Levels of lipoprotein(a), apolipoprotein B, and lipoprotein cholesterol distribution in IDDM. Results from follow-up in the Diabetes Control and Complications Trial

Abstract

Levels of lipoprotein(a) [Lp(a)], apolipoprotein (apo) B, and lipoprotein cholesterol distribution using density-gradient ultracentrifugation were measured as part of a cross-sectional study at the final follow-up examination (mean 6.2 years) in the Diabetes Control and Complications Trial. Compared with the subjects in the conventionally treated group (n = 680), those subjects receiving intensive diabetes therapy (n = 667) had a lower level of Lp(a) (Caucasian subjects only, median 10.7 vs 12.5 mg/dl, respectively; P = 0.03), lower apo B (mean 83 vs. 86 mg/dl, respectively; P = 0.01), and a more favorable distribution of cholesterol in the lipoprotein fractions as measured by density-gradient ultracentrifugation with less cholesterol in the very-low-density lipoprotein and the dense low-density lipoprotein fractions and greater cholesterol content of the more buoyant low-density lipoprotein. Compared with a nondiabetic Caucasian control group (n = 2,158), Lp(a) levels were not different in the intensive treatment group (median 9.6 vs. 10.7 mg/dl, respectively; NS) and higher in the conventional treatment group (9.6 vs. 12.5 mg/dl, respectively; P < 0.01). No effect of renal dysfunction as measured by increasing albuminuria or reduced creatinine clearance on Lp(a) levels could be demonstrated in the diabetic subjects. Prospective follow-up of these subjects will determine whether these favorable lipoprotein differences in the intensive treatment group persist and whether they influence the onset of atherosclerosis in insulin-dependent diabetes.

Figure 1

Mean distribution of lipoprotein cholesterol across nonequilibrium DGUC (line) and 1 SD (bars) of 15 repeat runs on a single sample stored at −70 degrees C for 12–24 months

Figure 2

Frequency distribution histogram of Lp(a) levels in 1,299 Caucasian IDDM patients (A) and 2,158 Caucasian control subjects (B).

Figure 3

Relationship between Lp(a) level and HbA_1c in the Caucasian subjects of the conventionally treated group (n = 653). r = 0.052; P = 0.18.

Figure 4

Relationship between Lp(a) level and HbA_1c in the Caucasian subjects of the intensively treated group (n = 646). r = 0.022; P = 0.59.

Figure 5

Distribution of lipoprotein cholesterol across nonequilibrium density-gradient ultracentrifugation of the conventionally treated group [open bullet] (n = 698) and the intensively treated group [bullet] (n = 680). HDL is located in fractions 0–6, LDL in fractions 7 to approximately 18, IDL in fractions 19–30, and VLDL in fractions 31–38.

Figure 6

Difference plot comparing the mean cholesterol levels of each fraction from the DGUC for differences from 0, with 95 percent CI (bars), between the intensively and conventionally treated groups. The fractional location of each of the lipoprotein classes (VLDL, IDL, LDL, and HDL) is the same as in Figure 3.

Figure 7

Difference plot comparing the mean cholesterol levels of each fraction for differences from 0, with 95 percent CI (bars), for intensively treated women (n = 323) versus conventionally treated women (n = 315). The location of each of the lipoprotein classes (VLDL, IDL, LDL, and HDL) is the same as in Figure 3.

Figure 8

Difference plot comparing the mean cholesterol levels of each fraction for differences from 0, with 95 percent CI (bars), for intensively treated men (n = 357) versus conventionally treated men (n = 383). The location of each of the lipoprotein classes (VLDL, IDL, LDL, and HDL) is the same as in Figure 3.