Effects of 2-year calorie restriction on circulating levels of IGF-1, IGF-binding proteins and cortisol in nonobese men and women: a randomized clinical trial.

Young-onset calorie restriction (CR) in rodents decreases serum IGF-1 concentration and increases serum corticosterone levels, which have been hypothesized to play major roles in mediating its anticancer and anti-aging effects. However, little is known on the effects of CR on the IGF-1 system and cortisol in humans. To test the sustained effects of CR on these key hormonal adaptations, we performed a multicenter randomized trial of a 2-year 25% CR intervention in 218 nonobese (body mass index between 22 and 27.8 kg m(-2) ) young and middle-aged (20-50 years age range) men and women. Average CR during the first 6 months was 19.5 ± 0.8% and 9.1 ± 0.7% over the next 18 months of the study. Weight loss averaged 7.6 ± 0.3 kg over the 2-years period of which 71% was fat mass loss (P < 0.0001). Average CR during the CR caused a significant 21% increase in serum IGFBP-1 and a 42% reduction in IGF-1:IGFBP-1 ratio at 2 years (P < 0.008), but did not change IGF-1 and IGF-1:IGFBP-3 ratio levels. Serum cortisol concentrations were slightly but significantly increased by CR at 1 year only (P = 0.003). Calorie restriction had no effect on serum concentrations of PDGF-AB and TGFß-1. We conclude, on the basis of the present and previous findings, that, in contrast to rodents, humans do not respond to CR with a decrease in serum IGF-1 concentration or with a sustained and biological relevant increase in serum cortisol. However, long-term CR in humans significantly and persistently increases serum IGFBP-1 concentration.

A 2-Year Randomized Controlled Trial of Human Caloric Restriction: Feasibility and Effects on Predictors of Health Span and Longevity.

BACKGROUND: Caloric restriction (CR), energy intake reduced below ad libitum (AL) intake, increases life span in many species. The implications for humans can be clarified by randomized controlled trials of CR. METHODS: To determine CR's feasibility, safety, and effects on predictors of longevity, disease risk factors, and quality of life in nonobese humans aged 21-51 years, 218 persons were randomized to a 2-year intervention designed to achieve 25% CR or to AL diet. Outcomes were change from baseline resting metabolic rate adjusted for weight change ("RMR residual") and core temperature (primary); plasma triiodothyronine (T3) and tumor necrosis factor-α (secondary); and exploratory physiological and psychological measures. RESULTS: Body mass index averaged 25.1 (range: 21.9-28.0 kg/m(2)). Eighty-two percent of CR and 95% of AL participants completed the protocol. The CR group achieved 11.7±0.7 %CR (mean ± standard error) and maintained 10.4±0.4% weight loss. Weight change in AL was negligible. RMR residual decreased significantly more in CR than AL at 12 months (p = .04) but not 24 months (M24). Core temperature change differed little between groups. T3 decreased more in CR at M12 and M24 (p < .001), while tumor necrosis factor-α decreased significantly more only at M24 (p = .02). CR had larger decreases in cardiometabolic risk factors and in daily energy expenditure adjusted for weight change, without adverse effects on quality of life. CONCLUSIONS: Sustained CR is feasible in nonobese humans. The effects of the achieved CR on correlates of human survival and disease risk factors suggest potential benefits for aging-related outcomes that could be elucidated by further human studies.

The Study of the Effects of Diet on Metabolism and Nutrition (STEDMAN) weight loss project: Rationale and design.

This paper outlines the rationale and design of the Study of the Effects of Diet on Metabolism and Nutrition (STEDMAN) weight loss project, in which detailed biologic profiling of three hundred and fifty obese individuals (body mass index (BMI): 30-50 kg/m(2)) will be conducted as they lose weight via seven distinct interventions. These profiles will be compared to those of fifty normal, healthy, control participants (BMI: 18.5-24.9 kg/m(2)). The interventions include the following: Roux-en-Y gastric bypass surgery, dietary interventions of differing macronutrient composition and diverse pharmacologic interventions. Outcome variables include eight conventional metabolites and CRP measured by standard clinical chemistry techniques, twenty hormones of energy balance and fuel homeostasis measured by radioimmunoassay (RIA) or by enzyme-linked Immunosorbent assay (ELISA), ten pro- and anti-inflammatory cytokines measured using Luminex xMAP technology, one hundred and one intermediary metabolites measured by targeted mass-spectrometry-based methods, and physiologic variables such as body composition measured by dual energy X-ray absorptiometry (DEXA), air displacement plethysmography, and abdominal computerized tomography (CT), insulin sensitivity measured by intravenous glucose tolerance test (IV-GTT) and metabolic rate measured by indirect calorimetry. Results from this study will expand our knowledge of the biology of obesity and weight regulation and may lead to targeted strategies for its treatment and control.

Efficacy and safety of heparinase I versus protamine in patients undergoing coronary artery bypass grafting with and without cardiopulmonary bypass.

BACKGROUND: Hemodynamic protamine reactions with heparin reversal during cardiac surgery are common and associated with adverse outcomes. As an alternative to protamine, the authors examined heparinase I reversal of heparin after aortocoronary bypass graft surgery. METHODS: In a randomized, double-blind, double-dummy trial, 167 on- and off-pump aortocoronary bypass graft surgery patients received either heparinase I (maximum 35 microg/kg) or protamine (maximum 650 mg) for heparin reversal, monitored by activated clotting time values and clinical assessment. Hemodynamic parameters were recorded electronically; safety evaluation was to 30 days postoperatively. Noninferiority was predefined as 400 ml or less median 12-h chest tube drainage from intensive care unit arrival for heparinase I patients, after risk adjustment. Hemodynamic instability was defined as systemic hypotension (> or = 30 mmHg decrease) and/or pulmonary hypertension (> or = 40 mmHg with an increase > or = 10 mmHg) within 30 min of heparin reversal initiation. RESULTS: Patient enrollment was terminated on advisement of the Data Safety Monitoring Board. Although heparinase I was noninferior for 12-h chest tube drainage, protamine had a superior safety profile. Overall, heparinase I subjects had longer hospital stays (P = 0.04), were more likely to experience a serious adverse event (P = 0.01), and were less likely to avoid transfusion (P = 0.006). A composite morbidity score was not different (P = 0.24), and similar rates of hemodynamic instability were observed between groups. Findings were consistent in analyses stratified by on- and off-pump surgery. CONCLUSIONS: Heparinase I reverses heparin anticoagulation after aortocoronary bypass graft surgery but is not equivalent to protamine because of its inferior safety profile.

Common design elements of the Girls health Enrichment Multi-site Studies (GEMS).

The Girls health Enrichment Multi-site Studies (GEMS) was a multi-center research program created for the purpose of testing interventions designed to prevent excess weight gain by African-American girls, as they enter and proceed through puberty. However, GEMS was not a "multi-center clinical trial" in the usual sense. Although these studies applied similar eligibility criteria, observed a similar follow-up schedule, and followed a similar measurement protocol, important differences existed, as well. Each field center developed its own intervention(s) and corresponding control, and tailored its study to the specific hypothesis being tested. Therefore, the study populations were somewhat different, with recruitment strategies that varied accordingly, and supplemental evaluations appropriate to the specific interventions were conducted on a site-specific basis. The purpose of this paper is to describe the common design elements of the GEMS Phase 1 pilot studies. This report presents the basic study design, a brief overview of the interventions, the measurements taken and their rationale, and procedures both for compiling the collaborative database, and performing site-specific analyses.

The Fun, Food, and Fitness Project (FFFP): the Baylor GEMS pilot study.

OBJECTIVE: The Girls health Enrichment Multisite Studies (GEMS) Fun, Food, and Fitness Project (FFFP) was designed to prevent obesity among 8-year-old African-American girls. DESIGN: Twelve-week, two-arm parallel group randomized controlled pilot study. SETTING: Summer day camp and homes in Houston, Texas. PARTICIPANTS: Thirty-five girls and their parents or caregivers were randomly assigned to treatment (N=19) or control groups (N=16). INTERVENTION: Girls in the intervention group attended a special 4-week summer day camp, followed by a special 8-week home Internet intervention for the girls and their parents. Control group girls attended a different 4-week summer day camp, followed by a monthly home Internet intervention, neither of which components included the GEMS-FFFP enhancements. MAIN OUTCOME MEASURES: Body mass index (BMI), consumption of fruit, 100% fruit juice, and vegetables (FJV), physical activity. RESULTS: After adjusting for baseline BMI, there were no significant differences in BMI between treatment and control group girls, either at the end of the 4-week summer day camp, or after the full 12-week intervention. By the end of the summer camp, the subgroup of treatment group girls heavier at baseline exhibited a trend (P<.08) toward lower BMI, compared to their heavier counterparts in the control group. Overall results at the end of the 12-week program demonstrated substantial, although not significant, differences between treatment and control groups in the hypothesized directions. On average, less than half the treatment sample logged onto the Website, which limited intervention dose. CONCLUSIONS: Summer day camp appears to offer promise for initiating health behavior change. Effective methods must be developed and tested to enhance log-on rates among healthy children and their parents before Internet programs can achieve their potential.

Child- and parent-targeted interventions: the Memphis GEMS pilot study.

OBJECTIVE: To assess the feasibility, acceptability, and outcomes of 2 versions of a culturally relevant, family-based intervention to prevent excess weight gain in pre-adolescent African-American girls. DESIGN: Three-arm, 12-week parallel group randomized controlled pilot trial. SETTING: Community centers in Memphis, Tennessee. PARTICIPANTS: Sixty African-American girls, aged 8 to 10 years, with a body mass index (BMI) > or = 25th percentile of the CDC growth charts, along with their parents/caregivers. INTERVENTIONS: The active interventions involved highly interactive weekly group sessions with either girls (child-targeted program) or parents/caregivers (parent-targeted program). Content focused on knowledge and behavior change skills to promote healthy eating and increased physical activity. The comparison intervention focused on global self-esteem. MAIN OUTCOME MEASURES: Given the lack of power and the limited time frame of the pilot study, outcomes were evaluated on the basis of implementation measures and changes in physical activity (accelerometer data), and in consumption of sweetened beverages and water, as estimated from questionnaires. Changes in body mass index, waist circumference, and body composition were also examined. RESULTS: The Memphis GEMS pilot intervention met all recruitment, retention, implementation, and participation goals, and was given high rating by both participants and interventionists. With respect to the comparison intervention, girls in both the child-targeted and parent-targeted interventions demonstrated a trend toward reduced body mass index and waist circumference. In addition, girls in the active intervention groups reduced their consumption of sweetened beverages by 34%, increased their level of moderate-to-vigorous activity by 12%, and increased their serving; of water by 1.5%. CONCLUSIONS: The findings from this pilot study demonstrated the feasibility, perceived acceptability, and efficacy of culturally relevant, obesity prevention interventions for pre-adolescent African-American girls and their parents/caregivers.

An after-school obesity prevention program for African-American girls: the Minnesota GEMS pilot study.

OBJECTIVE: This paper describes the development of an after-school obesity-prevention program for African-American girls, and presents findings from a 12-week pilot trial conducted by the University of Minnesota. This study was part of the GEMS project, created to test interventions designed to reduce excess weight gain in African-American girls. DESIGN: Two-arm parallel group, randomized controlled trial. Measures were taken at baseline and at 12 weeks follow up. SETTING: An after-school community program. PARTICIPANTS: Fifty-four African-American girls, 8- to 10-years of age, and their parents/caregivers. INTERVENTION: The after-school intervention was conducted twice a week for 12 weeks, and focused on increasing physical activity and healthy eating. A family component was also included. Girls in the control group received a program over 12 weeks unrelated to nutrition and physical activity. OUTCOMES: Measures included height and weight (body mass index), percent body fat (DEXA), physical activity, assessed using a CSA accelerometer and self-report, two 24-hour dietary recalls, and psycho-social and demographic variables. Parental data included demographic and psycho-social characteristics, and dietary measures. Additionally, process evaluation data on the intervention were collected. RESULTS: Recruitment goals were met. After adjustment for baseline level, follow-up BMI did not differ between the treatment groups, an expected finding, given that this was a pilot study. At 12 weeks follow up, differences between the intervention and control groups were in the hypothesized direction of change for most variables, among both the girls and their parents. Process evaluation results demonstrated that the program was well attended, and well received, by girls and parents. CONCLUSIONS: An after-school obesity prevention program for low-income African-American girls is a promising model for future efforts.

Dance and reducing television viewing to prevent weight gain in African-American girls: the Stanford GEMS pilot study.

OBJECTIVE: To test the feasibility, acceptability, and potential efficacy of after-school dance classes and a family-based intervention to reduce television viewing, thereby reducing weight gain, among African-American girls. DESIGN: Twelve-week, 2-arm parallel group, randomized controlled trial. SETTING: Low-income neighborhoods. PARTICIPANTS: Sixty-one 8-10-year-old African-American girls and their parents/guardians. INTERVENTIONS: The treatment intervention consisted of after-school dance classes at 3 community centers, and a 5-lesson intervention, delivered in participants' homes, and designed to reduce television, videotape, and video game use. The active control intervention consisted of disseminating newsletters and delivering health education lectures. MAIN OUTCOME MEASURES: Implementation and process measures, body mass index, waist circumference, physical activity measured by accelerometry, self-reported media use, and meals eaten with TV. RESULTS: Recruitment and retention goals were exceeded. High rates of participation were achieved for assessments and intervention activities, except where transportation was lacking. All interventions received high satisfaction ratings. At follow up, girls in the treatment group, as compared to the control group, exhibited trends toward lower body mass index (adjusted difference = -.32 kg/m2, 95% confidence interval [CI] -.77, .12; Cohen's d = .38 standard deviation units) and waist circumference (adjusted difference = -.63 cm, 95% CI -1.92, .67; d = .25); increased after-school physical activity (adjusted difference = 55.1 counts/minute, 95% CI -115.6, 225.8; d = .21); and reduced television, videotape, and video game use (adjusted difference = -4.96 hours/week, 95% CI -11.41, 1.49; d = .40). The treatment group reported significantly reduced household television viewing (d = .73, P = .007) and fewer dinners eaten while watching TV (adjusted difference = -1.60 meals/week, 95% CI -2.99, -.21; d = .59; P = .03). Treatment group girls also reported less concern about weight (d = .60; P = .03), and a trend toward improved school grades (d = .51; P = .07). CONCLUSIONS: This study confirmed the feasibility, acceptability, and potential efficacy of using dance classes and a family-based intervention to reduce television viewing, thereby reducing weight gain, in African-American girls.