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

Abstract

Background: We aimed to establish the relationship between glycated haemoglobin (HbA1c), 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. HbA1c, 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 HbA1c and with the presence of high blood pressure. Homocysteinaemia significantly correlated with creatinine clearance in diabetes. Linoleic acid (C18:2ω6) did not differ between groups. C18:2ω6/C18:3ω3 ratio was three times higher in diabetics than in controls. Total saturated fatty acids, homocysteine, H2O 2 and LDL-thiobarbituric reactive substances significantly increased in microalbuminuric when compared with normoalbuminuric diabetes. Total polyunsaturated fatty acids, arachidonic acid (C20:4ω6), 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 H2O2 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.