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Atherosclerosis and Lipoproteins |
From the UFR de Pharmacie et INSERM U539 (J.M.B.), Centre de Recherche en Nutrition Humaine, Nantes, France; INSERM U21-258 (M.A.C., P.A., E.E.), Villejuif, France; CJF INSERM (I.J.-V., P.V.), Laboratoire dHématologie, Marseille, France; INSERM U337 (M.S.), Paris, France; and INSERM U325 (J.C.F.), Lille, France.
Correspondence to Prof J.M. Bard, UFR de Pharmacie Laboratoire de Biochimie, 1 rue Gaston Veil, BP 1024, F-44035 Nantes cedex, France. E-mail Jean-Marie.bard{at}sante.univ-nantes.fr
AbstractThe
present study represents a new insight into the Biguanides
and the Prevention of the Risk of Obesity (BIGPRO) 1 study population
at inclusion. This population, selected basically on the basis of a
high waist-to-hip ratio (
0.95 for men and
0.80 for women), is
supposed to represent a group of patients with insulin
resistance. The present study was undergone to establish whether
apolipoprotein C-III (apoC-III) and apolipoprotein E (apoE) associated
with apo B (apoC-III LpB and apoE LpB, respectively), considered to be
markers of remnant accumulation, play a role in the
hypertriglyceridemia associated with
insulin resistance and whether they are related to other biological
abnormalities frequently observed in this syndrome. In this population,
the concentration of the markers of remnant accumulation increases with
triglyceride levels. Therefore, correlation studies were
realized to assess the relative effect of insulin and the markers of
remnant accumulation on triglyceride plasma level. As a
first attempt, a simple correlation analysis revealed that
insulin is positively related to the markers of remnant accumulation
only in hypertriglyceridemic patients
(triglycerides
1.7 mmol/L). To assess the
independent contribution of these markers, insulin, and other
parameters related to the plasma triglyceride
concentration, a stepwise multiple regression analysis was run.
Results revealed that insulin and the markers of remnant accumulation
(specifically, apoE LpB) are independent contributors to the plasma
triglyceride concentration. Markers of the
endothelial damage, plasminogen
activator inhibitor-1, tissue
plasminogen activator, and von
Willebrand factor, which are often increased in the case of
insulin resistance, were tested for their correlation with the markers
of remnant accumulation. Plasminogen activator
inhibitor-1 is positively correlated with these markers
only in hypertriglyceridemic male subjects.
It is concluded that increased insulin levels found in insulin
resistance syndrome are associated with an increased production
of triglyceride-rich lipoproteins enriched in apoC-III and
apoE. The accumulation of these remnants and/or their abnormal
composition in apoC-III and apoE could be an explanation for the
development of hypertriglyceridemia in this
syndrome.
Key Words: insulin resistance syndrome central fat distribution triglyceride-rich lipoproteins apolipoproteins lipoprotein particles
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