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Herpesviruses Linked to Increased Risk of Prediabetes, Impaired Glucose Control

An analysis of data from the KORA study suggests HSV 2 and CMV seropositivity were independently associated with increased odds of developing prediabetes.

New research from a team in Germany suggests a pair of common herpesviruses could be contributing to impaired glucose metabolism and risk of developing type 2 diabetes among impacted individuals.

An analysis of the health impact of 7 herpesviruses on the incidence of prediabetes, results of the study provide evidence of associations of herpes simplex virus (HSV) 2 and cytomegalovirus (CMV) serostatus with incidence of diabetes and prediabetes, which investigators suggest indicates these herpesviruses may contribute to development of impaired glucose metabolism.

“Our study suggested that while prediabetes incidence was primarily explained by age, BMI, cholesterol and fasting glucose, both HSV2 and CMV added additional complementary risk information, despite high viral prevalence and co-occurrence,” wrote investigators.

Citing cross-sectional and population-based studies providing data in support of an association between herpesvirus and risk of type 2 diabetes, Tim Woelfle and colleagues from Ludwig-Maximilians University and Helmholtz Munich sought to provide clinicians with insight into the relationship between different herpesviruses and incidence of prediabetes. With this in mind, investigators designed their study as an analysis of the KORA cohort to assess incidence of prediabetes using antibody measurements for HSV 1, HSV 2, varicella-zoster virus, Epstein-Barr virus, CMV, human herpesvirus (HHV) 6, and HHV7. A population-based health research platform in the south of Germany, the KORA F4 study and FF4 study provided investigators with information related to more than 5000 individuals.

For the purpose of analysis, regression models were used to estimate associations between serostatus of each herpesvirus and prediabetes incidence after 7 years of follow-up, with adjustment for sex, age, BMI, education, smoking, physical activity, parental diabetes, hypertension, lipid levels, insulin resistance, and fasting glucose.

Of the 3077 and 2279 participants originally included in the F4 and FF4 studies, investigators identified 1967 individuals who had undergone extensive phenotyping, including viral multiplex serology for human herpesviruses, and met additional inclusion criteria for the study. Of these, 1257 had normal glucose tolerance at baseline and meta criterion for being at risk of prediabetes. This cohort had a median age of 54 (range 32-81) at baseline, 49.2% were men, and the mean follow-up duration was 6.5 years. During the follow-up period, 364 patients developed prediabetes and 17 developed type 2 diabetes. Among the study cohort, Epstein-Barr virus was the most prevalent herpesvirus at F4, with a reported prevalence of98%. This was followed by HSV1 (88%), HHV7 (85%), VZV (79%), CMV (46%), HHV6 (39%) and HSV2 (11%) , which had prevalence rates of 88%, 85%, 79%, 46%, 39%, and 11%, respectively.

Results of the investigators’ analyses suggest HSV2 and CMV were associated with prediabetes coincidence among the study cohort, with these associations being independent of sex, age, BMI, smoking, education, physical activity, parental diabetes, hypertension, lipid levels, insulin resistance, and fasting glucose. Results of the analyses indicated those who were seropositive for HSV2 had increased odds of developing prediabetes during the 6.5 years between F4 and FF4 (OR, 1.66 [95% CI, 1.13-2.43]) in unadjusted models, but this was slightly attenuated in adjusted models (OR, 1.59 [95% CI, 1.01-2.48]). Similarly, those who were seropositive for CMV had an increased incidence of prediabetes (OR, 1.47 [95% CI, 1.15-1.87]), which was attenuated slightly when adjusted for potential confounders (OR, 1.31 [95% CI, 1.00-1.78]).

“These results highlight the link between viruses and (pre)diabetes, and the need for more research evaluating public health viral prevention strategies, possibly including the development of effective vaccines against herpesviruses,” investigators wrote.

This study, “Health impact of seven herpesviruses on (pre)diabetes incidence and HbA1c: results from the KORA cohort,” was published in Diabetologia.