Apolipoproteins and Diabetic Retinopathy

In this issue of Diabetes Care Sasongko et al. (1) make the intriguing observation that apolipoprotein (apo)B and apoA-I, and particularly the apoB-to-apoA-I ratio, are related to the presence of diabetic retinopathy in a small cohort of type 1 and type 2 diabetic patients. Moreover, this ratio correlated with the retinopathy severity and also was a better predictor of retinopathy than traditional lipid measures such as total cholesterol, LDL or HDL cholesterol, or even the LDL-to-HDL cholesterol ratio. This study raises many important questions. For example, why are these relationships between retinopathy and lipoproteins seen in this small study, whereas previous studies, some in much larger cohorts, have not shown a consistent relationship? Did measurement of apolipoproteins rather than the lipid components of the lipoproteins make the difference? Lipids and lipoproteins are well-accepted risk factors for macrovascular disease in diabetes via mechanisms that are reasonably well understood. However, do lipids and lipoproteins play a role in microvascular complications such as retinopathy in addition to better known risk factors such as diabetes duration, glycemic control, and hypertension? And if so, by what mechanisms does HDL protect and the apoB-containing lipoproteins increase the risk of retinopathy? In the current study, stronger relationships were observed between retinopathy and apolipoproteins than with lipid components of the lipoproteins. ApoA-I is the major structural apolipoprotein present in HDL and is reflective of the number of HDL particles. A single molecule of apoB is present in LDL, as well as in VLDL, remnant lipoproteins (often present in the intermediate-density lipoprotein [IDL] density range) and lipoprotein(a) (Lp(a)), another atherogenic lipoprotein. Because each of these lipoproteins contains a single molecule of apoB, apoB concentration is a measure of the total number of these atherogenic particles. If these lipoproteins also have an adverse effect on microvascular complications such as retinopathy, …