The association between prior infection with five serotypes of Coxsackievirus B and incident type 2 diabetes mellitus in the EPIC-Norfolk study.
OBJECTIVE
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 n = 603 cases of incident type 2 diabetes. From within the entire cohort we identified a random subcohort of n = 835, 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 5.7 years (HR [95% CIs] 0.94 [0.72,1.25], 0.92 [0.68, 1.23], 1.33 [0.98,1.81], 1.16 [0.83,1.61] and 1.03 [0.77,1.39] for CBV1-5, respectively).


CONCLUSIONS
The presence of antibodies against any of five serotypes of Coxsackievirus B was not associated with incident type 2 diabetes.
Addenbrooke's Hospital, Cambridge, UK. eg318@cam.ac.uk
E
E
Gkrania-Klotsas
C
C
Langenberg
S
S
Tauriainen
S J
SJ
Sharp
R
R
Luben
N G
NG
Forouhi
K T
KT
Khaw
H
H
Hyöty
N J
NJ
Wareham
D000328:Adult; D003384:Coxsackievirus Infections / Q000150:complications*; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000175:diagnosis / Q000453:epidemiology* / Q000821:virology*; D029822:Enterovirus B, Human; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D008297:Male; D012307:Risk Factors