Association between low-density lipoprotein composition and its metabolismin non-insulin-dependent diabetes mellitus

Atheroma is related to low-density lipoprotein (LDL) composition. LDL in di abetic patients-a group with increased risk of severe atheroma-has been sho wn by our group and others to have various compositional alterations that a re potentially atherogenic. Little is known about the relationship between LDL turnover and composition. This study examined the relationship between LDL composition and turnover in non-insulin-dependent diabetes mellitus (NI DDM) patients. Twenty-two NIDDM patients with a mean plasma cholesterol of 6.6 +/- 1.5 mmol/L were studied. Twelve subjects were hypercholesterolemic (mean cholesterol, 7.7 +/- 0.8 mmol/L), and eight of these agreed to be stu died a second time after 4 weeks of treatment with simvastatin. LDL was iso lated by density gradient ultracentrifugation, iodinated, and reinjected in to the patient. LDL turnover was determined by measuring the clearance of [ I-125]-LDL from plasma over a 10-day period. The LDL residence time, determ ined using a biexponential model, correlated negatively with the body mass index (BMI) (r = -.73, P <.001) and serum triglycerides (r -.57, P <.01). T here was a significant inverse correlation between LDL residence time and t he LDL esterified to free cholesterol ratio in hypercholesterolemic subject s (r = -.94, P <.001). There was a significant inverse relationship between LDL residence time and both hemoglobin A(1c) (HbA(1c),) and fasting blood glucose in these subjects before treatment (P <.005). After simvastatin the rapy, the relationships were no longer significant. Simvastatin treatment w as associated with a shorter LDL residence time (P <.01) and a decrease in LDL glycation (P <.001) with virtually no change in diabetic control (HbA(1 c) 6.0% +/- 3.1% v 6.3% +/- 3.3%, NS). This study suggests that a decrease in residence time by upregulation of the LDL receptor with simvastatin alte rs LDL composition in a way that is likely to render the particle less athe rogenic. Copyright (C) 1999 by W.B. Saunders Company.