Plasma Apolipoproteins Predicting the Occurrence and Severity of Diabetic Retinopathy in Patients With Type 2 Diabetes Mellitus

Abstract

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.