SaaG e-Posters: Removing cholesterol: efflux and reverse cholesterol transport

184 - HDL efflux capacity, and particle remodelling in patients with type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) (ID 1163)

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Session Name
SaaG e-Posters: Removing cholesterol: efflux and reverse cholesterol transport
Presentation Topic
2.3 HDL

Abstract

Background and Aims

Men with diabetes have a 2-fold higher risk of cardiovascular disease (CVD), while women with diabetes have a 3-fold higher risk. HDL-C levels are often unchanged/raised in T1DM and reduced in T2DM. HDL cholesterol efflux capacity (CEC) is a stronger predictor of CVD than HDL-C. Within this study we investigated the impact of diabetes on HDL-CEC in males and females, and age/BMI-matched control groups.

Methods

Serum samples from patients with T1DM or T2DM, and age/sex-matched control subjects (n=39-42) were collected at Tallaght University Hospital. Total, ABCA1-dependent and ABCA1-independent HDL-CEC were determined after 4h incubation with 3H-cholesterol labeled J774 macrophages ex vivo. Lipoprotein profiles were characterized by fast protein liquid chromatography (FPLC) in a sub-group (n=12-18).

Results

Women, and to a lesser extent men, with T1DM exhibited significantly increased cholesterol on large HDL particles relative to BMI-matched controls. Women with T2DM and their BMI-matched controls exhibited a specific reduction in cholesterol content within large HDL-fractions. Total and ABCA1-dependent CEC were significantly reduced in women, but not men, with T2DM relative to BMI-matched controls. A significant increase in total and ABCA1-independent efflux was evident in men, but not women, with T1DM.

Conclusions

The protective effect of the female sex on lipoprotein profiles is negated with obesity and T2DM, with a progressive deterioration in HDL-CEC evident in T2DM relative to BMI-matched controls. HDL-CEC is not impaired in T1DM and likely does not contribute to enhanced CVD risk. HDL remodelling, and reduced CEC may contribute to the residual CVD risk evident in women relative to men with diabetes.

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