Type-2 diabetes (T2D) and its cardiovascular complications are related to sex. Increasing evidence suggests that paraoxonase 1 (PON1) activity, an antioxidant enzyme bound to high-density lipoproteins (HDL), is implicated in the onset and clinical progression of T2D. Since we previously showed that PON1 is a sexual dimorphic protein, we now investigated whether sex might impact the relationship between PON1 and this chronic disease. To address this aim, we assessed PON1 activity in the sera of 778 patients, including controls (women, n = 383; men, n = 198) and diabetics (women, n = 79; men = 118). PON1 activity decreased in both women and men with T2D compared with controls (p < 0.05 and p > 0.001, respectively), but the change was 50% larger in the female cohort. In line with this result, the enzyme activity was associated with serum glucose level only in women (r = −0.160, p = 0.002). Notably, only within this gender category, lower PON1 activity was independently associated with increased odds of being diabetic (odds ratio (95% Confidence interval: 2.162 (1.075–5.678)). In conclusion, our study suggests that PON1-deficiency in T2D is a gender-specific phenomenon, with women being more affected than men. This could contribute to the partial loss of female cardiovascular advantage associated with T2D.

中文翻译：

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性别差异影响对氧磷酶-1（PON1）和2型糖尿病之间的关系。

2型糖尿病（T2D）及其心血管并发症与性别有关。越来越多的证据表明，对氧磷酶1（PON1）活性是一种与高密度脂蛋白（HDL）结合的抗氧化酶，与T2D的发作和临床进展有关。由于我们之前已经证明PON1是一种有性双态蛋白，因此我们现在研究了性别是否会影响PON1与这种慢性疾病之间的关系。为了实现此目标，我们评估了778例患者的血清中PON1的活性，包括对照组（女性，n = 383；男性，n = 198）和糖尿病患者（女性，n = 79；男性= 118）。与对照组相比，患有T2D的女性和男性的PON1活性均下降（p <0.05和p> 0.001），但女性队列的变化大了50％。与该结果一致，该酶活性仅与女性的血清葡萄糖水平相关（r = -0.160，p = 0.002）。值得注意的是，仅在该性别类别内，较低的PON1活性与糖尿病几率增加相关（几率（95％置信区间：2.162（1.075-5.678）））总之，我们的研究表明PON1在T2D中的缺乏是这是一种针对性别的现象，女性比男性受影响更大，这可能会导致女性与T2D相关的心血管优势部分丧失。