Abstract
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.
Highlights
Increasing evidence suggests that type-2 diabetes (T2D) and its macro- and micro-vascular complications are influenced by gender [1,2]
Total cholesterol (Tc), high-density lipoprotein cholesterol (HDL-c), triglycerides, and glucose were assayed by routine enzymatic-colorimetric methods and low-density lipoprotein (LDL)-c was calculated according to the Friedewald formula
The present study confirms and extends previous findings on the implication of Paraoxonase 1 (PON1) in T2D, and demonstrated for the first time that sex significantly affects the interplay between the antioxidant enzyme and this disease
Summary
Increasing evidence suggests that type-2 diabetes (T2D) and its macro- and micro-vascular complications are influenced by gender [1,2]. Lipid abnormalities are important features in patients with T2D, who typically present high triglycerides and low high-density lipoprotein cholesterol (HDL-c) [6], contributing as main morbidity and mortality factors Since it is well-known that this lipid pattern is similar in diabetic men and women [7], it cannot be the cause of the aforementioned sex-difference in T2D complications. It has been shown to possess antioxidant, anti-inflammatory, and endothelial cell maintenance functions as well as playing a role in mediating reverse cholesterol transport [10,11,12] These beneficial aspects of HDL are impaired in T2D, which significantly increases the risk of developing atherosclerosis and related diseases [13]. We investigated in a large population of men and women whether the effect of gender on PON1 might contribute to the sexual dimorphism that characterizes complicated T2D
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