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Biomedical subjects

Frank L Greenway

Publications and source records attributed to Frank L Greenway.

14 recordsLinked to original sources
PubMed2006

Lack of an effect of a novel beta3-adrenoceptor agonist, TAK-677, on energy metabolism in obese individuals: a double-blind, placebo-controlled randomized study.

OBJECTIVE: Our objective was to test the safety and metabolic effects of a novel beta(3)-adrenoreceptor agonist (TAK-677) in humans. DESIGN, SETTING, AND PARTICIPANTS: Sixty-five obese (body mass index = 33.9 +/- 2.1 kg/m2, mean +/- se) men and women (31.4 +/- 0.9 yr) participated in a double-blind placebo-controlled study at an institutional research center. INTERVENTION: Participants were randomized to 0.1 mg TAK-677 twice daily (BID) (n = 21), 0.5 mg TAK-677 BID (n = 22), or placebo BID (n = 22) for 29 d. OUTCOMES: Drug safety, 24-h respiratory quotient (RQ), 24-h energy expenditure (EE), body composition, fat distribution, and fasting plasma concentration of substrates and hormones were assessed. An acute-response study was also conducted. RESULTS: The drug was well tolerated by all participants; however, heart rate was elevated (9 +/- 2 beats per minute) with the 0.5-mg BID dose. After 28 d of treatment and when compared with placebo, there was no change in 24-h RQ with either 0.1-mg BID (P = 0.1) or 0.5-mg BID (P = 1.0) doses of TAK-677. However, TAK, 0.5 mg BID, resulted in a small increase in 24-h EE that was significantly different from placebo [change from baseline, 13 +/- 17 (0.5 mg BID) vs.-39 +/- 18 (placebo) kcal/d, P < 0.05]. Changes in weight, fat-free mass, and abdominal fat depots (visceral or sc) were not different between the three groups, nor were changes in fasting insulin, free fatty acid, or glucose concentrations. CONCLUSION: TAK-677 has no effect on 24-h RQ or fat oxidation but does slightly increase 24-h EE at the highest dose (0.5 mg BID). The acute studies showed large interindividual variability in plasma concentrations of TAK-677 indicating some possible problems with bioavailability and therefore efficacy.

Abdominal Fat↗
PubMed2006

Effect of 6-month calorie restriction on biomarkers of longevity, metabolic adaptation, and oxidative stress in overweight individuals: a randomized controlled trial.

CONTEXT: Prolonged calorie restriction increases life span in rodents. Whether prolonged calorie restriction affects biomarkers of longevity or markers of oxidative stress, or reduces metabolic rate beyond that expected from reduced metabolic mass, has not been investigated in humans. OBJECTIVE: To examine the effects of 6 months of calorie restriction, with or without exercise, in overweight, nonobese (body mass index, 25 to <30) men and women. DESIGN, SETTING, AND PARTICIPANTS: Randomized controlled trial of healthy, sedentary men and women (N = 48) conducted between March 2002 and August 2004 at a research center in Baton Rouge, La. INTERVENTION: Participants were randomized to 1 of 4 groups for 6 months: control (weight maintenance diet); calorie restriction (25% calorie restriction of baseline energy requirements); calorie restriction with exercise (12.5% calorie restriction plus 12.5% increase in energy expenditure by structured exercise); very low-calorie diet (890 kcal/d until 15% weight reduction, followed by a weight maintenance diet). MAIN OUTCOME MEASURES: Body composition; dehydroepiandrosterone sulfate (DHEAS), glucose, and insulin levels; protein carbonyls; DNA damage; 24-hour energy expenditure; and core body temperature. RESULTS: Mean (SEM) weight change at 6 months in the 4 groups was as follows: controls, -1.0% (1.1%); calorie restriction, -10.4% (0.9%); calorie restriction with exercise, -10.0% (0.8%); and very low-calorie diet, -13.9% (0.7%). At 6 months, fasting insulin levels were significantly reduced from baseline in the intervention groups (all P<.01), whereas DHEAS and glucose levels were unchanged. Core body temperature was reduced in the calorie restriction and calorie restriction with exercise groups (both P<.05). After adjustment for changes in body composition, sedentary 24-hour energy expenditure was unchanged in controls, but decreased in the calorie restriction (-135 kcal/d [42 kcal/d]), calorie restriction with exercise (-117 kcal/d [52 kcal/d]), and very low-calorie diet (-125 kcal/d [35 kcal/d]) groups (all P<.008). These "metabolic adaptations" (~ 6% more than expected based on loss of metabolic mass) were statistically different from controls (P<.05). Protein carbonyl concentrations were not changed from baseline to month 6 in any group, whereas DNA damage was also reduced from baseline in all intervention groups (P <.005). CONCLUSIONS: Our findings suggest that 2 biomarkers of longevity (fasting insulin level and body temperature) are decreased by prolonged calorie restriction in humans and support the theory that metabolic rate is reduced beyond the level expected from reduced metabolic body mass. Studies of longer duration are required to determine if calorie restriction attenuates the aging process in humans. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00099151.

Adult↗
PubMed2006

Gallic acid is partially responsible for the antiangiogenic activities of Rubus leaf extract.

An aqueous extract of leaves from Rubus suavissimus S. Lee (Rosaceae) or sweet leaf tea was tested for antiangiogenic activity in a human tissue-based fibrin-thrombin clot angiogenesis assay. Further fractionation of this crude extract was performed and the antiangiogenic effect of individual fractions was assessed. The extract was also tested for its oral bioavailability by using the serum of normal rats gavaged with the extract in the assay. At a 0.1% w/v concentration, the extract inhibited initiation of the angiogenic response and subsequent neovessel growth from samples that had already initiated an angiogenic response. Two subfractions of the extract showed significant inhibition of angiogenesis at 0.1% w/w. Gallic acid was elucidated as one of the active angiogenesis inhibitors in one fraction. A 1 mm concentration of gallic acid totally inhibited angiogenesis. In the form of leaf extract, a one-tenth concentration produced the same total inhibition as pure gallic acid. The 10-fold difference in potency suggests the presence of other active compounds contributing to the overall antiangiogenic effect of the extract. The oral absorption of this extract was tested by using serum from rats given the extract orally (gavage) in the angiogenesis assay system. The serum of rats orally administered the sweet leaf tea extract at doses of 0.1% w/w and 0.3% w/w did not significantly inhibit angiogenesis. However, the serum of rats injected intraperitoneally at a dose of 0.1% w/w caused a 41% inhibition of angiogenesis compared with saline injected controls. These preliminary results warrant further bioassay directed identification of other responsible compounds.

Absorption↗
PubMed2005

Black raspberry extract and fractions contain angiogenesis inhibitors.

Targeted therapies, such as agents that inhibit angiogenesis, offer hope as complementary agents in cancer therapy. Angiogenesis-inhibiting agents have the potential for inhibiting tumor growth and limiting the dissemination of metastasis, thus keeping cancers in a static growth state for prolonged periods. Black raspberry (Rubus occidentalis) extract was discovered to be antiangiogenic (0.1% w/v) in a novel human tissue-based in vitro fibrin clot angiogenesis assay. Assay-guided fractionation of a crude black raspberry extract resulted in a highly potent antiangiogenic fraction that accounted for only 1% of the fresh weight of whole black raspberries. At 0.075% (w/v), the active fraction completely inhibited angiogenic initiation and angiogenic vessel growth. Further subfractionation of this active fraction revealed the coexistence of multiple antiangiogenic compounds, one of which has been identified as gallic acid. However, the individual subfractions did not outperform the active whole fraction. These findings suggest that an active black raspberry fraction may be a promising complementary cancer therapy. It is natural and potent enough for manageable dosing regimens. These extracts contain multiple active ingredients that may be additive or synergistic in their antiangiogenic effects. These observations warrant further investigations in animals and human trials.

Angiogenesis Inhibitors↗
PubMed2005

Comparison of methods to assess body composition changes during a period of weight loss.

OBJECTIVE: To assess the accuracy of body composition measurements by air displacement plethysmography and bioelectrical impedance analysis (BIA) compared with DXA during weight loss. RESEARCH METHODS AND PROCEDURES: Fifty-six healthy but overweight participants, 34 women and 22 men (age, 52 +/- 8.6 years; weight, 92.2 +/- 11.6 kg; BMI, 33.3 +/- 2.9 kg/m(2)) were studied in an outpatient setting before and after 6 months of weight loss (weight loss, 5.6 +/- 5.5 kg). Subjects were excluded if they had initiated a new drug therapy within 30 days of randomization, were in a weight loss program, or took a weight loss drug within 90 days of randomization. Subjects were randomly assigned either to a self-help program, consisting of two 20-minute sessions with a nutritionist and provision of printed materials and other self-help resources, or to attendance at meetings of a commercial program (Weight Watchers). Body composition was examined by each of the methods before and after weight loss. RESULTS: BIA (42.4 +/- 5.8%) underestimated percentage fat, whereas the BodPod (Siri = 51.7 +/- 6.9%; Brozek = 48.5 +/- 6.5%) overestimated percentage fat compared with DXA (46.1 +/- 7.9%) before weight loss. Correlation coefficients for detecting changes in body composition between DXA and the other methods were relatively high, with Brozek Deltafat mass (FM; r(2) = 0.63), Siri FM (r(2) = 0.65), tetrapolar BIA percentage fat (r(2) = 0.57), and Tanita FM (r(2) = 0.61) being the highest. DISCUSSION: In conclusion, all of the methods were relatively accurate for assessing body composition compared with DXA, although there were biases. Furthermore, each of the methods was sensitive enough to detect changes with weight loss.

Absorptiometry, Photon↗
PubMed2005

Safety of obesity drugs.

The safety of obesity drugs has historically been poor. This and the stigmatisation of obesity in society ensured that a higher standard of safety for obesity drugs must be met. The authors review the safety disasters of obesity drugs that were withdrawn. The authors then review the safety of presently available drugs--benzphetamine, phendimetrazine, diethylpropion, phentermine, sibutramine and orlistat. The safety of rimonabant, a drug with a pending new drug application that has an independent effect on metabolic syndrome, is also reviewed. The authors compare the stage of obesity drug development to that of hypertension in the 1950s. As new and safer drugs with more downstream mechanisms are developed that have independent effects on the cardiovascular risks associated with obesity, third party reimbursement for obesity medicine is likely to improve. This may lead to obesity being treated like hypertension and other chronic diseases with long-term medication. With improved technological tools, the authors believe this process will be more rapid for obesity than it was for hypertension.

Appetite Depressants↗
PubMed2004

Effect of a dietary herbal supplement containing caffeine and ephedra on weight, metabolic rate, and body composition.

OBJECTIVE: To evaluate the effect of a dietary supplement containing herbal caffeine (70 mg/dose) and ephedra (24 mg/dose; C&E) on metabolic rate, weight loss, body composition, and safety parameters. RESEARCH METHODS AND PROCEDURES: In phase I, 12 healthy subjects with a BMI of 25 to 35 kg/m2 had resting metabolic rate (RMR) measured for 2 hours after ingesting C&E or a placebo on two occasions 1 week apart, followed by a 1-week washout before phase II. In phase II, these 12 and 28 additional subjects were randomized to a 12-week, double-blind trial comparing C&E (3 times/day) to placebo. In phase III, the C&E group was given open-label C&E for 3 months, and the placebo group was given C&E for 6 months. RESULTS: In phase I, C&E gave an average 8 +/- 0.1% (SE) rise in RMR over 2 hours compared with placebo (p < 0.01). In phase II, weight loss at 12 weeks was 3.5 +/- 0.6 kg with C&E compared with 0.8 +/- 0.5 kg with placebo (p < 0.02). The percentage fat lost, shown by DXA, was 7.9 +/- 2.9% with C&E and 1.9 +/- 1.1% with placebo (p < 0.05). Pulse decreased more in the placebo group that in the C&E group (p < 0.03). There were no differences in lipid levels or blood pressure. In phase III, there was a 6-month loss of 7.3% and 7.8% of initial body weight for the groups on placebo and C&E during phase II, respectively. There were no serious adverse events. DISCUSSION: C&E increased RMR significantly by 8% compared with placebo, promoted more weight and fat loss than placebo, and was well tolerated.

Adolescent↗
PubMed2003

Weight loss with self-help compared with a structured commercial program: a randomized trial.

CONTEXT: Although commercial weight loss programs provide treatment to millions of clients, their efficacy has not been evaluated in rigorous long-term trials. OBJECTIVE: To compare weight loss and health benefits achieved and maintained through self-help weight loss vs with a structured commercial program. DESIGN AND SETTING: A 2-year, multicenter randomized clinical trial with clinic visits at 12, 26, 52, 78, and 104 weeks conducted at 6 academic research centers in the United States between January 1998 and January 2001. PARTICIPANTS: Overweight and obese men (n = 65) and women (n = 358) (body mass index, 27-40) aged 18 to 65 years. INTERVENTION: Random assignment to either a self-help program (n = 212) consisting of two 20-minute counseling sessions with a nutritionist and provision of self-help resources or to a commercial weight loss program (n = 211) consisting of a food plan, an activity plan, and a cognitive restructuring behavior modification plan, delivered at weekly meetings. MAIN OUTCOME MEASURES: Weight change was the primary outcome measure. Secondary outcomes included waist circumference, body mass index, blood pressure, serum lipids, glucose, and insulin levels. RESULTS: At 2 years, 150 participants (71%) in the commercial group and 159 (75%) in the self-help group completed the study. In the intent-to-treat analysis, mean (SD) weight loss of participants in the commercial group was greater than in the self-help group at 1 year (-4.3 [6.1] kg vs -1.3 [6.1] kg, respectively; P<.001) and at 2 years (-2.9 [6.5] kg vs -0.2 [6.5] kg, respectively; P<.001). Waist circumference (P =.003) and body mass index (P<.001) decreased more in the commercial group. Changes in blood pressure, lipids, glucose, and insulin levels were related to changes in weight in both groups, but between-group differences in biological parameters were mainly nonsignificant by year 2. CONCLUSION: The structured commercial weight loss program provided modest weight loss but more than self-help over a 2-year period.

Adult↗
PubMed2002

Effects of obesity surgery on non-insulin-dependent diabetes mellitus.

CONTEXT: Most individuals who have non-insulin-dependent diabetes mellitus are obese. The obese population has proved a frustrating entity regarding weight loss and diabetes control. Results of medical weight loss programs, medications, and behavior therapy have proved disappointing. HYPOTHESIS: Bariatric surgery is the most effective method of diabetes management and cure in the morbidly obese population. Surgical procedures to cause malabsorption provide a more dramatic effect on diabetes owing to the imparted bypass of the hormonally active foregut. DATA SOURCES: Pertinent journal articles spanning the last 40 years, as well as textbooks. CONCLUSIONS: Bariatric surgical procedures have proven a much more successful method of weight loss and diabetes control in the obese population than conservative methods. These surgical procedures have proven safe with reported mortality rates of 0% to 1.5%. Bariatric operations may be divided based on the method of weight loss and effect on diabetes. The first category is restrictive and includes vertical banded gastroplasty and adjustable silicone gastric banding. These operations improve diabetes by decreasing food intake and body weight with a slowing of gastric emptying. The second category not only contains restrictive components but also elements of malabsorption. This category includes the Roux-en-Y gastric bypass and biliary-pancreatic diversion, which bypass the foregut. Although all of the surgical procedures for obesity offer improved weight loss and diabetes control compared with conservative methods, the Roux-en-Y gastric bypass and biliary-pancreatic diversion offer superior weight loss and resolution of diabetes. The more dramatic effect seen in the surgical procedures to cause malabsorption is likely secondary to the bypass of the foregut resulting in increased weight loss and elevation of the enteroglucagon level.

Anastomosis, Roux-en-Y↗
PubMed2002

Development and validation of the food-craving inventory.

OBJECTIVE: The primary aim of this study was to develop and validate the Food-Craving Inventory (FCI), a self-report measure of specific food cravings. RESEARCH METHODS AND PROCEDURES: In a preliminary study, participants (n = 474) completed the initial version of the FCI. The results from this study were used in developing the revised FCI. Participants (n = 379) completed the revised FCI in the primary study designed to develop a self-report measure of specific food cravings. RESULTS: Common factor analysis yielded four conceptual factors (subscales) that were interpreted as high fats, sweets, carbohydrates/starches, and fast-food fats. Confirmatory factor analysis found that the four factors could be modeled as dimensions (or first-order factors) of a higher order construct-food craving. Test-retest and internal consistency analyses indicated good reliability for the total score and each of the subscales. Subscale scores were compared with scores on the Three Factor Eating Questionnaire and a conceptual measure of food craving. We found support for the content, concurrent, construct, and discriminant validity of the FCI. DISCUSSION: The FCI was found to be a reliable and valid measure of general and specific food cravings. The FCI can be used in research related to overeating and binge eating. Also, it may be useful in treatment studies that target obesity and/or food cravings.

Adult↗
PubMed2002

Bupropion SR enhances weight loss: a 48-week double-blind, placebo- controlled trial.

OBJECTIVE: To critically examine the efficacy of bupropion SR for weight loss. RESEARCH METHODS AND PROCEDURES: This 24-week multicenter, double-blind, placebo-controlled study randomized obese adults to placebo, bupropion SR 300, or 400 mg/d. Subjects were counseled on energy-restricted diets, meal replacements, and exercise. During a 24-week extension, placebo subjects were randomized to bupropion SR 300 or 400 mg/d in a double-blinded manner. RESULTS: Of 327 subjects enrolled, 227 completed 24 weeks; 192 completed 48 weeks. Percentage losses of initial body weight for subjects completing 24 weeks were 5.0%, 7.2%, and 10.1% for placebo, bupropion SR 300, and 400 mg/d, respectively. Compared with placebo, net weight losses were 2.2% (p = 0.0468) and 5.1% (p < 0.0001) for bupropion SR 300 and 400 mg/d, respectively. The percentages of subjects who lost >or=5% of initial body weight were 46%, 59%, and 83% (p vs. placebo < 0.0001) for placebo, bupropion SR 300, and 400 mg/d, respectively; weight losses of >or=10% were 20%, 33%, and 46% (p vs. placebo = 0.0008) for placebo, bupropion SR 300, and 400 mg/d, respectively. Withdrawals, changes in pulse and blood pressure did not differ significantly from placebo at 24 weeks. Subjects who completed 48 weeks maintained mean losses of initial body weight of 7.5% and 8.6% for bupropion SR 300 and 400 mg/d, respectively. DISCUSSION: Bupropion SR 300 and 400 mg/d were well-tolerated by obese adults and were associated with a 24-week weight loss of 7.2% and 10.1% and sustained weight losses at 48 weeks.

Adolescent↗
PubMed2002

Effect of diets enriched in almonds on insulin action and serum lipids in adults with normal glucose tolerance or type 2 diabetes.

BACKGROUND: Nuts appear to have cardiovascular benefits but their effect in diabetic patients is unclear. OBJECTIVE: The objective was to assess effects of almond-enriched diets on insulin sensitivity and lipids in patients with normoglycemia or type 2 diabetes. DESIGN: Study 1 assessed the effect of almonds on insulin sensitivity in 20 free-living healthy volunteers who received 100 g almonds/d for 4 wk. Study 2 was a randomized crossover study that compared 4 diets in 30 volunteers with type 2 diabetes: 1) high-fat, high-almond (HFA; 37% total fat, 10% from almonds); 2) low-fat, high-almond (LFA; 25% total fat, 10% from almonds); 3) high-fat control (HFC; 37% total fat, 10% from olive or canola oil); and 4) low-fat control (LFC; 25% total fat, 10% from olive or canola oil). After each 4-wk diet, serum lipids and oral glucose tolerance were measured. RESULTS: In study 1, almond consumption did not change insulin sensitivity significantly, although body weight increased and total and LDL cholesterol decreased by 21% and 29%, respectively (P < 0.05). In study 2, total cholesterol was lowest with the HFA diet (4.46 +/- 0.14, 4.52 +/- 0.14, 4.63 +/- 0.14, and 4.63 +/- 0.14 mmol/L with the HFA, HFC, LFA, and LFC diets, respectively; P = 0.0004 for fat level). HDL cholesterol was significantly lower with the almond diets (P = 0.002); however, no significant effect of fat source on LDL:HDL was observed. Glycemia was unaffected. CONCLUSIONS: Almond-enriched diets do not alter insulin sensitivity in healthy adults or glycemia in patients with diabetes. Almonds had beneficial effects on serum lipids in healthy adults and produced changes similar to high monounsaturated fat oils in diabetic patients.

Adult↗
PubMedDate not supplied

The cost effectiveness of three different measures of breast volume.

BACKGROUND: Several methods including water displacement, casting, the Grossman-Roudner measuring device, photographs, mammograms, ultrasound, and magnetic resonance imaging (MRI) have been proposed for the measurement of breast volume. The most cost-effective method has not been determined. METHODS: This study compared breast volume measurements using the Grossman-Roudner measuring device (a piece of circular plastic with a cut along a radius line), plaster casting, and MRI. The Grossman-Roudner measuring device was formed into a cone around the breast, and the volume was read from a graduated scale on the overlapping edges. The volume of the cast was measured using a butter-sand mixture and water displacement. The volume from the MRI slices was calculated using the ANALYZE bioimaging software. For five women with breast sizes AA, A, B, C, and D, the three volume measures were repeated three times. For a single volume measurement, the cost of the time and materials was 1 US dollar for the Grossman-Roudner cone, 20 US dollars for the cast, and 1,400 US dollars for the MRI. Using the mean and standard deviations of the measurements, a power analysis determined the number of subjects needed to detect a 5% change in volume. The number of subjects was multiplied by the price per test to determine relative cost. RESULTS: As compared with the cost for the Grossman-Roudner cone method, the cost for the volume measurements was 64 to 189 times more using the cast and 373 to 33,500 more using MRI. CONCLUSIONS: The Grossman-Roudner cone was clearly the most cost-effective method for determining breast volume changes in studies testing topical therapies to alter breast size.

Breast↗