Decreased VLDL-Apo B 100 Fractional Synthesis Rate Despite Hypertriglyceridemia in Subjects With Type 2 Diabetes and Nephropathy.

Abstract

Subjects with type 2 diabetes mellitus (T2DM) and diabetic nephropathy (DN) often exhibit hypertriglyceridemia. The mechanism(s) of such an increase are poorly known. We investigated very low-density lipoprotein (VLDL)-Apo B 100 kinetics in T2DM subjects with and without DN, and in healthy controls. Stable isotope (13)C-leucine infusion and modeling analysis of tracer-to-tracee ratio dynamics in the protein product pool in the 6-8-h period following tracer infusion were employed. Male subjects affected by T2DM, either with (n = 9) or without (n = 5) DN, and healthy male controls (n = 6), were studied under spontaneous glycemic levels in the post-absorptive state. In the T2DM patients with DN, plasma triglyceride (TG) (mean ± SD; 2.2 ± 0.8 mmol/L) and VLDL-Apo B 100 (17.4 ± 10.4 mg/dL) concentrations, and VLDL-Apo B 100 pool (0.56 ± 0.29 g), were ∼60-80% greater (P < .05 or less) than those of the T2DM subjects without DN (TG, 1.4 ± 0.5 mmol/L; VLDL-Apo B 100, 9.9 ± 2.5 mg/dL; VLDL-Apo B 100 pool, 0.36 ± 0.09 g), and ∼80-110% greater (P < .04 or less) than those of nondiabetic controls (TG, 1.2 ± 0.4 mmol/L; VLDL-Apo B 100, 8.2 ± 1.7 mg/dL; VLDL-Apo B 100, 0.32 ± 0.09 g). In sharp contrast however, in the subjects with T2DM and DN, VLDL-Apo B 100 fractional synthesis rate was ≥50% lower (4.8 ± 2.2 pools/d) than that of either the T2DM subjects without DN (9.9 ± 4.3 pools/d; P < .025) or the control subjects (12.5 ± 9.1 pools/d; P < .04). The hypertriglyceridemia of T2DM patients with DN is not due to hepatic VLDL-Apo B 100 overproduction, which is decreased, but it should be attributed to decreased apolipoprotein removal.