Correlation of microvascular abnormalities and endothelial dysfunction in Type-1 Diabetes Mellitus (T1DM): a real-time intravital microscopy study

Clin Hemorheol Microcirc. 2009;42(4):285-95. doi: 10.3233/CH-2009-1199.

Abstract

We hypothesize that real-time in vivo microvascular abnormalities should correlate with biochemical markers of inflammation/endothelial dysfunction in T1DM. Real-time quantification of T1DM and healthy non-diabetic control microcirculation was conducted utilizing computer-assisted intravital microscopy. Selected biochemical markers (high sensitivity C-reactive protein (hsCRP), soluble vascular cell adhesion molecules (sVCAM), soluble intercellular adhesion molecules (sICAM), soluble E-selectin (sE-selectin), nitrotyrosine, superoxide anion (O2-), interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha)) were used for correlation. The severity of microvascular abnormalities, as reflected by the arithmetic severity index (SI), was significantly increased in T1DM vs. controls (5.89 +/- 1.47 vs. 2.34 +/- 1.48; P<0.001). In addition several of the specific microvascular abnormalities (related to flow and morphometry) were significantly more prevalent in the T1DM patients. Finally, the following significant positive correlations existed between the inflammatory/endothelial dysfunction markers and specific microvascular abnormalities: sVCAM and abnormal vessel diameter (P=0.004, OR =1.033, 95% CI for OR =(1.01, 1.056)), superoxide (O2-) release and abnormal vessel distribution (P=0.032, OR =1.798, 95% CI for OR =(1.051, 3.075)), and sE-selectin and abnormal vessel distribution (P=0.036, OR =1.118, 95% CI for OR =(1.007, 1.241)). In view of such significant correlations, we conclude that these specific microvascular abnormalities can serve as unique physiologic markers of endothelial dysfunction to correlate with the biochemical markers of inflammatory/endothelial dysfunction in disease progression and therapeutic efficacy studies.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • C-Reactive Protein / analysis
  • Cell Adhesion Molecules / blood
  • Diabetes Mellitus, Type 1 / physiopathology*
  • E-Selectin / blood
  • Endothelium, Vascular / immunology*
  • Endothelium, Vascular / physiopathology
  • Female
  • Humans
  • Interleukin-1beta / analysis
  • Male
  • Microscopy, Video / methods*
  • Microvessels / pathology*
  • Middle Aged
  • Superoxides / analysis
  • Tumor Necrosis Factor-alpha / analysis
  • Vascular Cell Adhesion Molecule-1 / blood
  • Young Adult

Substances

  • Cell Adhesion Molecules
  • E-Selectin
  • Interleukin-1beta
  • Tumor Necrosis Factor-alpha
  • Vascular Cell Adhesion Molecule-1
  • Superoxides
  • C-Reactive Protein