Lipoprotein composition in NIDDM: effects of dietary oleic acid on the composition, oxidisability and function of low and high density lipoproteins.
ABSTRACT Oxidation of low density lipoprotein (LDL) plays an important role in the pathogenesis of atherosclerosis and is related to the fatty acid composition which is altered in diabetes mellitus. This study examines the relationship between the fatty acid composition of LDL and high density lipoprotein (HDL) and lipoprotein oxidation. A group of nine non-insulin-dependent diabetic (NIDDM) patients were compared to seven healthy control subjects before and after a high monounsaturated diet. Lipoproteins were isolated and oxidisability was measured by conjugated diene formation and lipid peroxide analysis. Serum HDL cholesterol was significantly lower in the diabetic patients. LDL cholesteryl ester linoleic acid in the diabetic patients was significantly higher at baseline and decreased after diet (p < 0.05) while oleic acid increased in both diabetic and non-diabetic subjects (p < 0.05). HDL cholesteryl ester oleic acid was lower in the diabetic patients compared with control subjects (p < 0.05) before diet and it increased significantly after diet (p < 0.05). LDL lipid peroxides and conjugated diene formation were related to LDL glycation (r = 0.46, p < 0.05 and r = 0.49, p < 0.05, respectively). Both decreased following diet (lipid peroxides for diabetic patients from 476 +/- 30 to 390 +/- 20 nmol/mg protein p < 0.05 and for control subjects from 350 +/- 36 to 198 +/- 30 nmol/mg protein p < 0.05). HDL conjugated diene formation decreased in both groups after diet but only significantly in the control group (55.4 +/- 7.5 to 53.2 +/- 6.7 nmol/mg protein for diabetic patients and 45.8 +/- 6.4 to 31.6 +/- 4.8 nmol/mg protein p < 0.05 for control subjects). There was a positive correlation between LDL lipid peroxide formation and percentage of cholesteryl ester linoleic acid in LDL from diabetic patients (r = 0.61, p < 0.05) and control subjects (r = 0.91, p < 0.01). Fatty acid composition of LDL was reflected in the composition of HDL. In the presence of HDL lipoprotein peroxidation decreased. This decrease in lipoprotein peroxidation was positively related to the percentage of linoleic acid in LDL (r = 0.71, p < 0.05). This study confirms the close relationship between the fatty acid composition of LDL and HDL and demonstrates the importance of the fatty acid composition of the cholesteryl ester fraction in relation to LDL oxidation in diabetes. Linoleic acid in HDL appears to be a protecting factor against oxidation.
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ABSTRACT: Insulin resistance and hyperinsulinemia are features of obesity, non-insulin-dependent diabetes mellitus, and other disorders. Skeletal muscle is a major site of insulin action, and insulin sensitivity may be related to the fatty-acid composition of the phospholipids within the muscle membranes involved in the action of insulin. We determined the relation between the fatty-acid composition of skeletal-muscle phospholipids and insulin sensitivity in two groups of subjects. In one study, we obtained samples of the rectus abdominis muscle from 27 patients undergoing coronary artery surgery; fasting serum insulin levels provided an index of insulin sensitivity. In the second study, a biopsy of the vastus lateralis muscle was performed in 13 normal men, and insulin sensitivity was assessed by euglycemic-clamp studies. In the patients undergoing surgery, the fasting serum insulin concentration (a measure of insulin resistance) was negatively correlated with the percentage of individual long-chain polyunsaturated fatty acids in the phospholipid fraction of muscle, particularly arachidonic acid (r = -0.63, P < 0.001); the total percentage of C20-22 polyunsaturated fatty acids (r = -0.68, P < 0.001); the average degree of fatty-acid unsaturation (r = -0.61, P < 0.001); and the ratio of the percentage of C20:4 n-6 fatty acids to the percentage of C20:3 n-6 fatty acids (r = -0.55, P < 0.01), an index of fatty-acid desaturase activity. In the normal men, insulin sensitivity was positively correlated with the percentage of arachidonic acid in muscle (r = 0.76, P < 0.01), the total percentage of C20-22 polyunsaturated fatty acids (r = 0.76, P < 0.01), the average degree of fatty-acid unsaturation (r = 0.62, P < 0.05), and the ratio of C20:4 n-6 to C20:3 n-6 (rho = 0.76, P = 0.007). Decreased insulin sensitivity is associated with decreased concentrations of polyunsaturated fatty acids in skeletal-muscle phospholipids, raising the possibility that changes in the fatty-acid composition of muscles modulate the action of insulin.New England Journal of Medicine 02/1993; 328(4):238-44. · 51.66 Impact Factor
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ABSTRACT: Using a precise technique for measuring authentic plasma lipid hydroperoxides (ROOHs), we show that individuals with non-insulin-dependent diabetes mellitus (NIDDM) have higher levels of ROOH than do control subjects. ROOHs were measured by the ferrous oxidation with xylenol orange assay coupled with the selective ROOH reductant triphenylphosphine. Formation of the ferric xylenol orange complex was determined at 560 nm and calibrated against H2O2. For 22 individuals with NIDDM, a concentration of 9.04 +/- 4.3 mumol/l (mean +/- SD) ROOH was recorded. This concentration was higher (P < 0.0005 by separate-variance t test) than that of plasma ROOHs from control subjects (3.76 +/- 2.48 mumol/l). There was no difference between concentrations of plasma malondialdehyde measured as thiobarbituric acid-reactive material (TBARM) in NIDDM or control subjects (1.00 +/- 0.70 vs. 1.21 +/- 0.62 mumol/l, respectively; P > 0.1). A trend to lower vitamin E levels in the NIDDM group (9.03 +/- 3.31 vs. 10.31 +/- 5.02 micrograms/ml in control subjects) failed to achieve significance at the 95% confidence level. Plasma ROOHs in the diabetic group did not correlate with total plasma cholesterol, triglyceride, fasting glucose, HbA1, vitamin E, or TBARM levels. These data indicate that measurement of authentic ROOHs shows NIDDM to be associated with oxidative stress, which may be unrelated to abnormalities in lipid metabolism and glycemic control.Diabetes 10/1995; 44(9):1054-8. · 7.90 Impact Factor
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ABSTRACT: A method is described for measuring lipid peroxides by means of the color reagent of a commercially available test kit for cholesterol estimation. In principle, this assay makes use of the oxidative capacity of lipid peroxides to convert iodide to iodine, which can be measured photometrically at 365 nm. Calibration curves were obtained using peroxides such as H2O2, t-butyl hydroperoxide, and cumene hydroperoxide. A stoichiometric relationship was observed between the amount of organic peroxides assayed and the concentration of iodine produced. Concentrations of lipid peroxides as small as 1 nmol/ml could be measured. The ability to estimate lipid peroxides of isolated low density lipoprotein was demonstrated.The Journal of Lipid Research 05/1989; 30(4):627-30. · 4.39 Impact Factor