Insulin resistance and hyperinsulinemia in individuals with small, dense low density lipoprotein particles.

Reaven, Gerald M.; Chen, Y D; Jeppesen, Jørgen; Maheux, Pierre; Krauss, Ronald M.

doi:10.1172/jci116541

Cited by 630 publications

(298 citation statements)

References 29 publications

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“…The variable most closely related to LDL particle size in the present study was plasma triglyceride levels (rZ0.372, P!0.001) as previously reported (41). At present, the reason why LDL particle size was elevated in Asp298 allele carriers cannot be explained.…”

Section: Discussionsupporting

confidence: 85%

The effects of endothelial nitric oxide synthase gene polymorphisms on endothelial function and metabolic risk factors in healthy subjects: the significance of plasma adiponectin levels

Imamura

Takahashi²,

Murakami³

et al. 2008

European Journal of Endocrinology

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Objective: Genetic variants of the endothelial nitric oxide synthase (eNOS) gene, Glu298Asp and T-786C, have been reported to be associated with cardiovascular disease. Adiponectin is an adipocytederived plasma protein with insulin-sensitizing and vascular protective effects; its levels are typically low in metabolic syndrome. Therefore, eNOS gene polymorphisms may also be associated with specific metabolic profiles, including plasma adiponectin levels and atherogenic lipids. Methods: We evaluated the functional significance of eNOS gene Glu298Asp and T-786C polymorphisms on endothelial function and metabolic profiles in 101 healthy young men (mean age 30.3 years) before the progression of atherosclerotic lesions. Results: No linkage disequilibrium was found between the two genotypes. The Asp298 allele carriers of the eNOS gene presented significantly higher plasma low density lipoprotein (LDL) cholesterol, LDL particle size, malondialdehyde-modified LDL (MDA-LDL), and fasting insulin levels and lower plasma high density lipoprotein (HDL) cholesterol, apolipoprotein A-I levels, and endothelium-dependent vasodilation when compared with noncarriers. In spite of higher MDA-LDL levels, Asp298 carriers had significantly larger LDL particle size. By contrast, in C-786 allele carriers, systolic blood pressure was significantly higher, and plasma high-molecular-weight adiponectin levels and endotheliumdependent vasodilation were significantly lower than those in non-carriers. Conclusions: Although both eNOS polymorphisms induced endothelial dysfunction, the eNOS T-786C polymorphism may be associated with adiponectin levels, whereas the Glu298Asp polymorphism may be associated with atherogenic lipid levels.

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Section: Discussionsupporting

confidence: 85%

The effects of endothelial nitric oxide synthase gene polymorphisms on endothelial function and metabolic risk factors in healthy subjects: the significance of plasma adiponectin levels

Imamura

Takahashi²,

Murakami³

et al. 2008

European Journal of Endocrinology

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“…The unique findings of the present study are that subjects with metabolic syndrome identified by clinically applicable criteria showed an independent association with LDL-C to influence on carotid IMT. Hulthe et al (29) reported that subjects with metabolic syndrome had an increased carotid IMT compared to that of subjects with no risk factors, and components of the metabolic syndrome such as insulin resistance, dyslipidemia, and glucose intolerance are significantly associated with increasing LDL-C (30) and also related to small LDL particles (31)(32)(33). In addition, LDL-C (12) and small LDL particle sizes are also associated with the occurrence and size of plaques in the carotid artery (29).…”

Section: Disucussionmentioning

confidence: 99%

Metabolic Syndrome Amplifies the LDL-Cholesterol Associated Increases in Carotid Atherosclerosis

et al. 2005

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Objective Carotid intima-media thickness (IMT) is a useful surrogate marker of cardiovascular disease. In addition to low-density lipoprotein cholesterol (LDL-C), metabolic syndrome has been linked to the pathogenesis of atherosclerosis. The present study investigated whether the clustering of multiple components of metabolic syndrome has a greater impact on vascular parameters than individual components of metabolic syndrome, and assessed the association between carotid IMT and LDL-C and metabolic syndrome.Methods Carotid

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“…7 -11 Adverse effects of insulin resistance on lipid metabolism, with consequent effects on circulating TAG concentrations, may be the primary metabolic defect that leads to low HDL and increased prevalence of small dense LDL, 12,13 which are the key features of the atherogenic lipoprotein phenotype. 14 Greater tendency for central fat deposition after the menopause may be particularly relevant to the higher incidence of CHD in post-menopausal women, since, although central obesity has been shown to be a strong risk factor for both men and women, studies in women generally produce values for relative risk that are higher than those found in men.…”

Section: Introductionmentioning

confidence: 99%

Adiposity, insulin and lipid metabolism in post-menopausal women

et al. 2002

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OBJECTIVE:To investigate relationships between body fat and its distribution and carbohydrate and lipid tolerance using statistical comparisons in post-menopausal women. DESIGN: Sequential meal, postprandial study (600 min) which included a mixed standard breakfast (30 g fat) and lunch (44 g fat) given at 0 and 270 min, respectively, after an overnight fast. SUBJECTS: Twenty-eight post-menopausal women with a diverse range of body weight (body mass index (BMI), mean 27.2, range 20.5 -38.8 kg=m 2 ) and abdominal fat deposition (waist, mean 86.4, range 63.5 -124.0 cm). Women with BMI < 18 or > 37 kg=m 2 , age > 80 y and taking hormone replacement therapy (HRT) were excluded. MEASUREMENTS: Anthropometric measurements were performed to assess total and regional fat deposits. The concentrations of plasma total cholesterol, high density lipoprotein (HDL) cholesterol, triacylglycerol (TAG), glucose, insulin (ins), non-esterified fatty acids (NEFA) and apolipoprotein (apo) B-48 were analysed in plasma collected at baseline (fasted state) and at 13 postprandial time points for a 600 min period. RESULTS: Insulin concentrations in the fasted and fed state were significantly correlated with all measures of adiposity (BMI, waist, waist -hip ratio (W=H), waist -height ratio (W=Ht) and sum of skinfold thickness (SSk)). After controlling for BMI, waist remained significantly and positively associated with fasted insulin (r ¼ 0.559) with waist contributing 53% to the variability after multiple regression analysis. After controlling for waist, BMI remained significantly correlated with postprandial (IAUC) insulin (r ¼ 0.535) contributing 66% of the variability of this measurement. No association was found between any measures of adiposity and glucose concentrations, although insulin concentration in relation to glucose concentration (glucose -insulin ratio) was significantly negatively correlated with all measures of adiposity. A significant positive correlation was found between fasted TAG and BMI (r ¼ 0.416), waist (r ¼ 0.393) and Ssk (r ¼ 0.457) and postprandial (AUC) TAG with BMI (r ¼ 0.385) and Ssk (r ¼ 0.406). A significantly higher postprandial apolipoprotein (apo) B-48 response was observed in those women with high BMI ( > 27 kg=m 2 ). Fasting levels of NEFA were significantly and positively correlated with all measures of adiposity (except W=H). No association was found between cholesterol containing particles and any measure of adiposity. CONCLUSION: Hyperinsulinaemia associated with increasing body fat and central fat distribution is associated with normal glucose but not TAG or NEFA concentrations in postmenopausal women.

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Insulin resistance and hyperinsulinemia in individuals with small, dense low density lipoprotein particles.

Abstract: Subjects characterized by a predominance of small LDL particles (pattern B) have changes in plasma triglyceride (TG) and HDL-cholesterol concentrations consistent with the presence of resistance to insulin-mediated glucose uptake. To

Cited by 630 publications

References 29 publications

The effects of endothelial nitric oxide synthase gene polymorphisms on endothelial function and metabolic risk factors in healthy subjects: the significance of plasma adiponectin levels

The effects of endothelial nitric oxide synthase gene polymorphisms on endothelial function and metabolic risk factors in healthy subjects: the significance of plasma adiponectin levels

Metabolic Syndrome Amplifies the LDL-Cholesterol Associated Increases in Carotid Atherosclerosis

Adiposity, insulin and lipid metabolism in post-menopausal women

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