Introduction: T2D prevalence is increasing worldwide and previous studies suggested that it
is higher in individuals seropositive for herpesviruses. This study examines the prospective
association of herpesviruses with (pre)diabetes to evaluate their potential role in diabetes
aetiology.
Methods: Two follow–up examinations of the German population–based KORA cohort (F4
and FF4) were used to identify participants with normal glucose tolerance at baseline at risk
for seven–year (pre)diabetes incidence (n=1257). All participants had repeated oral glucose
tolerance tests and antibody measurements for herpes simplex virus (HSV) 1 & 2, varicella–
zoster virus, Epstein–Barr virus, cytomegalovirus (CMV), and human herpesvirus 6 & 7.
Regression models were used to evaluate the association linking serostatus with
(pre)diabetes incidence and HbA1c.
Results: HSV–2 and CMV were associated with (pre)diabetes incidence after adjustment for
sex, age, BMI, education, smoking, physical activity, parental diabetes, hypertension, lipid
levels, insulin resistance, and fasting glucose. Seropositivity of both viruses was also cross–
sectionally associated with higher HbA1c at baseline, with the association of HSV–2 being
independent of confounders, including prevalence of (pre)diabetes itself. While
seropositivity for multiple herpesviruses was associated with a higher incidence of
(pre)diabetes, this association was not independent of confounders.
Conclusion: The novel associations of HSV–2 and CMV serostatus with (pre)diabetes
incidence indicate that these herpesviruses may contribute to the development of impaired
glucose metabolism. Our results highlight the link between viruses and (pre)diabetes and the
need for more research evaluating viral prevention strategies.