Elevated Serum Sialic Acid Concentration in NIDDM and Its Relationship to Blood Pressure and Retinopathy

Crook, Martin; Tutt, P; Pickup, John C.

doi:10.2337/diacare.16.1.57

Cited by 119 publications

(77 citation statements)

References 12 publications

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“…A relationship between serum or plasma sialic acid levels and microvascular complications has been observed before in small-scale studies for microalbuminuria and clinical proteinuria in type 1 (6,7) and type 2 diabetes (18), and for retinopathy in type 1 (19) and type 2 diabetes (20). An association with neuropathy has not been reported before.…”

Section: Conclusion -mentioning

confidence: 76%

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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Section: Conclusion -mentioning

confidence: 76%

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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“…We showed, however, that concentrations of the acutephase marker, serum sialic acid, are raised in Type II diabetes, even in those without diabetic tissue complications, but are not altered in uncomplicated Type I diabetic subjects of similar age and glycaemic control to the Type II diabetic group [19,20].…”

Section: Evidence For An Acute-phase Response In Type II Diabetesmentioning

confidence: 67%

Is Type II diabetes mellitus a disease of the innate immune system?

1998

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The cause of the common type of Type II (non-insulin-dependent) diabetes mellitus, which affects at least 100 million people throughout the world, is not known. One of the foremost challenges we face is to account mechanistically for not only the defining hyperglycaemia but also for the myriad of other biochemical and physiological abnormalities which are characteristic of this disease. For example, it is now clear that Type II diabetes and lesser degrees of glucose intolerance commonly occur together with a collection of clinical and biochemical features which have been called metabolic syndrome X [1, 2].These features include central obesity, hypertension, accelerated atherosclerosis, hypertriglyceridaemia and low serum concentrations of high-density lipoprotein (HDL) cholesterol. Though insulin resistance seems to be a central abnormality, the origin of the impaired insulin action and how it explains the many other abnormalities of Type II diabetes is not known.In recent years, we have been gathering evidence that in Type II diabetes there is a cytokine-associated acute-phase reaction, part of the innate immune response. As an alternative direction for research into the aetiology of Type II diabetes, we propose that it may be helpful to consider whether the mechanisms involved in the acute-phase response can be major contributors to the pathophysiology of many of the features of Type II diabetes and syndrome X, including glucose intolerance, insulin resistance, impair- Diabetologia (1998) Summary Type II (non-insulin-dependent) diabetes mellitus is associated with increased blood concentrations of markers of the acute-phase response, including sialic acid, a-1 acid glycoprotein, serum amyloid A, C-reactive protein and cortisol, and the main cytokine mediator of the response, interleukin-6. The dyslipidaemia common in Type II diabetes (hypertriglyceridaemia and low serum levels of HDL cholesterol) is also a feature of natural and experimental acutephase reactions. We review evidence that a long-term cytokine-mediated acute-phase reaction occurs in Type II diabetes and is part of a wide-ranging innate immune response. Through the action of cytokines on the brain, liver, endothelium, adipose tissue and elsewhere, this process could be a major contributor to the biochemical and clinical features of metabolic syndrome X (glucose intolerance, dyslipidaemia, insulin resistance, hypertension, central obesity, accelerated atherosclerosis) but also provides a mechanism for many other abnormalities seen in Type II diabetes, including those in blood clotting, the reproductive system, metal ion metabolism, psychological behaviour and capillary permeability. In the short-term, the innate immune system restores homeostasis after environmental threats; we suggest that in Type II diabetes and impaired glucose tolerance long-term lifestyle and environmental stimulants, probably in those with an innately hypersensitive acute-phase response, produce disease instead of repair. [Diabetologia (1998

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“…serum sialic acid is a marker of the acute-phase response (5,12), acute-phase glycoproteins with sialic acid as a component of the oligosaccharide side chain being produced by the liver, stimulated by pro inflammatory cytokines such as interleukin-1, interleukin-6, and tumor necrosis factor (13,14).So the present finding explains that tissue injury caused by diabetic vascular complications and endothelial dysfunction. Previous studies in NIDDM and IDDM with incipient nephropathy demonstrated increased serum total Sialicacid levels [15,16] which is claimed to be a strong predictor of cardiovascular mortality [11,17,18]. Serum total sialic acid was significantly increased in patients undergoing cardiopulmonary bypass, which is known to induce an inflammatory response [19] and correlated with inflammatory, but not ischaemic markers, following cross-clamp removal [20].And interestingly serum total sialic acid, total and LDL cholesterol were significantly decreased in growth hormone-deficient adults who were randomized to receive 3 months of growth hormone replacement therapy, compared to placebo therapy [21].…”

Section: Discussionmentioning

confidence: 99%

“…some prospective studies that have investigated the relation between sialic acid and risk of cardiovascular disease. An elevated serum concentration of sialic acid (N-acetylneuraminic acid) is a strong predictor in the general population of cardiovascular death [8][9][10][11].…”

Section: Introductionmentioning

confidence: 99%