Homocysteine enhances LDL fatty acid peroxidation, promoting microalbuminuria in type 2 diabetes

Abstract

Background: We aimed to establish the relationship between glycated haemoglobin (HbA 1c ), hypertension and microalbuminuria onset in type 2 diabetes. We also intended to ascertain the metabolic action of homocysteine on LDL fatty acids and on renal function. Methods: The study was carried out on 200 patients with type 2 diabetes and 200 healthy subjects. HbA 1c , apolipoprotein B (apo B) and microalbuminuria were measured using immunoturbidimetric methods. Cholesterol, peroxide, urea and uric acid were assayed using colorimetric methods. Creatinine clearance was calculated using the Cockroft-Gault equation. Homocysteine was measured by immunological fluorescence polarization. LDL fatty acids were quantified by gas chromatography. Results: Creatinine and microalbuminuria significantly increased in type 2 diabetes when compared with controls. Microalbuminuria was significantly correlated with HbA 1c and with the presence of high blood pressure. Homocysteinaemia significantly correlated with creatinine clearance in diabetes. Linoleic acid (C18:2v6) did not differ between groups. C18:2v6/ C18:3v3 ratio was three times higher in diabetics than in controls. Total saturated fatty acids, homocysteine, H 2 O 2 and LDLthiobarbituric reactive substances significantly increased in microalbuminuric when compared with normoalbuminuric diabetes. Total polyunsaturated fatty acids, arachidonic acid (C20:4v6), LDL-cholesterol, apo B and creatinine clearance significantly decreased in microalbuminuric when compared with normoalbuminuric diabetes. Conclusion: Microalbuminuria onset is associated with renal protein oxidation that is preceded by LDL fatty acid oxidation. The latter is initiated by H 2 O 2 produced from an auto-oxidation of homocysteine and increased metabolism of arachidonic acid towards its pro-inflammatory eicosanoids. An oxidative stress state is the common ground of diffused vasculopathy.

Red cell distribution width as a significant indicator of medication and prognosis in type 2 diabetic patients

“…Therefore, proteinuria could be used to reflect the level of inflammation, providing a reasonable explanation for the close association between RDW and proteinuria. Interestingly, proteinuria was significantly related to oxidative stress, which is involved in the oxidation of the LDL fatty acids, and it was also associated with RBC fragments 41, 42 that give rise to incremental increases in RDW 43 .…”

Relationship between Red Cell Distribution Width and Microalbuminuria: A Population-Based Study of Multiethnic Representative US Adults

“…Increased oxidative stress can induce glomerular disruption and MA [19,22], which in turn might explain the association with elevated RDW values. …”

“…Likewise, an increasing body of evidence suggests that microalbuminuria (MA), a renal marker of vascular damage, is also a reliable predictor of CV risk [13,14,15] and mortality [16,17]. Again, the association with chronic subclinical inflammation [18], oxidative stress [19] and endothelial dysfunction [20] are thought to be proximate mediating mechanisms. We hypothesized that a common interaction of the aforementioned pathophysiological processes might link RDW with MA and potentially offer further insight into the observed utility of these biomarkers in ascertaining CV risk.…”

Oxidative stress in diabetes – circulating advanced glycation end products, lipid oxidation and vascular disease

“…The backdrop of increased oxidative stress promotes a state of diffuse vasculopathy. 7 In both Type 1 and Type 2 diabetes, there is an increased risk of cognitive impairment in later life. In the glucose control intervention study, cognitive function was an independent predictor of glycaemic control, but the risk of cognitive decline or dementia was not decreased by improving glycaemic control.…”