Diabetic conditions differentially affect the endothelial function, arterial stiffness and carotid atherosclerosis

J Atheroscler Thromb. 2014;21(5):486-500. doi: 10.5551/jat.20834. Epub 2014 Jan 8.


Aim: The levels of fasting and postprandial plasma glucose, HbA1c and other risk factors for atherosclerosis have distinct effects in patients with and those without diabetes mellitus. The aim of this study was to determine the impact of diabetic surrogate markers on the endothelial function, arterial stiffness and carotid atherosclerosis in individuals with and without diabetes.

Methods: A total of 320 Japanese subjects(mean age: 61.2 ± 12.1 years) were recruited in this study. Demographic, clinical and laboratory parameters, including 75 g OGTT(155 subjects) results, were examined. The endothelial function was evaluated according to the flow-mediated vasodilation of the brachial artery(%FMD). In addition, arterial stiffness was evaluated according to the brachial-ankle pulse wave velocity(baPWV), and carotid atherosclerotic changes were estimated according to the maximum intima-media thickness(max-IMT) and resistive index of the common carotid artery(CCA-RI). A multiple regression analysis was performed to identify independent determinants of these vascular surrogate markers.

Results: None of the glucose-related parameters were associated with the %FMD. In contrast, the presence of T2DM, the HbA1c level and an increased plasma glucose level at 60 minutes during 75 g OGTT were associated with an increased baPWV. The HbA1c level was also correlated with an increased max-IMT. The fasting plasma glucose(FPG) level and the presence of T2DM correlated with an increased CCA-RI. In the subjects with T2DM, the protective effects of high-density lipoprotein cholesterol(HDL-C) on the %FMD and baPWV were abolished.

Conclusions: Various glucose metabolism parameters have different effects the degree of arterial stiffness and presence of carotid atherosclerosis, but not the endothelial function, suggesting that pharmacological intervention has the potential to preserve the endothelial function in diabetic individuals. In addition, the presence of T2DM blunts the vascular protective effects of HDL-C on the endothelial function and progression of arterial stiffness.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Ankle Brachial Index
  • Atherosclerosis / epidemiology
  • Atherosclerosis / etiology
  • Atherosclerosis / physiopathology*
  • Blood Flow Velocity
  • Carotid Artery Diseases / epidemiology
  • Carotid Artery Diseases / etiology
  • Carotid Artery Diseases / physiopathology*
  • Carotid Artery, Common / diagnostic imaging
  • Carotid Artery, Common / physiopathology*
  • Diabetes Mellitus, Type 2 / complications*
  • Diabetes Mellitus, Type 2 / physiopathology
  • Endothelium, Vascular / physiopathology*
  • Female
  • Follow-Up Studies
  • Humans
  • Incidence
  • Japan / epidemiology
  • Male
  • Middle Aged
  • Retrospective Studies
  • Ultrasonography
  • Vascular Stiffness / physiology*
  • Vasodilation / physiology*