Appetite-suppressant drugs and valvular heart disease.
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Appetite Depressants↗
Biomedical subjects
S Z Yanovski
Publications and source records attributed to S Z Yanovski.
Report of a National Institutes of Health--Centers for Disease Control and Prevention workshop on the feasibility of conducting a randomized clinical trial to estimate the long-term health effects of intentional weight loss in obese persons.
A workshop was convened in 1997 by the National Institutes of Health and the Centers for Disease Control and Prevention to consider the need for and feasibility of conducting a randomized clinical trial to estimate the long-term health effects of intentional weight loss in obese persons. Although the benefits of weight loss in obese individuals may seem obvious, little information is available showing that intentional weight loss improves long-term health outcomes. Observational studies may be unable to provide convincing answers about the magnitude and direction of the health effects of intentional weight loss. Workshop participants agreed that a well-designed randomized clinical trial could answer several questions necessary for developing a rational clinical and public health policy for treating obesity. Such information will ultimately provide needed guidance on the risks and benefits of weight loss to health care providers and payers, as well as to millions of obese Americans.
Animals↗
Resting metabolic rate in African-American and Caucasian girls.
Recent studies have found a lower resting metabolic rate (RMR) in African-American (AA) women with obesity as compared with Caucasian (C) women with obesity. It is unknown if this difference in RMR is seen in prepubertal girls or in those of average body weight. Therefore, we studied RMR in 21 AA and 24 C girls, ages 7-10, who were well matched for age, weight, body mass index (BMI), and pubertal status. All had BMI between 15% and 85% for age and race, based on data from the First National Health and Nutrition Examination Survey. Fat free mass (FFM) was measured by dual-energy X-ray absorptiometry. RMR was measured with a Deltatrac indirect calorimeter under controlled conditions after the subjects underwent an overnight fast. The slopes of the regression equations were similar for both groups (p = 0.7). After adjustment for FEM, the AA girls had a significantly lower RMR than did the C girls (-92 +/- 32 kcal/d, p = 0.007 by analysis of covariance). This significance was maintained after exclusion of total body bone mineral content. These data suggest that normal-weight prepubertal AA girls may have reduced resting energy expenditure compared with C girls.
Adipose Tissue↗
Differences in corticotropin-releasing hormone-stimulated adrenocorticotropin and cortisol before and after weight loss.
Little is known about the effects of intentional weight loss on the function of the hypothalamic-pituitary-adrenal (HPA) axis of obese individuals. We studied the HPA axis of 34 healthy obese women (body mass index, 40.2 +/- 7.9 kg/m2) before and after a 21.0 +/- 7.9-kg weight loss induced by a 26-week weight loss program that included 12 weeks of a 3350 kJ/day (800 Cal/day) liquid formula diet, 6 weeks of gradual refeeding, and 6 weeks of caloric stabilization at 5020-6280 kJ/day (1200-1500 Cal/day). Obese subjects were evaluated twice: before caloric restriction and during the last 3 weeks of caloric stabilization with a 3-h evening 1 microg/kg ovine CRH (oCRH) stimulation test. CRH-stimulated ACTH and cortisol values were compared to those of a control group of 12 normal weight women. Before caloric restriction, both ACTH and cortisol responses to oCRH were similar in obese women and normal weight controls. Weight loss did not significantly alter the ACTH response to oCRH; however, the total plasma cortisol response to oCRH decreased significantly with weight loss (area under the curve, 96,320 +/- 21,040 nmol/L x min before weight loss; 82,450 +/- 22,460 nmol/L x min after weight loss; P < 0.001). Cortisol-binding globulin also decreased significantly after weight loss (2,270 +/- 1,050 nmol/L) compared either to values obtained before weight loss (3,590 +/- 1,360 nmol/L; P < 0.001) or to those of normal weight controls (3,910 +/- 1,400 nmol/L; P < 0.001). Assay for plasma free cortisol, either before or 180 min after oCRH treatment, showed no significant changes in cortisol responses resulting from weight loss. As plasma free cortisol was not altered by weight reduction, the decrease in the total cortisol response to oCRH after weight loss appears to be secondary to significant decreases in cortisol-binding globulin. We conclude that when obese women lose large amounts of weight with a 3350 kJ/day, very low energy diet, such weight reduction does not significantly affect the HPA axis.
Adrenocorticotropic Hormone↗
Report of the National Institutes of Health (NIH) Workshop on the Development of Research Priorities in Eating Disorders.
The National Institutes of Health (NIH) Workshop on the Development of Research Priorities in Eating Disorders was convened in New York on April 24 and 25, 1996. The goals of the workshop were (1) to identify important unanswered questions in the study and treatment of eating disorders, (2) to discuss potentially fruitful approaches to answering these questions through basic and clinical research, and (3) to assist the NIH and other funding agencies in assigning priorities for research on eating disorders. The program consisted of a series of brief presentations by moderators, each followed by facilitated discussion of the topic with members of the audience. Three reporters (CMG, MJD, FMC) took detailed notes of the proceedings, which have been incorporated into this article. A summary of this workshop is presented, along with recommendations for future research that were identified by workshop participants.
Feeding and Eating Disorders↗
Differences in the hypothalamic-pituitary-adrenal axis of black girls and white girls.
After intravenous administration of ovine corticotropin-releasing hormone (CRH), the plasma corticotropin (ACTH) concentrations of adult black women and men are approximately twice as high as those of adult white women and men; however, there are no corresponding differences in cortisol response. To determine whether these differences in ACTH secretion are also present in prepubertal and early pubertal girls, we studied the hypothalamic-pituitary-adrenal axis of 19 black and 19 white girls of normal weight (age 7 to 10 years) who were matched for body mass index, age, and socioeconomic status. Measures of cortisol's effects, including waist circumference, waist/hip ratio, and fasting insulin and glucose levels, were obtained and related to the ACTH and cortisol responses to 1 micrograms/kg CRH. There were no racial differences in waist circumference, waist/hip ratio, fasting glucose or insulin levels, baseline free or total plasma cortisol levels, baseline ACTH concentrations, or the plasma cortisol response to CRH. However, CRH-stimulated plasma ACTH concentrations, measured in a polyclonal radio-immunoassay, were significantly greater in prepubertal and early pubertal black girls than in white girls at all time points between 15 and 90 minutes after administration of CRH (area under curve (AUC 1754 +/- 121 pmol/L/min in black girls vs 1304 +/- 124 pmol/L/min in white girls, p < 0.001). This difference was confirmed by an immunoradiometric assay believed to be specific for intact ACTH (AUC 1634 +/- 139 pmol/L/min in black girls vs 1224 +/- 104 pmol/L/min in white girls, p < 0.001). Neither ACTH AUC nor cortisol AUC was significantly correlated with body mass index in either black or white girls. We conclude that there are differences in the hypothalamic-pituitary-adrenal axis of prepubertal and early pubertal black and white girls similar to those found previously in adult women. The cause of these differences remains to be elucidated.
Adrenocorticotropic Hormone↗
Differences in body composition of black and white girls.
Adults have racial differences in body composition that may modulate risks resulting from obesity. Although black and white children have been shown previously to have differences in bone mineral density and subcutaneous body fat, differences in visceral adipose tissue have not been evaluated. We studied 20 black and 20 white normal-weight girls aged 7-10 y, who were matched for weight, body mass index (BMI), bone age, chronological age, Tanner breast stage, and socioeconomic status. Each underwent anthropometric measurements, bioelectrical impedance analysis, dual-energy X-ray absorptiometry (DXA), and abdominal magnetic resonance imaging (MRI) for determination of total (TAT), visceral (VAT), and subcutaneous (SAT) adipose tissue. Serum lipids and fasting and 2-h oral-glucose-tolerance test (OGTT) glucose and insulin concentrations were also measured. There were no differences between groups in absolute waist circumference or waist-to-hip ratio, but waist-to-thigh ratio was smaller in black than in white girls. Black girls had greater bone mineral density and less TAT, VAT, and SAT than whites. VAT was not significantly correlated with any measure of insulin, or with serum lipids. However, both basal and 2-h OGTT serum insulin were significantly correlated with SAT as assessed by MRI in black girls (r2 = 0.46 for basal insulin, P = 0.001: r2 = 0.31 for 2-h insulin, P = 0.01) but not in white girls (r2 < 0.05, for basal and 2-h insulin, NS). We conclude that there are significant racial differences in body composition and differences in the strength of association between abdominal adipose tissue depots and insulin sensitivity in black and white girls.
Abdomen↗
Etiology of the differences in corticotropin-releasing hormone-induced adrenocorticotropin secretion of black and white women.
After i.v. oCRH, plasma immunoreactive ACTH (ACTH-IR) is significantly greater in blacks than in whites; however, there is no corresponding increase in cortisol secretion. To test the hypothesis that there are black-white differences in adrenal responsiveness to ACTH that underlie this phenomenon, weight-, age-, and education-matched black (n = 10) and white (n = 10) women were i.v. infused with 5 differing doses of ACTH1-24 (0, 0.003, 0.01, 0.1, and 1 microgram/kg) with measured plasma cortisol and DHEA. To test the alternative hypothesis that greater post-CRH plasma ACTH-IR in blacks is caused by qualitative differences in circulating ACTH-immunoreactive peptides, we collected pre- and post-CRH plasma from 5 black and 5 white women and measured ACTH-IR after sample fractionation, using high-pressure liquid chromatography. There were no racial differences in adrenal responsiveness to differing doses of ACTH1-24 and no differences in the distribution of the forms of ACTH-IR before CRH. After CRH, whites had predominant ACTH-IR peaks at the retention times of ACTH1-39 and ACTH1-39-sulfoxide, whereas blacks had prominent peaks at several additional retention times. The post-CRH ratio of intact to total ACTH was significantly lower in blacks than in whites (0.27 +/- 0.17 vs. 0.71 +/- 0.17, P < 0.003). We conclude that there are qualitative differences in post-CRH circulating ACTH-IR in blacks and whites, leading to a greater immunoreactive to bioactive ACTH ratio in blacks. Such differences in the circulating forms of ACTH can account for greater CRH-stimulated ACTH-IR in blacks.
Adrenocorticotropic Hormone↗
The chicken or the egg: binge eating disorder and dietary restraint.
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Anorexia↗
Visceral adipose tissue differences in black and white women.
Fat distribution and metabolic variables were studied in 8 black and 10 white age- and weight-matched obese women undergoing a 6-mo weight-reducing regimen. Fat patterning was determined by using anthropometry and computed tomography to quantitate total, subcutaneous, and visceral adipose tissue (VAT) areas at the L2-L3 and L4-L5 levels of the lumbar spine, before, during, and after a modified fast. Black women had smaller depots of VAT than white women at both the L2-L3 (P = 0.004) and L4-L5 (P = 0.054) sites. Differences persisted after an average 17.2-kg weight loss. Although waist-hip ratio was similar in both groups, black women had 23% less VAT than white women (P = 0.007). Black women had significantly lower plasma glucose (P = 0.031) and triglycerides (P = 0.006) with significantly higher plasma high-density-lipoprotein concentrations (P < 0.001). Data from this study suggest that racial differences exist in VAT and metabolic risk factors for obesity-related illness.
Adipose Tissue↗
Differences in the hypothalamic-pituitary-adrenal axis of black and white men.
We previously found that, following intravenous administration of ovine corticotropin-releasing hormone (CRH), the plasma ACTH concentrations of Black women were approximately twice as high as those of White women; however, there were no corresponding differences in cortisol response. To determine whether this difference in ACTH secretion is also present in men, we studied the hypothalamic-pituitary-adrenal axis of 10 Black and 10 White weight-, age-, and education-matched men. Waist-to-hip ratio, 24-hour urine free cortisol excretion, and ACTH and cortisol responses to 1 microgram/kg ovine CRH were determined. There were no racial differences in waist-to-hip ratio, 24-hour urine free cortisol excretion, baseline free or total plasma cortisol and ACTH concentrations, or plasma cortisol response to CRH. However, CRH-stimulated plasma ACTH concentrations, measured in an extraction polyclonal radioimmunoassay, were significantly greater in Blacks than in Whites at all time points between 30 and 180 min after administration of CRH (area under curve (AUC) 1,796 +/- 245 pmol/l.min in Blacks vs. 1,278 +/- 121 pmol/l.min in Whites, p < 0.001). Neither cortisol nor ACTH AUCs were significantly correlated with Body Mass Index in Black or White men. We conclude that there are differences in the HPA axis of Black and White men similar to those found previously in women. The physiology underlying these differences remains to be understood.
Adrenocorticotropic Hormone↗
Pyroglutamyl peptidase-II ("thyroliberinase") activity in human serum: influence of weight and thyroid status.
The tripeptide hormone, TRH, is metabolized by three enzymes, the most specific of which is pyroglutamyl peptide hydrolase-II (also termed thyroliberinase), a metalloenzyme present in serum and brain. Because pyroglutamyl peptidase-II activity in rat serum is regulated by thyroid hormone levels, we tested the hypothesis that this activity is similarly altered in humans. We studied serum pyroglutamyl peptidase-II activity in 6 patients with hyperthyroidism, 18 patients with hypothyroidism, and 31 euthyroid, normal weight volunteers. Because TRH [or its metabolite cyclo(His-Pro)] is believed to be an important hormone regulating appetite and metabolism, we also evaluated pyroglutamyl peptidase-II activity in 27 euthyroid patients with obesity. Serum pyroglutamyl peptidase-II activity was elevated in patients with hypothyroidism (mean +/- SEM, 33.9 +/- 3.7 nmol/mL.h) compared to that in euthyroid, normal weight volunteers (24.5 +/- 2.8 nmol/mL.h; P < 0.05), but not that in patients with hyperthyroidism (28.3 +/- 4.1 nmol/mL.h; P = NS). Euthyroid obese patients had the highest pyroglutamyl peptidase-II activity (43.6 +/- 2.8 nmol/mL.h; P < 0.0001 vs. normal weight volunteers). Pyroglutamyl peptidase-II activity was positively correlated with body mass index (r2 = 0.30; P < 0.0001). After correction for body mass index, there were no difference in pyroglutamyl peptidase-II activity in hypothyroid, hyperthyroid, and euthyroid individuals. We conclude that serum pyroglutamyl peptidase-II activity is regulated by, or regulates, body weight.
Adult↗
Recorded food intake of obese women with binge eating disorder before and after weight loss.
Because binge eating in obese individuals has been postulated to be a reaction to dietary restriction, we examined the recorded food intake of 17 obese women with and 16 obese women without binge eating disorder (BED) during 1-week periods before and 3 months after a very low calorie diet program in order to determine the effects of dietary restriction on binge eating frequency and severity. Before weight loss, rather than reporting severe caloric restriction, women with BED reported greater average energy intake than nonbinge eaters on both a total (2707 vs. 1869 k cal/day, p < .01) and weight-adjusted (25.1 vs. 18.1 kcal/kg, p < .01) basis, with both higher intake on nonbinge days and an increased frequency of binge days. After weight loss, there was no significant difference in energy intake, on either a total or weight-adjusted basis, between subjects with and without BED. Although average daily energy intake fell for both groups after weight loss, only subjects with BED reported significantly decreased energy intake when adjusted for change in body weight. This resulted from decreased intake on nonbinge days and a decreased frequency of binge days. Before weight loss, subjects with BED reported an average energy intake equivalent to 94% of their predicted energy expenditure. Whereas subjects without BED reported intake only 64% of predicted (p = .002). After weight loss, there was no significant difference between subjects with and without BED in the percentage of predicted energy expenditure reported as intake (64% vs. 58%). Restraint was similar in both groups before weight loss, but those with BED reported greater hunger and disinhibition. After weight loss treatment, restraint increased significantly, whereas disinhibition and hunger remained elevated in subjects with BED. Disinhibition, rather than restraint, appears to be a major contributor to the disordered eating of these individuals. Unlike normal-weight women with bulimia nervosa, dietary restriction does not appear to worsen symptoms of binge eating in obese women with BED. Over the short term, subjects with BED may respond to a standard weight loss treatment program with improvements in binge eating behaviors.
Adolescent↗
Are anorectic agents the 'magic bullet' for obesity?
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Appetite Depressants↗
A practical approach to treatment of the obese patient.
Obesity is one of the most common conditions encountered by primary care physicians, yet both physicians and patients are often frustrated by current approaches to its management. Recent advances in our understanding of obesity enable the physician to evaluate the contributions of biologic and environmental factors to the patient's obesity, to determine the degree of medical risk posed by the obesity, and to establish realistic goals for treatment. The chronic and relapsing nature of obesity requires ongoing support and vigilance. An individualized approach to obesity management, based on careful evaluation of biologic, psychologic, and social factors, can be successfully developed and implemented by the office-based primary care physician.
Adult↗
Association of binge eating disorder and psychiatric comorbidity in obese subjects.
OBJECTIVE: The authors determined the prevalence of binge eating disorder in a self-referred study group of moderately and severely obese subjects and investigated whether binge eating disorder was associated with psychiatric disorders, a history of psychotherapy, a family history of psychiatric illness, or a history of sexual abuse. METHOD: They interviewed 89 obese women and 39 obese men (body mass index > 30 kg/m2) who were not currently in weight loss treatment, using the Binge Eating Disorder Clinical Interview, the Structured Clinical Interview for DSM-III-R, and the Structured Clinical Interview for DSM-III-R Personality Disorders. RESULTS: Forty-three (34%) of the subjects met criteria for binge eating disorder--33 women and 10 men. Black and white subjects had similar rates of binge eating disorder. Subjects with binge eating disorder were significantly more likely than those without the disorder to have a lifetime prevalence of a DSM-III-R axis I or axis II diagnosis and to have undergone psychotherapy or counseling. The lifetime rates of major depression, panic disorder, bulimia nervosa, borderline personality disorder, and avoidant personality disorder were all significantly higher in subjects with binge eating disorder. The rate of reported sexual abuse was not higher among subjects with binge eating disorder; however, they were significantly more likely to have a family history of substance abuse. The relative risks for psychiatric disorders were higher in both moderately and severely obese subjects with binge eating disorder than in those without the disorder. CONCLUSIONS: Among both moderately and severely obese subjects, binge eating disorder is associated with higher rates of axis I and axis II psychiatric disorders.
Adolescent↗
Normal dexamethasone suppression in obese binge and nonbinge eaters with rapid weight loss.
Natural or experimental starvation is frequently associated with hypercortisolism, reflected as incomplete suppression of serum cortisol after dexamethasone. To determine whether rapid weight loss per se or some other aspect of starvation induces disruption of the hypothalamic-pituitary-adrenal (HPA) axis, we evaluated 2 categories of obese women (body mass index > 30 kg/m2) undergoing rapid weight loss: binge eaters (n = 12) and nonbinge eaters (n = 8). We performed psychometric evaluation and 1 mg overnight dexamethasone suppression tests in the obese subjects, as well as in 12 race- and age-matched normal-weight women. The obese women were tested before and after 12 weeks of a 3349 kJ/day (800 kcal/day) liquid formula diet, and lost an average of 19.3 kg, which represented 17.3% of their total body weight. Binge eaters, who were initially more depressed than either nonbinge eaters or normal-weight controls, had a significant amelioration of their symptoms with weight loss. Neither group had evidence of disruption of the HPA axis before or after weight loss. Thus, the rate of failure to suppress cortisol after dexamethasone was approximately 10% in each of the obese and control groups, and did not differ between the pre- and postweight loss condition or between binge eaters and nonbinge eaters. Serum free T4 was unchanged, whereas T3 fell significantly with weight loss. We conclude that weight loss may improve affect in the obese without altering HPA axis activity, and postulate that one of the concomitants of restricted energy intake, perhaps in combination with a threshold body weight, may be of greater importance in causing abnormalities of dexamethasone suppression testing than rapid weight loss per se.
Adolescent↗
Differences in the hypothalamic-pituitary-adrenal axis of black and white women.
Alterations in the activity of the hypothalamic-pituitary-adrenal (HPA) axis have been associated with obesity in humans and animals. To explore possible mechanisms responsible for the higher prevalence of obesity and its associated comorbid conditions in the black population, we studied the HPA axis of 18 black and 30 white weight- and age-matched nonobese and obese women. Waist to hip ratio, 24-h urinary free cortisol excretion, plasma cortisol responses to dexamethasone, and plasma ACTH and cortisol responses to 1 micrograms/kg ovine CRH were determined. There were no racial differences in waist to hip ratio, 24-h urinary free cortisol excretion, dexamethasone suppressibility of plasma cortisol, baseline plasma cortisol and ACTH concentrations, or plasma cortisol response to CRH. However, CRH-stimulated plasma ACTH concentrations, measured in an extraction polyclonal RIA, were significantly greater in blacks than in whites at all time points, beginning 5 min after the administration of CRH [area under the curve (AUC), 2463 +/- 288 pmol/L.min in blacks vs. 1185 +/- 78 in whites; P < 0.001]. These differences persisted when ACTH was measured by a 2-site direct immunoradiometric assay measuring the intact ACTH-(1-39) molecule (AUC, 1292 +/- 177 pmol/L.min in blacks vs. 504 +/- 95 in whites; P < 0.002). There was no significant correlation between body mass index and either cortisol or ACTH AUCs for either race, with blacks showing persistently elevated AUC for ACTH compared to whites, regardless of weight. We conclude that there are differences in the HPA axis of black and white women. How these differences may relate to the increased prevalence of obesity in the black population remains to be determined.
Adrenocorticotropic Hormone↗