Reductions in plasma cytokine levels with weight loss improve insulin sensitivity in overweight and obese postmenopausal women.

OBJECTIVE: The purpose of this study was to determine whether improvements in insulin sensitivity with weight loss are mediated by changes in inflammation in obese, postmenopausal women. RESEARCH DESIGN AND METHODS: We studied 58 sedentary, overweight, and obese (BMI 33 +/- 1 kg/m(2), means +/- SEM) postmenopausal (58 +/- 1 year) women at baseline and 37 women who completed 6 months of weight loss induced by diet and exercise. The women underwent 3-h hyperinsulinemic-euglycemic clamps (40 mU x m(-2) x min(-1)) to determine glucose utilization (M). Insulin sensitivity was determined as M/I, the amount of glucose metabolized per unit of plasma insulin (I). Visceral adipose tissue (VAT) and plasma concentrations of C-reactive protein (CRP), cytokines interleukin (IL)-6, and tumor necrosis factor (TNF)-alpha, as well as their soluble receptors, were measured. RESULTS: At baseline, CRP concentration was a predictor of both glucose utilization and insulin sensitivity, independent of adiposity, race, and aerobic fitness (M: partial r = -0.30, P = 0.03, and M/I: partial r = -0.32, P = 0.02). weight loss resulted in significant reductions in body weight, fat mass, VAT, and fasting glucose and insulin levels (P < 0.05). Both glucose utilization and insulin sensitivity increased by 16% (P < 0.05). CRP, IL-6, and soluble TNF receptor (sTNFR)-1 concentrations decreased (P < 0.05), but concentrations of TNF-alpha, sTNFR-2, and soluble IL-6 receptor (IL-6sR) did not change. In stepwise regression models to predict changes in glucose homeostasis, changes in VAT and sTNF-R1 independently predicted changes in glucose utilization (r = -0.49 and cumulative r = -0.64, P < 0.01), while changes in VAT and IL-6 were both independent predictors of changes in insulin sensitivity (r = -0.57 and cumulative r = -0.68, P < 0.01). CONCLUSIONS: Improvements in glucose metabolism with weight loss programs are independently associated with decreases in cytokine concentrations, suggesting that a reduction in inflammation is a potential mechanism that mediates improvements in insulin sensitivity.

Effects of outcome-driven insurance reimbursement on short-term weight control.

CONTEXT: Although most health insurers exclude coverage of weight control therapy, one local insurer offered partial reimbursement of the cost of a weight control program, using an incentive plan. OBJECTIVE: To determine whether outcome-driven insurer-based reimbursement improves participation in a weight control program and short-term weight loss outcomes. DESIGN: Cohort follow-up study between January 1998 and February 2001. SETTING: Community weight management program operated by an academic medical center. SUBJECTS: Obese participants who had the potential for reimbursement (Group A, n=25) and participants in the same program classes (Group B, n=100) who had no possibility for reimbursement. Subjects in Group B were selected from among 206 potential participants using a propensity score to match them with subjects in Group A on age, gender, ethnicity, starting BMI, starting weight, and educational, economic, and demographic variables. INTERVENTION: Group lifestyle-based weight management program. The insurer reimbursed half the cost of the program to obese participants who met minimum weight criteria, paid the program fee at enrollment, attended > or =10 of the 12 classes, and lost > or =6% of initial body weight after 12 weeks. MAIN OUTCOME MEASURES: Participation rates and weight loss outcomes. RESULTS: Group A subjects attended significantly more classes (mean+/-s.d.: 10.1+/-1.8 vs 8.2+/-2.5, P<0.001) and lost more weight than Group B subjects (6.1+/-3.1 vs 3.7+/-3.6%, P=0.002). While 84% of Group A subjects attended > or =10 classes, only 37% of Group B subjects did so (P<0.001); 56% of Group A subjects lost > or =6% of body weight, but only 20% of Group B subjects did so (P<0.001); 56% of Group A subjects achieved both the class attendance and weight loss goals, but only 14% of Group B subjects did so (P<0.001). Logistic regression estimated that Group A subjects had 8.2 times the odds of attending > or =10 classes and 4.5 times the odds of losing > or =6% of body weight of Group B subjects, after controlling for class attendance. CONCLUSIONS: Insurer-based reimbursement that is contingent upon initial financial commitment on the part of the patient, consistent program participation, and successful weight loss is associated with significantly better short-term weight control outcomes.

Body composition analysis and changes in airways function in obese adults after hypocaloric diet.

STUDY OBJECTIVES: To determine the relationship between weight-loss and pulmonary function indexes, focusing on forced expiratory flows (ie, FEV(1), forced expiratory flow at 50% of vital capacity [FEF(50)], forced expiratory flow at 75% of vital capacity, and forced expiratory flow at 25 to 75% of vital capacity [FEF(25--75)]). Specifically, to determine the effect of losses in total and segmental fat mass (FM) and of modifications in lean body mass, after restricted hypocaloric diet, on pulmonary function among obese adults. DESIGN: Cross-sectional, observational. SETTINGS: Human Physiology Division, Faculty of Medicine and Surgery, "Tor Vergata" University, Rome, Italy. PATIENTS: Thirty obese adults (mean [+/- SD] baseline body mass index [BMI], 32.25 +/- 3.99 kg/m(2)), without significant obstructive airway disease, were selected from among participants in a weight-loss program. MEASUREMENTS AND RESULTS: Anthropometric, body composition (BC), and respiratory parameters of all participants were measured before and after weight loss. Total and segmental lean body and FM were obtained by dual-energy x-ray absorptiometry. Dynamic spirometric tests and maximum voluntary ventilation (MVV) were performed. The BC parameters (ie, body weight [BW], BMI, the sum skinfold thicknesses, thoracic inhalation circumference, thoracic expiration circumference, total FM, and trunk FM [FMtrunk]) were significantly decreased (p < or = .0001) after a hypocaloric diet. The mean vital capacity, FEV(1), FEF(50), FEF(25-75), expiratory reserve volume, and MVV significantly increased (p < or = 0.05) with weight loss. The correlation coefficient for Delta FEF(25--75) (r = 0.20) was numerically higher than Delta FEF(50) and Delta FEV(1) (r = 0.14 and r = 0.08, respectively) for the BW loss. Moreover, the correlation coefficient for Delta FEF(25--75) (r = 0.45) was significantly higher (p < or = 0.02) than those for Delta FEF(50) and Delta FEV(1) (r = 0.38 and r = 0.15, respectively) for FMtrunk loss. CONCLUSIONS: This study shows that a decrease in total and upper body fat obtained by restricted diet was not accompanied by a decrease in ventilatory muscle mass. FMtrunk loss was found to have improved airflow limitation, which can be correlated to peripheral airways function.

Does prior authorization of Sibutramine ( Meridia ) improve medication compliance or weight loss?

OBJECTIVE: This study was designed to examine whether prior authorization for insurer reimbursement of weight loss medication affects compliance with taking Sibutramine ( Meridia ) or adherence to a medical weight control program. The underlying hypothesis is that physician advocacy through prior authorization increases patient compliance and treatment outcomes. RESEARCH METHODS AND PROCEDURES: A retrospective review was conducted of 22 subjects who had received a prescription for Sibutramine ( Meridia ) that was reimbursed through their health insurer by prior authorization (PAR) and compared them with 47 randomly selected subjects who were also prescribed Sibutramine ( Meridia ) but did not receive reimbursement (non-PAR). Outcome measures included the percentage weight lost, visits to the clinic, and number of prescriptions received at 3, 6, 9, and 12 months. RESULTS: The proportion of subjects remaining in the clinic program, the number of clinic visits made, the number of prescriptions received, and the amount of weight lost were all significantly greater among PAR subjects than among non-PAR subjects. PAR subjects used the medication 37% longer by month 6 (2.43 vs. 1.52 prescriptions; p < 0.02), visited the clinic 44% more often (72.5 vs. 40.5 visits in 12 months; p < 0.0006), and achieved 38% better maximal weight loss (16% vs. 9.9% at 6 months; p < 0.49) than non-PAR subjects. DISCUSSION: This study suggests that, when those medications are not included on a health insurer's formulary, the use of the prior authorization process may improve both medication and behavioral compliance.

Weight requirements for return of menstruations in teenage girls with eating disorders, weight loss and secondary amenorrhoea.

AIM: To investigate the weight requirements for return of menstruation in teenage girls with eating disorders (ED), weight loss and secondary amenorrhoea. METHODS: Growth charts from the school health services and measurements of weight and stature at assessment and during follow-up were obtained for 127 girls with ED, secondary amenorrhoea and subsequent return of menstruation. Measurements were used to estimate weight and body mass index (BMI) before puberty, at menarche, at the highest weight prior to the onset of the ED, at the last menstruation preceding amenorrhoea, at the lowest weight during treatment, and at return of menstruation. RESULTS: Before onset of the ED, the girls were taller, heavier and less lean than the population average as evidenced by standard deviation scores (SDS) for weight, height and BMI above zero. weight loss started from an average weight of 58.9 +/- 9.8 kg (mean +/- SD), a last menstruation occurred at 51.5 +/- 6.9 kg, the lowest weight during treatment was 45.6 +/- 7.0 kg and menstruation returned at 52.9 +/- 6.0 kg. Return of menstruation occurred within a wide weight range. However, if weight at return of menstruation was expressed in SDS, it could be predicted by a linear regression on weight SDS at loss of menstruation (r2 = 0.76; p < 0.001). CONCLUSIONS: The weight level required for return of menstruation is highly individual but can be predicted by the weight at which menstruations cease. In the treatment of ED, there is a need for such individual weight targets--a target based on the population weight for height and/or age may be too generalized and too low.

Carbon dioxide and ethylene interactions in tulip bulbs.

The effect of CO2 on ethylene-induced gummosis (secretion of polysaccharides), weight loss and respiration in tulip bulbs (Tulipa gesneriana L.) was investigated. A pretreatment with 1-MCP prevented these ethylene-induced effects, indicating that ethylene action must have been directed via the ethylene receptor. Treatment with 0.3 Pa ethylene for 2 days caused gummosis on 50% of the total number of bulbs of cultivar Apeldoorn, known to be sensitive for gummosis. Addition of CO2 (10 kPa) reduced the ethylene-induced gummosis to 18%. In a second experiment the influence of ethylene and CO2 on respiration and FW loss of bulbs of the cultivar Leen van der Mark was studied. A range of ethylene partial pressures (0.003-0.3 Pa) was applied continuously for 29 days. Ethylene caused a transient peak in O2 consumption rate during the first days after the start of application. The relation between O2 consumption rate and ethylene partial pressure could be described by Michaelis-Menten kinetics. Respiratory peaks were reduced by CO2. This inhibition by CO2 could not totally be due to competition with ethylene at the receptor binding-site, as was indicated by the use of an O2 consumption model. Pre-treatment of bulbs with 1-MCP and subsequent exposure to CO2 showed that CO2 could influence respiration irrespective of any interaction with ethylene. Ethylene and CO2 both stimulated weight loss. The effect of combined treatments of ethylene and CO2 on weight loss was at least as strong as the sum of the separate effects, which implies that competition between ethylene and CO2 at the receptor binding-site was unlikely.

A 6-month observational study of the relationship between weight loss and behavioral symptoms in institutionalized Alzheimer's disease subjects.

OBJECTIVE: weight loss is a common occurrence in Alzheimer's disease (AD). This study was undertaken to investigate the relationship between weight loss and behavioral symptoms in institutionalized AD subjects. DESIGN: Observational study. SETTING: Two facilities that included assisted living and nursing care. PARTICIPANTS: Residents with probable or possible AD (n = 32). MEASUREMENTS: Weight was measured monthly. At baseline, month 3, and month 6, a knowledgeable staff member provided information that included the Neuropsychiatric Inventory: Nursing Home Version (NPI-NH, ie, a measure of behavioral symptoms) and a questionnaire regarding eating habits, food intake, and appetite. Two-day calorie counts were done and accelerometers were worn to monitor physical activity. RESULTS: At baseline, the mean body mass index (BMI) was 24.0 (standard deviation, 3.5) with 12 subjects exhibiting a BMI <22. BMI was negatively associated with the baseline NPI-NH total score (Spearman Correlation Coefficient -0.52, P <0.01), which indicates that subjects with low BMIs were more likely to have higher frequency and severity of behavioral problems. Individual behavior scores for agitation/aggression (-0.40, P <0.05), depression (-0.31, P = 0.08), irritability/lability (-0.47, P <0.01), aberrant motor behavior (ie, pacing, -0.42, P <0.05), nighttime behavior (-0.37, P = 0.05), and appetite/eating (-0.48, P <0.01) at baseline were negatively correlated with baseline BMI. Behaviors not correlated with BMI were delusions, hallucinations, elation, apathy, and disinhibition. Although this was a small sample followed for a relatively short time period, change in specific NPI-NH scores from baseline to month 6 were correlated with the change in weight over the 6-month period. Both agitation/aggression (-0.37, P = 0.05) and disinhibition (-0.45, P <0.05) showed negative correlation with weight change, which indicates an association between changes in these behaviors and weight loss. There were no significant differences between those who lost weight (n = 13) and those who did not (n = 19) on baseline variables, which included age, comorbidity, functional status, and NPI-NH. However, those who lost weight had a significantly higher BMI at baseline than those who gained weight. CONCLUSIONS: These preliminary results suggest that behavioral disturbances play a role in low body weight and weight loss in AD subjects.

Time-course changes in macronutrient metabolism induced by a nutritionally balanced low-calorie diet in obese women.

The use of low-calorie diets is a common strategy for body-weight reduction purposes, but the time-course of the metabolic changes induced by moderately energy-restricted, otherwise balanced, diets is still poorly known. The aim of this nutritional intervention design was to study in obese women the effect of a balanced low-calorie diet on the metabolic rate, and metabolic fuel utilization changes during the weight loss process through the application of breath tests with stable isotope-labeled tracers. Seven obese (body mass index >30 kg/m(2)) women were assigned to a 10-week dietary hypoenergetic intervention regime supplying 55% of energy as carbohydrate, 30% as fat and 15% as protein. Metabolic rate and substrate utilization were evaluated for 6 h in separate occasions during the weight loss program by indirect calorimetry and after 13C-labeled glucose, triolein and leucine administration. Body weight loss after 10 weeks was 4.2+/-1.1 kg, while the percent body fat decrease was about 5%. Slimming was accompanied by a marked decrease in fasting leptin (about 25%). Postprandial carbohydrate utilization after the administration of a test meal with the same macronutrient distribution as the experimental low-energy diet was decreased (24.1%, P<0.05) as a consequence of the dietary restriction, which was associated with lower insulin plasma levels (P<0.05). Although protein and lipid oxidation were not significantly different after weight reduction (day 1 versus day 70), the metabolic utilization of these substrates tended to increase. Moreover, marginally significant indications obtained on days 15 and 45 suggest that the weight and body composition changes are attributable to a shift in endogenous and exogenous glucose utilization in favor of lipid burning. The breath tests determinations, which were performed on different occasions along the experimental trial, confirmed that the cumulative 13C output decreased for labeled tracers with time, being only statistically significant for the glucose utilization between days 15 and 45. In summary, the weight and fat mass losses were associated with a lower carbohydrate oxidation, which were probably compensated by an increase in lipid oxidation without major changes in protein mobilization.