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This version published online on May 17, 2005
Journal of Clinical Endocrinology & Metabolism, doi:10.1210/jc.2004-2420
A more recent version of this article appeared on August 1, 2005
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Submitted on December 9, 2004
Accepted on May 10, 2005

Increased transvascular lipoprotein transport in diabetes: association with albuminuria and systolic hypertension

Jan Skov Jensen*, Bo Feldt-Rasmussen, Knut Borch-Johnsen, Kurt Svarre Jensen, and Børge Grønne Nordestgaard

Department of Nephrology and Endocrinology P, The National University Hospital; Steno Diabetes Center, Department of Clinical Biochemistry, Herlev University Hospital, and The Copenhagen City Heart Study, Bispebjerg University Hospital, Copenhagen, Denmark

* To whom correspondence should be addressed. E-mail: jsje{at}c.dk.

Context: Diabetes is associated with highly increased risk of atherosclerosis, especially if hypertension or albuminuria is present.

Objective: We hypothesized that the increased transvascular lipoprotein transport in diabetes may be further accelerated if hypertension or albuminuria is present, possibly explaining increased intimal lipoprotein accumulation and thus atherosclerosis.

Design: Cross sectional study performed in 1999-2002.

Setting: Referral center.

Patients: 60 patients with diabetes mellitus (27 with type 1 diabetes and 33 with type 2 diabetes) and 42 healthy controls. All were randomly recruited.

Main outcome measure: We used an in vivo method for measurement of transvascular transport of low density lipoprotein (LDL) and applied it in Autologous 131-iodinated LDL was reinjected intravenously, and the 1-hour fractional escape rate was taken as an index of transvascular transport.

Results: Transvascular LDL transport was 1.8 (1.6-2.0); 2.3 (2.0-2.6); and 2.6 (1.3-4.0) %/(h x (L/m2)) in healthy controls; diabetic controls; and diabetes patients with systolic hypertension or albuminuria, respectively (P = 0.013, F=4.5, df=2 (ANOVA)). These differences most likely were not caused by altered hepatic LDL receptor expression, glycosylation of LDL, small LDL size, or medicine use.

Conclusions: Transvascular LDL transport is increased in patients with diabetes mellitus, especially if systolic hypertension or albuminuria is present. Accordingly, lipoprotein flux into the arterial wall could be increased in these patients, possibly explaining accelerated development of atherosclerosis.


Key words: Albuminuria • atherosclerosis • diabetes mellitus • hypertension • low density lipoprotein • tracer kinetics • transvascular lipoprotein transport




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