The VLDL and LDL fractions were isolated from 29 patients with type 1 diabetes at the time of admission to the hospital to restore glycemic control and again at discharge. These lipoprotein fractions were incubated with human monocyte-derived macrophages, and the rates of macrophage CE synthesis were determined. The rates of CE synthesis in human macrophages were significantly greater (P < 0.005) when incubated with VLDL isolated from type I diabetic patients before compared with after glycemic control was attained and averaged 1.84 ± 0.52 and 1.09 ± 0.27 nmol (1.20 ± 0.34 and 0.71 ± 0.18 μg) [14C]cholesteryl oleate synthesized mg cell protein−1 · 20 h−1 respectively. In contrast, when LDL isolated from the same patient during the same period was incubated with human macrophages, the rates of cellular cholesteryl ester synthesis did not differ significantly and averaged 4.23 ± 1.26 and 3.91 ± 0.96 nmol (2.75 ± 0.82 and 2.55 ± 0.63 μg) [14C]cholesteryl oleate synthesized · mg−1 cell protein · 20 h−1, respectively. There was a significant increase in the total cholesterol content of VLDL isolated before glycemic control compared with that isolated after glycemic control was attained (P < 0.05) resulting from a significant increase in the FC and CE (P < 0.05) contents of these VLDL particles. There was a significant decrease in the ratio of FC to PL in VLDL, but not LDL, isolated after glycemic control (P < 0.05).
The percentage of apoE in VLDL was significantly decreased (P < 0.05) after glycemic control was attained. In LDL isolated after glycemic control was achieved, a significant decrease (P < 0.005) in the percentage of triglycerides was observed. In addition, there was a significant decrease (P < 0.0001) in the extent of glycation of LDL isolated after glycemic control. These studies suggest that during periods of poor glycemic control, the composition of VLDL isolated from type 1 diabetic patients is altered. These modified VLDLs stimulate CE synthesis rates in human macrophages and, thus, may contribute to the increased prevalence of atherosclerosis in diabetic patients.
