Health impact of seven herpesviruses on (pre)diabetes incidence and HbA1c: results from the KORA cohort

Abstract

Aims/hypothesis The prevalence of type 2 diabetes is increasing worldwide, and previous studies have suggested that it is higher in individuals who are 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, thus being at risk for (pre)diabetes (n = 1257). All participants had repeated OGTTs and antibody measurements for herpes simplex virus (HSV) 1 and 2, varicella-zoster virus, Epstein–Barr virus, cytomegalovirus (CMV) and human herpesvirus 6 and 7. Regression models were used to evaluate the association between serostatus with (pre)diabetes incidence after a 7 year follow-up and HbA1c. Results HSV2 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 HSV2 being independent of confounders, including the 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. Conclusions/interpretation The associations of HSV2 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 viral infection and (pre)diabetes, and the need for more research evaluating viral prevention strategies. Graphical abstract

Integrative deep immune profiling of the elderly reveals systems-level signatures of aging, sex, smoking, and clinical traits

“…Body mass index (BMI) correlated significantly with HbA1c levels, as expected, but interestingly, a significant positive correlation was also observed between HbA1c levels and HSV seropositivity, in line with a recent population-based study reporting a possible link between HSV type 2 infection and prediabetes. 18 In a multiplex analysis of 48 cytokines, we found plasma concentrations of several pro-inflammatory chemokines, such as CCL27, CXCL9, and CXCL10, to increase with age (Fig. 1D).…”

An analysis of risk factors for spontaneously occurring type 2 diabetes mellitus in rhesus macaques (Macaca mulatta)

“…Over the 5-year follow-up, new-onset cases were significantly higher in the group with CMV disease compared to case controls. 9 Other studies have also shown relationships between seropositivity for CMV and T2D 10,11 and with pre-diabetes incidence, 12 even in the absence of CMV disease per se. As studies of CMV pathogenesis are a significant research focus at our institution, 13 we have serology on hundreds of animals that can be used to address this question.…”

A Narrative Review of Alternative Symptomatic Treatments for Herpes Simplex Virus

“…In human studies, it was shown that acute hyperglycemia impaired IL-6 and IL-17 expression, particularly in CD14+CD16+ intermediate monocytes [ 77 ]. More recently, it is widely believed that consumption of a “Western diet” (i.e., high in refined carbohydrates and saturated fats) contributed to both incidence and mortality during the COVID-19 pandemic [ 78 ], while recent support for a link between HSV and type II diabetes is also noteworthy [ 79 ].…”