Imbalanced Low-Grade Inflammation and Endothelial Activation in Patients with Type 2 Diabetes Mellitus and Erectile Dysfunction

Abstract

Introduction Erectile dysfunction (ED) is highly prevalent among type 2 diabetes mellitus patients (T2DM). Although a link among systemic inflammation, endothelial dysfunction, and ED is described in clinical situations mainly related with coronary heart disease (CHD) risk, evidences of this link in T2DM patients are rather limited. Aims To evaluate the association between endothelial dysfunction and balance of pro-/anti-inflammatory mediators with ED presence and severity in T2DM. Methods We conducted a cross-sectional study of 190 T2DM patients without symptomatic CHD, 150 out of them with ED and 40 without ED. Serum levels of E-selectin, intercellular adhesion molecule-1, tumor necrosis factor-α (TNF-α), and interleukin (IL)-10 were measured using specific enzyme-linked immunosorbent assays (ELISAs). ED presence and severity were tested by the five-item version of the International Index of Erectile Function questionnaire. Main Outcome Measures Differences in circulating levels of endothelial dysfunction (ICAM-1, E-selectin) and inflammatory/anti-inflammatory (TNF-α, IL-10, TNF-α : IL-10 ratio) markers between T2DM patients with and without ED, and assessment of biomarkers ED predictive value while adjusting for other known ED risk factors. Results Patients with ED were older and had longer duration of diabetes than patients without ED. E-selectin serum levels were significantly increased, while IL-10 were lower in patients with ED; because TNF-α levels tend to be higher, TNF-α : IL-10 ratio was more elevated in ED patients. No significant differences of ICAM-1 levels were observed between study groups. Endothelial activation markers and TNF-α, as well as diabetes duration, were negatively correlated with erectile function. On multivariate analysis including age, duration of diabetes, insulin treatment, hypertension, insulin resistance, fair-to-poor glycemic control, and metabolic syndrome, increments in E-selectin levels and TNF-α : IL-10 ratio predicted independently ED presence, while IL-10 increases were associated with lower risk of ED in T2DM patients. Conclusions ED in T2DM patients without symptomatic CHD is associated with systemic endothelial dysfunction and a predominant, imbalanced low-grade inflammatory response.

Nonalcoholic steatohepatitis as a novel player in metabolic syndrome-induced erectile dysfunction: an experimental study in the rabbit

“…Blood levels of TNFa, along with other pro-inflammatory (IL-6, IL-1b) and prothrombotic factors, were significantly increased in ED patients and negatively related to sexual performance (Vlachopoulos et al, 2006). Similar results were also found in patients with type 2 diabetes mellitus (Araña Rosaínz Mde et al, 2011) and in patients with obstructive sleep apnea syndrome (Matos et al, 2013). Animal models involving genetic manipulation of TNFa, have shown peculiar alterations of erectile function.…”

Erectile Dysfunction

“…Low-grade subclinical inflammation affects endothelial function and might lead to a prothrombotic status. Inflammatory markers and mediators (i.e., C-reactive protein, intercellular adhesion molecule 1, interleukin [IL]-6, IL-10, IL-1b, and tumor necrosis factor a) and endothelial/prothrombotic factors (i.e., von Willebrand factor, tissue plasminogen activator, plasminogen activator inhibitor 1, and fibrinogen) have been shown to be expressed at higher levels in patients with ED [195][196][197][198]. Inflammatory markers and mediators (i.e., C-reactive protein, intercellular adhesion molecule 1, interleukin [IL]-6, IL-10, IL-1b, and tumor necrosis factor a) and endothelial/prothrombotic factors (i.e., von Willebrand factor, tissue plasminogen activator, plasminogen activator inhibitor 1, and fibrinogen) have been shown to be expressed at higher levels in patients with ED [195][196][197][198].…”

“…Several studies reported that ED onset and severity are associated with an increased expression of markers of inflammation [195][196][197][198]. Chronic inflammation is involved in the pathogenesis of metabolic syndrome, and an increased expression of proinflammatory cytokines has been reported in obese and diabetic patients [197,198], linking these conditions with ED. Chronic inflammation is involved in the pathogenesis of metabolic syndrome, and an increased expression of proinflammatory cytokines has been reported in obese and diabetic patients [197,198], linking these conditions with ED.…”

Sexual Dysfunction as a Marker of Cardiovascular Disease in Males With 50 or More Years of Type 1 Diabetes

“…In studies of those with type 2 diabetes, the relationship of ED and CVD is thought to begin with the damage caused by the milieu of metabolic changes associated with the metabolic syndrome, established as a direct predecessor of CVD (29–33). However, as the Medalists do not have the same lipid profile (total cholesterol levels <200 mg/dL, HDL levels >35 mg/dL, and a triglyceride level <70 mg/dL), increased weight, and insulin resistance characteristic of type 2 diabetes (insulin dose, 0.5 units/kg [0.37–0.57]), the same early warning signs for CVD are not present.…”

“…However, as the Medalists do not have the same lipid profile (total cholesterol levels <200 mg/dL, HDL levels >35 mg/dL, and a triglyceride level <70 mg/dL), increased weight, and insulin resistance characteristic of type 2 diabetes (insulin dose, 0.5 units/kg [0.37–0.57]), the same early warning signs for CVD are not present. Of the Medalists who have died, 58.6% died of CVD, demonstrating a significant mortality from this disease risk that necessitates early detection (29–33). Findings of this analysis indicate that history of SD provides an important screening tool in the absence of the typical risk profile of glycemic control, BMI, and dyslipidemia in patients with type 1 or type 2 diabetes.…”