title: 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.
abstract: 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.
  
  
  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.
authors: aboratory of Clinical Pharmacology Q7642, Rigshospitalet, Copenhagen, Denmark. kasper.broedbaek@rh.regionh.dk
authors: Kasper
authors: K
authors: Broedbaek
authors: Trine
authors: T
authors: Henriksen
authors: Allan
authors: A
authors: Weimann
authors: Morten
authors: M
authors: Petersen
authors: Jon T
authors: JT
authors: Andersen
authors: Shoaib
authors: S
authors: Afzal
authors: Espen
authors: E
authors: Jimenez-Solem
authors: Frederik
authors: F
authors: Persson
authors: Hans-Henrik
authors: HH
authors: Parving
authors: Peter
authors: P
authors: Rossing
authors: Henrik E
authors: HE
authors: Poulsen
mesh_terms: D000368:Aged; D000419:Albuminuria / Q000188:drug therapy* / Q000378:metabolism*; D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use; D001713:Biphenyl Compounds / Q000494:pharmacology* / Q000627:therapeutic use*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D000077405:Irbesartan; D008297:Male; D008875:Middle Aged; D009696:Nucleic Acids / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D012907:Smoking / Q000009:adverse effects; D013777:Tetrazoles / Q000494:pharmacology* / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D009696:Nucleic Acids; D013777:Tetrazoles; D000077405:Irbesartan