Oxidized-LDL levels are changed during short-term serum glucose variations and lowered with statin treatment in early Type 2 diabetes: a study of endothelial function and microalbuminuria.
OBJECTIVE
To investigate the role of HMG-CoA reductase inhibitor (statin) treatment during serum glucose variations on plasma oxidized LDL (ox-LDL) levels in obese patients with early Type 2 diabetes mellitus (T2D) and its relationship to endothelial biomarkers.


METHODS
In a double-blind, randomized crossover study, 15 obese diet-treated T2D patients received cerivastatin (0.4 mg/day) or placebo for 3 months. Circulating ox-LDL levels were measured fasting and during a euglycaemic-hyperinsulinaemic clamp (approximately 5.5 mmol/l; EHC) and a hyperglycemic clamp (approximately 20 mmol/l; HC). An endothelium-dependent flow-mediated dilation (FMD) study was carried out and urinary albumin excretion (UAE) was measured at rest and during EHC. S-ICAM, s-VCAM and basal prothrombotic factors were also measured.


RESULTS
During cerivastatin treatment, basal circulating ox-LDL levels decreased by 48% (P<0.001) compared with placebo. Serum ox-LDL levels decreased during EHC and remained unchanged during HC compared with the fasting state; with cerivastatin treatment these levels were lower compared with placebo both in the fasting state and during the clamp studies. FMD was higher with cerivastatin than with placebo (P<0.001) and the increments in FMD correlated with decrements in serum ox-LDL levels (r=0.78, P=0.001). Microalbuminuria increased during EHC but this was blunted during cerivastatin therapy compared with placebo (P<0.05). Basal sICAM-1 and sVCAM-1 levels decreased (P<0.01 and P<0.05, respectively).


CONCLUSIONS
In early obese Type 2 diabetic patients, serum ox-LDL levels are influenced by short-term serum glucose variations and lowered with cerivastatin therapy. During cerivastatin treatment, improved flow-mediated endothelium-dependent dilation was associated with decrements in circulating ox-LDL levels and the hyperinsulinaemia-induced urinary albumin excretion was blunted.
Paniagua
J A
JA
Lipid and Atherosclerosis Unit, University Hospital Reina Sofia, Córdoba, Spain. jpaniaguag@supercable.es
López-Miranda
J
J
Pérez-Martínez
P
P
Marín
C
C
Vida
J M
JM
Fuentes
F
F
Fernández de la Puebla
R A
RA
Pérez-Jiménez
F
F
D000328:Adult; D000368:Aged; D000419:Albuminuria / Q000188:drug therapy / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000188:drug therapy; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000187:drug effects; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D008077:Lipoproteins, LDL / Q000097:blood* / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D011725:Pyridines / Q000627:therapeutic use*; D014664:Vasodilation / Q000187:drug effects
D001786:Blood Glucose; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008077:Lipoproteins, LDL; D011725:Pyridines; C099252:oxidized low density lipoprotein; C086276:cerivastatin