Type 1 Diabetes Is Associated With Enterovirus Infection in Gut Mucosa

Oikarinen, Maarit; Tauriainen, Sisko; Oikarinen, Sami; Honkanen, Teemu; Collin, Pekka; Rantala, Immo; Mäki, Markku; Kaukinen, Katri; Hyöty, Heikki

doi:10.2337/db11-1157

Cited by 137 publications

(127 citation statements)

References 35 publications

(35 reference statements)

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“…A recent study on intrafamilial spread of EV infections reported that 20% of siblings of diabetic probands acquired type 1 diabetes with a latency of 3-25 months [19]. Evidence for this association is supported by detection of EVs in the blood [13,14,17,22], pancreas [15,[23][24][25][26] and gut mucosa [27] of patients with type 1 diabetes. Histopathologic evidence indicates that expression of enteroviral capsid protein VP1 in islet cells of patients with type 1 diabetes is related to induction of protein kinase R and downregulation of Mcl-1 [23,24].…”

Section: Introductionmentioning

confidence: 97%

Enterovirus infection is associated with an increased risk of childhood type 1 diabetes in Taiwan: a nationwide population-based cohort study

et al. 2014

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Aims/hypothesis This study compared the incidence rate of type 1 diabetes in children diagnosed with enterovirus (EV) infections with that in age-and sex-matched children without EV infection in a population-based cohort. In addition, we examined whether the direction or magnitude of the association between EV infection and type 1 diabetes differs according to atopic disease status in children.Methods We used insurance claims data from Taiwan's National Health Insurance Research Database to derive type 1 diabetes incidence in children aged up to 18 years with or without a diagnosis of EV infection during 2000-2008. Incidence rate ratios and HRs of type 1 diabetes for EV infection were estimated by Poisson regression and Cox's proportional hazard regression model. Results Overall incidence of type 1 diabetes was higher in the EV than in the non-EV infection cohort (5.73 vs 3.89 per 100,000 person-years; incidence rate ratio 1.48 [95% CI 1.19, 1.83]), with an adjusted HR of 1.48 (95% CI 1.19, 1.83). Among children without EV, incidence increased with age at diagnosis of EV infection, except in those aged 5-10 years. The HRs of type 1 diabetes in children with allergic rhinitis, bronchial asthma or either one of these atopic diseases showed more variation than in those children without these diseases. Conclusions/interpretation This nationwide retrospective cohort study found a positive correlation between type 1 diabetes and EV infection. The results suggest that a preventive strategy, such as an effective vaccine against EV infection, may lessen the incidence of type 1 diabetes in Taiwan.

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Section: Introductionmentioning

confidence: 97%

Enterovirus infection is associated with an increased risk of childhood type 1 diabetes in Taiwan: a nationwide population-based cohort study

et al. 2014

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“…Epidemiological studies have suggested that infections with enteroviruses, in particular those of the coxsackie B virus (CVB) serotypes, may be linked to islet autoimmunity and development of type 1 diabetes [1][2][3][4][5]. Other observations suggesting that infections with these viruses have a causative role in diabetes development come from studies that found enteroviruses more frequently in pancreases [6][7][8] and, in some studies, also gut biopsies [9][10][11], from patients with type 1 diabetes compared with healthy controls. Some enteroviruses, including the CVBs, are pancreatropic and can infect human beta cells in vitro, often with a detrimental outcome (e.g.…”

Section: Introductionmentioning

confidence: 99%

Previous maternal infection protects offspring from enterovirus infection and prevents experimental diabetes development in mice

et al. 2013

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Aims/hypothesis Enterovirus (e.g. Coxsackie B virus serotypes [CVBs]) infections may be associated with development of type 1 diabetes. Studies conducted in several European countries have, however, shown an inverse correlation between the incidence of type 1 diabetes and the prevalence of enterovirus infections. These findings could in part be explained by an extension of the poliovirus hypothesis, suggesting that the absence of maternally transferred antibodies protecting offspring from early infection increases the risk for diabetes development. Experimental evidence supporting this hypothesis in type 1 diabetes is, however, lacking. As maternally transferred protection from infection is a crucial component of the extended poliovirus hypothesis, we here tested the hypothesis that previously infected females transfer protection against infection and diabetes to offspring.Methods The induction of CVB-specific maternal antibodies and transfer of protection from virus infection, replication and development of virus-induced diabetes to offspring was assessed using NOD and Socs1-transgenic NOD mice. Results Infected mice produced neutralising antibodies to CVB. Offspring from infected females were positive for neutralising antibodies and were strongly protected from both infection and experimental diabetes. Conclusions/interpretation Our study shows that maternally transferred antibodies protect offspring from enterovirus infection and virus-induced diabetes. This suggests that the absence of maternally provided protection increases the risk for severe outcomes after an enterovirus infection in offspring. Moreover, our findings may have implications for the design of prospective studies aimed at investigating the possible role of enterovirus infections in the aetiology of human type 1 diabetes.

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“…EV infections are associated with the initiation of β cell destruction [10]. Evidence for this association has been supported by the detection of EVs in the blood [15], pancreas and islets [12], and gut mucosa [16] of patients with T1D. Our study indicated a prevalence of EV infection in the blood of T1D children is 26.2%.…”

Section: Discussionmentioning

confidence: 57%

Association between Antioxidant Enzyme Activities and <b><i>Enterovirus</i></b>-Infected Type 1 Diabetic Children

et al. 2018

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Significance of the Study• This study revealed that children with type 1 diabetes (T1D) infected with Enterovirus (EV) show a marked decrease in glutathione peroxidase, superoxide dismutase, and catalase activity, and a noticeable elevation in C-reactive protein compared to noninfected diabetic children. Our results confirm an association of EV infection with the inflammation and β cell damage seen in T1D, and suggest that antioxidant supplementation can play a protective role. DOI: 10.1159/000486718Keywords Type 1 diabetes · Enterovirus · Antioxidant enzymes · Diabetic children Abstract Objective: To examine the effect of infection with Enterovirus (EV) in children with type 1 diabetes (T1D) on the activities of serum antioxidant enzymes in diabetic and nondiabetic controls. Subjects and Methods: Three hundred and eighty-two diabetic and 100 nondiabetic children were tested for EV RNA using reverse transcriptase (RT)-PCR. The activities of serum superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) were also estimated in diabetic patients infected with EV (T1D-EV+), those not infected with EV (T1D-EV-), and in nondiabetic controls. Results: The frequency of EV was higher in diabetic children (100/382; 26.2%) than in healthy controls (0/100). Levels of fasting blood glucose (FBG), glycosylated hemoglobin (HbA 1c ) and C-reactive protein (CRP) were significantly higher but C-peptide was significantly lower in diabetic children than in controls. CRP levels were higher in the T1D-EV+ group than in the T1D-EV-group, and higher in all diabetic children than in nondiabetic controls. The activities of the antioxidant enzymes GPx, SOD, and CAT decreased significantly in diabetic children compared to in controls. Moreover, the activities of the enzymes tested were significantly reduced in the T1D-EV+ group compared to in the T1D-EVgroup. Conclusion: Our data indicate that EV infection correlated with a decrease in the activity of antioxidant enzymes in the T1D-EV+ group compared to in the T1D-EVgroup; this may contribute to β cell damage and increased inflammation.

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Type 1 Diabetes Is Associated With Enterovirus Infection in Gut Mucosa

Cited by 137 publications

References 35 publications

Enterovirus infection is associated with an increased risk of childhood type 1 diabetes in Taiwan: a nationwide population-based cohort study

Enterovirus infection is associated with an increased risk of childhood type 1 diabetes in Taiwan: a nationwide population-based cohort study

Previous maternal infection protects offspring from enterovirus infection and prevents experimental diabetes development in mice

Association between Antioxidant Enzyme Activities and <b><i>Enterovirus</i></b>-Infected Type 1 Diabetic Children

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