AIMS/HYPOTHESIS: Plasma soluble receptor for AGE (sRAGE) may reflect the activity of the AGE-RAGE axis, which has been proposed as a potential mechanism linking hyperglycaemia to vascular complications in diabetes. We have therefore investigated: (1) whether sRAGE is associated with greater prevalence of cardiovascular disease (CVD) and microvascular complications in type 1 diabetic individuals; and (2) the extent to which any such associations are explained by markers of endothelial and renal dysfunction and inflammation. METHODS: The study included 477 individuals (234 women; mean age 42 +/- 10 [SD] years) from the EURODIAB Prospective Complications Study. We used linear regression analyses to investigate the differences in sRAGE levels between individuals with and without vascular complications. All analyses were adjusted for age, sex, HbA(1c), duration of diabetes and other risk factors. RESULTS: Individuals with CVD (n = 116) had higher levels of sRAGE than those without CVD or any microvascular complications (n = 178): beta = 0.15 (95% CI 0.04-0.27). Further adjustments for markers of endothelial (beta = 0.13 [0.02-0.24]) and renal dysfunction (beta = 0.10 [-0.01, 0.20]) and inflammation (beta = 0.12 [0.01-0.23]) attenuated these differences; altogether these variables explained about 50% of the association between sRAGE and prevalent CVD. sRAGE levels tended to be higher in the presence and across the levels of severity of albuminuria (p for trend = 0.087) and retinopathy (p for trend = 0.057); adjustments for endothelial and renal dysfunction and inflammation also attenuated these differences. CONCLUSIONS/ INTERPRETATION: sRAGE is associated with greater prevalence of CVD in type 1 diabetic individuals, and these associations may be partly explained by endothelial and renal dysfunction and low-grade inflammation.
AIMS/HYPOTHESIS: Plasma soluble receptor for AGE (sRAGE) may reflect the activity of the AGE-RAGE axis, which has been proposed as a potential mechanism linking hyperglycaemia to vascular complications in diabetes. We have therefore investigated: (1) whether sRAGE is associated with greater prevalence of cardiovascular disease (CVD) and microvascular complications in type 1 diabetic individuals; and (2) the extent to which any such associations are explained by markers of endothelial and renal dysfunction and inflammation. METHODS: The study included 477 individuals (234 women; mean age 42 +/- 10 [SD] years) from the EURODIAB Prospective Complications Study. We used linear regression analyses to investigate the differences in sRAGE levels between individuals with and without vascular complications. All analyses were adjusted for age, sex, HbA(1c), duration of diabetes and other risk factors. RESULTS: Individuals with CVD (n = 116) had higher levels of sRAGE than those without CVD or any microvascular complications (n = 178): beta = 0.15 (95% CI 0.04-0.27). Further adjustments for markers of endothelial (beta = 0.13 [0.02-0.24]) and renal dysfunction (beta = 0.10 [-0.01, 0.20]) and inflammation (beta = 0.12 [0.01-0.23]) attenuated these differences; altogether these variables explained about 50% of the association between sRAGE and prevalent CVD. sRAGE levels tended to be higher in the presence and across the levels of severity of albuminuria (p for trend = 0.087) and retinopathy (p for trend = 0.057); adjustments for endothelial and renal dysfunction and inflammation also attenuated these differences. CONCLUSIONS/ INTERPRETATION: sRAGE is associated with greater prevalence of CVD in type 1 diabetic individuals, and these associations may be partly explained by endothelial and renal dysfunction and low-grade inflammation.
Authors: Miranda T Schram; Casper G Schalkwijk; Aart H Bootsma; John H Fuller; Nish Chaturvedi; Coen D A Stehouwer Journal: Hypertension Date: 2005-04-25 Impact factor: 10.190
Authors: Evis Harja; De-xiu Bu; Barry I Hudson; Jong Sun Chang; Xiaoping Shen; Kellie Hallam; Anastasia Z Kalea; Yan Lu; Rosa H Rosario; Sai Oruganti; Zana Nikolla; Dmitri Belov; Evanthia Lalla; Ravichandran Ramasamy; Shi Fang Yan; Ann Marie Schmidt Journal: J Clin Invest Date: 2008-01 Impact factor: 14.808
Authors: Barry I Hudson; Angela M Carter; Evis Harja; Anastasia Z Kalea; Maria Arriero; Hojin Yang; Peter J Grant; Ann Marie Schmidt Journal: FASEB J Date: 2007-12-18 Impact factor: 5.191
Authors: Per M Humpert; Zdenka Djuric; Stefan Kopf; Gottfried Rudofsky; Michael Morcos; Peter P Nawroth; Angelika Bierhaus Journal: Cardiovasc Diabetol Date: 2007-03-07 Impact factor: 9.951
Authors: Mohamed M Nasrallah; Amal R El-Shehaby; Noha A Osman; Mona M Salem; Amr Nassef; Usama A A Sharaf El Din Journal: Int Urol Nephrol Date: 2011-06-04 Impact factor: 2.370
Authors: M C Thomas; J Söderlund; M Lehto; V-P Mäkinen; J L Moran; M E Cooper; C Forsblom; P-H Groop Journal: Diabetologia Date: 2011-05-24 Impact factor: 10.122
Authors: Y Yu; K F Hanssen; V Kalyanaraman; A Chirindel; A J Jenkins; A J Nankervis; P A Torjesen; H Scholz; T Henriksen; B Lorentzen; S K Garg; M K Menard; S M Hammad; J A Scardo; J R Stanley; M Wu; A Basu; C E Aston; T J Lyons Journal: BJOG Date: 2012-08-20 Impact factor: 6.531
Authors: Johanna W M Nin; Anders Jorsal; Isabel Ferreira; Casper G Schalkwijk; Martin H Prins; Hans-Henrik Parving; Lise Tarnow; Peter Rossing; Coen D A Stehouwer Journal: Diabetes Date: 2010-06-03 Impact factor: 9.461