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PubMed1997

Effect of obesity and regional adiposity on the QTc interval in women.

OBJECTIVE: To determine whether differences in body fat composition and body fat distribution patterns are associated with a prolongation of the corrected QT interval for heart rate (QTc) on the electrocardiogram (EKG) during rest and exercise. DESIGN: Cross-sectional evaluation of the Qtc interval in three groups of premenopausal women during rest and two exercise conditions (50% VO2 max and VO2 max). SUBJECTS: Thirty-one healthy women with a mean age of 35 y (27-44 y) were classified as either obese (n = 22; percent body fat [%BF] > 30%) or nonobese (NO; n = 9; %BF < or = or 27%) by hydrostatic weighing. Obese subjects matched for age and %BF were grouped by waist to hip ratio (WHR) into two groups: upper body obesity (UBO; n = 11; WHR > or = 0.85) and lower body obesity (LBO; n = 11; WHR < or = 0.75. MEASUREMENTS: RR and QT intervals were measured in a double-blind design with the aid of calipers and magnifying lens for seven consecutive beats in lead II from a 12-lead EKG at a paper speed of 25 mm/sec. Five consecutive cardiac cycles excluding the longest and shortest RR and QT intervals were averaged and calculated for QTc interval using Bazett's formula. RESULTS: Mean QTc intervals were significantly different (P < 0.001) across the groups for each condition. For all conditions, UBO had the longest QTc interval as compared to LBO and NO respectively (i.e., Rest: 0.426; 0.413; 0.399sec1/2, Mid50%: 0.447; 0.426; 0.409sec1/2; Max: 0.390; 0.374; 0.357sec1/2). CONCLUSIONS: The QTc interval is positively associated with UBO even at the same level of body fat in moderately obese women. It is clear that abdominal obesity may be one of the risk factors for a prolonged QTc interval in premenopausal women.

Adult↗
PubMed2000

Bromocriptine: a novel approach to the treatment of type 2 diabetes.

OBJECTIVE: In vertebrates, body fat stores and insulin action are controlled by the temporal interaction of circadian neuroendocrine oscillations. Bromocriptine modulates neurotransmitter action in the brain and has been shown to improve glucose tolerance and insulin resistance in animal models of obesity and diabetes. We studied the effect of a quick-release bromocriptine formulation on glucose homeostasis and insulin sensitivity in obese type 2 diabetic subjects. RESEARCH DESIGN AND METHODS: There were 22 obese subjects with type 2 diabetes randomized to receive a quick-release formulation of bromocriptine (n = 15) or placebo (n = 7) in a 16-week double-blind study. Subjects were prescribed a weight-maintaining diet to exclude any effect of changes in body weight on the primary outcome measurements. Fasting plasma glucose concentration and HbA(1c) were measured at 2- to 4-week intervals during treatment. Body composition (underwater weighing), body fat distribution (magnetic resonance imaging), oral glucose tolerance (oral glucose tolerance test [OGTT]), insulin-mediated glucose disposal, and endogenous glucose production (2-step euglycemic insulin clamp, 40 and 160 mU x min(-1) x m(-2)) were measured before and after treatment. RESULTS: No changes in body weight or body composition occurred during the study in either placebo- or bromocriptine-treated subjects. Bromocriptine significantly reduced HbA(1c) (from 8.7 to 8.1%, P = 0.009) and fasting plasma glucose (from 190 to 172 mg/dl, P = 0.02) levels, whereas these variables increased during placebo treatment (from 8.5 to 9.1%, NS, and from 187 to 223 mg/dl, P = 0.02, respectively). The differences in HbA(1c) (delta = 1.2%, P = 0.01) and fasting glucose (delta = 54 mg/dl, P < 0.001) levels between the bromocriptine and placebo group at 16 weeks were highly significant. The mean plasma glucose concentration during OGTT was significantly reduced by bromocriptine (from 294 to 272 mg/dl, P = 0.005), whereas it increased in the placebo group. No change in glucose disposal occurred during the first step of the insulin clamp in either the bromocriptine- or placebo-treated group. During the second insulin clamp step, bromocriptine improved total glucose disposal from 6.8 to 8.4 mg x min(-1) kg(-1) fat-free mass (FFM) (P = 0.01) and nonoxidative glucose disposal from 3.3 to 4.3 mg min(-1) x kg(-1) FFM (P < 0.05), whereas both of these variables deteriorated significantly (P < or = 0.02) in the placebo group. CONCLUSIONS: Bromocriptine improves glycemic control and glucose tolerance in obese type 2 diabetic patients. Both reductions in fasting and postprandial plasma glucose levels appear to contribute to the improvement in glucose tolerance. The bromocriptine-induced improvement in glycemic control is associated with enhanced maximally stimulated insulin-mediated glucose disposal.

Abdomen↗
PubMed1995

Age- and menopause-associated variations in body composition and fat distribution in healthy women as measured by dual-energy X-ray absorptiometry.

To assess the variation with age and menopause, 407 healthy normal women aged 18 to 75 years had body composition and fat distribution measured by dual-energy x-ray absorptiometry (DEXA). The mean +/- SD are given for different age decades. Postmenopausal women had significantly more fat, a more central fat distribution, and less lean tissue mass (LTM) than premenopausal women. In premenopausal and postmenopausal women, age only correlated with the abdominal to total-body fat tissue ratio (r approximately .24, P < .05), whereas the years since onset of menopause correlated with fat tissue mass (FTM), fat%, abdominal fat%, and the abdominal to total-body fat tissue ratio (r approximately .2, P < .05). To assess the independent impact of age, menopausal status, and years since menopause, multiple linear regressions were performed. FTM, fat%, and abdominal fat% were significantly related to menopausal status and years since menopause independently of age. The abdominal to total-body fat tissue ratio was statistically significantly related to age, but tended also to be independently related to years since menopause. LTM was statistically significantly related to menopausal status independently of age and years since menopause. In summary, we suggest that in healthy women total-body and abdominal fat may increase and LTM may decrease in the years after menopause, primarily in the perimenopausal years, without significant changes before menopause.

Absorptiometry, Photon↗
PubMed1990

The relationships of concentrations of insulin, intact proinsulin and 32-33 split proinsulin with cardiovascular risk factors in type 2 (non-insulin-dependent) diabetic subjects.

Standard radioimmunoassay for insulin may substantially overestimate levels of insulin because of cross-reaction with other insulin-like molecules. We have measured concentrations of insulin, intact proinsulin and 32-33 split proinsulin using two-site monoclonal antibody based immunoradiometric assays, and of insulin by a standard radioimmunoassay ("immunoreactive insulin") in 51 Type 2 (non-insulin-dependent) diabetic subjects in the fasting state. The relationships of these concentrations were sought with those of total cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol, triglyceride, plasminogen activator inhibitor, blood pressure, and indices of body fat distribution. Significant relationships were apparent between concentrations of "immunoreactive insulin" as measured by standard radioimmunoassay and triglyceride (rs = 0.42, p less than 0.001), total cholesterol (rs = 0.25, p = 0.038), high density lipoprotein cholesterol (rs = -0.30, p = 0.018) and body mass index (rs = 0.30, p = 0.017), but only the relationships with triglyceride (rs = 0.36, p = 0.006) and body mass index (rs = 0.26, p = 0.34) remained significant when concentrations of immunoradiometrically measured insulin were employed. Concentrations of 32-33 split proinsulin, which comprises the major insulin-like molecule in these subjects, correlated positively with triglyceride (rs = 0.33, p = 0.009), total cholesterol (rs = 0.23, p = 0.050), and plasminogen activator inhibitor (rs = 0.26, p = 0.049), and negatively with high density lipoprotein cholesterol (rs = -0.29, p = 0.021).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1996

Hyperinsulinemia is associated with ventricular premature complexes.

The study investigated a possible association between fasting plasma insulin (FPI) levels and ventricular premature complexes (VPCs). One hundred eighty-six subjects without coronary artery disease (CAD), diabetes, hypertension, and left ventricular hypertrophy were recruited. All subjects underwent 24-hour electrocardiographic monitoring and oral glucose tolerance testing. The subjects were slightly overweight, normotensive, and nondiabetic. Subjects at the third tertile of FPI concentrations were the oldest and heaviest, with prevalent upper-body fat distribution, and had enhanced fasting plasma triglyceride and potassium concentrations, lower fasting plasma high-density lipoprotein (HDL) cholesterol concentration, and a greater number of VPCs versus subjects at the first and second tertiles. Independently of age, sex, body mass index (BMI), and waist to hip ratio (WHR), VPCs were correlated with FPI concentration (r = .19, P < .01). Multiple logistic regression analyses in which the presence or absence of VPCs was the dependent variable demonstrated that FPI concentrations were associated with VPCs independently of age, sex, BMI, WHR, daily physical activity (DPA), left ventricular mass index (LVMI), plasma low-density lipoprotein (LDL)/HDL cholesterol ratio, and triglyceride concentration (odds ratio [OR], 1.2; 95% confidence interval [CI], 1.0 to 1.6). After addition to the model of fasting plasma free fatty acids ([FFA] OR, 0.7; 95% CI, 0.6 to 1.3) or potassium (OR, 0.7; 95% CI, 0.6 to 1.1) concentrations, the association between FPI concentrations and VPCs is no longer significant. In conclusion, FPI concentrations are associated with VPCs in nondiabetic, normotensive, nonischemic subjects.

Adult↗
PubMed1989

The relationship between subsets of anthropometric upper versus lower body measurements and coronary heart disease risk in middle-aged men. The Paris Prospective Study. I.

The importance of body fat distribution as one determinant of various metabolic disorders associated with obesity is now recognized and some epidemiological evidence exists that it might be related to the onset of coronary heart disease (CHD) in men and women. The Paris Prospective Study data permitted exploration of the relationship between three subsets of anthropometric upper versus lower body measurements (waist-thigh circumferences, subumbilical-thigh skinfolds, bideltoid-bitrochanter diameters) and CHD risk in a middle-aged male population. The analysis successively disclosed the simple measurement ratio for both girth and diameters and the subumbilical2: thigh skinfold ratio as the best predictors of CHD outcome. The girth and skinfold but not the diameter ratios were positively correlated with body mass index and usual CHD risk factors except smoking. The relationship of upper versus lower fat localization (girth and skinfold ratios) with CHD incidence confirmed previous results obtained in this population but its magnitude is low in comparison with usual CHD risk factors. The association of the diameter ratio as an index of upper body frame with CHD occurrence remains to be confirmed by further studies.

Adult↗
PubMed1996

Waist to hip ratio and psychosocial factors in adults with insulin-dependent diabetes mellitus: the Pittsburgh Epidemiology of Diabetes Complications study.

The relationship between waist to hip ratio (WHR) and psychosocial factors has seldom been investigated, although both may contribute to cardiovascular risk. Therefore, these variables were examined in adults with insulin-dependent diabetes mellitus ([IDDM] N = 592; mean age, 29 years; mean duration, 20 years), a population at increased risk of developing cardiovascular disease. Moreover, the association between changes in psychosocial factors and change in WHR was considered. After adjusting for body mass index (BMI), WHR in men was correlated with higher levels of depressive symptomatology (r = .19, P < .001), greater anxiety (r = .13, P < .05), less social support (r = -.20, P < .01), and lower type A scores (r = -.25, P < .001). In women, WHR was significantly correlated with higher levels of depressive symptomatology (r = .18, P < .01), greater stress (r = .16, P < .01), and alcohol consumption (r = .12, P < .05). For both sexes, smokers had a significantly greater mean WHR than nonsmokers (P < .01). For men, multiple regression analyses adjusting for BMI and age demonstrated that smoking, lower income, less exercise, and lower type A scores were the most significant variables associated with WHR. In women, the independent predictors of WHR were a history of smoking, lower educational level, and depressive symptomatology. The most significant independent predictors of change in WHR from baseline to 2-year follow-up study were change in weight (men), change in BMI (women), and change in depression scores (both sexes). These results suggest that psychosocial factors may affect cardiovascular disease risk through their influence on body fat distribution, and both may be important in identifying those most at risk for cardiovascular disease in populations with IDDM.

Adult↗
PubMed1998

Microalbuminuria, renal function and waist:hip ratio in black hypertensive Jamaicans.

OBJECTIVE: To investigate the relationship between blood pressure (BP), renal haemodynamics, anthropometric measures of obesity and urinary albumin excretion in hypertension and in a control group. METHODS: Urinary albumin, BP and anthropometric measurements were carried out in patients attending the hypertension clinic of the University Hospital of the West Indies. A randomised stratified sample was then selected for renal haemodynamic assessment. A normoalbuminuric control group without hypertension or diabetes was also selected. Renal haemodynamics was assessed by measuring glomerular filtration rate using 51-chromium edetic acid (51Cr-EDTA) and renal blood flow using 125-iodohippurate (125-PAH). RESULTS: Urinary albumin excretion was positively and significantly correlated with systolic pressure (beta = 0.011, P < 0.003, R = 0.22), current body weight (beta = 0.014, P < 0.04, R = 0.15) and the presence of diabetes (beta = 0.9, P < 0.001, R = 0.3). In the sample selected for renal haemodynamics, patients with microalbuminuria had lower age-adjusted corrected renal blood flow (P < 0.006), effective renal plasma flow (P < 0.006) and higher filtration fraction (P < 0.006) when compared with patients without microalbuminuria. Glomerular filtration rate in patients with microalbuminuria was not different from those without. Urinary albumin excretion was positively and significantly correlated with systolic pressure (beta = 0.016, P < 0.003, R = 0.40) and inversely related to corrected renal blood flow (beta = -1.13, P < 0.0002, R = 0.46). Waist:hip ratio was inversely related to corrected renal blood flow (beta = -1.74, P < 0.02, adjusted R = 0.48). CONCLUSION: Systolic BP, diabetes and body weight were significant predictors of albuminuria in our patients. Microalbuminuria and body fat distribution as assessed by waist:hip ratio were important determinants of renal haemodynamics in this population.

Albuminuria↗
PubMed1999

Comparison of verapamil and felodipine treatment on lipid and glucose metabolism in obese female SHHF/Mcc-facp rats.

Calcium channel blockers, verapamil or felodipine, were given to genetically obese 6 and 11-month-old female SHHF/Mcc-facp (SHHF: Spontaneous Hypertension Heart Failure) rats for 8 weeks to investigate their effects on glucose and lipid metabolism and obesity. Both antihypertensive agents significantly decreased systolic blood pressure. In 11-month-old rats, verapamil treatment significantly decreased body weight after 4 weeks whereas with felodipine it was only significantly reduced after 8 weeks. In 6-month-old rats, verapamil significantly curtailed body weight gain. Subcutaneous fat depots were smaller, and abdominal fat depots were larger in verapamil rats compared to felodipine or control rats. Oral glucose tolerance tests in the 6-month-old verapamil and the 11-month-old felodipine groups showed improved glucose tolerance compared to their respective control groups. After 8 weeks of treatment, fasting plasma glucose levels were lower in 6-month-old verapamil rats compared to felodipine and control rats and were decreased by both verapamil and felodipine treatments as compared to control in 11-month-old rats. During the oral glucose tolerance test in 6-month-old rats, both fasting plasma insulin and the area under the insulin curve were increased in verapamil compared to both control and felodipine groups. When compared to controls, plasma cholesterol was increased by verapamil in both age groups, but was significantly decreased by felodipine after 8 weeks of treatment in the 11-month-old group. Plasma triglycerides increased in all control rats compared to initial levels; however, verapamil and felodipine groups showed lower triglycerides in both age groups. In 6-month-old rats, the percentages of plasma HDL significantly increased in both treatment groups as compared to control. This study shows that verapamil and felodipine depressed body weight gain in the young rats, reduced body weight in the old rats, improved lipid parameters and glucose tolerance, but had the opposite effects on body fat distribution and insulin levels in obese female SHHF rats.

Age Factors↗
PubMed2005

Differences in skinfold thicknesses and fat distribution among top-class runners.

AIM: The purpose of this research was to determine skinfolds values in male and female top-class runners who competed in different distances in order to identify the association of sex and event with fatness and distribution of subcutaneous fat. METHODS: Eight skinfolds were measured on male (n=130) and female (n=56) top-class runners. Sum of 6 skinfolds and extremity/trunk fat ratio was calculated. Runners were distributed into groups according to the event in which they obtained their best performance. RESULTS: The skinfolds values found in our athletes were very low. Female runners obtained higher values in extremity skinfolds than male runners; the differences in chest, biceps and abdominal skinfolds are only significant in short duration events; no differences were found in suprailiac and subscapular skinfolds. In both sexes, all skinfolds showed significantly lower values among marathon runners; no differences were found in skinfolds values among runners competing in distances ranging from 100 m to 10,000 m. Extremity/trunk fat ratio was not related to event. CONCLUSIONS: The lower skinfold values found in all groups of runners may be due to a high performance; this analysis shows that a slight excess of fat is not beneficial in order to obtain a high performance in any distance. Fatness is only associated to marathon events, probably due to the fact that these runners are engaged in higher training volume and that only in this event fat metabolism prevails in training and competition. Distribution of subcutaneous fat may be more dependent on biological or environmental factors unrelated to type of training.

Adult↗
PubMed2003

Association of the mitochondrial DNA 15497G/A polymorphism with obesity in a middle-aged and elderly Japanese population.

Although polymorphism of the mitochondrial DNA 15497guanine/adenine (Mt15497G-->A) leads to the Gly251Ser amino acid replacement on human cytochrome b, it is unknown whether functional alteration of the mitochondrion is induced by the Gly251Ser replacement. To see if an association exists between the Mt15497G-->A polymorphism and obesity, we examined differences in body size, body composition, and regional body fat distribution between the two genotypes in middle-aged and elderly Japanese individuals (825 women and 906 men). The Mt15497 genotype was determined with an automated colorimetric allele-specific DNA probe assay system using the polymerase chain reaction (PCR) method. The Mt15497G-->A polymorphism was detected in 3.5% ( n=60) of all subjects: 2.8% ( n=23) among women and 4.1% ( n=37) among men. After adjusting for age and smoking, we found that body weight, body mass index, waist and hip circumferences, fat mass, fat-free mass, intra-abdominal fat and triglycerides were significantly greater in women with the A allele compared with the G allele ( p=0.001-0.025). For men, waist to hip ratio was significantly greater ( p=0.032), and waist circumference, intra-abdominal fat and triglycerides had a trend to be significantly greater ( p=0.062-0.087) in subjects with the A allele compared with the G allele. These data suggest that the Mt15497 polymorphism may be associated with obesity-related variables and lipid metabolism.

Absorptiometry, Photon↗
PubMed1993

Structural changes in the subcutaneous compartment in morbid obesity.

Most of the excess fat that accumulates in the morbidly obese is accommodated in the subcutaneous compartment (SCC), specifically in the adipose tissue lobules of the panniculus adiposus which enlarge and expand the SCC. However, the fibroelastic septa that are attached to the skin on one side of the SCC and to the deep fascia on the other invest each lobule and thereby offer resistance to the enlarging lobules. We report observations made during pathologic examinations of the abdominal wall SCC that were surgically excised by abdominal dermo-panniculectomy from 48 morbidly obese subjects after gastroplasty and weight loss. Lobules were large but varied notably upwards in size and, to some extent, shape. Simultaneously upon incision of the SCC, the lobules bulged above and the septa retracted below the same cut surfaces. Light microscopy revealed disruptions of septal elastic fibers, calcification of septa and septal arteries and necrosis of adipocytes, all sparsely distributed. Certain questions and facts emerge from these observations. Are the variations in lobule sizes normal, or do they reflect uneven fat deposition or mobilization during weight gain or loss respectively? Is there any correlation between lobule and adipocyte sizes? The tightly coupled phenomena of lobule-bulging and septal-retraction indicate that the lobules and septa are subjected to compressional and tensile stresses respectively in the intact, non-incised SCC. The histologic changes might be consequences of these stresses. Studies of the variations in body fat distribution and in adipocyte size have contributed to an understanding of obesity pathogenesis. The relevance of the present findings is unknown at this time, but these appear to have potential implications for studies of the morphogenesis of obesity. Confirmation of these findings, particularly the lobule variations, is required so that these can be compared with those in never-obese subjects and in morbidly obese subjects without prior weight loss.

Abdomen↗
PubMed1995

Better breast cancer survival for postmenopausal women who are less overweight and eat less fat. The Iowa Women's Health Study.

BACKGROUND: The authors sought to determine whether prediagnosis obesity, body-fat distribution, and dietary intake of fats, antioxidants, and fiber may be related to survival after the diagnosis of breast cancer. METHODS: The mortality rates of 698 postmenopausal patients with unilateral breast cancer in a large cohort study were analyzed. Body-mass index, waist-to-hip ratio, and food-frequency data were collected by questionnaire within 6 years before breast cancer was diagnosed. RESULTS: Adjusted for age, women in the highest tertile of body mass index had a 1.9-fold higher risk (95% confidence interval = 1.0-3.7) of dying after breast cancer than those in the lowest tertile; adjusted for other prognostic variables (age, smoking, education level, extent of breast cancer, and tumor size), this relative risk was 1.5 (95% CI = 0.7 to 2.9). Waist-to-hip ratio was not related to risk of dying nor was intake of fiber or several dietary antioxidants. Independent of other prognostic variables, risk of death after breast cancer was statistically significantly elevated, with a relative risk greater than 2.0 for the highest tertiles of total fat, saturated fat, and monounsaturated fat intake, expressed as grams per day. An adjustment for energy intake, which also was associated positively with fatality, weakened these associations somewhat. CONCLUSIONS: Although clinical trials are required, these findings support the hypothesis that a high fat intake is associated with reduced survival of postmenopausal women with breast cancer and suggest that women with breast cancer should consider limiting their intake of fat.

Aged↗
PubMed1997

Resting metabolic rate in obese, premenopausal black women.

In the United States, obesity is more prevalent in black than in non-Hispanic white women. Because low resting metabolic rate (RMR) has been suggested as a risk factor for weight gain, we compared RMR in 22 black and 20 white obese [body mass index (BMI; in kg/m2) range: 28.9-48.6 and 26.9-44.1, respectively], weight-stable, premenopausal, nondiabetic women. RMR was measured on two or three different occasions within a 1-wk period. The black and white groups did not differ significantly in age, degree of fitness, BMI, fat mass, or fat-free mass (FFM). In each group, RMR was predicted independently by FFM but not by age, degree of fitness, body fat mass, or body fat distribution. The slopes of the equations predicting RMR from FFM in black and white groups were not significantly different. However, the black women had significantly lower RMRs than the white women after adjustment for FFM measured by five body-composition models: dual-photon X-ray absorptiometry (DXA), hydrodensitometry, total body water, a three-compartment model, a four-compartment model, as well as for the absolute total-body potassium content as a measure of metabolically active FFM. By each analysis, the black women had significantly lower (P < 0.01) FFM-adjusted RMR than the white women; this difference ranged from 671 to 889 kJ/d depending on the body-composition method used to estimate FFM. This could contribute to the difference in the prevalence of obesity in the populations represented by these groups.

Adipose Tissue↗
PubMed1992

A family study of coronary risk factors in Geelong.

A study of coronary risk factor relationships was carried out in 213 families with adolescents in Geelong, Victoria, Australia, in 1987. Weight, height, skinfold thicknesses, body circumferences, blood pressure and serum cholesterol were measured in both parents and children and other relevant information was obtained by questionnaire. The study group did not differ significantly from the Geelong population with respect to the proportion of Australian-born parents but contained a significantly higher proportion than expected of fathers who had a university degree or diploma. Twenty-five per cent of adolescents, 30% of mothers and 38% of fathers were positive for at least one of the three major established coronary risk factors. Significant correlations between parents and children, but not between parents, were found for total cholesterol and systolic blood pressure, while significant correlations were observed both between parents and children and between parents for measures of body size, body fatness and body fat distribution. The strongest predictors of risk factor status in adolescence were both parents with total cholesterol at or above 5.5 mmol/l, one or more parents who smoked and one or more grandparents with a history of coronary heart disease. Body mass index in adolescence was unrelated to heart disease risk factor status in adolescence or to a family history of heart disease. During early childhood and adolescence, parental risk factor status, rather than anthropometric or risk factor screening of the children themselves, is likely to provide the best guide to those at risk for an adverse coronary risk factor profile.

Adolescent↗
PubMed1990

Overweight: assessment and management issues.

Obesity is associated with an increased risk of coronary artery disease, hypertension, diabetes, hypercholesterolemia, cancer and other conditions. Although generalized obesity is associated with increased risk, the android pattern of body fat distribution may be a more sensitive predictor of coronary artery disease. A gradual weight reduction program, including adherence to a low-fat, calorie-restricted diet and participation in daily exercise, is the best approach to reduce weight and body fat.

Diet, Reducing↗
PubMed2003

Acipimox enhances spontaneous growth hormone secretion in obese women.

We hypothesized that a high circulating free fatty acid (FFA) concentration is involved in the pathogenesis of hyposomatotropism associated with obesity. To evaluate this hypothesis, 10 healthy premenopausal women (body mass index 33.8 +/- 1.0 kg/m(2)) were studied in the follicular phase of their menstrual cycle at two occasions with a time interval of at least 8 wk, where body weight remained stable. Subjects were randomly assigned to treatment with either acipimox (an inhibitor of lipolysis, 250 mg orally 4 times daily) or placebo in a double-blind crossover design, starting 1 day before admission until the end of the blood sampling period. Blood samples were taken during 24 h with a sampling interval of 10 min for assessment of growth hormone (GH) concentrations, and GH secretion was estimated by deconvolution analysis. Identical methodology was used to study GH secretion in a historical control group of age-matched normal weight women. GH secretion was clearly blunted in obese women (total daily release 66 +/- 10 vs. lean controls: 201 +/- 23 mU x l(Vd)(-1) x 24 h(-1), P = 0.005, where l(Vd) is lite of distribution volume). Acipimox considerably enhanced total (113 +/- 50 vs. 66 +/- 10 mU x l(Vd)(-1) x 24 h(-1), P = 0.02) and pulsatile GH secretion (109 +/- 49 vs. 62 +/- 30 mU x l(Vd)(-1) x 24 h(-1), P = 0.02), but GH output remained lower compared with lean controls. Further analysis did not show any relationship between the effects of acipimox on GH secretion and regional body fat distribution. In conclusion, acipimox unleashes spontaneous GH secretion in obese women. It specifically enhances GH secretory burst mass. This might mean that lowering of systemic FFA concentrations by acipimox modulates neuroendocrine mechanisms that orchestrate the activity of the somatotropic ensemble.

Adipose Tissue↗
PubMed2002

Obesity, body size, and risk of postmenopausal breast cancer: the Women's Health Initiative (United States).

OBJECTIVE: Body size is an important modifiable risk factor for breast cancer. Although obesity has generally been found to be associated with increased risk for postmenopausal breast cancer, there remain questions concerning the role of body fat distribution, lifetime weight history, and effects within specific subgroups of women. METHODS: We assessed the relationship of several anthropometric measures and risk of postmenopausal breast cancer in 85,917 women aged 50-79 at entry in the Women's Health Initiative Observational Study. Women were enrolled during 1993-1998 at 40 clinics in the US and 1030 developed invasive breast cancer by April 2000. Upon entry, trained clinical center staff measured each woman's height, weight, and waist and hip circumference. RESULTS: Anthropometric factors were not associated with breast cancer among women who had ever used hormone replacement therapy (HRT). Among HRT non-users, heavier women (baseline body mass index (BMI) >31.1) had an elevated risk of postmenopausal breast cancer (relative risk (RR) = 2.52; 95% confidence interval (CI) = 1.62-3.93), compared to slimmer women (baseline BMI < 22.6). The elevation in risk associated with increasing BMI appeared to be most pronounced among younger postmenopausal women. Change in BMI since age 18, maximum BMI, and weight were also associated with breast cancer in HRT non-users. While both waist and hip circumference were associated with breast cancer risk, their ratio, a measure of fat distribution, was not (RR = 1.33; 95% CI = 0.88-2.01). CONCLUSIONS: Our study confirms previously reported findings that generalized obesity is an important risk factor for postmenopausal breast cancer, but only among women who have never taken HRT. Lifetime weight gain is also a strong predictor of breast cancer. Waist to hip ratio, a measure of weight distribution, does not appear to be related to postmenopausal breast cancer risk.

Aged↗