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Microvascular Residual Risk THROUGH LANDMARK STUDY

13 October 2011
DCCT/EDIC: High triglyceride levels and other features of atherogenic dyslipidemia are associated with renal dysfunction in patients with type 1 diabetes

Lipoproteins in the DCCT/EDIC cohort: Associations with diabetic nephropathy. Kidney Int, 2003;64:817-28

Jenkins AJ, Lyons TJ, Zheng D, Otvos JD, Lackland DT, McGee D, Garvey WT, Klein R
Summary
Comments & References
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STUDY SUMMARY
Objective: To determine associations between nephropathy and detailed serum lipoprotein subclass profiles in patients with type 1 diabetes.
Study population: 428 women and 540 men from the DCCT/EDIC study.
Study design:

Cross-sectional.

Methods:
  • Determination from fasting blood samples of conventional lipid profile, lipoprotein size using nuclear magnetic resonance (NMR), apolipoprotein A1 (apoA1), apolipoprotein B100 (apoB), lipoprotein(a) (Lp(a)), and susceptibility of LDL to oxidation.
  • Determination of albumin excretion rate using 4-h urine collections.
  • Univariate and multivariate regression analyses of relationship between AER categories (normal, microalbuminuria or albuminuria) and each lipoprotein parameter.
Results:
  • Multivariate analysis revealed an association of AER with
    • total triglycerides, total- and LDL cholesterol, but not high-density lipoprotein (HDL) cholesterol (Table 1)
    • large, medium,and small very low-density lipoproteins (VLDL), except large VLDL in women
    • intermediate density lipoprotein (IDL) in men only
    • LDL particle concentration
    • ApoB (in men and in the total cohort)
    • small HDL
  • An inverse association was found between AER and
    • LDL diameter
    • large HDL
  • Within the LDL class, diabetic nephropathy was associated with a shift in subclass distribution toward smaller-diameter particles.
  • No associations of nephropathy were found with apoA1, Lp(a) or susceptibility of LDL to oxidation.
Author's conclusion:

Potentially atherogenic lipoprotein profiles are associated with renal dysfunction in type 1 diabetes and further details are gained from NMR analysis.

COMMENT

Using conventional lipid profile refined by NMR determination of lipoprotein subclasses, Jenkins et al. clearly demonstrated an association between several lipid abnormalities and diabetic nephropathy in patients with type 1 diabetes. An association between diabetic nephropathy and hypertriglyceridemia was found in both genders. In line with this finding, NMR measurements confirmed the association of diabetic nephropathy with triglyceride-rich VLDLs, mainly those of the smaller size. Although conventional lipid measurements did not point to HDL cholesterol (Table 1), NMR measurement showed an association of diabetic nephropathy with smaller HDL particles, which are not cardioprotective. More associations, in particular with a shift from larger toward smaller LDLs were found in men. Small, dense LDL particles have been reported to be more atherogenic than their large, “buoyant” counterparts, and are often associated with higher absolute number of LDL particles. The authors stress that the overall pattern of associations in men conforms to the atherogenic dyslipidemia which is a hallmark of insulin resistance, the metabolic syndrome, and type 2 diabetes. Due to its cross-sectional design, this study cannot tell whether dyslipidemia is a cause or an effect of diabetic nephropathy, or both. In a separate analysis published at a later date, the authors reported an association between dyslipoproteinemia and diabetic retinopathy.1 As they rightly stress, it is unlikely that diabetic retinopathy may affect whole-body plasma lipoprotein profile. Longitudinal studies are needed to determine whether lipoprotein-related intervention retard nephropathy.

 

Table 1. Relation between conventional lipid profile and albumin excretion rate in patients with type 1 diabetes

Conventional lipid profile

Albumin excretion rate

p value*

<40 mg/24 h
(normal)

40-299 mg/24 (microalbuminuria)

≥300 mg/24 h
(albuminuria)

Total cholesterol 187.1 ± 1.2 191.8 ± 3.5 212.8 ± 4.9 <0.0001
Total triglycerides 84.4 ± 2.1 94.0 ± 4.6 141.5 ± 11.6 <0.0001
LDL cholesterol 112.9 ± 1.0 120.3 ± 3.2 133.8 ± 4.8 <0.002
HDL cholesterol 56.8 ± 0.5 53.6 ± 1.5 56.2 ± 2.2 NS

*after adjustment on age, diabetes duration, hypertension, HbA1c, BMI, waist-to-hip ratio, and DCCT randomization group.
Further analyses revealed no significant differences between genders.

References
  1. 1. Lyons TJ et al. Diabetic retinopathy and serum lipoprotein subclasses in the DCCT/EDIC cohort. Invest Ophthalmol Vis Sci 2004;45:910-8.
Key words diabetic nephropathy; lipoproteins; lipoprotein subclasses