LDL subclass phenotypes and the insulin resistance syndrome in women.

Selby, Joe V.; Austin, Melissa A.; Newman, Beth; Zhang, D; Quesenberry, C.P.; Mayer, Elizabeth J.; Krauss, Ronald M.

doi:10.1161/01.cir.88.2.381

Cited by 220 publications

(120 citation statements)

References 29 publications

(6 reference statements)

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“…Although the most common means of de®ning fat distribution and a good correlate of deep, abdominal fat, 7,32 it does not give as precise a description of abdominal fat distribution as more sophisticated techniques. 7,32 Nevertheless, within these limitations, the present and previous studies 15,16 have shown that the corrections can re®ne our perception of the relationship between body fat distribution and lipoproteins.…”

Section: Discussionmentioning

confidence: 71%

“…Triglycerides have the strongest impact on the lipoprotein pro®le. 13,14 To our knowledge, only two studies, focusing on the LDL pro®le, have adjusted for triglycerides; in one 15 the presence of small, dense LDL was independently related to visceral fat accumulation, whilst the association was no longer signi®cant when corrected for triglycerides in a more recent study. 16 It thus remains unclear whether central obesity could in¯u-ence lipoprotein metabolism directly or via the agency of raised triglyceride levels.…”

Section: Introductionmentioning

confidence: 98%

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Lipoprotein distribution and composition in obesity: their association with central adiposity

Lehmann

et al. 1997

Int J Obes

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OBJECTIVE: To examine the relationships between the distribution and composition of subfractions of very low density (VLDL), low density (LDL) and high density (HDL) lipoproteins and central fat deposition as measured by the waist-to-hip ratio (WHR). DESIGN: Participants (n 62, 44 women and 18 men; body mass index (BMI) ! 25.0) were recruited from those consecutively attending the outpatient obesity clinic at the University Hospital, Geneva. MEASUREMENTS: Lipoprotein subfractions were isolated from fasting blood samples by cumulative¯otation or density gradient ultracentrifugation. Concentration and composition were analysed as a function of obesity indices. RESULTS: There were signi®cant correlations between the WHR and the pro®les of the three major lipoprotein subclasses. Central obesity was associated with larger VLDL, small, dense LDL and lower levels of HDL-2 independently of other indices of obesity and plasma triglycerides. Central obesity was also signi®cantly and independently associated with compositional anomalies, speci®cally an increased free cholesterol content of VLDL and LDL. CONCLUSIONS: Central body fat was associated with modi®cations of an atherogenic nature to lipoprotein distribution and composition. The data are consistent with an impact of body fat distribution on cardiovascular disease (CVD) via the agency of modi®ed lipoprotein metabolism independently of raised triglycerides.

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Section: Discussionmentioning

confidence: 71%

Section: Introductionmentioning

confidence: 98%

Lipoprotein distribution and composition in obesity: their association with central adiposity

Lehmann

et al. 1997

Int J Obes

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“…16,17 Because WHR is frequently interpreted to indicate deposition of visceral fat, 9 this ®nding suggests a signi®cant relationship between visceral adiposity and LDL size phenotypes. Waist circumference also re¯ects visceral adiposity and may actually be a better indicator than WHR.…”

Section: Discussionmentioning

confidence: 99%

“…12,14 ± 18 Moreover, LDL size phenotypes were signi®cantly associated with visceral adiposity, as estimated by WHR 14 ± 17 and also as directly measured by computed tomography. 18 In some of these studies, 16,17 WHR was more strongly associated with LDL size phenotype than was body-mass index (BMI), a global measure of adiposity. These results suggest that regional patterns of fat deposition might be differentially associated with dyslipidaemia and, perhaps, risk of CVD.…”

Section: Introductionmentioning

confidence: 99%

Relationship of low-density lipoprotein particle size and measures of adiposity

et al. 1999

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OBJECTIVE: To determine if obesity measures are related to measures of low-density lipoprotein (LDL) size and LDL subfractions in a population of Mexican-Americans with high prevalence of obesity. METHODS: LDL size phenotypes, based on nondenaturing gradient gel electrophoresis and staining for cholesterol (using Sudan black B), were determined for 313 unrelated Mexican-American participants in the San Antonio Family Heart Study. LDL size measures included predominant particle diameter, median diameter (particle diameter, where half the LDL absorbance is on larger and half on smaller LDLs) and cholesterol level in various LDL subfractions. Adiposity traits included two measures of general body fatness (body-mass index (BMI) and fat mass determined with bioimpedance) and three measures of regional fat deposition (waist-to-hip ratio (WHR), waist circumference and subscapular-triceps skinfold ratio (STR)). RESULTS: Gender and diabetes were signi®cantly associated with most LDL size measures. In addition, BMI, WHR, waist circumference and STR were signi®cantly (P`0.05) associated with several LDL size measures. Stepwise regression analysis (including adjustment for age, gender and diabetes status) showed that in every case, the strongest adiposity correlate of LDL size, was WHR, which re¯ects deposition of visceral fat. If triglyceride (TG) concentration was also included in the models, no fat measure was independently correlated with LDL size, suggesting that elevation of TG, associated with increased adiposity, was more directly correlated with LDL size. Supporting this interpretation, we found that WHR was also the strongest correlate of TG among adiposity measures. Regression analysis of the LDL particle size cholesterol pro®le expressed in 0.1 nm increments revealed a positive correlation of WHR and LDLs in the interval 25.9 ± 26.3 nm (P`0.05) and a negative correlation of BMI with LDLs in the interval 27.3 ± 28.1 nm (P`0.05). CONCLUSION: These results suggest that different adiposity measures, re¯ecting different aspects of fat deposition, are related to speci®c LDL size intervals. We speculate that increased deposition of fat, particularly visceral fat, is associated with increased TG, which in turn is associated with decreases in LDL particle size.

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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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LDL subclass phenotypes and the insulin resistance syndrome in women.

Abstract: Small, dense LDL is an integral feature of the insulin resistance syndrome. Nongenetic (ie, behavioral or environmental) factors are important for the expression of the phenotype and for its association with other heart disease risk factors.

Cited by 220 publications

References 29 publications

Lipoprotein distribution and composition in obesity: their association with central adiposity

Lipoprotein distribution and composition in obesity: their association with central adiposity

Relationship of low-density lipoprotein particle size and measures of adiposity

Adiposity, insulin and lipid metabolism in post-menopausal women

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