Transvascular Low-Density Lipoprotein Transport in Patients With Diabetes Mellitus (Type 2): A Noninvasive In Vivo Isotope Technique

Abstract

Objective—The increased risk of atherosclerosis associated with diabetes cannot be explained by conventional cardiovascular risk factors alone. We hypothesized that transvascular lipoprotein transport may be increased in patients with diabetes, possibly explaining increased intimal lipoprotein accumulation and, thus, atherosclerosis. Methods and Results—We developed an in vivo method for measurement of transvascular transport of low density lipoprotein (LDL) and applied it in 16 patients with maturity-onset diabetes (type 2) and 29 healthy control subjects. Autologous 131I-labeled LDL was reinjected intravenously in addition to 125I-labeled albumin, and the 1-hour fractional escape rates were taken as indices of transvascular transport. Both parameters were normally distributed, and they were tightly correlated (R2=0.69, P <0.0001). Transvascular LDL transport was 5.4±2.9%/h and 4.1±1.5%/h in patients with diabetes and control subjects, respectively (P <0.05); equivalent values for albumin were 6.5±2.5%/h and 5.3±1.6%/h (P <0.05). This difference most likely was not caused by altered hepatic LDL receptor expression, glycosylation of LDL, small LDL size, nephropathy, statin use, or different plasma insulin levels in diabetic patients. Conclusions—Transvascular LDL transport may be increased in patients with type 2 diabetes. This suggests that lipoprotein flux into the arterial wall is increased in people with diabetes, possibly explaining the accelerated development of atherosclerosis.