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Microvascular Residual Risk THROUGH LANDMARK STUDY

1 October 2009
DCCT/EDIC: Beyond conventional lipid profile: NMR provides another vision of lipid-related risk of diabetic retinopathy

Diabetic retinopathy and serum lipoprotein subclasses in the DCCT/EDIC cohort. Invest Ophthalmol Vis Sci 2004;45:910-8.

Lyons TJ, Jenkins AJ, Zheng D, Lackland DT, McGee D, Garvey WT, Klein RL.
Summary
Comments & References
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STUDY SUMMARY
Objective: To determine associations between retinopathy status and detailed serum lipoprotein subclass profiles in patients with type 1 diabetes.
Study population: 440 women and 548 men from the DCCT/EDIC study.
Type of study: Cross-sectional.
Method:
  • Determination from fasting blood samples of conventional lipid profile, lipoprotein subclass profile using nuclear magnetic resonance (NMR), apolipoprotein A1 (apoA1), apolipoprotein B (apoB), lipoprotein(a) (Lp(a)), and susceptibility of LDL to oxidation.
  • Determination of retinopathy ETDRS scores.
  • Univariate and multivariate regression analyses, stratified by gender, of relationship between ETDRS score and each lipoprotein parameter.
Results:
  • Within all three major lipoprotein classes (VLDL, LDL, and HDL), diabetic retinopathy was associated with a shift in subclass distribution toward smaller-diameter particles, and with an increase in LDL particle concentration.
  • In multivariate analyses, results in relation to VLDL applied to both men and women, whereas those in relation to LDL and HDL applied much more strongly to men.
  • Retinopathy was associated with apoB and Lp(a) in men but not in women.
  • A negative association of retinopathy with apoA1 was found but did not reach significance either for men or women.
  • No associations of retinopathy with Lp(a) and susceptibility of LDL to oxidation were found.
Author's conclusion: Dyslipoproteinemia may act as a common risk factor for retinopathy and atherosclerosis in diabetes. The different associations of retinopathy with lipoprotein parameters between men and women suggest a gender differential in risk for retinopathy related to lipids.

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.

 

References
  1. Orchard TJ, Dorman JS, Maser RE, et al. Factors associated with avoidance of severe complications after 25 yr of IDDM. Pittsburg Epidemiology of Diabetes Complications Study I. Diabetes Care. 1990;13:741–7.
  2. Larsson LI, Alm A, Bergenheim T, Lithner F, Bergstrom R. Retinopathy in diabetic patients aged 15–50 years in the county of Umea, Sweden. Acta Ophthalmol Scand. 1999;77:430–6.
  3. Orchard TJ, Dorman JS, Maser RE, et al. Prevalence of complications in IDDM by sex and duration. Pittsburgh Epidemiology of Diabetes Complications Study II. Diabetes. 1990;39:1116–24.
Key words diabetic retinopathy - lipoprotins - apolipoproteins