Oxidative damage indices for the assessment of subclinical diabetic macrovascular complications

Abstract

Subclinical cardiovascular disease (SCVD), including complications in diabetes, is associated with oxidative damage and precedes future cardiovascular disease (CVD). Hence, assessment and management of oxidative damage is imperative. This study investigates biomarkers associated with CVD, diabetes and oxidative stress in order to determine a set of indices that could be useful to assess oxidative damage in diabetic macrovascular pathogenesis. A total of 266 participants were selected and divided into seven groups (control, family history of diabetes, prediabetes, prediabetes with CVD, diabetes mellitus [DM], DM+CVD and CVD) based on clinical history/status. Blood glucose (BG) level, erythrocyte glutathione (GSH), malondialdehyde, methaemoglobin, D-dimer, homocysteine, blood viscosity and cholesterol profile were determined. Factorial MANOVA and independent univariate analyses were performed. Prevalence of significant biomarkers was assessed following a 3.5-year retrospective study. Multivariate analysis showed statistically significant differences between groups (P<0.0001) with post hoc tests identifying a statistically significant association for BG level (P<0.0001), GSH (P<0.0001), D-dimer (P<0.02) and total cholesterol (P<0.0001). Of the subjects who showed hyperglycaemia-associated progression in clinical and biochemistry status, 89% had low-level GSH and 44% had high-level D-dimer. Four individuals exhibited prediabetic status at some stage and would qualify for macrovascular disease intervention. The results of this study suggest that BG level, D-dimer, GSH and total cholesterol contribute significantly to a diabetic oxidative damage panel of markers that could assist in evidence-based pharmacological intervention with anti-aggregation and/or antioxidant agents against future CVD in diabetes.