[Molecular biology in the diagnosis and phenotypic expression of familial hypercholesterolemia in French Canadians].
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Adolescent↗
Biomedical subjects
S Moorjani
Publications and source records attributed to S Moorjani.
[Familial hypercholesterolemia in eastern Quebec: a public health problem? The experience of the hyperlipidemia clinic of Chicoutimi].
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Adult↗
Waist circumference and abdominal sagittal diameter: best simple anthropometric indexes of abdominal visceral adipose tissue accumulation and related cardiovascular risk in men and women.
The amount of abdominal visceral adipose tissue measured by computed tomography is a critical correlate of the potentially "atherogenic" metabolic disturbances associated with abdominal obesity. In this study conducted in samples of 81 men and 70 women, data are presented on the anthropometric correlates of abdominal visceral adipose tissue accumulation and related cardiovascular disease risk factors (triglyceride and high-density lipoprotein cholesterol levels, fasting and postglucose insulin and glucose levels). Results indicate that the waist circumference and the abdominal sagittal diameter are better correlates of abdominal visceral adipose tissue accumulation than the commonly used waist-to-hip ratio (WHR). In women, the waist circumference and the abdominal sagittal diameter also appeared more closely related to the metabolic variables than the WHR. When the samples were divided into quintiles of waist circumference, WHR or abdominal sagittal diameter, it was noted that increasing values of waist circumference and abdominal sagittal diameter were more consistently associated with increases in fasting and postglucose insulin levels than increasing values of WHR, especially in women. These findings suggest that the waist circumference or the abdominal sagittal diameter, rather than the WHR, should be used as indexes of abdominal visceral adipose tissue deposition and in the assessment of cardiovascular risk. It is suggested from these data that waist circumference values above approximately 100 cm, or abdominal sagittal diameter values > 25 cm are most likely to be associated with potentially "atherogenic" metabolic disturbances.
Abdomen↗
Homozygous familial hypercholesterolaemia.
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Homozygote↗
The response to exercise with constant energy intake in identical twins.
Seven pairs of young adult male identical twins completed a negative energy balance protocol during which they exercised on cycle ergometers twice a day, 9 out of 10 days, over a period of 93 days while being kept on a constant daily energy and nutrient intake. The total energy deficit caused by exercise above the estimated energy cost of body weight maintenance reached 244 +/- 9.8 MJ (Mean +/- SEM). Baseline energy intake was estimated over a period of 17 days preceding the negative energy balance protocol. Mean body weight loss was 5.0 kg (SEM = 0.6) (p < 0.001) and it was entirely accounted for by the loss of fat mass (p < 0.001). Fat-free mass was unchanged. Body energy losses reached 191 MJ (SEM = 24) (p < 0.001) which represented about 78% of the estimated energy deficit. Subcutaneous fat loss was slightly more pronounced on the trunk than on the limbs as estimated from skinfolds, circumferences, and computed tomograply (CT). The reduction in CT-assessed abdominal visceral fat was quite striking, from 81 cm2 (SEM = 5) to 52 cm2 (SEM = 6) (p < 0.001). At the same submaximal power output level, subjects oxidized more lipids than carbohydrates after the program as indicated by the changes in the respiratory exchange ratio (p < or = 0.05). Intrapair resemblance was observed for the changes in body weight (p < 0.05), fat mass (P < 0.01), percent fat (p < 0.01), body energy content (p < 0.01), sum of 10 skinfolds (p < 0.01), abdominal visceral fat (p < 0.01), fasting plasma triglycerides (p < 0.05) and cholesterol (p < 0.05), maximal oxygen uptake (p < 0.05), and respiratory exchange ratio during submaximal work (p < 0.01). We conclude that even though there were large individual differences in response to the negative energy balance and exercise protocol, subjects with the same genotype were more alike in responses than subjects with different genotypes particularly for body fat, body energy, and abdominal visceral fat changes. High lipid oxidizers and low lipid oxidizers during submaximal exercise were also seen despite the fact that all subjects had experienced the same exercise and nutritional conditions for about three months.
Adipose Tissue↗
Are gender differences in cardiovascular disease risk factors explained by the level of visceral adipose tissue?
It has been suggested that the lower prevalence of cardiovascular disease in women before menopause in comparison with men may be explained by differences in body fat distribution, plasma lipoprotein levels and indices of plasma glucose-insulin homeostasis. Thus, gender differences in visceral adipose tissue accumulation measured by computed tomography and metabolic variables were studied in 80 men and 69 pre-menopausal women, aged 23-50 years. Despite the fact that women had higher levels of total body fat (p < 0.0001), they displayed lower areas of abdominal visceral adipose tissue (p < 0.06) and a lower ratio of abdominal visceral to mid-thigh adipose tissue areas than men (p < 0.0001). After adjustment for body fat mass, women generally displayed a more favourable risk profile than men which included higher plasma HDL2-cholesterol and lower plasma insulin, apolipoprotein B and triglyceride levels (p < 0.01). Metabolic variables adjusted for body fat mass were then compared between genders after control for differences in abdominal visceral adipose tissue area. After such controls, variables related to plasma glucose-insulin homeostasis were no longer significantly different between men and women. Gender differences for plasma concentrations of triglyceride, apolipoprotein B and the ratio of HDL2-cholesterol/HDL3-cholesterol also disappeared, whereas plasma concentrations of HDL-cholesterol, HDL2-cholesterol as well as the ratio of HDL-cholesterol/total cholesterol remained significantly higher in women than in men (p < 0.01). These results suggest that abdominal visceral adipose tissue is an important correlate of gender differences in cardiovascular disease risk. However, additional factors are likely to be involved in gender differences in plasma HDL-cholesterol levels.
Adipose Tissue↗
Systolic blood pressure during submaximal exercise: an important correlate of cardiovascular disease risk factors in normotensive obese women.
Body fatness, plasma lipids, lipoproteins, indicators of glucose metabolism, and resting as well as submaximal treadmill exercise systolic blood pressures (BPs) were measured in a sample of 25 normotensive obese premenopausal women. No association was observed between body fatness, risk factors for cardiovascular disease, and resting BP. However, body fatness and plasma cholesterol, low-density lipoprotein cholesterol (LDL-CHOL), LDL apolipoprotein B (apo B), and apo B concentrations, as well as the high-density lipoprotein cholesterol to cholesterol (HDL-CHOL/CHOL) ratio, showed significant correlations with systolic BP measured during submaximal exercise. In addition, fasting plasma insulin concentrations and the glucose and insulin areas under the oral glucose tolerance test (OGTT) curve were both significantly associated with systolic BP during submaximal exercise. Partial correlation analyses revealed that the associations between submaximal exercise systolic BP and plasma apo B and LDL apo B levels were in part independent from the level of obesity. These results indicate that plasma concentrations of lipoproteins and insulin are important correlates of the systolic BP during submaximal exercise in obese premenopausal women. Further analyses performed on two subgroups indicated that women with high exercise systolic BP values exhibited significant differences in their metabolic profile in comparison to women with low BP during exercise. These results suggest that the absolute systolic BP recorded during submaximal exercise may be useful in the early detection of individuals at risk for the development of cardiovascular disease in resting normotensive obese women.
Adult↗
Detection of a novel mutation (stop 468) in exon 10 of the low-density lipoprotein receptor gene causing familial hypercholesterolemia among French Canadians.
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Adolescent↗
ApoB-100 gene EcoRI polymorphism. Relations to plasma lipoprotein changes associated with abdominal visceral obesity.
The aim of this study was to investigate whether the EcoRI restriction fragment length polymorphism (RFLP) of the apolipoprotein (apo) B-100 gene influences the associations described among obesity, regional adipose tissue distribution, and plasma lipoprotein levels. For this purpose, blood samples were collected from 56 healthy men for whom we had extensive measurements of regional adipose tissue distribution (both anthropometric and computed tomography-derived measurements) and data on the plasma lipoprotein-lipid profile. DNA was extracted from white blood cells, and RFLP analysis was performed. Subjects were classified into two groups on the basis of their apoB-100 EcoRI genotype: subjects homozygous for the major 11-kb allele, the 11/11 group (n = 40), and subjects carrying the minor 13-kb allele, the 13/11 group (n = 16). Subjects carrying the 13-kb allele had lower percent body fat and abdominal adipose tissue accumulation than subjects homozygous for the 11-kb allele (P < .05). Although leaner, the 13/11 group did not show a more favorable plasma lipoprotein-lipid profile than the group homozygous for the 11-kb allele. In fact, after statistical control for the difference in percent body fat between the two genotype groups, the 13/11 group showed significantly higher plasma cholesterol levels (P < .05) and nearly significantly higher apoB levels than the 11/11 group (P = .06). The association patterns between indices of regional adiposity and plasma cholesterol and apoB levels were also different between the two EcoRI genotype groups. Only in the 13/11 group was the abdominal visceral adipose tissue area significantly associated with these plasma variables.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Mutations of low-density-lipoprotein-receptor gene, variation in plasma cholesterol, and expression of coronary heart disease in homozygous familial hypercholesterolaemia.
Variation in plasma-cholesterol concentration and the expression of coronary heart disease in patients with homozygous familial hypercholesterolaemia (FH) is well documented, but the underlying reasons for variation are not clearly defined. Because FH is caused by mutations at the low-density-lipoprotein-gene locus, we compared plasma-cholesterol concentrations in 21 FH homozygotes with either the greater than 10 kb deletion (promoter region and exon 1) (11 subjects) or the exon 3 missense (trp66-->gly) mutation (10 subjects) of the low-density-lipoprotein gene. Subjects with the greater than 10 kb deletion had a higher mean plasma-cholesterol concentration than those with the exon 3 mutations (26.7 vs 16.1 mmol/L; p = 0.000006), and there was no overlap in individual plasma-cholesterol concentrations between subjects in the two groups. Although the frequency of coronary heart disease was similar in the two groups, age-of-onset was earlier in subjects with the greater than 10 kb deletion (p = 0.059). Also, coronary deaths were more frequent (p = 0.044) and occurred at an earlier age (p = 0.009) in subjects with the greater than 10 kb deletion. Our results provide evidence that there is less variation in plasma-cholesterol concentrations among FH homozygotes when they are subdivided into groups according to low-density-lipoprotein-receptor-gene defect. Furthermore, differences in plasma-cholesterol concentrations are reflected in the severity of coronary heart disease expression.
Adolescent↗
Prevention of raised low-density lipoprotein cholesterol in a patient with familial hypercholesterolaemia and lipoprotein lipase deficiency.
Raised low-density lipoprotein (LDL) cholesterol is believed to predispose to development of atherosclerosis and coronary heart disease. Increased plasma LDL concentrations and premature coronary heart disease are present in familial hypercholesterolemia (FH), and the enzyme lipoprotein lipase (LPL) seems to have a key role in production of LDL. We describe a unique French Canadian individual who is both heterozygous for FH and homozygous for LPL deficiency (FH/LPL). In this patient, LDL cholesterol was strikingly low compared with both his FH (0.65 vs 5.84 mmol/L) and normolipidaemic (2.77 mmol/L) age-matched relatives despite the defect of LDL-receptor-mediated removal. No LDL peak was present in the cholesterol profile of the FH/LPL-deficient subject, as determined by density-gradient ultracentrifugation. Our results suggest that most LDL particles, in vivo, originate from triglyceride-rich lipoproteins, that LPL plays a vital part in this process, and that absence of LPL activity protects FH subjects against the increase in LDL cholesterol.
Adolescent↗
Abdominal and femoral adipose tissue lipolysis and cardiovascular disease risk factors in men.
The relationships between subcutaneous abdominal and femoral fat cell lipolyses, plasma free-fatty acid (FFA) levels and metabolic variables considered as risk factors for cardiovascular disease (CVD) (plasma glucose, insulin and lipoprotein levels) were investigated in 54 men, aged 36 +/- 3 (SD) years, covering a wide range of body fatness values (body mass indices from 19 to 34 kg m-2). Although there were no consistent relationships between femoral fat cell weight and the metabolic profile, positive and significant associations were found between abdominal fat cell weight and most of the metabolic indices. However, abdominal fat cell lipolysis measured with an alpha 2-(clonidine) or a beta-agonist (isoproterenol) was unrelated to metabolic variables. In contrast, femoral fat cell lipolysis measured in the presence of clonidine was positively associated with fasting plasma insulin, cholesterol (CHOL) and apolipoprotein (apo) B levels, as well as with LDL-CHOL and LDL-apo B concentrations. No association was found between isoproterenol-stimulated lipolysis of femoral adipocytes and the metabolic profile. Comparison of two subgroups of men with either low or high femoral residual lipolysis with clonidine revealed that subjects with the lowest femoral alpha 2-adrenergic component (i.e. the highest residual lipolysis) displayed significant alterations in both plasma lipid-lipoprotein and glucose-insulin levels which could be predictive of an increased risk of CVD. Free fatty acid (FFA) levels measured in the fasting state and during an oral glucose tolerance test (OGTT) were positively associated with fasting plasma insulin and triglyceride levels as well as with both glucose and insulin areas measured during the OGTT. However, regional adipose tissue lipolysis measured in vitro was unrelated to plasma FFA levels. These results support the view that both femoral adipose tissue lipolysis and plasma FFA levels are significant correlates of plasma glucose-insulin homeostasis and lipoprotein-lipid levels, in men. However, as adipose tissue lipolysis and plasma FFA are unrelated to each other, they may be associated with risk variables through independent mechanisms.
Abdomen↗
Metabolic heterogeneity associated with high plasma triglyceride or low HDL cholesterol levels in men.
To further understand the factors involved in the regulation of high plasma triglyceride (TG) or low plasma high density lipoprotein cholesterol (HDL-C) levels, three groups of male subjects (normal TG with low HDL-C levels, high TG with normal HDL-C levels, and high TG with low HDL-C levels) were compared with a sample of normolipemic men with normal TG and HDL-C plasma levels. Mean age was 34 years (range, 20-42 years), and none of the subjects had plasma TG levels > 4.0 mmol/l or familial hypercholesterolemia. Both groups of subjects with high TG levels had a higher body mass index, waist circumference, waist-to-hip circumferences ratio, and a higher ratio of abdominal to femoral adipose tissue areas as measured by computed tomography when compared with normolipemic control subjects. However, during an oral glucose tolerance test only high TG-low HDL-C men had fasting hyperinsulinemia and higher plasma insulin levels compared with normolipemic subjects. In addition, the high TG-low HDL-C group showed reduced HDL apoprotein (apo) A-I levels and a low HDL2-C/HDL3-C ratio. These changes were observed along with a nonsignificant trend for a lower plasma postheparin lipoprotein lipase activity. However, among subjects with high TG and normal HDL-C levels, no evidence of insulin resistance or of a reduction in postheparin lipoprotein lipase activity was observed, suggesting that the high plasma TG levels could be attributed to an increased production of apo B-containing lipoproteins, as high plasma apo B and low density lipoprotein (LDL)-apo B levels were observed in this group.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Apolipoprotein E polymorphism modifies relation of hyperinsulinemia to hypertriglyceridemia.
The effect of apolipoprotein E polymorphism on the established relationships between glucose tolerance, plasma insulin levels, and plasma lipoprotein concentrations were investigated in a sample of women defined on the basis of apolipoprotein E phenotypes. In women with the apolipoprotein E epsilon 2 allele (n = 22), fasting plasma insulin and glucose and insulin areas under the curve measured during an oral glucose tolerance test were positively correlated with plasma triglyceride levels (0.48 < or = r < or = 0.70; P < 0.05). In this group, very-low-density lipoprotein cholesterol and very-low-density lipoprotein triglyceride concentrations were positively correlated with fasting insulin levels, the insulin area, and with the ratio of insulin area to glucose area. In women (n = 24) homozygous for the apolipoprotein E epsilon 3 allele (the most common allele), essentially similar associations were found. In contrast, in women (n = 17) with the apolipoprotein E epsilon 4 allele, no association was found between glucose tolerance, fasting and postglucose plasma insulin levels, and plasma lipid and lipoprotein levels. These results suggest that apolipoprotein E polymorphism substantially modifies the associations between glucose tolerance, plasma insulin levels, and plasma lipoprotein concentrations. Additional analysis of the data revealed that apolipoprotein E polymorphism did not alter the relationships between body fat distribution and fasting insulin and postglucose insulin levels, but no correlation was observed between fatness indexes and glucose tolerance among apolipoprotein E epsilon 2 carriers.(ABSTRACT TRUNCATED AT 250 WORDS)
Adipose Tissue↗
Evidence for a role of insulin in the regulation of abdominal adipose tissue lipoprotein lipase response to exercise training in obese women.
Abdominal and femoral adipose tissue lipoprotein lipase (AT-LPL) activities were measured in ten obese premenopausal women (mean age 35 +/- 5 years) who took part in a six month endurance exercise training programme. The programme involved four to five 90 min training sessions per week at about 50 to 55% of maximal endurance power (VO2max). Before training, the ratio of insulin to glucose area measured during an oral glucose tolerance test (OGTT) was significantly correlated with fat mass (r = 0.72, P < 0.05) as well as with abdominal AT-LPL activity (r = 0.69, P < 0.05). The training programme induced a significant increase in VO2max (P < 0.05) whereas no significant change in the mean body composition was observed. Abdominal as well as femoral AT-LPL activities were significantly reduced after the exercise training programme (P < 0.05) whereas plasma post-heparin (PH) LPL activity was significantly increased by training (P < 0.05). No significant association was observed between changes in VO2max and in body composition parameters and changes in abdominal or femoral AT-LPL activities. However, changes in insulin sensitivity, as estimated by changes in the insulin area/glucose area ratio were positively correlated with changes in abdominal AT-LPL activity expressed on a per cell (r = 0.72, P < 0.05) or per surface area (r = 0.81, P < 0.01) basis. These results suggest that the reduction in AT-LPL activity in both fat depots following endurance training in obese women can occur despite the lack of significant decrease in body weight and average fat cell size.(ABSTRACT TRUNCATED AT 250 WORDS)
Abdomen↗
Genetic aspects of susceptibility to obesity and related dyslipidemias.
Obesity has a multifactorial origin. However, although environmental variables undoubtedly play a role in the development of obesity, it is now clear that genetic variation is also involved in the determination of an individual's susceptibility to body fat accumulation. In addition, it is also widely accepted that obesity is not a single homogeneous phenotype. It is also heterogeneous regarding its causes and metabolic complications. The regional distribution of body fat appears to be an important correlate of the metabolic complications that have been related to obesity. Due to their higher accumulation of abdominal fat, men are generally more at risk for the metabolic complications of obesity than women whereas some obese women, with large gluteal-femoral adipose depots may have a cosmetic problem which may not necessarily require medical intervention. Several studies have been conducted to understand the mechanisms by which abdominal obesity is related to diabetes, hypertension and cardiovascular disease. It appears that the increased risk of abdominal obesity is the result of complex hormonal and metabolic interactions. Studies in genetic epidemiology have shown that both total body fatness and the regional distribution of body fat have a significant genetic component. Standardized intervention studies using an identical twin design have shown that individuals that have the same genetic background tend to show similar changes in body fat and in plasma lipoprotein levels when exposed to standardized caloric excess or energy restriction. Finally, although abdominal obesity is a significant risk factor for cardiovascular disease, not every abdominal obese subject will experience metabolic complications, suggesting that some obese individuals may be more susceptible than others. Variation in several genes relevant to lipid and lipoprotein metabolism may alter the relation of abdominal obesity to dyslipoproteinemias. Abdominal obesity should therefore be considered as a factor that exacerbates an individual's susceptibility to cardiovascular disease.
Adipose Tissue↗
Is body fat loss a determinant factor in the improvement of carbohydrate and lipid metabolism following aerobic exercise training in obese women?
Thirty-one obese, premenopausal women aged 35.4 +/- 5.1 (SD) years exercised for 90 minutes at approximately 55% of maximal aerobic power (VO2max) four to five times a week for a period of 6 months. The training program induced a significant increase in VO2max (P < .001) and significant improvements in carbohydrate and lipid metabolism, as reflected by decreased plasma insulin (INS) concentrations measured in the fasting state and after glucose (GLU) ingestion (INS area, P < .001), by reduced plasma cholesterol (C) and low-density lipoprotein cholesterol (LDL-C) levels (P < .001), and by increased ratios of high-density lipoprotein cholesterol (HDL-C)/LDL-C and HDL2-C/HDL3-C (P < .05 and P < .001, respectively). Changes in body fat mass were positively associated with changes in the INS area/GLU area ratio (r = .49, P < .05) and with changes in very-low-density lipoprotein triglycerides ([VLDL-TG] r = .49, P < .05). Furthermore, changes in the INS area were positively associated with changes in VLDL-TG (r = .51, P < .05). Although no significant mean change in body composition was observed, important individual variation was noted. Twenty women showed a reduction in body fat mass (mean reduction, 2.63 +/- 2.2 kg), whereas 11 women showed an increase in adipose mass (mean increase, 2.79 +/- 2.36 kg). Comparable increases in VO2max were observed between the two groups. The group that showed a decrease in body fat mass with exercise also had significant improvements in carbohydrate and lipid metabolism.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Influence of diets containing cow's milk or soy protein beverage on plasma lipids in children with familial hypercholesterolemia.
The present article summarizes the effects of diets containing either cow's milk or soy protein beverage on plasma lipids and lipoproteins in children with familial hypercholesterolemia. After a stabilization period of 6 weeks without any hypolipemic medication, 10 subjects aged 6-12 years were randomly assigned to either cow's milk or soy protein beverage with subsequent crossover after a washout period, each of 4 weeks duration. During the experimental periods, subjects were fed diets containing 20% of energy as protein, of which 35% was from cow's milk protein or soy protein isolate, 28% of energy as fat with a polyunsaturated:monounsaturated:saturated fat ratio of 1:3:3, and less than 200 mg/day of cholesterol. The soy protein beverage, compared to cow's milk, induced significant reductions in plasma triglycerides and very-low-density lipoprotein cholesterol, as well as a significant increase in high-density lipoprotein cholesterol, indicating that consumption of soy protein beverage may be beneficial for the prevention of coronary heart disease in children with familial hypercholesterolemia.
Adult↗