ObjectiveApolipoproteins are amphipathic molecules and the major components of plasma lipoproteins. This study aims to investigate the effects of dysregulated apolipoprotein (apo) profiles and their ratios on type 2 diabetes mellitus (T2DM) and diabetic retinopathy (DR) further to test the hypothesis that altered serum level of apolipoproteins is strong biomarkers for DR. Research Design and MethodsThis case-control study consists of 157 patients with T2DM including DM without DR, non-proliferative DR (NPDR), and proliferative DR (PDR). Fifty-eight age- and sex-matched healthy subjects were enrolled as normal controls. Blood biochemistry profile including serum levels of glucose, glycated hemoglobin (HbA1c), lipid profile [total cholesterol (TC), Triglycerides (TG), high and low-density lipoprotein (HDL-C and LDL-C)] was estimated. Apolipoproteins (apos, A-I, A-II, B, C-II, C-III, and E) was evaluated by protein chips (Luminex technology). Apolipoprotein ratios and arteriosclerosis-associated plasma indices were calculated. The Kruskal-Wallis test, independent sample t-test or Mann-Whitney U test, and multivariate regression analysis were performed to investigate the association of serum lipid biomarkers and the DR severity. ResultsSerum level of apoA-I was negatively correlated with TC-(HDL-C)/HDL-C (p < 0.001), fasting glucose (p < 0.001), HbA1c (p < 0.001), and (p<0.001), while apoE, apoC-II/apoC-III, apoA-II/apoA-I were positively correlated with above traditional biomarkers (p < 0.001). Single variable logistic analysis results showed that body mass index (BMI) (p = 0.023), DM duration (p < 0.001), apoE (p < 0.001), apoC-II/apo C-III (p < 0.001), apoE/apoC-II (p < 0.001), atherogenic index (p = 0.013), fasting glucose (p < 0.001), HbA1c (p < 0.001), LPA (p = 0.001), and LDL-C/HDL-C (p = 0.031) were risk factors for the occurrence and severity of DR. Multivariate logistic regression mode showed that apoC-II/apoC-III and apoB/non-HDL-C (p < 0.001) as well as apoE/apoC-II (p = 0.001) were the independent risk factors for the occurrence and severity of DR-apopA-I and apoA-II are protective factors for DR-after controlling for the duration of DM, HbA1c, fasting glucose, and LPA. ConclusionsapoE, apoC-II/apoC-III, apoE/apoC-II, and apoB/non-HDL-C could be used as novel biomarkers for occurrence and severity of DR, whereas apoA-I and apoA-II resulted as protective factors for DR.