Endothelial inflammation in insulin resistance

Lancet. 2005 Feb 12-18;365(9459):610-2. doi: 10.1016/S0140-6736(05)17912-4.


Context: Type 2 diabetes and attendant cardiovascular morbidity are becoming major health concerns globally. Obesity-related type 2 diabetes is rapidly rising in prevalence, probably largely because of increased longevity and sedentary lifestyles. Insulin resistance and type 2 diabetes are associated with increased coronary heart disease, but the severity of glycaemia during the diabetic phase can only to a minor extent explain the increased risk. Increased levels of the acute-phase inflammatory marker, C-reactive protein (CRP), are related to insulin resistance and the metabolic syndrome, suggesting a role for chronic low-grade inflammation. CRP levels might predict the development of type 2 diabetes.

Starting point: Subodh Verma and associates (Circulation 2004; 109: 2058-67) recently showed that CRP attenuates the survival, differentiation, and function of endothelial progenitor cells, partly by CRP reducing expression of endothelial nitric-oxide synthase. Rosiglitazone, a peroxisome-proliferator-activator receptor gamma agonist, inhibits the negative effects of CRP on endothelial progenitor cells. The results are consistent with the suggestion that CRP directly promotes atherosclerotic processes and endothelial cell inflammation. CRP might thus directly trigger the development of a proinflammatory and proatherosclerotic state, leading to atherothrombosis.

Where next: Cell-surface CRP receptors and signalling pathways need to be characterised. From such study might come novel drugs that will defer proinflammatory reactions leading to insulin resistance and atherothrombosis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Arteriosclerosis / physiopathology
  • Biomarkers
  • C-Reactive Protein / analysis
  • C-Reactive Protein / physiology*
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / pathology
  • Diabetes Mellitus, Type 2 / physiopathology*
  • Endothelium, Vascular / pathology
  • Endothelium, Vascular / physiology*
  • Humans
  • Inflammation
  • Inflammation Mediators / physiology
  • Insulin Resistance / physiology*
  • Metabolic Syndrome / physiopathology


  • Biomarkers
  • Inflammation Mediators
  • C-Reactive Protein