Study: Herpesvirus Infection May Increase Risk of Diabetes

Of the 7 herpesviruses examined in the study, herpes simplex virus and cytomegalovirus were associated with incidence of prediabetes and diabetes among individuals with normal glucose tolerance.

A new study found that 2 common herpesviruses may contribute to impaired glucose metabolism and an increased risk of type 2 diabetes.

Herpesviruses are one of the most common viruses in humans, with 8 types currently known. Any of these can cause lifelong latent infections after an initial, usually mild or asymptomatic primary infection.

Type 2 diabetes is also common, with an estimated 9.3% of the world’s population diagnosed with the condition as of 2019. There are many known behavioral, environmental, and genetic risk factors but until recently, viruses had only been proposed as a potential cause for the development of type 1 diabetes.

The new study was based on health data from 1967 subjects in a population-based health research platform in southern Germany. Participants underwent detailed health examinations at baseline and at follow-up, which included testing for the presence of human herpesviruses, oral glucose tolerance tests, and measurement of glycated hemoglobin.

Participants in the study group had a median age of 54 years at baseline, 49% were men, and 51% were women. Incidence analysis for the development of diabetes used the data for those 1257 participants with normal glucose tolerance at baseline.

According to the study, participants with no prior diagnosis of type 2 diabetes underwent a standard oral glucose tolerance test with diabetes status assigned using thresholds recommended by the American Diabetes Association. Further analyses of blood samples were performed to detect the presence of antibodies to 7 of the 8 known human herpesviruses, which would indicate the presence of both primary and latent infections.

Other variables known to be associated with diabetes risk were also assessed, including sex, age, body mass index (BMI), years of education, ever-smoking status, physical activity during leisure time, parental diabetes, and hypertension.

Researchers found that the prevalence of prediabetes was 27.5% at baseline and 36.2% at follow-up, whereas type 2 diabetes was present in 8.5% of participants at baseline and 14.6% at follow-up.

Out of the 1257 volunteers with normal glucose tolerance at baseline, 364 went on to develop prediabetes and 17 developed type 2 diabetes during the mean follow-up period of 6.5 years. Furthermore, the authors found that age, BMI, smoking, and years of education were all associated with an individual’s risk of developing both prediabetes and type 2 diabetes.

Blood testing performed at the beginning of the study found that Epstein-Barr virus was the most prevalent herpesvirus, with 98% of the sample group being seropositive, followed by herpes simplex virus 1 (HSV1; 88%), human herpesvirus 7 (HHV7; 85%), varicella zoster virus (VZV; 79%), cytomegalovirus (CMV; 46%), human herpesvirus 6 (HHV6; 39%), and herpes simplex virus 2 (HSV2; 11%). Participants were seropositive for an average of 4.4 herpesviruses at baseline and 4.7 at follow-up. Furthermore, 34% tested positive for more viruses at the end of the follow-up period, 54% had the same number, and only 12% were positive for fewer viruses at the start.

Although herpesviruses are persistent in their hosts, they may not always be detectable by blood antibodies. Infection usually occurs in early childhood but can take place later in life, so although the observed seroconversions may be new cases, they are more likely to be due to the immune response to a previously undetected virus. Similarly, individuals who lose seropositivity cannot be considered free of the virus and are much more likely to be in an undetectable latency state.

Of the 7 herpesviruses examined in the study, HSV2 and CMV were associated with incidence of prediabetes and diabetes among individuals with normal glucose tolerance at baseline that were independent of other risk factors. Individuals with HSV2 were 59% more likely to develop either prediabetes or diabetes than those who were seronegative, although CMV infection was associated with a 33% increased incidence.

The researchers found that both HSV2 and CMV consistently and complementarily contributed to the development of prediabetes and diabetes, even after accounting for sex, age, BMI, education, smoking, physical activity, parental diabetes, hypertension, lipid levels, insulin resistance, and fasting glucose. HSV2 was also found to be associated with HbA1C levels, independent of other confounders and the prevalence of prediabetes or diabetes.

“Our study suggested that while (pre)diabetes 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,” the authors wrote.

REFERENCE

New study reveals that herpesvirus infection may increase the risk of developing diabetes. News release. EurekAlert; May 11, 2022. Accessed May 16, 2022. https://www.eurekalert.org/news-releases/952286