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Increased Transvascular Lipoprotein Transport in Diabetes: Association with Albuminuria and Systolic Hypertension

Department of Nephrology and Endocrinology P (J.S.J., B.F.-R., K.S.J.), The National University Hospital, DK-2100 Copenhagen, Denmark; Steno Diabetes Center (K.B.-J.), DK-2820 Gentofte, Denmark; Department of Clinical Biochemistry (B.G.N.), Herlev University Hospital, DK-2730 Herlev, Denmark; and The Copenhagen City Heart Study (J.S.J., B.G.N.), Bispebjerg University Hospital, DK-2400 Copenhagen, Denmark

Address all correspondence and requests for reprints to: Jan Skov Jensen, M.D., Ph.D., D.M.Sc., Department of Cardiology P, Gentofte University Hospital, Niels Andersens Vej 65, DK-2900 Hellerup, Denmark. E-mail: jsje{at}c.dk.

Abstract

Context: Diabetes is associated with a 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: The study was cross-sectional and was performed in 1999–2002.

Setting: The study took place in the referral center.

Patients: The patients included 60 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). Autologous ¹³¹I-LDL was reinjected iv, and the 1-h 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 (liter/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.

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