Increased transvascular low density lipoprotein transport in insulin dependent diabetes: a mechanistic model for development of atherosclerosis

Background: 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: We used an in vivo method for measurement of transvascular transport of low density lipoprotein (LDL) and applied it in 24 patients with insulin dependent diabetes mellitus (type 1) and in 30 healthy controls. LDL was individually sampled and autologous 131-iodinated LDL was reinjected intravenously in addition to 125-iodinated albumin, and the 1-h fractional escape rates were taken as indices of transvascular transport. Results: Transvascular LDL transport was 5.7±2.2 and 4.0±1.8%/h in patients with diabetes and controls (P<0.005); equivalent values for albumin were 6.8±2.5 and 5.4±2.0%/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 diabetes patients. Conclusion: Transvascular LDL transport may be increased in patients with type 1 diabetes. This suggests that lipoprotein flux into the arterial wall is increased in people with type 1 diabetes, possibly explaining accelerated development of atherosclerosis.