TY - JOUR

T1 - Long-Term Effects of Irbesartan Treatment and Smoking on Nucleic Acid Oxidation in Patients With Type 2 Diabetes and Microalbuminuria

T2 - An Irbesartan in Patients With Type 2 Diabetes and Microalbuminuria (IRMA 2) substudy

AU - Broedbaek, Kasper

AU - Henriksen, Trine

AU - Weimann, Allan

AU - Petersen, Morten

AU - Andersen, Jon T

AU - Afzal, Shoaib

AU - Jimenez-Solem, Espen

AU - Persson, Frederik

AU - Parving, Hans-Henrik

AU - Rossing, Peter

AU - Poulsen, Henrik E

PY - 2011

Y1 - 2011

N2 - 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.

AB - 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.

U2 - 10.2337/dc10-2214

DO - 10.2337/dc10-2214

M3 - Journal article

C2 - 21454798

VL - 34

SP - 1192

EP - 1198

JO - Diabetes Care

JF - Diabetes Care

SN - 0149-5992

IS - 5

ER -