Macrovascular Residual Risk Studies

COMMENT

Prior to this analysis conducted in patients with type 1 diabetes participating in the DCCT/EDIC study, associations between the severity or progression of diabetic retinopathy and elevated levels of total- and LDL cholesterol, LDL-HDL cholesterol ratio, and triglycerides had been reported in the literature. The Epidemiology of Diabetes Complications Study demonstrated that high triglycerides and high LDL at baseline are associated with subsequent progression of retinopathy over 2 years.1 However, conventional determination of lipid profile does not reflect the variations in size and density of particles within the major lipoprotein classes, which was difficult to determine before the introduction of nuclear magnetic resonance (NMR) to estimate lipoprotein subclasses profile. With this technique, analysis of the whole serum can rapidly determine the concentrations of 15 different lipoprotein subclasses, designated according to particle size (Figure 1).

In the present study, the severity of retinopathy was only weakly associated with conventional lipid profiles. There was a borderline association between the severity of retinopathy and triglycerides in the entire cohort. In men and in the entire cohort, retinopathy score was associated with lower HDL cholesterol.

Much stronger associations and gender differences were identified by NMR, which revealed associations between retinopathy status and lipoprotein subclasses that were previously unknown. In brief, associations involved subclasses within all three major lipoprotein classes (VLDL, LDL, HDL). Overall, smaller-sized lipoproteins were associated with an increased risk of retinopathy.

Retinopathy was associated with apoB (present on VLDL, LDL, IDL and Lp(a)) and Lp(a) in men and in the combined cohort. However, the negative association of retinopathy with apoA1 did not reach significance either for men or women. ApoB , low apoA1,and Lp(a) are known to be cardiovascular risk factors.

The authors stress that different associations of retinopathy with lipoprotein parameters between men and women suggest a gender difference in risk for retinopathy. Typically, men have a much less favorable lipoprotein subclass profile than women. Interestingly, it has been shown that diabetic men may be more susceptible than women to retinopathy.2,3

Whether similar associations exist in patients with type 2 diabetes cannot be inferred from the present study. Nevertheless, these data suggest that modification of lipoprotein subclass distribution in order to reduce the residual risk of diabetic retinopathy might be an emerging field of clinical research.