016/j.diabres.2013.11.005 · 2.54 Impact Factor
"Enterovirus infections have been shown to be a risk factor for several autoimmune diseases including insulin dependent diabetes mellitus (IDDM) (Dahlquist et al., 1995; Grist et al., 1978; Hiltunen et al., 1997; Hyoty et al., 1995). Multiple epidemiological studies in humans have established that children that manifest IDDM have had more exposures to enteroviruses than healthy subjects (Andreoletti et al., 1998; Clements et al., 1995; D'Alessio, 1992). "
[Show abstract][Hide abstract] ABSTRACT: A virus-virus interaction is a measurable difference in the course of infection of one virus as a result of a concurrent or prior infection by a different species or strain of virus. Many such interactions have been discovered by chance, yet they have rarely been studied systematically. Increasing evidence suggests that virus-virus interactions are common and may be critical to understanding viral pathogenesis in natural hosts. In this review we propose a system for classifying virus-virus interactions by organizing them into three main categories: (1) direct interactions of viral genes or gene products, (2) indirect interactions that result from alterations in the host environment, and (3) immunological interactions. We have so far identified 15 subtypes of interaction and assigned each to one of these categories. It is anticipated that this framework will provide for a more systematic approach to investigating virus-virus interactions, both at the cellular and organismal levels.
Virus Research 04/2010; 149(1):1-9. DOI:10.1016/j.virusres.2010.01.002 · 2.32 Impact Factor
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