Differential Associations of Apolipoproteins and Traditional Lipids with Diabetic Retinopathy and Diabetic Macular Edema

Abstract

Purpose: The role of dyslipidemia in the pathogenesis of diabetic retinopathy (DR) remains controversial. Recent data suggest that apolipoproteins may be more strongly associated with DR than traditional lipids, although whether this is also true in diabetic macular edema (DME) is not known. In this study, we examined the associations of apolipoproteins and traditional lipid levels with DR and DME.

Methods: Patients with type 2 diabetes were recruited from a tertiary eye hospital in Singapore. Each underwent a comprehensive eye examination and fasting blood samples were collected. Traditional serum lipids (i.e. total cholesterol [Tot Chol], LDL, HDL, triglycerides, and Tot Chol to HDL ratio); and apolipoprotein AI (apoAI), apolipoprotein B (apoB), and the apoB-to-apoAI ratio were assessed. Fundus images were graded for any DR and DME. Multiple logistic regression (MLR) models were used to determine the association of exposure variables with DR and DME, using stepwise regression for all lipids in one pool to choose the variable with the strongest association with DR or DME to be included in the model first. For both, stepwise stopped after choosing one variable to be included.

Results: 351 subjects (mean (SD) age=57.2 (7.7) yr, and 30% female), with type 2 diabetes were included in the analysis. Of these, 228 (65%) and 79 (22%) had any DR and DME, respectively. In MLR models adjusting for age, gender and ethnicity, duration of diabetes, glucose, BP, use of antihypertensive and anti-cholesterol medications; Tot Chol to HDL ratio (odds ratio [OR] per unit increase =1.22; 95% Confidence Interval [CI] 1.00-1.49), apoB to apoAI ratio (OR=1.20; 95% CI 1.05, 1.37) were independently associated with DR; while Tot Chol (OR=1.47; 95% CI -1.16, 1.88), LDL (OR=1.54; 95% CI-1.15, 2.08), apoB (OR=1.16; 95%CI 1.04, 1.29), apoB to apoAI ratio (OR=1.14; 95% CI 1.00, 1.29) were associated with DME. Stepwise models found that apoB to apoAI ratio had a stronger association with DR than Tot Chol to HDL ratio. In contrast, Tot Chol was more strongly associated with DME than LDL, apoB and apoB to apoAI ratio.

Conclusions: Although apolipoproteins are independently associated with DR and DME, apoB to apoAI ratio appears to be a stronger risk factor for DR and Tot Chol for DME. These data may reflect differential dyslipidemia pathways in DR and DME and may have implications in treatment modalities.

Keywords: 499 diabetic retinopathy • 505 edema • 583 lipids