The association between prior infection with five serotypes of Coxsackievirus B and incident type 2 diabetes mellitus in the EPIC-Norfolk study

Abstract

Aims/hypothesis Infections with Coxsackieviruses have been linked to beta cell dysfunction. Given the importance of beta cell dysfunction in the aetiology of type 2 diabetes, we hypothesised that prior infection with Coxsackieviruses B would increase the risk of type 2 diabetes. The aims of the study were to estimate cross-sectional associations between potential predictors of previous infection and seropositivity for Coxsackievirus B serotypes 1-5 (CBV1-5), and then to assess the association between seropositivity and incident type 2 diabetes.Methods Using a case-cohort design nested within the European Prospective Investigation of Cancer (EPIC)-Norfolk study, we ascertained n0603 cases of incident type 2 diabetes. From within the entire cohort we identified a random subcohort of n0835, without diabetes at baseline. The presence of Coxsackievirus B neutralising antibodies against serotypes 1-5 was assessed using a plaque neutralisation assay. Weighted Cox regression was used to examine the association between presence of antibodies to CBV1-5 and the development of type 2 diabetes. Results Seropositivity in the subcohort for CBV1-5 was 50%, 67%, 66%, 75% and 45%, respectively. After adjustment for age, sex, BMI, physical activity and family history of diabetes, the presence of antibodies against CBV1-5 was not associated with incident type 2 diabetes, over a mean follow-up of 5.

Identification of host-pathogen-disease relationships using a scalable Multiplex Serology platform in UK Biobank

“…Some bacterial, viral and parasitic infectious agents are well established causal factors for certain types of cancer 1 or have been linked to the development of inflammatory diseases such as multiple sclerosis 2 , and cardiovascular disease 3,4 . However, much of this evidence is derived from cross-sectional or case-control analyses that are unable to determine temporality, or from small nested case-control studies that have generally been small or have focused on a small number of infectious agents, leading to inconsistent findings 5 .…”

TYK2 Promoter Variant Is Associated with Impaired Insulin Secretion and Lower Insulin Resistance in Japanese Type 2 Diabetes Patients

“…Richardson et al reported that enterovirus-driven pancreatic inflammation stained with the enteroviral capsid antigen vp1 was identified in the 40% of type 2 diabetes patients, which was higher than the healthy non-diabetic control (13%) [21]. On the other hand, Gkrania-Klotsas et al reported that the prevalence of Coxsackievirus B neutralizing antibodies was not different between the type 2 diabetes patients and the subjects without diabetes [22]. In the type 2 diabetes patients of sub-Saharan African, positive human herpesvirus 8 DNA associated with lower insulin secretion and lower BMI comparing with the type 2 diabetes patients without human herpesvirus 8 infection [23].…”

Mapping of a quantitative trait locus controlling susceptibility to Coxsackievirus B3-induced viral hepatitis

“…Most individuals appear to become infected with CVB3 or closely related species at some point in their lives, 2,28,29 and systemic infection can be severe. [3][4][5] The contrast raised between comparatively rare reports of severe symptoms with a common infection suggests a non-uniform response to the virus.…”

“…1 A recent study based on seropositivity in diabetics estimates that up to 75% of people are seropositive to any given strain of coxsackievirus, 66% for CVB3 alone. 2 In contrast, severe symptoms are comparatively rare. In newborns, severe cases of viral hepatitis are periodically reported as a result of group B Coxsackieviruses, including CVB3.…”