Abstract
Background. Besides their role in reverse cholesterol transport, HDL particles may affect the atherosclerotic process through the modulation of subclinical inflammation. HDL particles differ in size, composition, and, probably, anti-inflammatory properties. This hypothesis has never been explored in diabetic women, frequently having dysfunctional HDL. The potential relationship between lipid profile, Apo-AI containing HDL subclasses distribution, and common inflammatory markers (hsCRP, IL-6) was examined in 160 coronary heart disease- (CHD-) free women with and without type 2 diabetes. Results. Compared to controls, diabetic women showed lower levels of the atheroprotective large α-1, α-2, and pre-α-1 and higher concentration of the small, lipid-poor α-3 HDL particles (P < 0.05 all); diabetic women also had higher hsCRP and IL-6 serum levels (age- and BMI-adjusted P < 0.001). Overall, HDL subclasses significantly correlated with inflammatory markers: hsCRP inversely correlated with α-1 (P = 0.01) and pre-α-1 (P = 0.003); IL-6 inversely correlated with α-1 (P = 0.003), α-2 (P = 0.004), and pre-α-1 (P = 0.002) and positively with α-3 HDL (P = 0.03). Similar correlations were confirmed at univariate regression analysis. Conclusions. More atheroprotective HDL subclasses are associated with lower levels of inflammatory markers, especially in diabetic women. These data suggest that different HDL subclasses may influence CHD risk also through the modulation of inflammation.
Highlights
Cardiovascular disease is the primary cause of death in diabetic women [1,2,3,4].Low plasma levels of high-density lipoprotein cholesterol (HDL-C) have been largely recognized as a risk factor for coronary heart disease (CHD) [5, 6] and they are a common feature of insulin resistance states [7].HDL class comprises very heterogeneous particles that can be separated by different methods, including twodimensional gel electrophoresis that separates Apo-AI containing HDL particles according to their size and lipid content [5]
We have recently shown that type 2 diabetes determines a shift in the distribution of HDL particles; in particular, when assessing HDL subpopulation distribution by twodimensional gel electrophoresis, diabetic women had HDL that are selectively depleted in the large lipid-rich α-1, α2, and pre-α-1 and enriched in the small, lipid-poor α-3 HDL subpopulations, resulting in HDL particles that were smaller in size and poor in cholesterol compared with those
Low levels of HDL-C are a mainstay of diabetic dyslipidemia and a largely recognized CHD risk factor [28,29,30], especially in insulin resistant patients [31]
Summary
Cardiovascular disease is the primary cause of death in diabetic women [1,2,3,4].Low plasma levels of high-density lipoprotein cholesterol (HDL-C) have been largely recognized as a risk factor for coronary heart disease (CHD) [5, 6] and they are a common feature of insulin resistance states [7].HDL class comprises very heterogeneous particles that can be separated by different methods, including twodimensional gel electrophoresis that separates Apo-AI containing HDL particles according to their size and lipid content [5]. It was documented that low levels of α-1 and α-2 HDL particles were better predictors of CHD risk than total HDLC concentration in both the Framingham Offspring Study and the VA-HIT study [12, 13] Besides their role in reverse cholesterol transport, HDL particles may affect the atherosclerotic process through the modulation of subclinical inflammation. The potential relationship between lipid profile, Apo-AI containing HDL subclasses distribution, and common inflammatory markers (hsCRP, IL-6) was examined in 160 coronary heart disease- (CHD-) free women with and without type 2 diabetes. More atheroprotective HDL subclasses are associated with lower levels of inflammatory markers, especially in diabetic women These data suggest that different HDL subclasses may influence CHD risk through the modulation of inflammation
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