Journal of Investigative Medicine

The data related to the association between hepatitis virus infections and diabetes mellitus (DM) are conflicting. The aim of this study was to investigate the seroprevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) and to determine the risk factors affecting the prevalence in Turkish patients with type 1 DM and type 2 DM.

The study consisted of 736 diabetic and 505 nondiabetic patients. Serological investigation for the hepatitis B surface antigen (HBsAg) and the HCV antibody (anti-HCV) was performed with a third-generation commercial chemiluminescence assay. The presence of HBsAg was considered as indicator of HBV infection. The HCV infection in the patients with positive anti-HCV was confirmed by a real-time polymerase chain reaction assay. The patients were divided according to their HBV and HCV infection status, and their demographic features, diabetes properties, general risk factors, and aminotransferase levels were analyzed.

There was no significant difference in the seropositivity rate for the HBsAg (3.8% vs 3.0%, P > 0.43; odds ratio, 1.292; 95% confidence interval, 0.683–2.444). However, anti-HCV seropositivity was significantly increased in the DM group (3.3% vs 1.8%, P < 0.03; odds ratio, 2.398; 95% confidence interval, 1.025–5.609). Increased aminotransferase levels and a history of blood transfusions were positively correlated with both HBV and HCV infection. Moreover, a history of surgical procedures and high glycated hemoglobin A1c levels were positively associated with HBsAg antigen seropositivity.

Although no significant difference in the seropositivity of the HBsAg was determined, a high prevalence of HCV infection was detected in the DM patients compared to healthy controls.

Chronic otitis media with effusion (COME) develops after sustained inflammation and is characterized by secretory middle ear epithelial metaplasia and effusion, most frequently mucoid. Staphylococcus epidermidis, typically considered a commensal organism, is very frequently recovered in chronic middle ear fluid and in middle ear biofilms. Although it has been shown to drive inflammation in sinonasal epithelium, the impact of S. epidermidis on COME is markedly understudied. The goal of this study was to examine the in vitro effects of S. epidermidis lysates on murine and human middle ear epithelial cells.

Staphylococcus epidermidis lysates were generated and used to stimulate submerged and differentiated human and murine epithelial cells (MEECs) for 24 to 48 hours. Quantitative real time-polymerase chain reaction, Western blot, enzyme-linked immunosorbent assay, and immunocytochemistry techniques were performed to interrogate the mucin gene MUC5AC and MUC5B expression and protein production, chemokine response, as well as NF-κB activation. Luciferase reporter assays were performed to further evaluate nuclear factor κB (NF-κB) activation and query specific promoter responses after S. epidermidis exposure.

Staphylococcus epidermidis induced a time- and dose-dependent MUC5AC and MUC5B overexpression along with a parallel overexpression of Cxcl2 in mouse MEEC and IL-8 in human MEEC. Further investigations in mMEEC showed a 1.3 to 1.5 induction of the MUC5AC and MUC5B promoters. As potential mechanisms for these responses, induction of an oxidative stress marker, along with early nuclear translocation and activation of NF-κB, was found. Finally, chronic exposure induced marked epithelial thickening of cells differentiated at the air liquid interface.

Staphylococcus epidermidis lysates activate a proinflammatory response in MEEC, including mucin gene expression and protein production. Although typically considered a nonpathogenic commensal organism in the ear, these results suggest that they may play a role in the perpetuation of an inflammatory and mucogenic response in COME.

Impaired insulin signaling pathway in the brain in type 2 diabetes (T2D) is a risk factor for Alzheimer disease (AD). Glucagon-like peptide-1 (GLP-1) and its receptor agonist are widely used for treatment of T2D. Here we studied whether the effects of exendin-4 (EX-4), a long-lasting GLP-1 receptor agonist, could reduce the risk of AD in T2D.

Type 2 diabetes rats were injected with EX-4 for 28 consecutive days. Blood glucose and insulin levels, as well as GLP-1 and insulin in cerebrospinal fluid, were determined during the experiment. The phosphorylation level of tau at individual phosphorylation sites, the activities of phosphatidylinositol 3 kinase/protein kinase B (PI3K/AKT), and glycogen synthase kinase-3β (GSK-3β) were analyzed with Western blots.

The levels of phosphorylated tau protein at site Ser199/202 and Thr217 level in the hippocampus of T2D rats were found to be raised notably and evidently decreased after EX-4 intervention. In addition, brain insulin signaling pathway was ameliorated after EX-4 treatment, and this result was reflected by a decreased activity of PI3K/AKT and an increased activity of GSK-3β in the hippocampus of T2D rats as well as a rise in PI3K/AKT activity and a decline in GSK-3β activity after 4 weeks intervention of EX-4.

These results demonstrate that multiple days with EX-4 appears to prevent the hyperphosphorylation of AD-associated tau protein due to increased insulin signaling pathway in the brain. These findings support the potential use of GLP-1 for the prevention and treatment of AD in individuals with T2D.