Diabetes Risk May Increase Due to Herpes Virus Infection

Two common herpesviruses may lead to impaired glucose metabolism and an increased risk of acquiring type 2 diabetes (T2D) among infected persons, according to a new study published in Diabetologia (the journal of the European Association for the Study of Diabetes [EASD]) on May 11, 2022. Dr. Tim Woelfle of Ludwig-Maximilians University (LMU) and Helmholtz Munich, Germany, and colleagues conducted the study.

Human herpesviruses (HHV) 6, 7, and 8 are among the most frequent viruses in humans. After an initial, typically mild or asymptomatic primary infection, they all induce lifelong latent infections in their hosts.

Type 2 diabetes is one of the most common and serious metabolic disorders, affecting an estimated 9.3 percent of the world's population as of 2019, and causing a significant mortality rate due to the resulting cardiovascular disease. There are numerous behavioral, environmental, and genetic risk factors for T2D, but viruses were previously thought to solely play a role in the development of type 1 diabetes, in which the pancreas fails to produce sufficient insulin.

When someone has impaired fasting glucose (IFG) or impaired glucose tolerance, they may be diagnosed with prediabetes (IGT). According to previous studies, the rate of T2D is substantially higher in people with prediabetes (7.6% per person-year) than in people with normal glucose tolerance (0.6% per person-year).

The study used health data from 1967 people in the population-based health research platform KORA (Cooperative Health Research in the Augsburg Region) in southern Germany. At baseline (2006-2008) and follow-up (2013-2014), participants completed extensive health examinations that included testing for the presence of human herpesviruses, oral glucose tolerance tests (OGTT), and glycated hemoglobin (HbA1c) assessment (a measure of blood sugar control over the previous 3 months).

At the outset, the study group had a median age of 54 years, with 962 (49%) men and 999 (51%) women. The data for the 1257 patients with normal glucose tolerance at baseline were included in the incidence analysis for the development of (pre)diabetes (median age 49 years, 42 percent male and 58 percent female [528 and 729 individuals, respectively]).

Participants who had never been diagnosed with T2D did a routine OGTT, with diabetes status determined using the American Diabetes Association's suggested thresholds. Antibodies to seven of the eight known human herpesviruses were found in blood samples, indicating the presence of both primary and latent infections. At the start of the study, the following characteristics were evaluated: sex, age, BMI, years of education, ever-smoking status (yes/no), leisure-time physical activity (active/inactive), parental diabetes (yes/no), and hypertension (yes/no, defined as blood pressure greater than 140/90mmHg).

Prediabetes (IFG and IGT) was found in 27.5 percent of patients at baseline and 36.2 percent at follow-up, whereas T2D was found in 8.5 percent at baseline and 14.6 percent at follow-up. During the 6.5-year follow-up period, 364 of the 1257 participants with normal glucose tolerance at baseline developed prediabetes, and 17 acquired T2D. Age, BMI, smoking, and years of schooling were all linked to a person's likelihood of getting both prediabetes and T2D, according to the researchers.

EBV was found to be the most common herpesvirus, with 98 percent of the sample group seropositive, followed by HSV1 (88 percent), HHV7 (85 percent), VZV (79 percent), CMV (46 percent), HHV6 (39 percent), and HSV2 (38 percent) (11 percent ). At baseline, participants had an average of 4.4 herpesviruses, and at follow-up, they had 4.7. Around a third (34%) tested positive for more viruses after the follow-up period, while 54% had the same number and only 12% had fewer infections than when they started. While herpesviruses are tenacious in their hosts, antibodies in the blood may not always identify them. While infection normally occurs in early childhood but can occur later in life, the reported seroconversions are more likely to be the result of an immune response to a previously undiagnosed virus. An individual who loses seropositivity cannot be deemed virus-free and is far more likely to be in an undetectable latency condition.

HSV2 and CMV were found to be related to the occurrence of (pre)diabetes among people who had normal glucose tolerance at the start of the study, regardless of other risk factors. HSV2 infection increased the risk of (pre)diabetes by 59 percent compared to seronegative individuals, while CMV infection increased the risk of (pre)diabetes by 33 percent.

Even after controlling for sex, age, BMI, education, smoking, physical activity, parental diabetes, hypertension, lipid levels, insulin resistance, and fasting glucose, the study indicated that both HSV2 and CMV contributed to the development of (pre)diabetes. HSV2 was similarly linked to HbA1c levels, despite the presence of additional factors and the prevalence of (pre)diabetes.

"Our investigation revealed that, despite significant viral prevalence and co-occurrence, both HSV2 and CMV offered important complementary risk information, although (pre)diabetes incidence was predominantly explained by age, BMI, cholesterol, and fasting glucose," the authors write.

The methods through which these viruses may have a role in the development of (pre)diabetes are still unknown. HSV2 and CMV both produce persistent infections that can affect the immune system by boosting or suppressing its activity, which can affect the endocrine (hormonal) system's function. Other than the development of metabolic syndrome, there are still unknown causes of T2D, according to a previous study.

The authors conclude, "These findings underscore the link between viruses and (pre)diabetes, as well as the need for more research evaluating public health viral preventive programs, including the development of effective herpesvirus vaccines."