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. 2011 Feb;34(2):442-7.
doi: 10.2337/dc10-1087.

Higher plasma levels of advanced glycation end products are associated with incident cardiovascular disease and all-cause mortality in type 1 diabetes: a 12-year follow-up study

Johanna W Nin  1 , Anders Jorsal, Isabel Ferreira, Casper G Schalkwijk, Martin H Prins, Hans-Henrik Parving, Lise Tarnow, Peter Rossing, Coen D Stehouwer
Affiliations

Higher plasma levels of advanced glycation end products are associated with incident cardiovascular disease and all-cause mortality in type 1 diabetes: a 12-year follow-up study

Johanna W Nin et al. Diabetes Care. 2011 Feb.

Abstract

Objective: To investigate the associations of plasma levels of advanced glycation end products (AGEs) with incident cardiovascular disease (CVD) and all-cause mortality in type 1 diabetes and the extent to which any such associations could be explained by endothelial and renal dysfunction, low-grade inflammation, and arterial stiffness.

Research design and methods: We prospectively followed 169 individuals with diabetic nephropathy and 170 individuals with persistent normoalbuminuria who were free of CVD at study entry and in whom levels of N(ε)-(carboxymethyl)lysine, N(ε)-(carboxyethyl)lysine, pentosidine and other biomarkers were measured at baseline. The median follow-up duration was 12.3 (interquartile range 7.6-12.5) years.

Results: During the course of follow-up, 82 individuals (24.2%) died; 85 (25.1%) suffered a fatal (n = 48) and/or nonfatal (n = 53) CVD event. The incidence of fatal and nonfatal CVD and of all-cause mortality increased with higher baseline levels of AGEs independently of traditional CVD risk factors: hazard ratio (HR) = 1.30 (95% CI = 1.03-1.66) and HR = 1.27 (1.00-1.62), respectively. These associations were not attenuated after further adjustments for markers of renal or endothelial dysfunction, low-grade inflammation, or arterial stiffness.

Conclusions: Higher levels of AGEs are associated with incident fatal and nonfatal CVD as well as all-cause mortality in individuals with type 1 diabetes, independently of other risk factors and of several potential AGEs-related pathophysiological mechanisms. Thus, AGEs may explain, in part, the increased cardiovascular disease and mortality attributable to type 1 diabetes and constitute a specific target for treatment in these patients.

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