High Prevalence of Human Herpesvirus 8 Infection in Diabetes Type 2 Patients and Detection of a New Virus Subtype

Piras, Enrica; Madeddu, Maria Antonietta; Angius, Fabrizio; Contini, Pierpaolo; Pompei, Raffaello; Ingianni, Angela

doi:10.1007/5584_2016_73

Cited by 11 publications

(18 citation statements)

References 34 publications

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“…The results were also strengthened by the observation of increased antibody titers and viral DNA load in participants with higher blood glucose levels. These findings are generally in agreement with those of recent studies on KSHV infection among diabetic patients from European and African countries (Caselli et al, 2014;Ingianni et al, 2007;Piras et al, 2017;Sobngwi et al, 2008). In addition, it was found that ethnicity might be inversely associated with the level of antibody titers and viral load: the Uygur population had increased antibody titer levels, while the viral DNA load was higher in the Han population.…”

Section: Discussionsupporting

confidence: 91%

“…Therefore, diabetic patients are at higher risk of KS and other KSHV-associated tumors (Anderson et al, 2008;Chang et al, 2017). Although the study results conflict with those of a study by Piras et al (Piras et al, 2017), this observation is supported by other studies that have shown that high glucose levels can significantly increase lytic reactivation of KSHV. Multiple signaling pathways involved in the lifecycle of KSHV have been proven to be modulated by high glucose in various cell types (Chang et al, 2017;Ye et al, 2016).…”

Section: Discussionsupporting

confidence: 44%

“…Therefore, the causal relationship between KSHV infection and DM-2 remains unresolved. It was not possible to determine whether diabetes increases susceptibility to KSHV infection by reducing the efficiency of the immune system, or, in contrast, whether the metabolism of the infecting virus modifies the microenvironment thus leading to the onset of DM-2 (Piras et al, 2017). These two hypotheses have both been supported by previous studies.…”

Section: Discussionmentioning

confidence: 94%

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Kaposi’s sarcoma-associated herpesvirus seropositivity is associated with type 2 diabetes mellitus: A case–control study in Xinjiang, China

Cui

Fang

Zheng

et al. 2019

International Journal of Infectious Diseases

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To assess the potential relationship between Kaposi's sarcoma-associated herpesvirus (KSHV) infection and type 2 diabetes mellitus (DM-2) in Xinjiang, China. Methods: A case-control study of consecutively included DM-2 patients and normal controls was conducted among the Uygur and Han populations in Xinjiang Uygur Autonomous Region, China. Blood samples were collected and KSHV seroprevalence, antibody titers, and viral load were investigated. Logistic regression analysis and multiple linear regression analysis were applied to explore determinants of the main outcome measures. Results: A total of 324 patients with DM-2 and 376 normal controls were included. The seroprevalence of KSHV was 49.1% (95% confidence interval (CI) 43.6-54.5%) for diabetic patients and 23.7% (95% CI 19.4-28.0%) for the control group. After adjusting for variables of ethnicity, sex, body mass index, occupation, educational level, marital status, age, and smoking and alcohol consumption habits, the association between DM-2 and KSHV infection still existed (odds ratio (OR) 2.94, 95% CI 2.05-4.22), and the risk of KSHV infection increased with glucose concentration (OR 1.35, 95% CI 1.21-1.51). KSHV was more likely to express both the latent and lytic antigens in diabetic patients (latent: OR 3.27, 95% CI 2.25-4.75; lytic: OR 3.99, 95% CI 2.68-5.93). Antibody titers and viral load increased in patients with higher blood glucose levels (p < 0.001). Conclusions: Patients with DM-2 have an elevated risk of KSHV infection. Both antibody titers and viral load increased with blood glucose levels.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionsupporting

confidence: 44%

Section: Discussionmentioning

confidence: 94%

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Kaposi’s sarcoma-associated herpesvirus seropositivity is associated with type 2 diabetes mellitus: A case–control study in Xinjiang, China

Cui

Fang

Zheng

et al. 2019

International Journal of Infectious Diseases

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“…A possible association of HHV8 infection with type-2 diabetes has recently been proposed [16][17][18][19]. Insulin hyper-secretion and consumption is considered a possible initiating event of obesity and diabetes, and discovering the causes that induce insulin hypersecretion could help to find a solution for diabetes treatment [20].…”

Section: Resultsmentioning

confidence: 99%

“…The increased insulin-uptake induced an increase of glucose accumulation in HUVEC cells. Recently, Piras and colleagues investigated the prevalence of HHV8 DNA and specific antiviral antibodies in diabetes mellitus type 2 (DM2) patients and control subjects [18]. They reported the presence of anti-lytic and -latent antibodies in HHV8-positive DM2 subjects and in non-DM2 controls.…”

Section: Introductionmentioning

confidence: 99%

Anti-Human Herpesvirus 8 antibodies affect both insulin and glucose uptake by virus-infected human endothelial cells

Angius

Piras

Spolitu

et al. 2018

J Infect Dev Ctries

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Introduction: Human Herpesvirus 8 (HHV8) is known to be the cause of the malignant tumour named Kaposi's sarcoma. It is believed to induce an intense modification of cell metabolism in endothelial cells. In this work we analysed the role of anti-HHV8 antibodies in both the insulin and glucose uptake of HHV8-infected primary human endothelial cells (HUVEC). Methodology: Western blotting, immunofluorescence and radiolabelled glucose were employed to assess the pPI3K expression, insulin binding and glucose-uptake by HUVEC cells, respectively. Results: We confirmed that HHV8-infection is able to enhance both insulin binding and glucose-uptake in HHV8-infected primary endothelial cells; in addition, we found that anti-HHV8 specific antibodies are able to further increase both insulin and glucose uptake during the late latent phase of HHV8-infection in vitro. Conclusions: These findings suggest that a specific immune response to HHV8-infection may cooperate in boosting the cell metabolism, further enhancing the already increased insulin binding and glucose-uptake in HHV8-infected cells, which is a peculiar property of several oncogenic viruses.

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

et al. 2022

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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

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High Prevalence of Human Herpesvirus 8 Infection in Diabetes Type 2 Patients and Detection of a New Virus Subtype

Cited by 11 publications

References 34 publications

Kaposi’s sarcoma-associated herpesvirus seropositivity is associated with type 2 diabetes mellitus: A case–control study in Xinjiang, China

Kaposi’s sarcoma-associated herpesvirus seropositivity is associated with type 2 diabetes mellitus: A case–control study in Xinjiang, China

Anti-Human Herpesvirus 8 antibodies affect both insulin and glucose uptake by virus-infected human endothelial cells

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

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