In the present study, T2DM overrided the effect of menopausal status, gender, and ageing on ox-LDL and MDA concentrations. In participants without T2DM, ox-LDL was 1.8 times higher in men compared to women; however, in participants without T2DM, ox-LDL was about 1.2 higher in women in comparison with men. The magnitude of the increase in ox-LDL and MDA levels in women with T2DM was significantly higher than men with T2DM. Diabetes could increase the concentration of lipid peroxidation products following the impairment of oxidation/ anti-oxidation balance induced by prolonged exposure to hyperglycemia . Here we observed that diabetes could eliminate the protective effect of female sex on ox-LDL and MDA and reverse the difference between men and women.
Our results indicated that although ox-LDL and MDA were higher in post-menopausal women without T2DM, this difference was disappeared in patients with T2DM, either pre- or post-menopausal (figure1). Yichuan Wen et al. reported that ox-LDL mainly increased following menopause in non-diabetic women due to loss of anti-oxidative properties of estrogen after menopause  similar to MDA . The interaction analysis showed that T2DM and menopausal status had no significant joint effects on ox-LDL and MDA levels.
The current study showed that ox-LDL levels had a powerful association with the 10-year ASCVD risk score. This result could support previous researches showing the association of cardiovascular events and ox-LDL concentration [27, 28]. In our study, men with T2DM had a lower 10-year ASCVD risk score compared to women; while among participants without T2DM, men had a higher 10-year ASCVD risk score compared to women. Some population-based studies have shown that diabetes imposes a greater risk of CVD in women than in men [29, 30]. It may suggest that diabetes could change the gender difference in ASCVD predisposition under the influence of ox-LDL levels. Moreover, our result indicated that the 10-year ASCVD risk score was higher in postmenopausal women without T2DM, while this difference was not present in patients with T2DM either pre- or post-menopausal. The same incidence of myocardial infarction in pre- and postmenopausal women with T2DM could support this issue . It could be stated that diabetes could eliminate the difference between pre- and postmenopausal women in ASCVD events subsequently by changing in ox-LDL levels.
Our result indicated that ox-LDL levels were higher among participants with MetS compared to participants without MetS. In this line, Holvoet et al. mentioned that individuals with the MetS had two-fold more elevated levels of ox-LDL compared to those without MetS, independent of age, sex, ethnicity, LDL-C, and smoking status. A population-based cohort study showed that higher concentrations of circulating ox-LDL are associated with the incidence of MetS as well as the accumulation of three of its component: hyperglycemia, abdominal obesity, and hyperglycemia . In consistence with a meta-analysis report, in participants without T2DM, MetS was more prevalent among post-menopausal women compared to pre-menopausal while participants with T2DM had the similar incidence of MetS. Based on our analysis, this difference was more attributed to BP among the components of MetS. It seems that T2DM made pre-menopausal women more susceptible to hypertension and the incidence of MetS as a result.
Our multivariate linear regression analysis showed that TG was an independent predictor for ox-LDL levels after adjusting for age, BMI, WC, duration of diabetes, SBP, HDL-C, LDL-C, FBS and HbA1c. We previously mentioned the higher prevalence of hypertriglyceridemia in women with T2DM compared to men with T2DM . Several studies have demonstrated the association between TG and oxidative markers [33, 36]. As plasma oxidized lipids have a relation with future subclinical and clinical atherosclerosis [14, 37]; this result could justify the long-standing association between hypertriglyceridemia and CVD [38, 39]. In this regard, the results of a decade follow-up of the Iranian population revealed that the increased risk for coronary heart disease (CHD) was attributed to TG . A possible explanation is that higher TG levels in plasma could enhance the production of small, dense LDL particles, which are known to be more susceptible to oxidation .
Another important finding is that although the ox-LDL/LDL, as a lipid biomarker for estimation of oxidation, was significantly different among the participants, mean levels of total cholesterol and LDL-C did not differ by gender and T2DM status in this study. Infact, we found no significant correlation between ox-LDL and LDL-C. Moreover, ox-LDL and MDA were not significantly different between patients who were and were not treated by lipid-lowering drugs. This finding is aligned with our previous study suggesting that maintaining an optimized level of LDL-C, according to guidelines for the management of lipids in patients with T2DM does not sufficiently influence the ox-LDL levels .
The strength of this research was an adequate sample size to show the age-adjusted joint effect of diabetes, menopausal status, and gender and the independent association of TG on serum ox-LDL levels. The current research was a cross-section from a cohort study, so the main limitation was the lack of follow-up of the patients. Also, accurate analysis of lipid peroxidation like MDA and ox-LDL in serum is confounded by enzymatic and non-enzymatic lipid peroxidation that occurs during serum formation. So further studies should be conducted using plasma to handle procedures for prevention of lipid peroxidation.
In conclusion, T2DM overrides the effect of menopausal status, gender, and age on ox-LDL and MDA concentrations. Differences between women in circulating ox-LDL and MDA mostly dependent on T2DM, regardless of menopausal status and ageing. Besides, TG was independently associated with ox-LDL concentration. Also, we could show a positive correlation between 10-year ASCVD risk score and MetS with serum levels of ox-LDL.