Elevated plasma levels of soluble receptor for advanced glycation endproducts (sRAGE) are associated with incident fatal and nonfatal cardiovascular disease (CVD) and all-cause mortality in patients with Type 1 diabetes, report researchers.

“Recent studies have suggested a potential role of the RAGE in the development of vascular disease in individuals with diabetes mellitus,” write Johanna Nin (Maastricht University Medical Centre, The Netherlands) and colleagues in the journal Diabetes.

They say: “RAGE-induced production of adhesion molecules and inflammatory cytokines could contribute to endothelial and renal dysfunction, low-grade inflammation and arterial stiffening, all of which may partially explain the increased CVD in diabetes.”

To investigate links between sRAGE and CVD in diabetes further, the researchers recruited 339 individuals with Type 1 diabetes, 169 with diabetic nephropathy, and 170 with persistent normoalbuminuria who were followed up for a combination of fatal and nonfatal CVD for a median period of 12.3 years.

CVD included: myocardial infarction, percutaneous coronary intervention, coronary bypass grafting, amputation due to ischemia, vascular surgery for peripheral atherosclerotic disease, and stroke. sRAGE and other biomarkers were measured at baseline.

During the follow-up period, 82 people died, 48 suffered fatal, and 53 nonfatal CVD. Fatal and nonfatal CVD and all-cause mortality increased significantly with higher baseline levels of sRAGE.

More specifically, for each unit increase in the natural log of sRAGE the risks for fatal and non fatal CVD increased 1.90 and 2.12 fold, respectively, even after adjusting for other CVD risk factors.

Further adjustment for estimated glomerular filtration rate (GFR), markers of endothelial dysfunction, low-grade inflammation, arterial stiffness, and AGEs, weakened the corresponding risk increases to 1.59 and 1.90 fold. However, they were still modestly statistically significant.

Increased sRAGE levels also contributed to decline in GFR in patients with nephropathy, with each 1-unit increase in the natural log of sRAGE associated with a 1.38 ml/min/1.73 m² per year greater rate of GFR decline.

The authors conclude: “Higher plasma sRAGE levels, as a reflection of RAGE expression, are associated with incident fatal and nonfatal CVD as well as all-cause mortality in Type 1 diabetes.”

They suggest that “this may partially be explained by sRAGE-associated renal dysfunction in patients with nephropathy.”

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2010

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