Increased levels of tumour necrosis factor-α (TNF-α) in patients with Type II diabetes mellitus after myocardial infarction are related to endothelial dysfunction

Abstract

The pathophysiology of insulin resistance and atherosclerosis may share a common inflammatory basis, maintaining endothelial dysfunction, suggesting why patients with T2DM (Type II diabetes mellitus) have an impaired prognosis after an MI (myocardial infarction), but it remains unclear how these parameters are inter-related. Forty patients with an MI (20 patients with and 20 patients without T2DM) took part in this cross-sectional study. Endothelium-dependent [FMD (flow-mediated dilation)] and -independent [NTG (nitroglycerine)] vasodilatation (determined by ultrasound), S(I) (insulin sensitivity index; determined by isoglycaemic-hyperinsulinaemic clamp) and serum levels of CRP (C-reactive protein), TNF-alpha (tumour necrosis factor-alpha), IL-6 (interleukin 6), resistin and adiponectin (determined by ELISA) were measured. Associations between FMD/NTG and S(I), and CRP, TNF-alpha, IL-6, adiponectin, resistin, lipids, blood pressure, BMI (body mass index) and brachial artery diameter were then assessed. FMD (2.1 compared with 4.7%; P<0.05), NTG (14.9 compared with 21.2%; P<0.05) and S(I) [4.3 compared with 6.6 10(-4) dl.kg(-1) of body weight.min(-1).(mu-units/ml)(-1); P<0.05], and adiponectin levels (3.1 compared with 6.4 microg/ml; P<0.01) were all lower in patients with T2DM. TNF-alpha (6.9 compared with 1.8 pg/ml; P<0.01) and IL-6 (2.3 compared with 1.2 pg/ml; P<0.01) levels were higher in patients with T2DM, whereas differences in CRP and resistin levels did not attain statistical significance between the two groups. TNF-alpha concentrations and brachial artery diameter were negatively, whereas S(I) was positively, correlated with FMD. Adjustment for age weakened the association for S(I), whereas TNF-alpha and brachial artery diameter remained significantly associated with FMD after adjustment for group, age and BMI. Endothelial dysfunction and low-grade inflammation co-exist in T2DM after MI. These results suggest that the endothelium is negatively impacted in multiple ways by the diabetic state after an MI.

Diabetic foot syndrome: Immune-inflammatory features as possible cardiovascular markers in diabetes

“…Other studies showed how adiponectin can inhibit TNF-α mediated expression of E-selectin, VCAM-1 and ICAM-1 in human endothelial cells [47][48][49]51,52] . These findings furtherly confirm the vasoprotective action of adiponectin45 [53][54][55][56][57][58][59][60] and how this molecule may negatively modulate atherogenesis also by means its influence on inflammatory variables such as TNF-α.…”

“…Thus most of research experiences seem to suggest that atherosclerosis in diabetes could be a real inflammatory disorder. A study [60] evaluated the prevalence of inflammatory markers such as high-sensitivity CRP, adiponectin, and nuclear factor-κB (NF-κB) expression, in peripheral blood mononuclear cells in patients with type 2 diabetes mellitus (T2DM) with and without macrovascular disease. Authors reported how diabetic subjects with T2DM showed a higher hsCRP and NF-κB expression and a lower degree of adiponectin serum levels compared to healthy controls.…”

Why is the world so poorly prepared for a pandemic of hypervirulent avian influenza?

“…in skeletal muscle (36,37), the heart (38 Á41) and adipose tissue (37,42,43). It also acts on endothelial cells (44,45) and on C-fibers (non-myelinated or very thinly myelinated sensory nerve fibres), which are made more sensitive by the action of TNF-a (46 Á 48). These effects (and similar effects caused by other cytokines) may help to explain skeletal symptoms and pain in patients suffering from influenza.…”

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“…114 Winederived phenolic compounds have anti-inflammatory actions including inhibition of reaction oxygen species in neutrophils, monocytes and macrophages. 115,116 In subjects with diabetes, red wine consumption, taken with meals, significantly reduces oxidative stress and the circulating concentration of pro-inflammatory cytokines from lymphocytes and macrophages such as C-reactive protein, tissue necrosis factor-alpha and interleukin-6, as well as improving cardiac function after a myocardial infarction.…”