Abstract
Aims/hypothesisThe aim of the study was to examine the association between lipoprotein-associated phospholipase A2 (Lp-PLA2) activity levels and incident diabetic retinopathy and change in retinopathy grade.MethodsThis was a cohort study of diabetic participants with serum collected at baseline and routinely collected diabetic retinal screening data. Participants with type 2 diabetes from the GoDARTS (Genetics of Diabetes Audit and Research in Tayside Scotland) cohort were used. This cohort is composed of individuals of white Scottish ancestry from the Tayside region of Scotland. Survival analysis accounting for informative censoring by modelling death as a competing risk was performed for the development of incident diabetic retinopathy from a disease-free state in a 3 year follow-up period (n = 1364) by stratified Lp-PLA2 activity levels (in quartiles). The same analysis was performed for transitions to more severe grades.ResultsThe hazard of developing incident diabetic retinopathy was 2.08 times higher (95% CI 1.64, 2.63) for the highest quartile of Lp-PLA2 activity compared with the lowest. Higher Lp-PLA2 activity levels were associated with a significantly increased risk for transitions to all grades. The hazards of developing observable (or more severe) and referable (or more severe) retinopathy were 2.82 (95% CI 1.71, 4.65) and 1.87 (95% CI 1.26, 2.77) times higher for the highest quartile of Lp-PLA2 activity compared with the lowest, respectively.Conclusions/interpretationHigher Lp-PLA2 levels are associated with increased risk of death and the development of incident diabetic retinopathy, as well as transitions to more severe grades of diabetic retinopathy. These associations are independent of calculated LDL-cholesterol and other traditional risk factors. Further, this biomarker study shows that the association is temporally sensitive to the proximity of the event to measurement of Lp-PLA2.
Highlights
Diabetic retinopathy is a leading cause of vision loss and blindness in the working age population (20–74 years of age) of most developed countries [1]
Smoking is generally not considered a risk factor; at least one study found a significant association between smoking and diabetic macular oedema (DME), a condition that progresses from retinopathy, in people with type 1 diabetes [15]
The purpose of this study is to explore whether variation in Lp-PLA2 activity measured in serum samples from a diabetic population is associated with subsequent incidence of, or progression from less to more severe, retinopathy
Summary
Diabetic retinopathy is a leading cause of vision loss and blindness in the working age population (20–74 years of age) of most developed countries [1]. The increasing number of individuals with diabetes worldwide suggests that diabetic retinopathy is likely to be a growing contributor to vision loss and associated functional impairment in the future [3]. Risk factors associated with diabetic retinopathy include age, race/ethnicity, longer duration of diabetes, insulin dependence, younger age of diabetes onset, higher HbA1c, insulin treatment and higher blood pressure [4,5,6,7,8,9,10]. Smoking is generally not considered a risk factor; at least one study found a significant association between smoking and diabetic macular oedema (DME), a condition that progresses from retinopathy, in people with type 1 diabetes [15]. A number of high-risk participants are not identified by current methods of screening [3]
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