Adipokine serum concentrations, anthropometric measurements and socio-economic status in two ethnic groups with different prevalence levels for cardiovascular diseases and type 2 diabetes.

Obesity is more common in African than Asian-Indian populations and yet type 2 diabetes and cardiovascular diseases are more common in the latter populations. The main purpose of the current study was therefore to determine whether ethnic differences in body fat distribution, adipokine levels, and socio-economic status may explain population differences in the prevalence of these metabolic disorders. Leptin, IL-6, CRP, visceral fat, education level, and socio-economic status were measured in 50 African and the same number of Indian women residing in Johannesburg, South Africa. Serum leptin levels were significantly higher in Indian than African subjects (41.3±2.0 and 34.2±2.9 ng/ml, respectively; p<0.05). TNF-α levels were significantly higher in the African group, (5.22±0.86 vs. 2.54±0.52 pg/ml; p<0.05), whilst visceral fat levels were significantly lower (56.1±5.5 vs. 77.9±6.5 cm(2); p<0.05). The CRP and IL-6 levels were not different between groups. Education levels (p<0.005) and socio-economic status (p<0.0001) were both lower in the African subjects, however, adjusting for these variables in ANCOVA did not attenuate differences in adipokine or visceral fat levels. We hypothesise that one of the reasons for the higher prevalence of obesity in the African than Indian population may be related to lower leptin levels, whilst ethnic differences in the prevalence of metabolic disorders cannot be explained by differences in adipokine levels, but maybe related to higher visceral adiposity in the Indian group.

Quantity versus quality of LDL cholesterol in patients with familial hypercholesterolemia--which is more important?

BACKGROUND: The aim of this study was to determine the effects of low-density lipoprotein (LDL) particle size and composition on the susceptibility of LDL to oxidation in subjects with Familial Hypercholesterolemia (FH). METHODS: LDL was isolated from 20 FH homozygotes, 20 FH heterozygotes and 20 normal controls. Susceptibility of LDL to ex vivo copper-mediated oxidation was assessed by measuring conjugated diene production at 234 nm. Other factors known to influence LDL oxidation, namely particle size, vitamin E levels, and fatty acid composition of the LDL particles were also measured. RESULTS: The mean duration of the lag phase was 1.42-fold longer in the FH homozygotes, and 1.21-fold longer in the FH heterozygotes than in the normal controls. LDL particle size was significantly larger in the FH homozygotes (26.45+/-0.37 nm) and FH heterozygotes (26.01+/-0.40 nm) compared to the normal control group (25.17+/-0.39 nm). LDL vitamin E concentrations, when expressed relative to LDL cholesterol concentrations, were similar in all the groups. In addition, no significant differences were observed in the total saturated, monounsaturated or polyunsaturated fatty acid content of LDL in the three groups of subjects. CONCLUSION: These results suggest that it is the great excess in LDL quantity, rather than LDL 'quality', that is responsible for the severe and premature atherosclerosis in patients with FH.

Low-density lipoprotein cholesterol bulk is the pivotal determinant of atherosclerosis in familial hypercholesterolemia.

This study's aim was to determine whether biochemical risk factors such as lipoprotein(a), fibrinogen, homocysteine, and insulin, as well as low-density lipoprotein (LDL) particle size, were predictive of carotid intimamedia thickness (IMT), an early marker of atherosclerosis, in subjects with familial hypercholesterolemia (FH). We also determined whether plasma 8-isoprostane, as a marker of in vivo lipid oxidation, correlated with carotid IMT. Twenty-two homozygous and 20 heterozygous subjects with FH were compared with 20 normocholesterolemic controls. On univariate analysis, plasma total and LDL cholesterol, the cholesterol-years score (CYS), lipoprotein(a), and fibrinogen, but not homocysteine or insulin, were positively related, and high-density lipoprotein (HDL) cholesterol was negatively related to carotid IMT. However, on multivariate analysis, only LDL cholesterol and the CYS predicted carotid IMT (multiple r = 0.82; r2 = 0.68; p <0.0001). The subjects with FH had large rather than small dense LDL particles, and plasma 8-isoprostane levels were not increased. LDL cholesterol and the CYS, or "cholesterol bulk" are the pivotal determinants of atherosclerosis and are the strongest predictors of carotid IMT in FH.

Susceptibility of low density lipoprotein to oxidation in familial hypercholesterolaemia.

There is increasing evidence that oxidative modification of low density lipoprotein (LDL) plays an important role in the pathogenesis of atherosclerosis. Subjects with familial hypercholesterolaemia (FH) have elevated concentrations of LDL and develop premature atherosclerosis. The aim of the study was to determine whether the susceptibility of LDL to in vitro oxidation is increased in FH subjects. LDL was isolated from 15 FH homozygotes (mean age +/- SD, 19 +/- 10 years; mean LDL-cholesterol 16.86 +/- 3.55 mmol/l), 15 FH heterozygotes (38 +/- 13 years; LDL-cholesterol 5.58 +/- 1.78 mmol/l) and 15 normocholesterolaemic subjects (31 +/- 8 years; LDL-cholesterol 3.07 +/- 0.77 mmol/l). Susceptibility of LDL to in vitro copper-mediated oxidation was assessed by measuring conjugated diene production at 234 nm, the lag phase being a measure of the resistance of LDL to oxidation. Unexpectedly, the mean duration of the lag phase was 2.2 fold longer in the FH homozygotes (123.8 +/- 45.0 min) and 1.75-fold longer in the FH heterozygotes (99.9 +/- 40.6 min) than in the controls (57.1 +/- 27.9 min; P < 0.0001). Serum and LDL vitamin E levels were higher in the FH patient, but not when expressed relative to LDL-cholesterol concentration. There was also no correlation between LDL vitamin E concentration and duration of the lag phase. LDL bulk rather than the susceptibility of LDL to oxidation is probably the more important factor for the initiation and progression of atherosclerosis in FH patients.