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


OBJECTIVE
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).


METHODS
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.
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.
Bruno
B
Vergès
Laurence
L
Duvillard
Laurent
L
Lagrost
Christelle
C
Vachoux
Céline
C
Garret
Karine
K
Bouyer
Michael
M
Courtney
Céline
C
Pomié
Rémy
R
Burcelin
D000293:Adolescent; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D005260:Female; D006801:Humans; D007700:Kinetics; D008070:Lipopolysaccharides / Q000097:blood* / Q000737:chemistry; D008074:Lipoproteins / Q000097:blood* / Q000737:chemistry; D008075:Lipoproteins, HDL / Q000097:blood / Q000737:chemistry; D008079:Lipoproteins, VLDL / Q000097:blood / Q000737:chemistry; D008297:Male; D008875:Middle Aged; D055815:Young Adult
D008070:Lipopolysaccharides; D008074:Lipoproteins; D008075:Lipoproteins, HDL; D008079:Lipoproteins, VLDL