Raised Serum Sialic Acid Concentration Precedes Onset of Microalbuminuria in IDDM: A 10-year follow-up study

Yokoyama, Hiroyuki; Jensen, Jan Skov; Myrup, B.; Mathiesen, Elisabeth R.; Rønn, Birgitte; Deckert, T.

doi:10.2337/diacare.19.5.435

Cited by 29 publications

(17 citation statements)

References 22 publications

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“…There are several possible explanations for these discrepant findings. First, studies that found high vWf levels to be associated with the development of elevated UAER 8 had a shorter duration of follow-up (3.1 to 5.3 years) than did studies that did not find this association (Yokoyama et al 29 and the present study, 6.6 to 10.0 years). Late-onset elevated UAER may have a different pathogenesis than does early-onset elevated UAER.…”

Section: Discussioncontrasting

confidence: 47%

“…28 Our findings on CRP support the hypothesis that low-grade inflammation is causally related to the development of elevated UAER. 15,29 The main stimulators of production of acute-phase reactants are proinflammatory cytokines. Interleukin-6 may be an important mediator of mesangial cell proliferation and matrix overproduction 30 but also of an increase in general vascular permeability without involvement of the kidney.…”

Section: Discussionmentioning

confidence: 99%

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C-Reactive Protein and Soluble Vascular Cell Adhesion Molecule-1 Are Associated With Elevated Urinary Albumin Excretion but Do Not Explain Its Link With Cardiovascular Risk

Jager

Hinsbergh

Kostense

et al. 2002

ATVB

114

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Abstract-An elevated urinary albumin excretion rate (UAER) is associated with an increased risk of cardiovascular mortality, but the pathophysiological mechanism underlying this association is poorly understood. To investigate the role of endothelial dysfunction, leukocyte adhesion, and low-grade inflammation (1) in the development of elevated UAER (study I) and (2) in linking elevated UAER with risk of cardiovascular mortality (study II), we performed a prospective study in an age-, sex-, and glucose tolerance-stratified sample of a population-based cohort aged 50 to 75 years. High levels of von Willebrand factor, soluble vascular cell adhesion molecule-1 (sVCAM-1), and C-reactive protein (CRP) were used as markers of endothelial dysfunction, leukocyte adhesion, and low-grade inflammation, respectively. For study I, subjects who had normal UAER at baseline (nϭ316 subjects, 66 with type 2 diabetes) were reexamined after a mean follow-up of 6.1 years. The development of elevated UAER was defined as a mean albumin-to-creatinine ratio Ͼ2.0 mg/mmol at follow-up. Age-, sex-, and glucose tolerance-adjusted logistic regression analyses showed the development of elevated UAER to be significantly associated with levels of sVCAM-1 and CRP (odds ratio 1.14 [95% CI 1.02 to 1.27] per 10% increase of sVCAM-1 and odds ratio 1.17 [95% CI 1.04 to 1.32] per 50% increase of CRP). The results were not materially different after additional adjustment for hypertension, body mass index, cardiovascular disease, and creatinine clearance or stratification by the presence of diabetes. For study II, the vital status of all subjects (nϭ575) was determined after a mean follow-up of 6.6 years. Eighty-one of 575 subjects died (30 died of cardiovascular disease). The presence of elevated UAER at baseline was associated with a 4.1-fold (1.94 to 8.73) increased risk of cardiovascular death after adjustment for age, sex, and glucose tolerance status. Adjustment for levels of von Willebrand factor, sVCAM-1, or CRP did not materially affect the results, nor did additional adjustment for the presence of hypertension, retinopathy, and cardiovascular disease and for levels of homocysteine, triglycerides, and high density lipoprotein cholesterol. Leukocyte adhesion (sVCAM-1) and low-grade inflammation (CRP) are determinants of the development of elevated UAER. However, these determinants do not explain the association between elevated UAER and cardiovascular mortality. Key Words: elevated urinary albumin excretion rate Ⅲ von Willebrand factor Ⅲ C-reactive protein Ⅲ soluble vascular cell adhesion molecule-1 Ⅲ cardiovascular mortality E levated urinary albumin excretion rate (UAER) is associated with an increased risk of cardiovascular disease among individuals with and without type 2 diabetes. 1,2 The pathophysiological mechanism linking elevated UAER to cardiovascular disease is unknown; the most commonly held view is that elevated UAER reflects a pathophysiological process predisposing an individual to atherothrombosis. 3 Atherothrombosis is a low-gr...

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Section: Discussioncontrasting

confidence: 47%

Section: Discussionmentioning

confidence: 99%

C-Reactive Protein and Soluble Vascular Cell Adhesion Molecule-1 Are Associated With Elevated Urinary Albumin Excretion but Do Not Explain Its Link With Cardiovascular Risk

Jager

Hinsbergh

Kostense

et al. 2002

ATVB

114

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“…Some patients with microalbuminuria, for example, have quite advanced renal structural changes, and microalbuminuria may here be a marker of microvascular damage that has already occurred. If circulating sialic acid increases before microangiopathy develops (33), it may be an early signal of processes such as hypercytokinemia that cause or drastically increase the risk of vasculopathy.…”

Section: Conclusion -mentioning

confidence: 99%

Relationship Between Plasma Sialic Acid Concentration and Microvascular and Macrovascular Complications in Type 1 Diabetes

Pj³

et al. 2001

Diabetes Care

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The APPENDIX section contains a complete list of centers that participated in the EURODIAB IDDM Complications Study.Abbreviations: AER, albumin excretion rate; CHD, coronary heart disease; CV, coefficient of variation. A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances. Relationship Between Plasma Sialic Acid Concentration and Microvascular and Macrovascular Complications in Type 1 DiabetesThe EURODIAB Complications StudyOBJECTIVE -To test the hypothesis that an increased plasma concentration of sialic acid, a marker of the acute-phase response, is related to the presence of diabetic micro-and macrovascular complications in type 1 diabetes. RESEARCH DESIGN AND METHODS -We investigated the relationship betweenplasma sialic acid concentration and nephropathy, retinopathy, neuropathy, and coronary heart disease (CHD) in a cross-sectional survey of 1,369 people with type 1 diabetes. Subjects were participants in the EURODIAB IDDM Complications Study, which involved 31 centers in 16 European countries.RESULTS -There was a significantly increasing trend of plasma sialic acid with severity of retinopathy (P Ͻ 0.001 in men) and with degree of urinary albumin excretion (P Ͻ 0.001 men, P Ͻ 0.01 women). Plasma sialic acid correlated with increasing plasma creatinine concentration (P Ͻ 0.009 men, P Ͻ 0.0002 women), and men with neuropathy had a higher plasma sialic acid concentration than those without (P Ͻ 0.006). There was no significant correlation between plasma sialic acid and CHD in either sex. Elevated plasma sialic acid concentrations were also associated with several risk factors for diabetic vascular disease: diabetes duration, HbA 1c , plasma triglyceride and cholesterol concentrations, waist-to-hip ratio, hypertension and smoking (in men), and low physical exercise (in women). In multiple logistic regression analysis, plasma sialic acid was independently related to proliferative retinopathy and urinary albumin excretion rate in men.CONCLUSIONS -We conclude that an elevated plasma sialic concentration is strongly related to the presence of microvascular complications in type 1 diabetes, especially retinopathy and nephropathy. Further study of acute-phase response markers and mediators as indicators or predictors of diabetic microvascular complications is therefore justified.

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“…It is likely that endothelial dysfunction and chronic low-grade inflammation, presumably provoked by hyperglycemia, precedes a slight elevation of UAE, leading to "microalbuminuria" [32][33][34] . However, endothelial dysfunction as well as chronic lowgrade inflammation was mostly studied by serum/ plasma concentrations, such as von Willebrand factor, tissue-type plasminogen activator, soluble vascular cell adhesion molecule 1, sialic acid and C-reactive protein [32][33][34] , while we investigated endothelial dysfunction through measurement of brachial artery FMD. Our finding of the close association between FMD and microalbuminuria, together with the findings of the above serum markers reported previously, indicates a close linkage between endothelial dysfunction and microalbuminuria, which may be an attractive explanation for the fact that microalbuminuria is a risk marker of CVD in diabetes.…”

Section: Fmd and Microalbuminuriamentioning

confidence: 99%

Flow-Mediated Dilation is Associated with Microalbuminuria Independent of Cardiovascular Risk Factors in Type 2 Diabetes

Yokoyama

Sone

Saito

et al. 2011

JAT

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Raised Serum Sialic Acid Concentration Precedes Onset of Microalbuminuria in IDDM: A 10-year follow-up study

Cited by 29 publications

References 22 publications

C-Reactive Protein and Soluble Vascular Cell Adhesion Molecule-1 Are Associated With Elevated Urinary Albumin Excretion but Do Not Explain Its Link With Cardiovascular Risk

C-Reactive Protein and Soluble Vascular Cell Adhesion Molecule-1 Are Associated With Elevated Urinary Albumin Excretion but Do Not Explain Its Link With Cardiovascular Risk

Relationship Between Plasma Sialic Acid Concentration and Microvascular and Macrovascular Complications in Type 1 Diabetes

Flow-Mediated Dilation is Associated with Microalbuminuria Independent of Cardiovascular Risk Factors in Type 2 Diabetes

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