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      High-density lipoprotein subclass and particle size in coronary heart disease patients with or without diabetes

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          Abstract

          Background

          A higher prevalence of coronary heart disease (CHD) in people with diabetes. We investigated the high-density lipoprotein (HDL) subclass profiles and alterations of particle size in CHD patients with diabetes or without diabetes.

          Methods

          Plasma HDL subclasses were quantified in CHD by 1-dimensional gel electrophoresis coupled with immunodetection.

          Results

          Although the particle size of HDL tend to small, the mean levels of low density lipoprotein cholesterol(LDL-C) and total cholesterol (TC) have achieved normal or desirable for CHD patients with or without diabetes who administered statins therapy. Fasting plasma glucose (FPG), triglyceride (TG), TC, LDL-C concentrations, and HDL 3 (HDL 3b and 3a) contents along with Gensini Score were significantly higher; but those of HDL-C, HDL 2b+preβ2, and HDL 2a were significantly lower in CHD patients with diabetes versus CHD patients without diabetes; The preβ 1-HDL contents did not differ significantly between these groups. Multivariate regression analysis revealed that Gensini Score was significantly and independently predicted by HDL 2a, and HDL 2b+preβ2.

          Conclusions

          The abnormality of HDL subpopulations distribution and particle size may contribute to CHD risk in diabetes patients. The HDL subclasses distribution may help in severity of coronary artery and risk stratification, especially in CHD patients with therapeutic LDL, TG and HDL levels.

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          Most cited references33

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          Effects of insulin resistance and type 2 diabetes on lipoprotein subclass particle size and concentration determined by nuclear magnetic resonance.

          The insulin resistance syndrome (IRS) is associated with dyslipidemia and increased cardiovascular disease risk. A novel method for detailed analyses of lipoprotein subclass sizes and particle concentrations that uses nuclear magnetic resonance (NMR) of whole sera has become available. To define the effects of insulin resistance, we measured dyslipidemia using both NMR lipoprotein subclass analysis and conventional lipid panel, and insulin sensitivity as the maximal glucose disposal rate (GDR) during hyperinsulinemic clamps in 56 insulin sensitive (IS; mean +/- SD: GDR 15.8 +/- 2.0 mg. kg(-1). min(-1), fasting blood glucose [FBG] 4.7 +/- 0.3 mmol/l, BMI 26 +/- 5), 46 insulin resistant (IR; GDR 10.2 +/- 1.9, FBG 4.9 +/- 0.5, BMI 29 +/- 5), and 46 untreated subjects with type 2 diabetes (GDR 7.4 +/- 2.8, FBG 10.8 +/- 3.7, BMI 30 +/- 5). In the group as a whole, regression analyses with GDR showed that progressive insulin resistance was associated with an increase in VLDL size (r = -0.40) and an increase in large VLDL particle concentrations (r = -0.42), a decrease in LDL size (r = 0.42) as a result of a marked increase in small LDL particles (r = -0.34) and reduced large LDL (r = 0.34), an overall increase in the number of LDL particles (r = -0.44), and a decrease in HDL size (r = 0.41) as a result of depletion of large HDL particles (r = 0.38) and a modest increase in small HDL (r = -0.21; all P < 0.01). These correlations were also evident when only normoglycemic individuals were included in the analyses (i.e., IS + IR but no diabetes), and persisted in multiple regression analyses adjusting for age, BMI, sex, and race. Discontinuous analyses were also performed. When compared with IS, the IR and diabetes subgroups exhibited a two- to threefold increase in large VLDL particle concentrations (no change in medium or small VLDL), which produced an increase in serum triglycerides; a decrease in LDL size as a result of an increase in small and a reduction in large LDL subclasses, plus an increase in overall LDL particle concentration, which together led to no difference (IS versus IR) or a minimal difference (IS versus diabetes) in LDL cholesterol; and a decrease in large cardioprotective HDL combined with an increase in the small HDL subclass such that there was no net significant difference in HDL cholesterol. We conclude that 1) insulin resistance had profound effects on lipoprotein size and subclass particle concentrations for VLDL, LDL, and HDL when measured by NMR; 2) in type 2 diabetes, the lipoprotein subclass alterations are moderately exacerbated but can be attributed primarily to the underlying insulin resistance; and 3) these insulin resistance-induced changes in the NMR lipoprotein subclass profile predictably increase risk of cardiovascular disease but were not fully apparent in the conventional lipid panel. It will be important to study whether NMR lipoprotein subclass parameters can be used to manage risk more effectively and prevent cardiovascular disease in patients with the IRS.
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            Diabetes and glucose tolerance as risk factors for cardiovascular disease: the Framingham study.

            This report examines prospectively, in the Framingham cohort, the relation of diabetes and impaired glucose tolerance to each of the cardiovascular sequelae, taking into account age, sex, and associated cardiovascular risk factors. The incidence of cardiovascular disease, as well as the levels of cardiovascular risk factors, were found to be higher in diabetic than in nondiabetic men and women. The relative impact of diabetes on coronary heart disease, peripheral vascular disease, or stroke incidence was the same in men and women, but for cardiovascular mortality and cardiac failure the impact is greater for women. Present evidence suggests that alleviation of associated cardiovascular risk factors is the most promising course in reducing cardiovascular sequelae in diabetic patients.
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              The impact of diabetes mellitus on mortality from all causes and coronary heart disease in women: 20 years of follow-up.

              Few data are available on the long-term impact of type 2 diabetes mellitus on total mortality and fatal coronary heart disease (CHD) in women. We examined prospectively the impact of type 2 diabetes and history of prior CHD on mortality from all causes and CHD among 121 046 women aged 30 to 55 years with type 2 diabetes in the Nurses' Health Study who were followed up for 20 years from 1976 to 1996. During 20 years of follow-up, we documented 8464 deaths from all causes, including 1239 fatal CHD events. Compared with women with no diabetes or CHD at baseline, age-adjusted relative risks (RRs) of overall mortality were 3.39 (95% confidence interval [CI], 3.08-3.73) for women with a history of diabetes and no CHD at baseline, 3.00 (95% CI, 2.50-3.60) for women with a history of CHD and no diabetes at baseline, and 6.84 (95% CI, 4.71-9.95) for women with both conditions at baseline. The corresponding age-adjusted RRs of fatal CHD across these 4 groups were 1.0, 8.70, 10.6, and 25.8, respectively. Multivariate adjustment for body mass index and other coronary risk factors only modestly attenuated the RRs. Compared with nondiabetic persons, the multivariate RRs of fatal CHD across categories of diabetes duration ( 25 years) were 2.75, 3.63, 5.51, 6.38, and 11.9 (P 15 years) was associated with a 30-fold (95% CI, 20.7-43.5) increased risk of fatal CHD. Our data indicate that among women, history of diabetes is associated with dramatically increased risks of death from all causes and fatal CHD. The combination of diabetes and prior CHD identifies particularly high-risk women.
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                Author and article information

                Journal
                Lipids Health Dis
                Lipids Health Dis
                Lipids in Health and Disease
                BioMed Central
                1476-511X
                2012
                15 May 2012
                : 11
                : 54
                Affiliations
                [1 ]Laboratory of Endocrinology and Metabolism, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, People’s Republic of China
                [2 ]State Key Laboratory of Biotherapy, Sichuan University, New building 6, #16 Section 3, People South Road, Chengdu, Sichuan, 610041, People’s Republic of China
                [3 ]Department of Biochemistry and Molecular Biology, University of South China, Hengyang, Hunan, People’s Republic of China
                [4 ]Cardiovascular department of West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, People’s Republic of China
                Article
                1476-511X-11-54
                10.1186/1476-511X-11-54
                3477075
                22584085
                70e436b0-9a8c-4afa-913f-b88809f52ead
                Copyright ©2012 Tian et al.; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 13 March 2012
                : 27 April 2012
                Categories
                Research

                Biochemistry
                diabetic mellitus,high density lipoprotein subclasses,fasting plasma glucose,coronary heart disease

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