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Clinical Trial
. 2013 Aug 8;8(8):e72763.
doi: 10.1371/journal.pone.0072763. eCollection 2013.

Small, dense LDL particles predict changes in intima media thickness and insulin resistance in men with type 2 diabetes and prediabetes--a prospective cohort study

Philipp A Gerber  1 , Christoph Thalhammer, Christian Schmied, Silviana Spring, Beatrice Amann-Vesti, Giatgen A Spinas, Kaspar Berneis
Affiliations
Clinical Trial

Small, dense LDL particles predict changes in intima media thickness and insulin resistance in men with type 2 diabetes and prediabetes--a prospective cohort study

Philipp A Gerber et al. PLoS One. .

Abstract

The association of small, dense low-density lipoprotein (sdLDL) particles with an increased cardiovascular risk is well established. However, its predictive value with regard to glucose metabolism and arterial disease in patients with type 2 diabetes has not been thoroughly investigated. We conducted a prospective longitudinal cohort study in patients with (pre)diabetes who were seen at baseline and after two years. sdLDL particles were determined by gradient gel electrophoresis. Insulin resistance was estimated by using the homeostatic model assessment 2 (HOMA2). Intima media thickness (IMT) and flow-mediated dilation (FMD) were assessed by ultrasound measurements. Fifty-nine patients (mean age 63.0 ± 12.2 years) were enrolled and 39 were seen at follow-up. IMT increased in the whole cohort during follow-up. The change in IMT was predicted by the proportion of sdLDL particles at baseline (p=0.03), and the change in FMD was predicted by LDL-cholesterol levels at baseline (p=0.049). HOMA2 and changes in HOMA2 correlated with the proportion of sdLDL particles and changes in this proportion, respectively (p<0.05 for both). Serum resistin levels increased in parallel with the increasing sdLDL particle number, while serum adiponectin increased only in patients with unaltered sdLDL particle number at follow-up (p<0.01 for both). In conclusion, the proportion of small, dense LDL particles and changes in this proportion are predictive of changes in intima media thickness and insulin resistance, and are closely associated with other determinants of an adverse metabolic status. Thus, this parameter extends the individual risk assessment beyond the limitations of traditional risk markers in patients with dysglycemia.

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Conflict of interest statement

Competing Interests: The authors have the following interests. This study was partly funded by an unrestricted grant from AstraZeneca. There are no patents, products in development or marketed products to declare. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials, as detailed online in the guide for authors.

Figures

Figure 1
Figure 1. Prediction of changes in IMT and FMD bei sdLDL and LDL-C.
Changes in IMT during the 2 year follow-up are shown in relation to the proportion of small, dense LDL particles at baseline (a). Changes in FMD during follow-up are shown in relation to the proportion of LDL-C levels at baseline (1B), p<0.05.
Figure 2
Figure 2. Changes in HOMA2 and resistin / adiponectin levels depend on changes in the proportion of sdLDL particles.
The Proportion of patients (%) with constant or improved insulin resistance (white) or worsened insulin resistance (black) (assessed by HOMA2 during 2 years of follow-up) is shown for those patients with and those without an increase in small, dense LDL particles (2A, p<0.05). Changes (%) of resistin and adiponectin levels during the 2 years of follow-up are shown in in patients with and those without an increase in small, dense LDL particles (2B). * Significantly different from baseline, p<0.05.
See this image and copyright information in PMC

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