Decreased VLDL-Apo B 100 fractional synthesis rate despite hypertriglyceridemia in subjects with type 2 diabetes and nephropathy

Subjects with Type 2 Diabetes Mellitus (T2DM) and diabetic nephropathy (DN) often exhibit hypertriglyceridemia. The mechanism(s) of such an increase are poorly known. OBJECTIVE: We investigated VLDL-Apo B 100 kinetics in T2DM subjects with and without DN, and in healthy controls. DESIGN: Stable isotope 13C-leucine infusion, and modelling analysis of tracer-to-tracee ratio dynamics in the protein product pool in the 6-8 hr period following tracer infusion, were employed. SETTING: 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. RESULTS: In the T2DM patients with DN, plasma triglyceride (TG) (2.2±0.8 mmol/L, Mean±SD) 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<0.05 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<0.04 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 FSR was ≥50% lower (4.8±2.2 pools/day) than that of either the T2DM subjects without DN (9.9±4.3 pools/day, p<0.025) or the control subjects (12.5±9.1 pools/day, p<0.04). CONCLUSIONS: 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.