Association of endothelial and vascular smooth muscle dysfunction with cardiovascular risk factors, vascular complications, and subclinical carotid atherosclerosis in type 2 diabetic patients

J Atheroscler Thromb. 2012;19(3):276-84. doi: 10.5551/jat.10629. Epub 2011 Dec 6.


Aim: Atherosclerosis and arteriosclerosis are mainly caused by the dysfunction of arterial components, namely, vascular endothelial cells, smooth muscle cells, and the extracellular matrix. Endothelial dysfunction is well established as a predictive surrogate marker of cardiovascular events; however, little is known regarding the clinical implications of vascular smooth muscle dysfunction for cardiovascular disease and microangiopathy. In the present study, we aimed to clarify the association of arterial dysfunction with micro-/macroangiopathy and conventional cardiovascular risk factors in 181 type 2 diabetic patients (T2DM; age ± SD, 64 ± 10 years; duration of diabetes, 12 ± 10 years).

Methods: Flow-mediated dilatation (FMD) and nitroglycerin-mediated dilatation (NMD) were assessed to evaluate endothelial dysfunction and vascular smooth muscle dysfunction, respectively, by using a novel ultrasound device, UNEXEF18G (Unex Co. Ltd., Japan).

Results: The FMD and NMD were 6.4 ± 3.9% and 13.4 ± 6.6%, respectively. No significant differences in FMD were noted between T2DM with and without micro- or macroangiopathy; however, NMD in T2DM patients with micro- and macroangiopathy was significantly lower than that in T2DM patients without angiopathy. NMD decreased with the progression of chronic kidney disease (CKD) stage (p = 0.005), but not FMD (p = 0.071). On multiple regression analysis, significant independent contributors to FMD were age, smoking, systolic blood pressure, glycosylated hemoglobin, and serum total cholesterol, while those for NMD were age, systolic blood pressure, and waist circumference.

Conclusion: The relationship of vascular complications and cardiovascular risk factors with NMD is different from that with FMD in type 2 diabetic patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blood Pressure
  • Cardiovascular Diseases / etiology*
  • Carotid Artery Diseases / etiology*
  • Diabetes Complications / etiology*
  • Diabetes Mellitus, Type 2 / physiopathology*
  • Endothelium, Vascular / pathology*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Muscle, Smooth, Vascular / pathology*
  • Risk Factors
  • Vascular Resistance*