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J Clin Endocrinol Metab. 2014 Jul;99(7):E1245-53. doi: 10.1210/jc.2013-3463. Epub 2014 Apr 2.

Changes in lipoprotein kinetics associated with type 2 diabetes affect the distribution of lipopolysaccharides among lipoproteins.

Author information

1
Department of Endocrinology-Diabetology (B.V.), University-Hospital, and INSERM CRI 866 (B.V., L.D., L.L.), Medicine University, 21000 Dijon, France; INSERM Unité 1048 (C.V., C.G., C.P., R.B.), Institut de Recherche sur les Maladies Métaboliques et Cardiovasculaires de Rangueil (I2MC), 31432 Toulouse, France; and VAIOMER SAS (K.B., M.C.), 31670 Labège, France.

Abstract

CONTEXT:

Lipopolysaccharides (LPSs) are inflammatory components of the outer membrane of Gram-negative bacteria and, in plasma, are mostly associated with lipoproteins. This association is thought to promote their catabolism while reducing their proinflammatory effects.

OBJECTIVES:

Our aim was to determine the impact of lipoprotein kinetics on plasma LPS distribution and how it may affect patients with type 2 diabetes mellitus (T2DM).

DESIGN:

We performed a kinetic study in 30 individuals (16 T2DM patients, 14 controls) and analyzed the impact of changes in lipoprotein kinetics on LPS distribution among lipoproteins.

RESULTS:

Plasma LPS levels in T2DM patients were not different from those in controls, but LPS distribution in the two groups was different. Patients with T2DM had higher LPS-very low-density lipoprotein (VLDL; 31% ± 7% vs 22% ± 11%, P = .002), LPS-high-density lipoprotein (HDL; 29% ± 9% vs 19% ± 10%, P = .015), free (nonlipoprotein bound) LPS (10% ± 4% vs 7% ± 4%, P = .043) and lower LPS-low-density lipoprotein (LDL; 30% ± 13% vs 52% ± 16%, P = .001). In multivariable analysis, VLDL-LPS was associated with HDL-LPS (P < .0001); LDL-LPS was associated with VLDL-LPS (P = .004), and VLDL apolipoprotein (apo) B100 catabolism (P = .002); HDL-LPS was associated with free LPS (P < .0001) and VLDL-LPS (P = .033); free LPS was associated with HDL-LPS (P < .0001). In a patient featuring a dramatic decrease in VLDL catabolism due to apoA-V mutation, LDL-LPS was severely decreased (0.044 EU/mL vs 0.788 EU/mL in controls). The difference between T2DM patients and controls for LDL-LPS fraction was no longer significant after controlling for VLDL apoB100 total fractional catabolic rate.

CONCLUSIONS:

Our data suggest that in humans, free LPS transfers first to HDL and then to VLDL, whereas the LPS-bound LDL fraction is mainly derived from VLDL catabolism; the latter may hence represent a LPS catabolic pathway. T2DM patients show lower LDL-LPS secondary to reduced VLDL catabolism, which may represent an impaired catabolic pathway.

PMID:
24694333
DOI:
10.1210/jc.2013-3463
[Indexed for MEDLINE]

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