Long-term effects of Irbesartan treatment and smoking on nucleic acid oxidation
in patients with type 2 diabetes and microalbuminuria: an Irbesartan in patients
with type 2 diabetes and Microalbuminuria (IRMA 2) substudy.
Author(s): Broedbaek K, Henriksen T, Weimann A, Petersen M, Andersen JT, Afzal S,
Jimenez-Solem E, Persson F, Parving HH, Rossing P, Poulsen HE.
Affiliation(s): aboratory of Clinical Pharmacology Q7642, Rigshospitalet, Copenhagen, Denmark.
kasper.broedbaek@rh.regionh.dk
Publication date & source: 2011, Diabetes Care. , 34(5):1192-8
OBJECTIVE: We tested whether long-term treatment with the angiotensin II receptor
antagonist irbesartan reduces nucleic acid oxidation in patients with type 2
diabetes and microalbuminuria.
RESEARCH DESIGN AND METHODS: The Irbesartan in Patients With Type 2 Diabetes and
Microalbuminuria (IRMA 2) study was a 2-year multicenter randomized double-blind
trial comparing irbesartan (150 and 300 mg once daily) with placebo. We studied a
subgroup of 50 patients where urine samples were available for analysis of
albumin and the oxidatively modified guanine nucleosides
8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) and 8-oxo-7,8-dihydroguanosine
(8-oxoGuo).
RESULTS: During the 2-year trial, no significant differences in 8-oxodG and
8-oxoGuo excretions between placebo and irbesartan treatment were seen. 8-oxodG
and albumin excretion decreased with time (P = 0.0004 and P < 0.0001,
respectively), whereas treatment-related differences were shown for albumin
excretion (P = 0.0008) only, as previously reported. Important secondary findings
were significant associations between changes in 8-oxodG excretion and changes in
albumin excretion and glycated hemoglobin (HbA(1c)). During the study period,
8-oxodG excretion decreased by 3 and 26% in smokers and nonsmokers, respectively
(P = 0.015), and urinary albumin excretion decreased 22% in smokers and 58% in
nonsmokers (P = 0.011).
CONCLUSIONS: Irbesartan treatment was not significantly more effective than
placebo in reducing nucleic acid oxidation. The results indicate that DNA
oxidation in diabetes patients is reduced by various components in the treatment
of diabetes where glycemic control seems to be important and addition of
angiotensin II receptor antagonists does not lead to any substantial additional
reduction. Furthermore, the reductions in DNA oxidation and albumin excretion
seem to be counteracted by smoking.
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