PMID- 26291068 OWN - NLM STAT- MEDLINE DCOM- 20160217 LR - 20161126 IS - 1945-7197 (Electronic) IS - 0021-972X (Linking) VI - 100 IP - 11 DP - 2015 Nov TI - Decreased VLDL-Apo B 100 Fractional Synthesis Rate Despite Hypertriglyceridemia in Subjects With Type 2 Diabetes and Nephropathy. PG - 4098-105 LID - 10.1210/jc.2015-2172 [doi] AB - CONTEXT: 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. DESIGN: 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. 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) (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 approximately 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 approximately 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. FAU - Tessari, Paolo AU - Tessari P AD - 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. FAU - Kiwanuka, Edward AU - Kiwanuka E AD - 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. FAU - Barazzoni, Rocco AU - Barazzoni R AD - 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. FAU - Toffolo, Gianna M AU - Toffolo GM AD - 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. FAU - Vettore, Monica AU - Vettore M AD - 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. FAU - Cortella, Irene AU - Cortella I AD - 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. FAU - Manesso, Erica AU - Manesso E AD - 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. FAU - Pasqualetto, Gloria AU - Pasqualetto G AD - 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. FAU - Puricelli, Lucia AU - Puricelli L AD - 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. FAU - Gabelli, Carlo AU - Gabelli C AD - 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. FAU - Zanetti, Michela AU - Zanetti M AD - 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. LA - eng PT - Journal Article DEP - 20150820 PL - United States TA - J Clin Endocrinol Metab JT - The Journal of clinical endocrinology and metabolism JID - 0375362 RN - 0 (Apolipoprotein B-100) RN - 0 (Blood Glucose) RN - 0 (Insulin) RN - 0 (Lipoproteins, VLDL) RN - 0 (Radiopharmaceuticals) RN - GMW67QNF9C (Leucine) SB - IM MH - Adult MH - Aged MH - Apolipoprotein B-100/*biosynthesis MH - Blood Glucose/metabolism MH - Diabetes Mellitus, Type 2/*blood/diagnostic imaging MH - Diabetic Nephropathies/*blood/diagnostic imaging MH - Female MH - Humans MH - Hypertriglyceridemia/*blood MH - Insulin/blood MH - Kinetics MH - Leucine MH - Lipoproteins, VLDL/*biosynthesis MH - Male MH - Middle Aged MH - Radionuclide Imaging MH - Radiopharmaceuticals EDAT- 2015/08/21 06:00 MHDA- 2016/02/18 06:00 CRDT- 2015/08/21 06:00 PHST- 2015/08/21 06:00 [entrez] PHST- 2015/08/21 06:00 [pubmed] PHST- 2016/02/18 06:00 [medline] AID - 10.1210/jc.2015-2172 [doi] PST - ppublish SO - J Clin Endocrinol Metab. 2015 Nov;100(11):4098-105. doi: 10.1210/jc.2015-2172. Epub 2015 Aug 20.