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PubMed1993

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↗

PubMed1998

Traversing the menopause: changes in energy expenditure and body composition.

The menopause transition is associated with several physiological changes that may impact women's health outcome. Among the changes associated with the loss of ovarian function is an increased risk of metabolic and cardiovascular disease. The present review focuses on changes in energy expenditure, body composition and body fat distribution during the postmenopausal transition. Previous work indicates that the most important component of total daily expenditure, resting metabolic rate, may be reduced by the menopause, independently of the effects of the normal aging process. This effect is mainly attributable to a decrease in fat-free mass. The energy expenditure associated with physical activity is the most variable component of total daily energy expenditure. However, small changes in this component may have a substantial impact on body composition. Longitudinal data from our laboratory indicate that the menopause transition also leads to significant decreases in physical activity energy expenditure. The changes in body composition that accompany the menopause transition have been studied by several groups and, although some studies suggested increases in body mass index or total body fat mass with the menopause, currently available cross-sectional data preclude a firm conclusion. Nevertheless, results from our longitudinal study showed significant increases in fat mass with the menopause. The accumulation of abdominal fat, which may be a better correlate of the comorbidities associated with obesity, has also been shown to be accelerated by the menopause transition. In this regard, it has been shown that treatment with hormone replacement therapy prevents the increase in the rate of abdominal adipose tissue accumulation that was noted with the menopause. Thus, it appears that the loss of ovarian function induces a reduction in resting metabolic rate, physical activity energy expenditure, fat-free mass, and an increase in fat mass and abdominal adipose tissue accumulation. These modifications probably contribute to the increased risk of cardiovascular disease of postmenopausal women.

Adipose Tissue↗

PubMed1995

The effect of the anti-estrogen tamoxifen on cardiovascular risk factors in normal postmenopausal women.

There is growing interest in the use of anti-estrogens as agents of disease prevention. Studies of women with breast cancer suggest that the synthetic anti-estrogen tamoxifen may reduce the incidence of cardiovascular disease, but the effects of this agent on cardiovascular risk factors in healthy women have not been studied. We have performed a two-year, randomized, placebo-controlled trial to assess the effects of tamoxifen 20 mg/day on serum lipids, fibrinogen, and body composition in 57 normal postmenopausal women. Tamoxifen treatment lowered levels of serum cholesterol by (mean +/- SE) 12 +/- 2%, low density lipoprotein cholesterol by 19 +/- 3%, and fibrinogen by 18 +/- 4% (P < 0.0001 vs. placebo for each). Levels of high density lipoprotein cholesterol were not altered by tamoxifen, but the ratio of total cholesterol to HDL-cholesterol decreased by 11 +/- 4% (P < 0.001 vs. placebo). Tamoxifen did not affect levels of triglycerides, high density lipoprotein cholesterol subfractions, apolipoprotein A1, or glucose, and did not change body weight, body mass index, or body fat distribution. We conclude that tamoxifen significantly reduces the levels of atherogenic lipids and fibrinogen in normal postmenopausal women. The results suggest that the anti-estrogens may substantially reduce the risk of cardiovascular disease, which remains the most common cause of death among postmenopausal women.

Adipose Tissue↗

PubMed2003

Lean adolescents with increased risk for metabolic syndrome.

The aim of the present study was to determine in adolescents the relationship between insulin levels and body mass index (BMI), body fat distribution, diet, life style and lipid profile. We studied 167 adolescents (68 boys and 99 girls) whose ages ranged from 14 to 17 years. A detailed medical (including pubertal stage) and nutritional record was obtained from each subject. Biochemical measurements included fasting serum insulin, glucose, total cholesterol (TC), triglycerides (Tg), HDL-C, LDL-C and VLDL-C. HOMA insulin resistance (IR) and HOMA beta-cell function (beta-cell) were calculated. Insulin levels were over 84 pmol/L (cut off normal value in our lab) in 56% of the boys and 43% of the girls. Thirty-seven percent of lean adolescents whose BMI was 21.5 +/- 1.9 kg/m2 presented higher fasting insulin levels. HOMA IR, Tg, systolic (SBP) and diastolic blood pressure (DBP) values when compared to a lean normoinsulinemic group. Insulin levels were correlated (p < 0.01) with body mass index. Both boys and girls in the highest BMI quartile (BMI > 24 kg/m2) had significantly higher serum insulin, HOMA beta-cell, and Tg levels, and the lowest HDL-C levels. A high-energy intake rich in saturated fat and low physical activity were found in this lean but metabolically altered adolescents. We conclude that even with a BMI as low as 21 kg/m2 an inappropriate diet and low physical activity might be responsible for the high insulin levels and dislipidemias in adolescents.

Adolescent↗

PubMed1995

Relative androgenicity, blood pressure levels, and cardiovascular risk factors in young healthy women.

To test the hypothesis that androgens may play a role in the pathogenesis of atherosclerosis and hypertension, we investigated the association of delta 5 dehydroepiandrosterone sulfate [DHEAS]) and delta 4 (free testosterone [FT]) androgens with the resting, seated blood pressure (BP) levels and cardiovascular risk factors in 280 young, healthy women 18 to 24 years of age. After application of multiple regression analysis, systolic BP was positively and independently correlated with the ratio of dehydroepiandrosterone sulfate to free testosterone (DHEAS/FT), fasting insulin levels, and the diastolic BP with DHEAS/FT only. The DHEAS/FT ratio proved to be a stronger predictor of the BP levels than either hormone alone. Further, uric acid concentrations and HDL/total cholesterol ratio were independently correlated with both FT and body mass index in these young women. Serum triglycerides were independently correlated with FT and central body fat distribution. These data suggest that serum androgen concentrations are important independent predictors of cardiovascular risk factors and that the ratio of dehydroepiandrosterone sulfate to free testosterone ratio is an independent predictor of blood pressure levels in young women.

Acetone↗

PubMed2001

Identification of an interactive effect of beta3- and alpha2b-adrenoceptor gene polymorphisms on fat mass in Caucasian women.

Several adrenoceptor subtypes are expressed in adipocytes, which together exert their influence on adipocyte metabolism. Therefore, we specifically examined the interactive effect of Trp64Arg (beta3) and Glu12/Glu9 (alpha2b) adrenoceptor (AR) polymorphisms on energy metabolism and body composition in healthy women with a wide range of body habitus. We genotyped 909 unrelated women (age 55 +/- 12 [mean +/- SD] years, range 19-87; body weight 88 +/- 22 kg, range 40-167; and BMI 33 +/- 8 kg/m2, range 16-64) for Trp64Arg beta3AR and Glu12/Glu9 alpha2bAR variants. We examined the independent effect of the Glu12/Glu9 alpha2bAR variant on body composition and energy balance, in a large cohort of Caucasian women (n = 909). A second goal was to examine the interaction effect of Glu12/Glu9 alpha2bAR and Trp64Arg beta3AR on the same phenotypes. The obesity-related phenotypes studied were as follows: body weight, BMI, fat mass, visceral fat, fat-free mass, resting metabolic rate (RMR), VO2max, leisure time physical activity, and daily energy intake. Body composition and body fat distribution were measured by dual-energy X-ray absorptiometry and radiographic imagery, VO2max by a treadmill test to exhaustion, and RMR by indirect calorimetry. An analysis of covariance indicated that in the entire cohort, there was no significant difference between Glu12/Glu9 alpha2bAR carriers and control subjects for any of the obesity-related phenotypes that were examined. However, we observed a significant interaction effect of the Trp64Arg and Glu12/Glu9 variants on fat mass (P = 0.009) and percent fat (P = 0.016). Age, height, body weight, BMI, fat-free mass, visceral fat, energy expenditure, respiratory quotient, physical fitness, and energy intake were not different among groups. Collectively, these findings support an interaction effect of the two adrenoceptor variants on body fatness in Caucasian women, although the physiological mechanism by which they exert this effect remains to be determined.

Adipose Tissue↗

PubMed1989

Anthropometric variables and metabolism in polycystic ovarian disease.

Anthropometric, endocrine and metabolic variables, were examined in women with polycystic ovarian syndrome (PCO), and in normal control women. Obese women with PCO had higher plasma insulin values than non obese women with PCO, but lean body mass, glucose tolerance, plasma triglycerides and blood pressure were not different in spite of almost twice the body fat mass in the obese PCO women. However, in comparisons between non-obese PCO and control women, with equal body fat mass, the PCO women had higher blood pressure, plasma triglycerides and insulin, as well as a tendency to increased lean body mass. Both PCO groups had a high waist/hip ratio and larger abdominal fat cells than controls, indicating a preferential abdominal accumulation of adipose tissue. In comparison with abdominal adipocytes, femoral adipocytes were larger and had higher lipoprotein lipase activity in the control women, while in the PCO women these regional differences were not found. Basal and norepinephrine stimulated lipolysis were higher in the abdominal than femoral adipocytes in all groups. Substitution of the PCO women with ethinyl estradiol plus desogestrel during 6 months resulted in a regression of clinical androgenic symptoms as well as a normalization of plasma concentrations of free testosterone and sex hormone binding globulin. However, neither body composition nor metabolism were normalized. It was concluded that body fat distribution is more closely related to hypertension and metabolic derangements than total fat mass in the PCO syndrome. It is suggested that the relative paucity of femoral adipose tissue is due to a lack of specific effects of progesterone on adipocytes in this region.

Adipose Tissue↗

PubMed2001

Review of anthropometric factors and breast cancer risk.

Epidemiological evidence implicating anthropometric risk factors in breast cancer aetiology is accumulating. For premenopausal women, breast cancer risk increases with increasing height, but decreases with higher weight or body mass index, and no association with increased central adiposity exists. For postmenopausal women, an increased risk of breast cancer is found with increasing levels of all the anthropometric variables including height, weight, body mass index, waist-hip ratio, waist circumference and weight gain. Weight loss appears to decrease risk, particularly if it occurs later in life. Breast size may be a risk factor for breast cancer, however, the current evidence is inconclusive. Several hypothesized biologic mechanisms exist to explain how anthropometric factors influence breast cancer risk. Obesity may increase levels of circulating endogenous sex hormones, insulin and insulin-like growth factors that all, in turn, increase breast cancer risk. Genetic predisposition to obesity and to specific body fat distributions are also implicated. With obesity, there are increased levels of fat tissue that can store toxins and can serve as a continuous source of carcinogens. Recommendations for future research on anthropometric factors and breast cancer are provided. Sufficient evidence exists to support strategies to avoid weight gain throughout life as a means of reducing postmenopausal breast cancer risk.

Anthropometry↗

PubMed1996

Increased insulin resistance and insulin secretion in nondiabetic African-Americans and Hispanics compared with non-Hispanic whites. The Insulin Resistance Atherosclerosis Study.

The etiology of NIDDM is still controversial, with both insulin resistance and decreased insulin secretion postulated as potential important factors. African-Americans and Hispanics have a two- to threefold excess risk of developing NIDDM compared with non-Hispanic whites. Yet little is known concerning the prevalence of insulin resistance and secretion defects in minorities, especially in African-Americans in population-based studies. Fasting and 2-h post-glucose load glucose and insulin levels, insulin-mediated glucose disposal (insulin sensitivity index) (S(I)), glucose effectiveness (S(G)), and first-phase insulin response (acute insulin response [AIR]) were determined in nondiabetic African-Americans (n= 288), Hispanics (n= 363), and non-Hispanic whites (n= 435) as part of the Insulin Resistance Atherosclerosis Study. Subjects received a standard 2-h oral glucose tolerance test on the first day and an insulin-modified frequently sampled intravenous glucose tolerance test on the second day. African-Americans and Hispanics were more obese than non-Hispanic whites. Both African-Americans and Hispanics had higher fasting and 2-h insulin concentrations and AIR but lower S(I) than non-Hispanic whites. No ethnic difference was observed in S(G). After further adjustments for obesity, body fat distribution, and behavioral factors, African-Americans continued to have higher fasting and 2-h insulin levels and AIR, but lower S(I) than non-Hispanic whites. In contrast, after adjustment for these covariates, no significant ethnic differences in S(I) or fasting insulin levels were observed between Hispanics and non-Hispanic whites. Hispanics continued to have higher 2-h insulin levels and AIRs than those in non-Hispanic whites. In this report, the association between S(I) and upper body adiposity (waist-to-hip, ratio) was similar in each ethnic group. Both nondiabetic African-Americans and Hispanics have increased insulin resistance and higher AIR than nondiabetic non-Hispanic whites, suggesting that greater insulin resistance may be in large part responsible for the higher prevalence of NIDDM in these minority groups. However, in Hispanics. the greater insulin resistance may be due to greater adiposity and other behavioral factors.

Africa↗

PubMed2004

Visceral and central abdominal fat and anthropometry in relation to diabetes in Asian Indians.

OBJECTIVE: The objective of the study was to examine body fat distribution using computed tomography (CT), dual-energy X-ray absorptiometry (DEXA), and anthropometry in relation to type 2 diabetes in urban Asian Indians. RESEARCH DESIGN AND METHODS: This is a case-control study of 82 type 2 diabetic and 82 age- and sex-matched nondiabetic subjects from the Chennai Urban Rural Epidemiology Study, an ongoing epidemiological study in southern India. Visceral, subcutaneous, and total abdominal fat were measured using CT, while DEXA was used to measure central abdominal and total body fat. Anthropometric measures included BMI, waist circumference, sagittal abdominal diameter (SAD), and waist-to-hip ratio. RESULTS: Visceral and central abdominal fat showed a strong correlation with each other (P <0.0001), and kappa analysis revealed a fairly good agreement between tertiles of visceral and central abdominal fat (kappa=0.44, P <0.0001). Diabetic subjects had significantly higher visceral (P=0.005) and central abdominal (P=0.011) fat compared with nondiabetic subjects. Waist circumference and SAD showed a strong correlation with visceral (P <0.01) and central abdominal (P <0.0001) fat in both diabetic and nondiabetic subjects. Logistic regression analysis revealed visceral (odds ratio [OR] 1.011, P=0.004) and central abdominal (OR 1.001, P=0.013) fat to be associated with diabetes, even after adjusting for age and sex. CONCLUSIONS: Visceral and central abdominal fat showed a strong association with type 2 diabetes. Both measures correlated well with each other and with waist circumference and SAD in diabetic and nondiabetic urban Asian Indians.

Abdomen↗

PubMed1991

Sex hormone metabolism in upper and lower body obesity.

Morbid obesity has been previously shown to be associated with excessive production and metabolism of a variety of androgens and estrogens. Further, SHBG is lowered, resulting in high levels of 'free' testosterone. We have re-examined these parameters in morbidly obese women with upper vs lower body adipose distribution. Upper body obesity was associated with greater increases in production and clearance of testosterone and dihydrotestosterone compared to lower body obesity. Further, SHBG levels were lower resulting in high serum levels of free T and free E2 in this obesity phenotype. By contrast, lower body obesity was associated with increased peripheral aromatization of androstenedione resulting in higher urinary E1 production rates. The biologic significance of these hormonal differences in obesity phenotypes as well as the potential role of the androgen-estrogen environment in determining body fat distribution is considered.

Adipose Tissue↗

PubMed1992

Lipoprotein(a) concentrations in Mexican Americans and non-Hispanic whites: the San Antonio Heart Study.

There is considerable evidence that lipoprotein(a) (Lp(a)) is a strong independent risk factor for coronary heart disease. Based on their risk factor profile, Mexican Americans have an increased risk of coronary heart disease, yet Mexican Americans have coronary heart disease mortality similar to or lower than that of non-Hispanic whites. The authors therefore attempted to determine whether Mexican Americans had decreased Lp(a) concentrations relative to non-Hispanic whites in the San Antonio Heart Study, a population-based study of diabetes and cardiovascular disease. Lp(a) concentrations (mg/dl) were significantly lower in Mexican Americans (n = 316) than in non-Hispanic whites (n = 242) (men: 10.4 vs. 16.3; women: 11.5 vs. 16.4). In addition, the proportion of persons with Lp(a) concentrations of > or = 30 mg/dl (the threshold at which increased risk of coronary heart disease is believed to occur) was significantly higher in non-Hispanic whites than in Mexican Americans (18.6% vs. 7.6%; Mantel-Haenszel odds ratio (adjusted for sex) = 2.79). Age, obesity, body fat distribution, cigarette smoking, alcohol consumption, and glucose and insulin concentrations were not significantly related to Lp(a) levels. Decreased Lp(a) concentrations may account in part for Mexican Americans' relative protection from coronary heart disease mortality.

Adult↗

PubMed2005

[Visceral obesity, hypertension and cardio-renal risk: a review].

Great part of obesity adversity is due to its cardiovascular/coronary risk, particularly present in obese with visceral adiposity distribution. Visceral fat deposition is known to be associated with a greater prevalence of metabolic, neurohormonal, inflammatory and hemodynamic disorders, which together will be implicated in microvascular and target organ involvement, particularly to the cardio-renal axis. In this aspect, beyond its classical association with coronary disease, visceral obesity has been associated with left ventricular hypertrophy and microalbuminuria, which are known cardiac and nephrologic risk factors. So, therapeutic tools for obese patients, specially for those with hypertension, must accomplish the risk stratification based on body fat distribution, which will allow a more adequate therapy in terms of risk factors control as well as target organ damage monitoring.

Albuminuria↗

PubMed1995

Low-dose iloprost infusion improves insulin action in aged healthy subjects and NIDDM patients.

OBJECTIVE: To investigate the effect of iloprost infusion on insulin action. RESEARCH DESIGN AND METHODS: Thirteen healthy subjects and 13 non-insulin-dependent diabetes mellitus (NIDDM) patients matched for age (68.2 +/- 0.5 vs. 67.9 +/- 0.5 years, NS), gender ratio (7 men:6 women vs. 6 men:7 women), body weight, body fat distribution, arterial blood pressure, and plasma triglyceride levels (1.89 +/- 0.09 vs. 1.87 +/- 0.08 mmol/l, NS) were studied. In eight healthy subjects and eight NIDDM patients, we studied insulin action by euglycemic glucose clamp (insulin infusion rate 2 mU.kg-1.min-1) along with saline and iloprost delivery (0.7 ng.kg-1.min-1). In the other five subjects of each group, forearm blood flow and insulin-mediated glucose uptake during saline and iloprost infusion (0.7 ng.kg-1.min-1) were investigated. RESULTS: Iloprost infusion improved insulin-stimulated whole-body glucose uptake and oxidative and nonoxidative glucose metabolism in both study groups. Forearm blood flow under basal conditions and with insulin infusion (2 mU.kg-1.min-1) did not show any significant difference from that during saline and iloprost infusion (0.7 ng.kg-1.min-1) in healthy subjects and diabetic patients. CONCLUSIONS: Iloprost infusion improves insulin action in healthy subjects and NIDDM patients.

Aged↗

PubMedDate not supplied

Gender differences in leptin levels and physiology: a role for leptin in human reproduction.

Leptin, an adipocyte-derived hormone known to play an important role in body-weight regulation, has been shown to be expressed differentially in men and women. These observations are potentially important for the understanding of differences between men and women in regulation of food intake, weight gain, and body fat distribution. Leptin is also involved in female fertility, especially in pubertal development. It may well be the triggering signal for the onset of puberty in girls. Although the exact mechanisms and interactions with sex steroids are not yet fully established, it is clear that leptin plays a role as an endocrine mediator in sexual development and reproduction.

Animals↗

PubMed2000

Relationship of subjective and objective social status with psychological and physiological functioning: preliminary data in healthy white women.

This preliminary study compared the associations between objective and subjective socioeconomic status (SES) with psychological and physical variables among 157 healthy White women, 59 of whom subsequently participated in a laboratory stress study. Compared with objective indicators, subjective social status was more consistently and strongly related to psychological functioning and health-related factors (self-rated health, heart rate, sleep latency, body fat distribution, and cortisol habituation to repeated stress). Most associations remained significant even after controlling for objective social status and negative affectivity. Results suggest that, in this sample with a moderately restricted range on SES and health, psychological perceptions of social status may be contributing to the SES-health gradient.

Adaptation, Psychological↗

PubMed2004

Effect of metformin on the clinical and metabolic assessment of women with polycystic ovary syndrome.

A longitudinal prospective study was conducted in 21 women with polycistic ovary syndrome (PCOS), aged 27.20 +/- 5.02 years and treated with metformin (1500 mg/day)for 8 weeks. The patients were assessed for spontaneous menstruation, weight, body mass index (BMI), waist circumference, waist/hip ratio (WHR), glucose and insulin concentrations under fasting conditions and after a 75-g glucose tolerance test, lipid profile, testosterone, androstenedione, dehydroepiandrosterone sulfate, sex-hormone binding globulin (SHBG), and insulin-like growth factor (IGF)-I. Spontaneous menstruation was observed in 81% of the women treated with metformin, with no changes in weight or BMI. Waist measurement and the WHR were reduced. The quantitative insulin sensitivity check index (QUICKI) improved from 0.33 +/- 0.03 to 0.35 +/- 0.04 (p < 0.005), and serum total cholesterol and low-density lipoprotein-cholesterol were reduced, while high-density lipoprotein-cholesterol was increased. Serum testosterone concentrations were also reduced. There were no differences in serum triglycerides, SHBG or IGF-I. The occurrence of spontaneous menstruation and changes in the pattern of body fat distribution, the reduction in serum testosterone concentrations, the improvement in lipid profile and the reduction of insulinemia with the use of metformin permit us to conclude that treatment with this drug is of benefit to women with PCOS.

Adolescent↗

PubMed2003

Childhood obesity in Canada: a review of prevalence estimates and risk factors for cardiovascular diseases and type 2 diabetes.

Childhood obesity in Canada has become increasingly prevalent over the past 2 decades. Despite inconsistencies regarding different anthropometric indicators, cut-offs, and reference populations, both regional and national investigations have revealed high numbers of overweight and obese children and adolescents. A number of risk factors and health consequences have been associated with increased levels of body fatness in youth. Specifically, risk factors for cardiovascular diseases (CVD) and type 2 diabetes are known to develop early in life and tend to emerge in clusters among overweight youngsters. Unhealthy lifestyle behaviours (i.e., physical inactivity), a genetic disposition, and a centralized body fat distribution, all contribute to increased risk. In order to prevent future generations of children from experiencing increased morbidity and mortality as overweight and obese adults, coordinated efforts at all levels (family, school, community, and government) must be established with a long-term commitment to promote healthy nutrition and physical activity behaviours in our youth.

Age Factors↗