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CLINICAL STUDIES

Endothelial vasodilator function is related to low-density lipoprotein particle size and low-density lipoprotein vitamin E content in type 1 diabetes

R. Andrew P. Skyrme-Jones, BSc, MB, ChB^*, Richard C. O’Brien, PhD, Ming Luo, PhD and Ian T. Meredith, MBBS, PhD, FACC^*

^* Centre for Heart and Chest Research, Monash Medical Centre and Monash University, Melbourne, Australia
Department of Medicine, Monash Medical Centre and Monash University, Melbourne, Australia

Manuscript received March 8, 1999; revised manuscript received August 16, 1999, accepted October 18, 1999.

Reprint requests and correspondence: Dr. Ian T. Meredith, Cardiovascular Centre, Monash Medical Centre, 246 Clayton Road, Clayton, Melbourne, Victoria, 3168, Australia
ian.meredith{at}med.monash.edu.au

OBJECTIVES

We sought to determine whether endothelial vasodilator function (EVF) in patients with type 1 diabetes was related to low-density lipoprotein (LDL) particle size (LDLPS), LDL vitamin E content (LDLVE) or the susceptibility of LDL to oxidation (OxLDL).

BACKGROUND

Impaired EVF is an early feature of diabetic vascular disease and may be related to oxidant stress. Although small, dense LDL and oxidized LDL are features of type 2 diabetes and predict the development of coronary artery disease, their role in type 1 diabetes is less clear.

METHODS

Endothelium-dependent vasodilation was assessed in the brachial artery (flow-mediated vasodilation [FMD]) and in the forearm resistance circulation using venous occlusion plethysmography in response to graded doses of intrabrachial acetylcholine (ACh). Thirty-seven patients with type 1 diabetes mellitus (DM) and 45 matched controls underwent flow-mediated dilation, while a subset of 19 DM and 20 controls underwent plethysmography.

RESULTS

Total, LDL and high-density lipoprotein cholesterol or triglycerides were not different in DM compared with controls, but LDLPS was smaller (25.6 ± 0.06 vs. 26.1 ± 0.1 nm, p < 0.05) and LDLVE was reduced (2.0 ± 0.25 vs. 2.6 ± 0.18 µmol/mmol LDL, p < 0.05). Oxidative susceptibility of LDL was not different. Flow-mediated vasodilation was impaired in DM compared with controls (3.6 ± 0.6% vs. 7.1 ± 0.5%, p < 0.005), as was the vasodilator response to ACh (p < 0.05). Flow-mediated vasodilation was directly related to LDLPS and LDLVE in both the entire study cohort and DM alone (p < 0.05), but not to other parameters of the standard lipid profile. Similarly, endothelium-dependent vasodilation in the resistance circulation was directly related to LDLPS and LDLVE, but not to OxLDL.

CONCLUSION

These results suggest, but do not prove, that LDL particle size and LDL vitamin E may be determinants of conduit and resistance vessel endothelial vasodilator function in type 1 diabetes. Further work will be required to prove cause and effect.

Abbreviations and Acronyms   ACh = acetylcholine   ANOVA = analysis of variance   DM = study patients with type 1 diabetes mellitus   EDTA = ethylenediamine tetra-acetic acid   FMD = flow-mediated dilation   FVR = forearm vascular resistance   GTN = nitroglycerin   HBA1c = glycosylated hemoglobin   HDL = high-density lipoprotein   HPLC = high-performance liquid chromatography   LDL = low-density lipoprotein   LDLPS = LDL particle size   LDLVE = LDL vitamin E content   OxLDL = oxidative susceptibility of LDL

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