High energy expenditure is not protective against increased adiposity in children.

BACKGROUND: Low levels of energy expenditure (TEE) may contribute to excess weight during childhood, but limited longitudinal data exist. OBJECTIVES: This is to test whether low TEE during the first 6 years of life could predict excess weight status at 8 years. METHODS: Total energy expenditure from doubly labelled water, weight, stature, waist circumference and fat mass and fat-free mass (FFM) in children at 0.25, 2, 4 and 6 years of age. This cohort includes individuals at high (n = 27) and low risk (n = 26) for childhood obesity, based upon whether pre-pregnant maternal obesity. A linear mixed effects model was fit to TEE. Individual variation was accounted for as a random effect. Residual TEE was calculated for age and individually averaged across time. RESULTS: Fat-free mass (kg) was highly correlated (R2 = 0.91) with TEE (kcal/day), and waist circumference and sex were also significant predictors of TEE. TEE residual tracked within individuals. TEE residuals did not correlate with either BMI or %fat at age 8 years. CONCLUSION: Using the residual TEE approach to identify high and low TEE during the first 6 years of life did not explain excess weight at 8 years of life in this cohort of children at high and low risk of obesity based upon maternal obesity status.

A biobehavioural model of the night eating syndrome.

This paper will propose a biobehavioral mechanism for the Night Eating Syndrome (NES), a disorder characterized by a delayed circadian rhythm of food intake and neuroendocrine function. Food intake consists of at least 25% of daily caloric intake after the evening meal and/or at least two nighttime awakenings with ingestions per week. This will be explored by reviewing neuroimaging of brain serotonin transporters (SERT) and treatment with selective serotonin reuptake inhibitors (SSRIs). SERT binding is elevated in the midbrain of night eaters, causing dysregulation of the circadian rhythm of both food intake and neuroendocrine function. The administration of SSRIs blocks the reuptake of serotonin and restores the circadian rhythm of both food intake and neuroendocrine function. This hypothesis implies that reduction of SERT activity should increase postsynaptic serotonin transmission and relieve NES. This is precisely the effect of SSRIs. NES is a function of elevated SERT, and blocking of SERT with an SSRI resolves NES. This model of NES attests to the validity of the diagnosis of NES and the criteria by which it is identified, and it provides an explanation of the mechanism.

Differences in serotonin transporter binding affinity in patients with major depressive disorder and night eating syndrome.

OBJECTIVE: We examined serotonin transporter (SERT) binding affinity using single photon emission computed tomography (SPECT) in patients with major depressive disorder (MDD) and night eating syndrome (NES). There are similarities between MDD and NES in affective symptoms, appetite disturbance, nighttime awakenings, and, particularly, response to selective serotonin reuptake inhibitors (SSRIs). METHODS: Six non-depressed patients with NES and seven patients with MDD underwent SPECT brain imaging with 123I-ADAM, a radiopharmaceutical agent selective for SERT sites. Uptake ratios of 123I-ADAM SERT binding were obtained for the midbrain, basal ganglia, and temporal lobe regions compared to the cerebellum reference region. RESULTS: Patients with NES had significantly greater SERT uptake ratios (effect size range 0.64-0.84) in the midbrain, right temporal lobe, and left temporal lobe regions than those with MDD whom we had previously studied. CONCLUSIONS: Pathophysiological differences in SERT uptake between patients with NES and MDD suggest these are distinct clinical syndromes.

Dietary energy density increases during early childhood irrespective of familial predisposition to obesity: results from a prospective cohort study.

OBJECTIVE: This study compared 4-year changes in daily energy density (ED; kcal/g) in children born at different risk for obesity, characterized the stability of ED and examined associations between ED and child body composition. DESIGN: Prospective cohort study to measure habitual dietary ED of children who are born at different risk for obesity. SUBJECTS: Children who were born at high risk (n=22) or low risk (n=27) for obesity based on maternal pre-pregnancy weight. MEASUREMENTS: Three-day food records were collected from children's mothers at child ages 3, 4, 5 and 6 years. Three categories of ED were computed (food only, food and milk, and food and all beverages) and body composition assessed at each year. RESULTS: The mean (+/-s.e.m.) ED increased over time across all children (linear trend: P<0.003): 2.18+/-0.07 to 2.32+/-0.06 kcal/g (food only); 1.66+/-0.07 to 1.82+/-0.06 kcal/g (food and milk); and 1.24+/-0.04 to 1.37+/-0.05 kcal/g (food and all beverages). Intraindividual coefficients of variation were smaller than those previously reported for adults. Weight indices were not correlated with dietary ED (P>0.05). CONCLUSION: Dietary ED increased in young children, irrespective of their predisposition to obesity, between the ages of 3 and 6 years. The genes that promote childhood obesity may not exert their influence through dietary ED, which may be more strongly influenced by environmental factors.

Night eating and weight change in middle-aged men and women.

OBJECTIVE: To examine the association between the habit of eating at night, and the 5-y preceding and 6-y subsequent weight changes in a middle-aged population, with particular focus on the obese. DESIGN: Prospective study with initial examination of the cohort in 1982-83, re-examination in 1987-88 and a third examination in 1992-93. SUBJECTS: The Danish MONICA cohort includes an age- and sex-stratified random sample of the population from the Western part of the Copenhagen County. Out of 2,987 subjects participating in 1987-88, a total of 1,050 women and 1,061 men had been examined in 1982-83, and 1993-94 too. Subjects working night shifts were excluded. MEASUREMENTS: Night eating in 1987-88, 5-y preceding and 6-y subsequent weight change. RESULTS: In total, 9.0% women and 7.4% men reported 'getting up at night to eat'. Obese women with night eating experienced an average 6-y weight gain of 5.2 kg (P=0.004), whereas only 0.9 kg average weight gain was seen among obese women who did not get up at night to eat. No significant associations were found among all women, or between night eating and the 5-y preceding weight change for women. Night eating and weight change were not associated among men. CONCLUSION: Night eating was not associated with later weight gain, except among already obese women, suggesting that getting up at night to eat may be a contributor to further weight gain among the obese.

Predictors of body size in the first 2 y of life: a high-risk study of human obesity.

OBJECTIVE: To ascertain the predictors of body size at 2 y of age. DESIGN: : Prospective, longitudinal study of risk factors for weight gain of infants at high or low risk of obesity by virtue of their mothers' obesity or leanness. SUBJECTS: A total of 40 infants of obese mothers and 38 infants of lean mothers, equally divided among boys and girls. METHODS: Measurement of dependent variables: weight, length and skinfold thicknesses at 3, 6, 9, 12, 18 and 24 months and percent body fat at 3, 12 and 24 months. Measurement of independent variables: average daily caloric consumption at 3, 6, 9, 12, 18 and 24 months; and, at 3 months, nutritive sucking behavior during a test meal, total energy expenditure (TEE), sleeping energy expenditure (SEE), estimation of nonsleeping energy expenditure (TEE-SEE) and socioeconomic status. Parental weights and heights were obtained by self-report at the time of recruitment. Partial correlation and mixed effects linear regression analyses were performed. RESULTS: Measures of body size (weight, length, skinfold thicknesses) and percent of body fat were almost identical between high- and low-risk groups at all times. Energy intake during six occasions over the 2 y, sucking behavior, family income and TEE predicted weight gain, controlling for body length. Parental body mass index was not associated with the child's body size during the first 2 y. During the first year, there were strong lagged correlations between energy intake and body weight and smaller correlations between protein intake and body weight. CONCLUSION: Energy intake, and not energy expenditure, was the determinant of body size in these infants at 2 y of age, as it had been at 1 y. Sucking behavior and TEE (positively) and family income (negatively) also contributed to body weight at 2 y. The novel finding of a lagged correlation between energy intake and body weight early in life suggests that energy intake is programmed for future growth and development.

A study of linkage and association of body mass index in the Old Order Amish.

Obesity is thought to have a genetic component with the estimates of heritability ranging from 0.25-0.40. As part of an ongoing study of obesity in the Old Order Amish, seven two- and three-generation families (157 individuals) were assessed for 21 traits related to obesity, including body mass index (BMI) and BMI-percentile (a standardized distribution of BMI adjusted for age and sex). Genotyping was performed using a panel of 384 short-tandem repeat markers. In this sample, the estimates of heritability ranged from 0.16-0.31 for BMI and from 0.40-0.52 for BMI-percentile. Model-independent linkage analysis identified candidate regions on chromosomes 1, 5, 7, 8, and 11. Given that several markers on 7q were significant for both BMI and BMI-percentile (P < or = 0.001) and that the structural locus for leptin was located on 7q, this region was considered to be the primary candidate region. Subsequent typing of additional flanking markers on 7q corroborated the original findings. Tests of intrafamilial association for alleles at markers in this candidate region were significant at similar levels. Although there is some evidence for linkage and association in the region containing leptin, there appears to be stronger evidence for linkage (P < or = 0.001) and association (P < or = 0.00001) with BMI in a region 10-15 cM further downstream of leptin, flanked by markers D7S1804 and D7S3070 with peak values from D7S495-D7S1798. Evidence from linkage and association studies suggests that this region (D7S1804-D7S3070) may be responsible, at least in part, for variation in BMI and BMI-percentile in the Old Order Amish.

Self-help and long-term behavior therapy for obesity.

The Trevose Behavior Modification Program, a self-help group offering continuing care for obesity, has recently been shown to produce large long-term weight losses. The present study aimed to replicate this finding across different settings and participants, assessing the weight losses and attrition rates of 128 participants in three Trevose program satellite groups that used the same treatment procedures and manual as the central Trevose group. The satellite groups' results closely paralleled those of the Central Group. Mean intent-to-treat weight loss, or final losses recorded for all participants regardless of their treatment termination date, was 13.7 +/- 0.7% of initial body weight (1.8 +/- 0.7 kg). At two years, 43.8% of participants remained in treatment, having lost a mean of 19.0 +/- 0.8% of their body weight (16.2 +/- 1.0 kg); at five years, 23.4% remained, having lost 18.4 +/- 1.1% of body weight (15.6 +/- 1.5 kg). These results demonstrate that the Trevose model of weight control, combining self-help and continuing care, can be extended and disseminated to other settings, with potentially significant public health consequences.

Expert opinion on body mass index percentiles for figure drawings at menarche.

We contacted clinicians and researchers who work in the area of childhood obesity to obtain a reasonable estimate of body mass index (BMI) percentile at menarche associated with a series of widely used figure drawings. Forty of 108 subscribers to the electronic listserv of the Pediatric Obesity Interest Group of the North American Association for the Study of Obesity responded to a request to estimate the BMI percentile at menarche for each of seven drawings. Median BMI percentile values ranged from three to 98 and means from 4.0 to 97.6, with the greatest agreement at the high end and the poorest agreement in the central part of the range. This approach may be useful in situations where weight and height are not readily recalled.

Relating body mass index to figural stimuli: population-based normative data for Caucasians.

OBJECTIVE: To establish body mass index (BMI) norms for standard figural stimuli using a large Caucasian population-based sample. In addition, we sought to determine the effectiveness of the figural stimuli to identify individuals as obese or thin. DESIGN: All Caucasian twins born in Virginia between 1915 and 1971 were identified by public birth record. In addition, 3347 individual twins responded to a letter published in the newsletter of the American Association of Retired Persons (AARP). All adult twins (aged 18 and over) from both of these sources and their family members were mailed a 16 page 'Health and Lifestyle' questionnaire. SUBJECTS: BMI and silhouette data were available on 16 728 females and 11 366 males ranging in age from 18-100. MEASUREMENTS: Self-report information on height-weight, current body size, desired body size and a discrepancy score using standard figural stimuli. RESULTS: Gender- and age-specific norms are presented linking BMI to each of the figural stimuli. Additional norms for desired body size and discrepancy scores are also presented. Receiver operating curves (ROC) indicate that the figural stimuli are effective in classifying individuals as obese or thin. CONCLUSIONS: With the establishment of these norms, the silhouettes used in standard body image assessment can now be linked to BMI. Differences were observed between women and men in terms of desired body size and discrepancy scores, with women preferring smaller sizes. The figural stimuli are a robust technique for classifying individuals as obese or thin.

The within-pair resemblance in serum levels of androgens, sex-hormone binding globulin and cortisol in female obese identical twins - effect of negative energy balance induced by very low-calorie diet.

The first aim of the present study was to evaluate the changes in serum levels of cortisol, testosterone, dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulphate (DHEA-S) and sex hormone-binding globulin (SHBG) in response to weight loss induced by one month of treatment with a very low-calorie diet (VLCD) in twelve pairs of female obese monozygotic twins. The second aim of the study was to investigate any within-pair resemblance in serum levels of steroids and SHBG before and after a negative balance protocol, as well as the resemblance in changes in response to therapeutic weight loss. VLCD-induced weight loss of 8.7+2.9 kg was associated with significant increases in serum testosterone (p<0.05) and SHBG (p<0.001) levels, whereas no significant changes in serum levels of cortisol, DHEA and DHEA-S were observed. Significant within-pair resemblances for both pre-treatment and post-treatment concentrations were revealed for DHEA-S (pre-treatment ICC = 0.795, p < 0.01, post-treatment ICC = 0.712, p < 0.01) and for testosterone (pre-treatment ICC = 0.594, p <0.05, post-treatment ICC = 0.735, p < 0.01). The baseline within-twin-pair resemblance in serum cortisol level at 7 a.m. (ICC=0.747, p < 0.05) was lost with VLCD treatment, while its concentration at 9 p.m. developed a within-pair similarity with weight loss (ICC = 0.824, p < 0.001). Similarly, VLCD treatment led to a significant within-pair resemblance in post-treatment level of DHEA (ICC = 0.755, p < 0.01), while no within-twin-pair resemblance was shown for either pre-treatment or post-treatment SHBG levels. None of the hormones measured exhibited any within-pair resemblance in response to VLCD-induced energy deficit, except for serum cortisol levels. A significant within-twin-pair resemblance in the changes in serum cortisol levels at 7 a. m. (ICC = 0.789, F = 8.5, p < 0.001), at 1 p.m. (ICC = 0.660, F = 4.9, p <0.01) and at 9 p.m. (ICC = 0.795, F = 8.8, p <0.001) were demonstrated even after adjustment for fat mass loss. An absence of any within-pair similarity was observed in both pretreatment and post-treatment levels of SHBG, while a significant within-pair resemblance in SHBG response to VLCD treatment (ICC = 0.658, p < 0.05) was recorded. We conclude that the significant within-twin-pair resemblance demonstrated for androgens and cortisol might suggest an important role for genetic factors in the regulation of their serum levels. Our results also suggest that the mechanisms controlling baseline levels of cortisol and SHBG differ from those influencing their responses to energy deficit induced by VLCD.

Body image in the old order Amish: a people separate from "the world".

OBJECTIVE: Body image measures were assessed among the Old Order Amish, a Protestant religious community living separate from Western industrialized society. METHOD: One hundred six Old Order Amish men (n = 50) and women (n = 56), aged 14-67 years, were studied by two measures of body image: (1) body dissatisfaction as assessed by the difference between subjects' body mass index (BMI, kg/m(2)) and the BMI that they chose as their ideal and (2) the relative accuracy of perception of body size assessed by comparing subjects' choice of body size on a Figure Rating Scale with the choice of a relative. RESULTS: Young persons and persons of normal weight of both genders showed no body dissatisfaction or inaccuracy in their perception of their body size. Older persons of both genders, on the other hand, manifested body dissatisfaction (actual BMI greater than ideal BMI). Older women also overestimated their body size. Obese persons of both genders manifested body dissatisfaction (actual BMI greater than ideal BMI) and obese men overestimated their body size. DISCUSSION: Young Amish people do not show the body image problems characteristic of young persons in Western industrial society. Their elders and obese persons may have some such problems. 2000 by John Wiley & Sons, Inc.

Effective long-term treatment of obesity: a continuing care model.

BACKGROUND: Despite the well-documented success of behavioral techniques in producing temporary weight loss, treatment is typically followed by weight regain. The maintenance of treatment effects may therefore be the greatest challenge in the long-term management of obesity, and continuous care may be necessary to achieve it. OBJECTIVE: To describe the design and evaluate the effectiveness of the Trevose Behavior Modification Program, a potentially widely replicable self-help weight loss program offering continuous care. DESIGN: A description of the course of all subjects (n=171) who entered the Trevose program during 1992 and 1993. SUBJECTS: One hundred and forty-six women aged 44.1+/-11.7 y with a body mass index (BMI, kg/m2) of 33.2+/-4.4, and 25 men aged 49. 0+/-19.6 with a BMI of 35.1+/-5.2 enrolled in the Trevose program during 1992-1993. RESULTS: Mean duration of treatment was 27.1 months, with 47.4% of members still in treatment at 2 y and 21.6% at 5 y. Mean intent-to-treat weight loss was 13.7+/-0.5% of initial weight, or 12.8+/-0.5 kg. As long as they remained in treatment, almost all participants lost at least 5% of their initial weight and at least 83% lost more than 10%. Members completing 2 y of treatment lost an average of 19.3% of their initial body weight (17.9 kg); at 5 y the loss was still 17.3% (15.7 kg). After leaving the program, subjects regained weight but remained 4.7% (4.5 kg) below their pretreatment weight. CONCLUSION: A low-cost program offering treatment of indefinite duration produced large long-term weight losses and may be suitable for widespread replication.

Intrapair resemblance in very low calorie diet-induced weight loss in female obese identical twins.

OBJECTIVE: To assess intrapair resemblance in changes of body weight, total body fat, fat distribution, resting metabolic rate, fasting respiratory quotient and cardiovascular disease risk factors in response to therapeutic weight loss in female obese identical twins. DESIGN: Patients stayed for 40 days on an inpatient metabolic unit under careful supervision. The stay was divided into three parts: an initial period of 7 days for adjustment to the hospital environment and for baseline measurements, 28 days of the weight reduction regimen when negative energy balance was achieved mainly by a very low calorie diet (1.6 MJ per day) and 5 days of testing after weight reduction. SUBJECTS: Fourteen pairs of premenopausal female obese identical twins (age: 39.0+/-1.7 y; body weight (BW): 93.9+/-21.2 kg; body mass index (BMI): 34.2+/-7.8 kg/m2) participated in the study. MEASUREMENTS: Before and after weight loss, the following measurements were made: body composition by anthropometry and hydrodensitometry, intra-abdominal fat by ultrasonography, resting metabolic rate by indirect calorimetry. Total cholesterol, high-density lipoprotein-cholesterol, triglycerides and uric acid were determined by standard laboratory procedures. Blood pressure was measured in the morning in the recumbent position. RESULTS: Subjects lost 8.8+/-1.9 kg of weight, from 93.9+/-21.2 to 85.1+/-10.9 kg (P<0.0001) and 6.5+/-2.3 kg of body fat (P<0.001). Weight losses varied widely among subjects, with a high correlation between losses of members of twin pairs for body weight (r=0.85; P<0.001) and for body fat (r=0.88; P<0.0001). Changes in uric acid resulting from weight loss were also correlated among members of twin pairs whereas changes in blood pressure, cholesterol and triglycerides were not. CONCLUSION: The great intrapair resemblance observed in very low calorie diet-induced weight and fat losses in female obese identical twins suggests an important role of genetic factors in response to the weight reduction regimen.

Long-term maintenance of weight loss: current status.

Intervention strategies for promoting long-term weight loss are examined empirically and conceptually. Weight control research over the last 20 years has dramatically improved short-term treatment efficacy but has been less successful in improving long-term success. Interventions in preadolescent children show greater long-term efficacy than in adults. Extending treatment length and putting more emphasis on energy expenditure have modestly improved long-term weight loss in adults. Fresh ideas are needed to push the field forward. Suggested research priorities are patient retention, natural history, assessment of intake and expenditure, obesity phenotypes, adolescence at a critical period, behavioral preference-reinforcement value, physical activity and social support, better linkage of new conceptual models to behavioral treatments, and the interface between pharmacological and behavioral methods.

Validation of the flexible and rigid control dimensions of dietary restraint.

OBJECTIVE: Two subscales for the Eating Inventory (Three-Factor Eating Questionnaire) are developed and validated: Rigid and Flexible control of eating behavior. METHOD: Study I is an analysis of questionnaire data and a 7-day food diary of 54,517 participants in a computer-assisted weight reduction program. Study II is a study of 85 subjects used to develop a final item pool. Study III is a questionnaire survey of a random sample (N = 1,838) from the West German population aged 14 years and above used to validate the developed subscales. RESULTS: Rigid control is associated with higher scores of Disinhibition, with higher body mass index (BMI), and more frequent and more severe binge eating episodes. Flexible control is associated with lower Disinhibition, lower BMI, less frequent and less severe binge eating episodes, lower self-reported energy intake, and a higher probability of successful weight reduction during the 1-year weight reduction program. DISCUSSION: Rigid and flexible control represent distinct aspects of restraint having different relations to disturbed eating patterns and successful weight control.

Energy intake, not energy output, is a determinant of body size in infants.

BACKGROUND: It has been proposed that the primary determinants of body weight at 1 y of age are genetic background, as represented by parental obesity, and low total energy expenditure. OBJECTIVE: The objective was to determine the relative contributions of genetic background and energy intake and expenditure as determinants of body weight at 1 y of age. DESIGN: Forty infants of obese and 38 infants of lean mothers, half boys and half girls, were assessed at 3 mo of age for 10 risk factors for obesity: sex, risk group (obese or nonobese mothers), maternal and paternal body mass index, body weight, feeding mode (breast, bottle, or both), 3-d energy intake, nutritive sucking behavior during a test meal, total energy expenditure, sleeping energy expenditure, and interactions among them. RESULTS: The only difference between risk groups at baseline was that the high-risk group sucked more vigorously during the test meal. Four measures accounted for 62% of the variability in weight at 12 mo: 3-mo weight (41%, P = 0.0001), nutritive sucking behavior (9%, P = 0.0002), 3-d food intake (8%, P = 0.0002), and male sex (3%, P = 0.05). Food intake and sucking behavior at 3 mo accounted for similar amounts of variability in weight-for-length, body fat, fat-free mass, and skinfold thickness at 12 mo. Contrary to expectations, neither total nor sleeping energy expenditure at 3 mo nor maternal obesity contributed to measures of body size at 12 mo. CONCLUSIONS: Energy intake contributes significantly to measures of body weight and composition at 1 y of age; parental obesity and energy expenditure do not.

Weights of parents and infants: is there a relationship?

OBJECTIVE: To assess the relationship between the measures of body weights of parents and those of their children during the first two years of life. SUBJECTS: Seventy-eight infants born to obese ('high risk') or nonobese ('low risk') mothers. METHODS: Weight, weight for length and skinfold thicknesses of the high and low risk infants were measured at 3 months, 12 months and 24 months of age. A multiple linear regression analysis assessed the contributions of nine risk factors, including paternal and maternal body mass index (BMI: kg/m2), to the weight and weight for length of infants at 12 months and 24 months of age. RESULTS: There were no differences between the high and low risk groups in weight, weight for length or skinfold thicknesses at 3 months, 12 months or 24 months of age. Neither paternal nor maternal BMI entered the multiple regression. CONCLUSIONS: These results suggest that genetic influences on the body weight of infants may be independent of those that influence BMI in adults, a circumstance that could complicate the search for genetic determinants of obesity.

The Eating Inventory in obese women: clinical correlates and relationship to weight loss.

OBJECTIVES: Describe the physical and psychological correlates of the Eating Inventory (EI) (also known as the Three-Factor Eating Questionnaire) factors in an obese sample, and determine the relationship between the three EI factors and weight loss. DESIGN: Consecutive series of obese women enrolled between 1987 and 1996 in clinical trials of weight loss treatments. PARTICIPANTS: 223 obese women with a weight of 100.7 +/- 15.5 kg, an age of 41.4 +/- 8.8 y and a body mass index (BMI) of 37.2 +/- 5.6 kg/m2. MEASURES: The EI and a variety of physical (weight, body composition and resting energy expenditure) and psychological (mood and binge eating) measures were assessed before and after 5-6 months of treatment. RESULTS: Before treatment, higher restraint scores were associated with lower body weights (P = 0.02), while higher disinhibition scores were associated with greater binge eating severity (P<0.0001). Weight loss treatment was associated with significant increases in restraint and decreases in disinhibition and hunger (all Ps<0.0001). Greater increases in restraint during treatment were associated with larger weight losses (P<0.0001). CONCLUSIONS: The three factors of the EI showed clinical utility in a sample of women receiving treatment for obesity.

The fen-phen finale: a study of weight loss and valvular heart disease.

OBJECTIVE: To assess weight loss, as well as the prevalence of valvular heart disease, in 21 obese women who completed 2 years of treatment by fenfluramine and phentermine (fen-phen) in June 1997. RESEARCH METHODS AND PROCEDURES: Patients were 21 of 22 women who had completed a 1-year, open-label trial of fen-phen combined with lifestyle modification. This study describes the results of a second year of treatment. The presence of valvular heart disease, defined as aortic regurgitation of mild or greater severity and/or mitral regurgitation of moderate or greater severity, was assessed using two-dimensional, color Doppler and pulsed- and continuous-wave Doppler examinations. RESULTS: At 2 years, the 21 patients had a mean reduction in initial weight of 13.9 + 10.0%, which was significantly (p<0.001) smaller than their 1-year loss of 17.1 +/- 8.7%. Nine of 21 patients reported that they took fen-phen irregularly during the last 4 months of the study because of fears of developing health complications. These nine patients had a 2-year weight loss of 8.7 +/- 7.5%, compared with a significantly (p<0.04) larger loss of 17.6 +/- 10.5% for participants who reported taking medication regularly. Six of 20 (30%) patients met criteria for valvular heart disease. None of the six had signs or symptoms of this condition. DISCUSSION: Fenfluramine was withdrawn from the market on September 15, 1997 because of concerns that it was associated with valvular heart disease. The present findings are discussed in terms of the potentially favorable long-term benefits of combining lifestyle modification with weight loss medications that are both safe and effective.