Levels of soluble receptor for AGE are cross-sectionally associated with cardiovascular disease in type 1 diabetes, and this association is partially mediated by endothelial and renal dysfunction and by low-grade inflammation: the EURODIAB Prospective Complications Study.

J.W.M. Nin; I. Ferreira; C.G. Schalkwijk; M.H. Prins; N. Chaturvedi; J.H. Fuller; C.D. Stehouwer

doi:10.1007/s00125-009-1263-5

Levels of soluble receptor for AGE are cross-sectionally associated with cardiovascular disease in type 1 diabetes, and this association is partially mediated by endothelial and renal dysfunction and by low-grade inflammation: the EURODIAB Prospective Complications Study.

J.W.M. Nin^*, I. Ferreira, C.G. Schalkwijk, M.H. Prins, N. Chaturvedi, J.H. Fuller, C.D. Stehouwer

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

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.

Original language	English
Pages (from-to)	705-714
Journal	Diabetologia
Volume	52
Issue number	4
DOIs	https://doi.org/10.1007/s00125-009-1263-5
Publication status	Published - 1 Jan 2009

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Nin, J. W. M., Ferreira, I., Schalkwijk, C. G., Prins, M. H., Chaturvedi, N., Fuller, J. H., & Stehouwer, C. D. (2009). Levels of soluble receptor for AGE are cross-sectionally associated with cardiovascular disease in type 1 diabetes, and this association is partially mediated by endothelial and renal dysfunction and by low-grade inflammation: the EURODIAB Prospective Complications Study. Diabetologia, 52(4), 705-714. https://doi.org/10.1007/s00125-009-1263-5

Nin, J.W.M. ; Ferreira, I. ; Schalkwijk, C.G. et al. / Levels of soluble receptor for AGE are cross-sectionally associated with cardiovascular disease in type 1 diabetes, and this association is partially mediated by endothelial and renal dysfunction and by low-grade inflammation: the EURODIAB Prospective Complications Study. In: Diabetologia. 2009 ; Vol. 52, No. 4. pp. 705-714.

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title = "Levels of soluble receptor for AGE are cross-sectionally associated with cardiovascular disease in type 1 diabetes, and this association is partially mediated by endothelial and renal dysfunction and by low-grade inflammation: the EURODIAB Prospective Complications Study.",

abstract = "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.",

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Nin, JWM, Ferreira, I, Schalkwijk, CG, Prins, MH, Chaturvedi, N, Fuller, JH & Stehouwer, CD 2009, 'Levels of soluble receptor for AGE are cross-sectionally associated with cardiovascular disease in type 1 diabetes, and this association is partially mediated by endothelial and renal dysfunction and by low-grade inflammation: the EURODIAB Prospective Complications Study.', Diabetologia, vol. 52, no. 4, pp. 705-714. https://doi.org/10.1007/s00125-009-1263-5

Levels of soluble receptor for AGE are cross-sectionally associated with cardiovascular disease in type 1 diabetes, and this association is partially mediated by endothelial and renal dysfunction and by low-grade inflammation: the EURODIAB Prospective Complications Study. / Nin, J.W.M.; Ferreira, I.; Schalkwijk, C.G. et al.
In: Diabetologia, Vol. 52, No. 4, 01.01.2009, p. 705-714.

Research output: Contribution to journal › Article › Academic › peer-review

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T1 - Levels of soluble receptor for AGE are cross-sectionally associated with cardiovascular disease in type 1 diabetes, and this association is partially mediated by endothelial and renal dysfunction and by low-grade inflammation: the EURODIAB Prospective Complications Study.

AU - Nin, J.W.M.

AU - Ferreira, I.

AU - Schalkwijk, C.G.

AU - Prins, M.H.

AU - Chaturvedi, N.

AU - Fuller, J.H.

AU - Stehouwer, C.D.

PY - 2009/1/1

Y1 - 2009/1/1

N2 - 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.

AB - 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.

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DO - 10.1007/s00125-009-1263-5

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Nin JWM, Ferreira I, Schalkwijk CG, Prins MH, Chaturvedi N, Fuller JH et al. Levels of soluble receptor for AGE are cross-sectionally associated with cardiovascular disease in type 1 diabetes, and this association is partially mediated by endothelial and renal dysfunction and by low-grade inflammation: the EURODIAB Prospective Complications Study. Diabetologia. 2009 Jan 1;52(4):705-714. doi: 10.1007/s00125-009-1263-5