High density lipoproteins in the intersection of diabetes mellitus, inflammation and cardiovascular disease

Curr Opin Lipidol. 2004 Jun;15(3):269-78. doi: 10.1097/00041433-200406000-00006.


Purpose of review: Low HDL-cholesterol, diabetes mellitus and elevated C-reactive protein as well as various inflammatory diseases are risk factors for coronary heart disease. Both diabetes mellitus and inflammation decrease HDL-cholesterol. We summarize recent findings on the mechanisms underlying low HDL-cholesterol in diabetes and inflammation, as well as on novel functions of HDL that may protect not only from atherosclerosis but also from diabetes mellitus and inflammation-induced organ damage.

Recent findings: Elevated levels of non-esterified fatty acids and disturbed insulin action contribute to low HDL-cholesterol in diabetes mellitus by modifying lipolysis, apolipoprotein A-I production, as well as the activities of adenosine triphosphate-binding cassette transporter A1 and lipid transfer. Inflammation causes low HDL-cholesterol by increasing the activities of endothelial lipase and soluble phospholipase A2 and by replacing apolipoprotein A-I in HDL with serum amyloid A. HDL and lysosphingolipids therein have been identified as activators of the protein kinase Akt, which in turn is a regulator of apoptosis in beta-cells, endothelial cells, and smooth muscle cells, as well as a regulator of nitric oxide production and adhesion molecule expression in endothelial cells.

Summary: The protective properties of HDL in cytokine production, lipid oxidation, cholesterol efflux and reverse cholesterol transport make HDL a protective agent in inflammation-induced organ damage including diabetes mellitus. However, inflammation and diabetes cause a decrease in HDL-cholesterol concentrations and impair HDL function, placing HDL into the centre of a vicious cycle that may escalate into diabetes mellitus, inflammation-induced organ damage and atherosclerosis.

Publication types

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

MeSH terms

  • Animals
  • Apolipoprotein A-I / metabolism
  • C-Reactive Protein / metabolism
  • Cardiovascular Diseases / metabolism*
  • Cholesterol, HDL / metabolism
  • Diabetes Mellitus / metabolism*
  • Endothelium, Vascular / metabolism
  • Endothelium, Vascular / pathology
  • Endothelium, Vascular / physiopathology
  • Humans
  • Inflammation / metabolism*
  • Inflammation / pathology
  • Lipoproteins, HDL / metabolism*


  • Apolipoprotein A-I
  • Cholesterol, HDL
  • Lipoproteins, HDL
  • C-Reactive Protein