d-ROM levels in long-standing type 1 diabetes: preliminary data on gender differences

Background and aims: Oxidative stress plays a role in the pathogenesis of atherosclerosis in type 1 diabetes (T1D) I density lipoprotein and expression of inflammation/adhesion molecules. Derivatives-reactive oxygen metabolites (d-ROMs) are an emerging biomarker of oxidative stress, but no studies have investigated gender differences in d- ROMs in T1D. Aim of this cross-sectional study was to estimate oxidative stress using the d-ROMs test in a cohort of long-standing and low complicated T1D subjects. Methods: In 85 (M/F=53/31) subjects with T1D (mean±SEM: age: 40.5±1.36 years; BMI: 25.04±0.4 kg/m2; HbA1c: 58.3±1.17 mmol/mol; duration of diabetes: 22.1±1.2 years) consecutively recruited at Verona Diabetes Center between November 2022 and December 2023, we assessed: 1. oxidative stress markers by d-ROMs and oxidized LDL-cholesterol [oxLDL]; 2. subclinical atherosclerosis (ATS) phenotypes by US-doppler scan of carotid, diabetic retinopathy (DR) by indirect ophthalmoscopy and chronic kidney disease (CKD) by estimated glomerular filtration rate <60ml/min. All analyses were adjusted for age, gender, HbA1c, disease duration and smoking. Results: Women showed higher HbA1c values without statistically significant difference with men (59.9±10 vs 57.5±10 mmol/mol; p=0.06). No gender differences have been observed in triglyceride levels (M/F=88.3±7.91 vs 74.8±5.31 mg/dl; p=0.62), c-LDL (M/F: 90.7±3.81 vs 99.7±7.27 mg/dl, p=0.41) and oxLDL levels (p=0.34), but d-ROMs were significantly higher in women than in men (496.5±9.20 vs 452.3±6.33 U.CARR, p<0.001). Finally, frequency of microvascular complications was low in overall subjects with no gender differences (ATS M/F: 42.1% vs 43.5%; p=0.56; DR M/F: 34.6% vs 23.3%; p=0.20; CKD M/F: 0.0% vs 6.9%; p=0.13). In regression analysis, gender and HbA1c were positively associated with d-ROMs levels (bstd=0.349, p<0.001 and bstd=0.211, p=0.05, respectively) but not with oxLDL levels (bstd=0.048, p=0.69 and bstd=0.119, p=0.32, respectively). Conclusions: In women with T1D, d-ROM’s quantification could be an oxidative-stress-related biomarker providing additional information to stratify atherosclerosis risk and to tailor the therapeutic strategies.