Oxidation of low-density lipoprotein in normotensive type 2 diabetic patients. Comparative effects of enalapril versus nifedipine: a randomized cross-over over study
R. Rachmani et al., Oxidation of low-density lipoprotein in normotensive type 2 diabetic patients. Comparative effects of enalapril versus nifedipine: a randomized cross-over over study, DIABET RE C, 48(2), 2000, pp. 139-145
The role of lipoprotein oxidation in promoting atherosclerosis is gaining r
ecognition as its spectrum of effects is being unveiled. Accelerated athero
sclerosis is a major cause of morbidity and mortality in diabetic patients.
Treatment with ACE inhibitors reduces oxidation of low-density lipoprotein
(LDL-ox) in hypertensive subjects, however, their effect on LDL-ox in diab
etic patients is yet obscure. To evaluate the effect of the ACE inhibitor e
nalapril and the calcium channel blocker nifedipine on LDL oxidation in nor
motensive type 2 diabetic patients. A randomized single blinded cross-eve!
study was conducted on 24 nonobese, metabolically stable, normotensive pati
ents with type 2 diabetes who were randomly allocated to receive either ena
lapril, 10 mg/day, or nifedipine, 30 mg:day, for 4 weeks followed by a 2-we
ek washout period. They were then crossed over to a Lt-week course with the
alternate drug. The oxidation of LDL was evaluated by three methods: diald
ehyde analysis using the thiobarbituric acid reactive substances assay with
and without the addition of CuSO4 as well as determination of conjugated d
ienes in the LDL lipid extract. The propensity of the serum to oxidize LDL
was reduced by enalapril by 17-28% depending on the laboratory method used
(P = 0.0001). Treatment with nifedipine resulted in a rise in LDL-ox of 7-1
1% as compared to baseline (P < 0.05). The difference between the effects o
f enalapril and nifedipine was statistically significant with all three lab
oratory methods used (P = 0.0001). Both drugs were equally effective in red
ucing systolic and diastolic blood pressure without affecting HbA(1c) level
s and lipid profile. The albumin excretion rate was significantly reduced d
uring treatment with enalapril returning to baseline levels during the wash
out period and the nifedipine treatment course. Our findings suggest that o
xidation of LDL is attenuated by ACE inhibition and augmented by some calci
um channel blockers. This observation may contribute insight into the under
lying mechanism of the therapeutic effects of ACE inhibition ill diabetic p
atients. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.