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  • Title: Homocysteine enhances LDL fatty acid peroxidation, promoting microalbuminuria in type 2 diabetes.
    Author: Kassab A, Ajmi T, Issaoui M, Chaeib L, Miled A, Hammami M.
    Journal: Ann Clin Biochem; 2008 Sep; 45(Pt 5):476-80. PubMed ID: 18753419.
    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 (C18:2omega6) did not differ between groups. C18:2omega6/C18:3omega3 ratio was three times higher in diabetics than in controls. Total saturated fatty acids, homocysteine, H(2)O(2) and LDL-thiobarbituric reactive substances significantly increased in microalbuminuric when compared with normoalbuminuric diabetes. Total polyunsaturated fatty acids, arachidonic acid (C20:4omega6), 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.
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