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In vivo oxidizability of LDL in type 2 diabetic patients in good and poor glycemic control

      Abstract

      We aimed to determine if increased non-enzymatic glycosylation of the LDL was sufficient to increase the susceptibility to in vivo oxidation of the LDL particles. Twenty-two type 2 diabetic patients (11 males and 11 females) were included in this study. They were enrolled on the basis of good [glycated hemoglobin (HbA1c)<7%] and poor glycemic control [(HbA1c)>8%]. LDL were isolated by sequential ultracentrifugation and analyzed by capillary electrophoresis (CE) for diene conjugate content and for electronegativity. The glyc-LDL levels were increased in all diabetic type 2 patients, peaking in the diabetic subjects in poor diabetic control (17.3±8.07%). The LDL content of diene conjugates was similar between the two groups (6.65±0.77% for the patients with good glycemic control versus 6.88±0.74% for those with poor glycemic control; P=0.49) as was the electrophoretic mobility (Math Eq for the patients with good glycemic control and Math Eq for those with poor glycemic control; P=0.80).
      The susceptibility to in vivo oxidation of LDL from type 2 diabetic patients in poor glycemic control did not differ from that of well-controlled diabetic patients. LDL glycosylation was not able to increase the oxidizability of LDL in the diabetic patients with poor glycemic control.

      Abbreviations:

      glyc-LDL (glycosylated LDL)

      Keywords

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      References

        • Kramer-Guth A.
        • Quaschning T.
        • Galle J.
        • Baumstark M.W.
        • Koniger M.
        • Nauck M.
        • et al.
        Structural and compositional modifications of diabetic low-density lipoproteins influence their receptor-mediated uptake by hepatocytes.
        Eur. J. Clin. Invest. 1997; 27: 460-468
        • Graier W.F.
        • Kostner G.M.
        Glycated low density lipoprotein and atherogenesis: the missing link between diabetes mellitus and hypercholesterolaemia?.
        Eur. J. Clin. Invest. 1997; 27: 457-459
        • Lyons T.J.
        Lipoprotein glycation and its metabolic consequences.
        Diabetes. 1992; 41: 68-73
        • Gugluicci-Creriche A.
        • Stahl A.J.C.
        Glycation and oxidation of human low density lipoproteins reduces heparin binding and modifies charge.
        Scand. J. Clin. Lab. Invest. 1993; 53: 125-132
        • Assmann G.
        • Schulte H.
        The Prospective Cardiovascular Munster (PROCAM) study: prevalence of hyperlipidemia in persons with hypertension and/or diabetes mellitus and the relationship to coronary heart disease.
        Am. Heart J. 1998; 116: 1713-1724
        • Brizzi M.F.
        • Dentelli P.
        • Gambino R.
        • Cabodi S.
        • Cassader M.
        • Castelli A.
        • et al.
        STAT5 activation induced by diabetic LDL depends on LDL glycation and occurs via src kinase activity.
        Diabetes. 2002; 51: 3311-3317
        • Steinbrecher U.P.
        • Witztum J.L.
        Glucosylation of low density lipoproteins to an extent comparable to that seen in diabetes slows their catabolism.
        Diabetes. 1984; 33: 130-134
        • Witztum J.L.
        • Mahoney E.M.
        • Branks M.J.
        • Fisher J.
        • Elam R.
        • Steinberg D.
        Non-enzymatic glucosylation of low density lipoprotein alters its biologic activity.
        Diabetes. 1982; 31: 283-291
        • Lyons T.J.
        • Klein R.L.
        • Baynes J.W.
        • Stevenson H.C.
        • Lopes-Virella M.S.
        Stimulation of cholesteryl ester synthesis in human monocyte-derived macrophages by low density lipoproteins from type I (insulin dependent) diabetic patients: the influence of non-enzymatic glycosylation of low density lipoprotein.
        Diabetologia. 1987; 30: 916-923
        • Brownlee M.
        Negative consequences of glycation.
        Metabolism. 2000; 49: 9-13
        • Baynes J.W.
        Role of oxidative stress in development of complications in diabetes.
        Diabetes. 1991; 40: 405-412
        • Yegin A.
        • Özben T.
        • Yegin H.
        Glycation of lipoproteins and accelarated atherosclerosis in non-insulin-dependent diabetes mellitus.
        Int. J. Clin. Lab. Res. 1995; 25: 157-161
        • Stock J.
        • Miller N.E.
        Capillary electrophoresis to monitor the oxidative modification of LDL.
        J. Lipid Res. 1998; 39: 1305-1309
        • Taskinen M.R.
        Quantitative and qualitative lipoprotein abnormalities in diabetes mellitus.
        Diabetes. 1992; 41: 12-17
        • Sobenin I.A.
        • Tertov V.W.
        • Orekhov A.N.
        Atherogenic modified LDL in diabetes.
        Diabetes. 1996; 45: S35-S39
        • Ahotupa M.
        • Vasankary T.J.
        Baseline diene conjugation in LDL lipids: an indicator of circulating oxidized LDL.
        Free Radic. Biol. Med. 1999; 27: 1141-1150
        • Ahotupa M.
        • Marniemi J.
        • Lehtimaki T.
        • Talvinen K.
        • Raitakari O.T.
        • Vasankari T.
        • et al.
        Baseline diene conjugation in LDL lipids as a direct measure of in vivo LDL oxidation.
        Clin. Biochem. 1998; 31: 257-261
      1. National Diabetes Data Group. Classification and diagnosis of diabetes mellitus and other categories of glucose intolerance. Diabetes 1979;28:1039–57.

      2. World Medical Association Declaration of Helsinki. Recommendations guiding physicians in biomedical research involving human subjects. JAMA 1997;277:925–6.

        • Heinecke J.W.
        • Rosen H.
        • Chait A.
        Iron and copper promote modification of low density lipoprotein by human arterial smooth muscle cells in culture.
        J. Clin. Invest. 1984; 74: 1890-1894
        • Makino K.
        • Furbee Jr., J.W.
        • Scanu A.M.
        • Fless G.M.
        Effects of glycation on the properties of lipoprotein(a).
        Arterioscler. Thromb. Vasc. Biol. 1995; 15: 385-391
        • Cruzado I.D.
        • Cockrill C.
        • McNeal C.J.
        • Macfarlane R.D.
        Characterization and quantitation of apolipoprotein B-100 by capillary electrophoresis.
        J. Lipid Res. 1998; 39: 205-217
        • Sánchez-Quesada J.L.
        • Pérez A.
        • Caixàs A.
        • Rigla M.
        • Payes A.
        • Benitez S.
        • et al.
        Effect of glycemic optimization on electronegative low-density lipoprotein in diabetes: relation to non-enzymatic glycosylation and oxidative modification.
        J. Clin. Endocrinol. Metab. 2001; 86: 3243-3249
        • Akanji A.O.
        • Abdella N.
        • Mojiminiyi O.A.
        Determinants of glycated LDL levels in non-diabetic and diabetic hyperlipidaemic patients in Kuwait.
        Clin. Chim. Acta. 2002; 317: 171-176
        • Esterbauer H.J.
        • Gebicki J.
        • Puhl H.
        • Jurgens G.
        The role of lipid-peroxidation and antioxidants in oxidative modification of LDL.
        Free Radic. Biol. Med. 1992; 13: 241-290
        • Halliwell B.
        Oxidation of low-density lipoproteins—questions of initiation, propagation, and the effect of antioxidants.
        Am. J. Clin. Nutr. 1995; 61: S670-S677
        • Pinchuk I.
        • Lichtenberg D.
        Continuous monitoring of intermediales and final products of oxidation of low density lipoprotein by means of UV-spectroscopy.
        Free Radic. Res. 1996; 24: 351-360
        • Jialal I.
        • Freeman D.A.
        • Grundy S.M.
        Varying susceptibility of different low density lipoproteins to oxidative modification.
        Arteriosclerosis. 1991; 11: 482-488
        • Hodis H.N.
        • Kramsch D.M.
        • Avogaro P.
        • Bittolo-Bon G.
        • Cazzolato G.
        • Hwang J.
        • et al.
        Biochemical and cytotoxic characteristics of an in vivo circulating oxidized low density lipoprotein (LDL-).
        J. Lipid Res. 1994; 35: 669-677
        • Babiy A.V.
        • Gebicki J.M.
        • Sullivan D.R.
        • Willey K.
        Increased oxidizability of plasma lipoprotein in diabetic patients can be decreased by probucol therapy and is not due to glycation.
        Biochem. Pharmacol. 1992; 43: 995-1000
        • Otero P.
        • Herrera E.
        • Bonet B.
        Dual effect of glucose on LDL oxidation: dependence on vitamin E.
        Free Radic. Biol. Med. 2002; 33: 1133-1140
        • Kilpatrick E.S.
        Problems in the assessment of glycaemic control in diabetes mellitus.
        Diab. Med. 1997; 14: 418-422
        • Cohen M.P.
        Perspective: measurement of circulating glycated proteins to monitor intermediate-term changes in glycaemic control.
        Eur. J. Clin. Chem. Clin. Biochem. 1992; 30: 851-859