title: Urinary F2-isoprostanes, obesity, and weight gain in the IRAS cohort.
abstract: Obesity has been associated with increased F(2)-isoprostane (F(2)-IsoP) levels cross-sectionally. However, the prospective association may be inverse, based on our earlier finding that elevated urinary F(2)-IsoP levels predict lower risk of diabetes. This earlier finding led us to hypothesize that urinary F(2)-IsoPs reflect the intensity of oxidative metabolism and as such predict lower risk of both diabetes and weight gain. We examined cross-sectional relationships with obesity and prospective relationships with weight gain using the data from 299 participants of the Insulin Resistance Atherosclerosis Study (IRAS), all of whom were free of diabetes at baseline. Four urinary F(2)-IsoPs were assayed in stored baseline urine samples using liquid chromatography with tandem mass spectrometry: iPF(2α)-III, 2,3-dinor-iPF(2α)-III, iPF(2α)-VI, and 8,12-iso-iPF(2α)-VI (F(2)-IsoP 1-4, respectively). Baseline F(2)-IsoPs were positively associated with baseline measures of obesity; the strongest associations were found with two F(2)-IsoPs: odds ratios (95% confidence intervals) for overall and abdominal obesity were 1.74 (1.26-2.40) and 1.63 (1.18-2.24) for F(2)-IsoP2 and 1.47 (1.12-1.94) and 1.64 (1.22-2.20) for F(2)-IsoP4. F(2)-IsoP2 showed the strongest and significant inverse association with weight gain during the 5-year follow-up period: increase in F(2)-IsoP2 equal to 1 s.d. was associated with 0.90 kg lower weight gain (P = 0.02) and the odds ratios for relative (≥5%) and absolute (≥5 kg) weight gain were 0.67 (0.47-0.96) and 0.57 (0.37-0.87), respectively. The other three F(2)-IsoPs were consistently inversely associated with weight gain, although not significantly, suggesting that different F(2)-IsoPs vary in their ability to detect the association with weight gain.
authors.affiliation: Duke University Medical Center, Duke Cancer Institute, Durham, North Carolina, USA. dora.ilyasova@duke.edu
authors.forename: Dora
authors.initials: D
authors.lastname: Il'yasova
authors.forename: Frances
authors.initials: F
authors.lastname: Wang
authors.forename: Ivan
authors.initials: I
authors.lastname: Spasojevic
authors.forename: Karel
authors.initials: K
authors.lastname: Base
authors.forename: Ralph B
authors.initials: RB
authors.lastname: D'Agostino
authors.forename: Lynne E
authors.initials: LE
authors.lastname: Wagenknecht
mesh_terms: D000328:Adult; D000368:Aged; D050197:Atherosclerosis / Q000453:epidemiology / Q000517:prevention & control / Q000652:urine*; D015415:Biomarkers / Q000652:urine; D002853:Chromatography, Liquid; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000517:prevention & control / Q000652:urine*; D028441:F2-Isoprostanes / Q000652:urine*; D005260:Female; D006801:Humans; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000453:epidemiology / Q000517:prevention & control / Q000652:urine*; D018384:Oxidative Stress; D010865:Pilot Projects; D011446:Prospective Studies; D017382:Reactive Oxygen Species; D053719:Tandem Mass Spectrometry; D014481:United States / Q000453:epidemiology; D015430:Weight Gain
chemical_list: D015415:Biomarkers; D028441:F2-Isoprostanes; D017382:Reactive Oxygen Species