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European Heart Journal 2001 22(22):2075-2084; doi:10.1053/euhj.2001.2655
Copyright © 2001 by the European Society of Cardiology.
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Effect of glycaemic control and age on low-density lipoprotein susceptibility to oxidation in diabetes mellitus type 1

A Liguoria, P Abeteb, J.M Haydenc, F Cacciatoreb, F Rengob, G Ambrosiod, D Bonaduceb, M Condorellib, P.D Reavenc and C Napolib,e,f1

a Division of Cardiology-CCU, "Pellegrini" Hospital, Naples, Italy
b Department of Clinical Medicine, Cardiovascular and Immunogical Science and Geriatrics, School of Medicine, Federico II University of Naples, Naples, Italy
c Division of Endocrinology, Metabolism and Nutrition, Department of Medicine, Carl T. Hayden VA Medical Center, Phoenix, Arizona, U.S.A.
d Division of Cardiology, University of Perugia School of Medicine, Perugia, Italy
e Department of Medicine-0682, School of Medicine, University of California, San Diego, La Jolla, U.S.A.

revised February 12, 2001; accepted February 15, 2001

Abstract

Background Although individuals with diabetes mellitus frequently have dyslipidaemias and high blood pressure, much of the increased risk for coronary heart disease is not explained by these and other classical risk factors. Thus, other less widely recognized risk factors, including increased susceptibility of low-density lipoprotein (LDL) to oxidation, might enhance vascular dysfunction and atherogenesis in diabetes.

Aims We compared both the rate and extent of LDL oxidation ex vivo between 78 poorly controlled individuals with type 1 diabetes and 78 age- and sex-matched non-diabetic controls. We then initiated intensive insulin therapy for 3 months to determine the impact of improved glucose control on LDL composition and oxidation.

Results Diabetic and non-diabetic individuals did not have significantly different body weights, dietary intake, blood pressure, renal function or plasma lipid levels. LDL composition was also similar in both groups. In contrast, vitamin E content in LDL was significantly lower in diabetic patients. Measures of LDL lipid oxidation, including conjugated diene, lipid peroxide and thiobarbituric acid reactive substances formation, as well as measures of LDL protein modification, were significantly greater in diabetic patients. Levels of hyperglycaemia correlated strongly with each measure of LDL lipid oxidation (r ranges from 0·60–0·81,P <0·05 for each correlation). After improved glucose control (average reduction in % HbAlcof 5·5 units) all measures of LDL oxidation improved dramatically and approached values for non-diabetics. Absolute values of LDL oxidation increased among all categories of age in both diabetic and control individuals, and this relationship persisted even after adjustment for differences in glucose concentrations.

Conclusions We demonstrate that hyperglycaemia has a potent but reversible effect on LDL oxidation and that age may independently enhance LDL susceptibility to oxidation. These pathophysiological effects may play an important role in determining vascular complications and atherogenesis in poorly controlled type 1 diabetic patients.

Key Words: LDL oxidation, diabetes, ageing, oxygen radicals, hyperglycaemia

f1 Correspondence: Claudio Napoli, MD, FACA, P.O. Box, Via B. Falcomata', 5, 80128 Naples, Italy.

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