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

Clin Sci (Lond). 2006 Jun;110(6):673-81. doi: 10.1042/CS20050353.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adiponectin / blood
  • Biomarkers / blood
  • C-Reactive Protein / analysis
  • Case-Control Studies
  • Cross-Sectional Studies
  • Diabetes Mellitus, Type 2 / immunology*
  • Endothelium, Vascular / immunology*
  • Humans
  • Insulin Resistance
  • Interleukin-6 / blood
  • Male
  • Middle Aged
  • Myocardial Infarction / immunology*
  • Resistin / blood
  • Tumor Necrosis Factor-alpha / analysis*

Substances

  • Adiponectin
  • Biomarkers
  • Interleukin-6
  • Resistin
  • Tumor Necrosis Factor-alpha
  • C-Reactive Protein