NIDDM subjects exhibit an increase in lipid peroxidation and augmented endothelial dysfunction in response to post-prandial lipaemia

Background. Secondary markers of lipid peroxidation are elevated in diseases with increased oxidative stress. Elevated levels of malondialdehyde (MDA)-LDL complexes are thought to suggest plaque instability in coronary artery disease patients and 4-hydroxynonenal (4-HNE) has been implicated in vascular smooth muscle mitogenesis and atherosclerosis. We therefore studied the effect of post-prandial lipaemia (PPL) on lipid peroxidation and endothelial function (EF) in NIDDM. Methods. 15 NIDDM patients (8M, 7F, mean age 47.7 yrs) with moderate glycaemic control (Av. HbA1c 8.2%) were studied following a 12 hour overnight fast and 4 hours after a standard fatty meal and were compared with 15 healthy controls (7M, 8F, mean age 42.3 yrs) with normal EF. EF was assessed by measuring flow-mediated vasodilatation (FMD) in the brachial artery and expressed as % change in brachial artery diameter. A commercially available (R&D Systems) colorimetric assay for products of lipid peroxidation was used, to measure MDA and 4-HNE from plasma frozen at -70°C. Results. [Mean + S.D.] There were significantly greater amounts of MDA and 4-HNE in NIDDM subjects compared to healthy controls (8.75 ± 4.7 vs. 5.55 ± 2.7 p<0.05) in association with endothelial dysfunction (ED) (3.4 ± 1.7% to 6.25 ± 1.3%, p<0.05) at baseline. PPL results in augmented ED (3.4 ± 1.7% to 1.6 ± 1.1%) and significantly higher TG levels (3.1 ± 2.1 to 7.9 ± 7.9mmol/L) and MDA/4-HNE (8.75 ± 4.7 to 10.38 ± 4.7 μmol/l) at 4 hours (both p<0.05). Conclusions. NIDDM subjects have enhanced lipid peroxidation in association with endothelial dysfunction compared to healthy controls. Furthermore PPL worsens endothelial dysfunction associated with an increase in MDA and 4-HNE, lipid peroxidation products. This offers a possible mechanistic explanation for the high incidence of myocardial infarction in NIDDM and the deleterious effects of PPL.