The HMG-CoA reductase inhibitor cerivastatin lowers advanced glycation end products in patients with type 2 diabetes.
Although the association between type 2 diabetes mellitus (DM) and cardiovascular diseases is well-documented, current knowledge regarding reasons for the increased prevalence of atherosclerosis in DM is incomplete. Advanced glycosylation end-products (AGE) may play an important role in the development of atherosclerosis in diabetic patients. We examined the effect of the HMG-CoA reductase inhibitor (HMGRI) cerivastatin on serum concentration of AGE-CML in patients with elevated fasting glucose, impaired glucose tolerance or DM. The study was a multicenter, double-blind, randomized, parallel-group comparison of cerivastatin at 0.4 mg daily for 12 weeks (n=34) and placebo (n=35). Patients were characterized by combined hyperlipoproteinemia and the preponderance of dense LDL. Primary objective of the study was the effect of cerivastatin on the concentration of dense LDL subfractions. Here we report on the effect of cerivastatin on the concentration of AGE-CML. After 12 weeks of treatment cerivastatin reduced cholesterol, apolipoprotein B, LDL cholesterol and the concentration of dense LDL. Furthermore, cerivastatin significantly lowered the concentration of AGE-CML by 21% ( P=0,005; compared to -7,5% in the placebo group). The effect on AGE-CML was correlated with the reduction in LDL cholesterol (r=0.355, P=0.003) and LDL apoB (r=0.239, P=0.05). In addition to the lipid-lowering effects of HMGRI, the reduction of AGE-CML observed in our study may entail an improvement of the cardiovascular prognosis in patients with chronic hyperglycemia.
Scharnagl
H
H
Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University Graz, Graz, Austria. hubert.scharnagl@klinikum-graz.at
Stojakovic
T
T
Winkler
K
K
Rosinger
S
S
März
W
W
Boehm
B O
BO
D000328:Adult; D000368:Aged; D001055:Apolipoproteins B / Q000097:blood; D050197:Atherosclerosis / Q000209:etiology / Q000517:prevention & control; D001786:Blood Glucose / Q000187:drug effects; D008078:Cholesterol, LDL / Q000097:blood; D048909:Diabetes Complications / Q000517:prevention & control; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D004311:Double-Blind Method; D015536:Down-Regulation; D005260:Female; D017127:Glycation End Products, Advanced / Q000097:blood*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D011725:Pyridines / Q000008:administration & dosage*; D016896:Treatment Outcome
D001055:Apolipoproteins B; D001786:Blood Glucose; D008078:Cholesterol, LDL; D017127:Glycation End Products, Advanced; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011725:Pyridines; C086276:cerivastatin