Duke University Medical Center, Duke Cancer Institute, Durham, North Carolina, USA.
Obesity (Silver Spring). 2012 Sep;20(9):1915-21. doi: 10.1038/oby.2011.292. Epub 2011 Sep 29.
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.
肥胖与 F2-异前列腺素（F2-IsoP）水平的横断面增加有关。然而，根据我们早期的发现，即升高的尿 F2-IsoP 水平预示着糖尿病风险较低，前瞻性关联可能是相反的。这一早期发现使我们假设尿 F2-IsoP 反映了氧化代谢的强度，因此可以预测糖尿病和体重增加的风险较低。我们使用来自胰岛素抵抗动脉粥样硬化研究（IRAS）的 299 名参与者的数据，检查了与肥胖的横断面关系和与体重增加的前瞻性关系，所有参与者在基线时均无糖尿病。使用液相色谱-串联质谱法在储存的基线尿液样本中检测了四种尿 F2-IsoP：iPF（2α）-III、2,3-二去甲-iPF（2α）-III、iPF（2α）-VI 和 8,12-异-iPF（2α）-VI（分别为 F2-IsoP1-4）。基线 F2-IsoP 与基线肥胖测量值呈正相关；与两种 F2-IsoP 相关性最强：F2-IsoP2 与整体肥胖和腹部肥胖的比值比（95%置信区间）分别为 1.74（1.26-2.40）和 1.63（1.18-2.24），F2-IsoP4 为 1.47（1.12-1.94）和 1.64（1.22-2.20）。F2-IsoP2 在 5 年随访期间与体重增加呈最强和显著的负相关：F2-IsoP2 增加 1 个标准差与体重减少 0.90 公斤相关（P=0.02），相对（≥5%）和绝对（≥5 公斤）体重增加的比值比分别为 0.67（0.47-0.96）和 0.57（0.37-0.87）。其他三种 F2-IsoP 与体重增加呈负相关，但不显著，这表明不同的 F2-IsoP 在检测与体重增加的关联方面存在差异。
