Serum Sialic Acid, a Risk Factor for Cardiovascular Disease, Is Increased in IDDM Patients With Microalbuminuria and Clinical Proteinuria

Crook, Martin; Earle, Kenneth; Morocutti, Anna; Yip, Jeannie; Viberti, Giancarlo; Pickup, John C.

doi:10.2337/diacare.17.4.305

Cited by 68 publications

(41 citation statements)

References 35 publications

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“…Our hypothesis is that the cytokine-induced acute-phase response is a pathophysiological mechanism that explains some of the features of Type II diabetes, whatever the cause of the stress response. A stress response does occur in Type I diabetic patients with nephropathy [77], but here the effects are altered by the superimposed biochemical and clinical manifestations of severe insulin deficiency. It remains possible that the acute-phase response contributes to the hypertension, hyperlipidaemia, insulin resistance and atherosclerosis which is seen in these Type I diabetic patients.…”

Section: Arguments Against the Hypothesismentioning

confidence: 98%

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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Section: Arguments Against the Hypothesismentioning

confidence: 98%

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

1998

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“…The causal mechanism of increased serum sialic acid concentration in diabetic patients is unknown. However, the loss of sialic acid-containing glycoproteins from vascular cells into the bloodstream, and cytokineinduced acute phase response (cytokines stimulate the hepatic production of acute phase proteins with notable sialic acid content) may lead to elevated serum sialic acid levels (10). Declining renal function can also impair the excretion of sialic acid-containing glycoconjugates and cause elevated levels of serum sialic acid (10,11).…”

Section: Discussionmentioning

confidence: 99%

Comparative study of total protein, and total and lipid‐associated serum sialic acid levels in patients with type 2 diabetes mellitus

Ekin

Meral

Gündüz

et al. 2003

Clinical Laboratory Analysis

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The aim of the present study was to investigate the serum total protein (TP), total sialic acid (TSA), lipid-associated sialic acid (LSA), LSA/TP, and LSA/TP values in type 2 diabetes mellitus (DM) patients. Two study groups (healthy controls and type 2 DM subjects) were examined. For the type 2 DM group, 120 patients (60 females and 60 males) who had been diagnosed and treated for type 2 DM in the Yuzuncu Yil University Hospital, Van, Turkey, were selected consecutively. Forty healthy individuals (20 females and 20 males) were selected from hospital staff and other outpatient clinics to serve as the control group. They were matched for age, sex, body mass index, and smoking status. None of the participants had taken vitamin or mineral supplements for at least 2 weeks before sampling. To determine serum glucose, TP, TSA, and LSA levels, blood samples were drawn after all of the subjects fasted overnight. It was found that diabetics had higher TSA, LSA, TSA/TP, and LSA/TP levels than controls. However, the TP levels were not significantly different between the groups. Our results showed that TSA, LSA, TSA/TP, and LSA/TP have interactive connections with DM. These parameters can be used as a diagnostic index for patients with DM.

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“…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%