Decreased VLDL-Apo B 100 Fractional Synthesis Rate Despite Hypertriglyceridemia in Subjects With Type 2 Diabetes and Nephropathy.
BACKGROUND
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 very low-density lipoprotein (VLDL)-Apo B 100 kinetics in T2DM subjects with and without DN, and in healthy controls.


METHODS
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.


METHODS
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) (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).


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.
Department of Medicine (P.T., E.K., R.B., M.V., I.C., L.P., C.G., M.Z.), University of Padova, 35128 Padova, Italy; Diabetic Centre (E.K.), 31100 Treviso, Italy; Department of Medical, Surgical and Health Sciences (R.B., M.Z.), University of Trieste, 34100 Trieste, Italy; and Department of Information Engineering (G.M.T., E.M., G.P.), University of Padova, 35131 Padova, Italy.
Paolo
P
Tessari
Department of Medicine (P.T., E.K., R.B., M.V., I.C., L.P., C.G., M.Z.), University of Padova, 35128 Padova, Italy; Diabetic Centre (E.K.), 31100 Treviso, Italy; Department of Medical, Surgical and Health Sciences (R.B., M.Z.), University of Trieste, 34100 Trieste, Italy; and Department of Information Engineering (G.M.T., E.M., G.P.), University of Padova, 35131 Padova, Italy.
Edward
E
Kiwanuka
Department of Medicine (P.T., E.K., R.B., M.V., I.C., L.P., C.G., M.Z.), University of Padova, 35128 Padova, Italy; Diabetic Centre (E.K.), 31100 Treviso, Italy; Department of Medical, Surgical and Health Sciences (R.B., M.Z.), University of Trieste, 34100 Trieste, Italy; and Department of Information Engineering (G.M.T., E.M., G.P.), University of Padova, 35131 Padova, Italy.
Rocco
R
Barazzoni
Department of Medicine (P.T., E.K., R.B., M.V., I.C., L.P., C.G., M.Z.), University of Padova, 35128 Padova, Italy; Diabetic Centre (E.K.), 31100 Treviso, Italy; Department of Medical, Surgical and Health Sciences (R.B., M.Z.), University of Trieste, 34100 Trieste, Italy; and Department of Information Engineering (G.M.T., E.M., G.P.), University of Padova, 35131 Padova, Italy.
Gianna M
GM
Toffolo
Department of Medicine (P.T., E.K., R.B., M.V., I.C., L.P., C.G., M.Z.), University of Padova, 35128 Padova, Italy; Diabetic Centre (E.K.), 31100 Treviso, Italy; Department of Medical, Surgical and Health Sciences (R.B., M.Z.), University of Trieste, 34100 Trieste, Italy; and Department of Information Engineering (G.M.T., E.M., G.P.), University of Padova, 35131 Padova, Italy.
Monica
M
Vettore
Department of Medicine (P.T., E.K., R.B., M.V., I.C., L.P., C.G., M.Z.), University of Padova, 35128 Padova, Italy; Diabetic Centre (E.K.), 31100 Treviso, Italy; Department of Medical, Surgical and Health Sciences (R.B., M.Z.), University of Trieste, 34100 Trieste, Italy; and Department of Information Engineering (G.M.T., E.M., G.P.), University of Padova, 35131 Padova, Italy.
Irene
I
Cortella
Department of Medicine (P.T., E.K., R.B., M.V., I.C., L.P., C.G., M.Z.), University of Padova, 35128 Padova, Italy; Diabetic Centre (E.K.), 31100 Treviso, Italy; Department of Medical, Surgical and Health Sciences (R.B., M.Z.), University of Trieste, 34100 Trieste, Italy; and Department of Information Engineering (G.M.T., E.M., G.P.), University of Padova, 35131 Padova, Italy.
Erica
E
Manesso
Department of Medicine (P.T., E.K., R.B., M.V., I.C., L.P., C.G., M.Z.), University of Padova, 35128 Padova, Italy; Diabetic Centre (E.K.), 31100 Treviso, Italy; Department of Medical, Surgical and Health Sciences (R.B., M.Z.), University of Trieste, 34100 Trieste, Italy; and Department of Information Engineering (G.M.T., E.M., G.P.), University of Padova, 35131 Padova, Italy.
Gloria
G
Pasqualetto
Department of Medicine (P.T., E.K., R.B., M.V., I.C., L.P., C.G., M.Z.), University of Padova, 35128 Padova, Italy; Diabetic Centre (E.K.), 31100 Treviso, Italy; Department of Medical, Surgical and Health Sciences (R.B., M.Z.), University of Trieste, 34100 Trieste, Italy; and Department of Information Engineering (G.M.T., E.M., G.P.), University of Padova, 35131 Padova, Italy.
Lucia
L
Puricelli
Department of Medicine (P.T., E.K., R.B., M.V., I.C., L.P., C.G., M.Z.), University of Padova, 35128 Padova, Italy; Diabetic Centre (E.K.), 31100 Treviso, Italy; Department of Medical, Surgical and Health Sciences (R.B., M.Z.), University of Trieste, 34100 Trieste, Italy; and Department of Information Engineering (G.M.T., E.M., G.P.), University of Padova, 35131 Padova, Italy.
Carlo
C
Gabelli
Department of Medicine (P.T., E.K., R.B., M.V., I.C., L.P., C.G., M.Z.), University of Padova, 35128 Padova, Italy; Diabetic Centre (E.K.), 31100 Treviso, Italy; Department of Medical, Surgical and Health Sciences (R.B., M.Z.), University of Trieste, 34100 Trieste, Italy; and Department of Information Engineering (G.M.T., E.M., G.P.), University of Padova, 35131 Padova, Italy.
Michela
M
Zanetti
D000328:Adult; D000368:Aged; D053299:Apolipoprotein B-100 / Q000096:biosynthesis*; D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000000981:diagnostic imaging; D003928:Diabetic Nephropathies / Q000097:blood* / Q000000981:diagnostic imaging; D005260:Female; D006801:Humans; D015228:Hypertriglyceridemia / Q000097:blood*; D007328:Insulin / Q000097:blood; D007700:Kinetics; D007930:Leucine; D008079:Lipoproteins, VLDL / Q000096:biosynthesis*; D008297:Male; D008875:Middle Aged; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals
D053299:Apolipoprotein B-100; D001786:Blood Glucose; D007328:Insulin; D008079:Lipoproteins, VLDL; D019275:Radiopharmaceuticals; D007930:Leucine