Prediction of weight loss and regain following dietary, lifestyle, and pharmacologic intervention

To develop statistical models for predicting weight loss and regain, we analyzed the phenotypic responses in an outpatient study of 60 obese subjects randomized to one of three 12-week interventions, diet (-600 kcal) alone, diet with exercise, and diet with sibutramine. This was followed by 12 weeks of observation. The best of the "baseline covariates" models was one that incorporated intervention group and baseline homeostasis model assessment-estimated insulin resistance (HOMA(IR)). It predicted week 12 weight change with R(2) of 0.38 and root mean square error (√MSE) of 2.92 kg. An alternative model incorporating baseline fat mass plus change in weight and HOMA(IR) at week 4 improved the prediction (R(2), 0.67, √MSE, 2.19 kg). We could not identify a satisfactory model to predict weight regain. We conclude that prediction of weight loss over 12 weeks is significantly improved when short-term weight change is incorporated into the model. This information could be utilized to forecast the success of a weight-loss program and to motivate and contribute to innovative designing of obesity trials.     

Effect of weight loss with lifestyle intervention on risk of diabetes

OBJECTIVE: Diabetes Prevention Program (DPP) participants randomized to the intensive lifestyle intervention (ILS) had significantly reduced risk of diabetes compared with placebo participants. We explored the contribution of changes in weight, diet, and physical activity on the risk of developing diabetes among ILS participants. RESEARCH DESIGN AND METHODS: For this study, we analyzed one arm of a randomized trial using Cox proportional hazards regression over 3.2 years of follow-up. RESULTS: A total of 1,079 participants were aged 25-84 years (mean 50.6 years, BMI 33.9 kg/m(2)). Weight loss was the dominant predictor of reduced diabetes incidence (hazard ratio per 5-kg weight loss 0.42 [95% CI 0.35-0.51]; P < 0.0001). For every kilogram of weight loss, there was a 16% reduction in risk, adjusted for changes in diet and activity. Lower percent of calories from fat and increased physical activity predicted weight loss. Increased physical activity was important to help sustain weight loss. Among 495 participants not meeting the weight loss goal at year 1, those who achieved the physical activity goal had 44% lower diabetes incidence. CONCLUSIONS: Interventions to reduce diabetes risk should primarily target weight reduction.     

Beyond weight reduction: Improvements in quality of life after an intensive lifestyle intervention in subjects with severe obesity

Abstract

Introduction. We examined the effects of 10–14 weeks of inpatient intensive lifestyle intervention (ILI), including a minimum of 90 minutes of adapted physical activity 5 days/week, with regard to changes in quality of life and associations with weight loss in subjects with severe obesity.

Methods. A total of 100 severely obese subjects (BMI 42.6 ± 5.3 kg/m²; 42.7 ± 10.6 years) were included. Quality of life was assessed by Binge Eating Scale, Hospital Anxiety, and Depression Scale, and SF- 36. The ILI group completed the questionnaires at inclusion, after 10–14 weeks and 12 months, and controls at inclusion and after 10–14 weeks.

Results. Compared to controls, self-reported binge eating (–6.4, P < 0.0001), anxiety (–1.7, P = 0.005), and depression (–3.0, P < 0.0001) were reduced, and physical (8.0, P < 0.0001) and mental (7.6, P < 0.0001) health increased in the ILI group. After 12 months, reduction in self-reported binge eating (–7.2, P < 0.0001) and depression (–3.4, P < 0.0001) and increase in physical (8.9, P < 0.0001) and mental (3.6, P = 0.035) health were maintained. Decreased self-reported binge eating (β = 0.555, P = 0.010) and increased physical health (β = –0.554, P = 0.003) were associated with weight loss.

Conclusion. ILI including a high volume of physical activity in subjects with severe obesity improved quality of life by favorable changes in self-reported binge eating, depression, and mental and physical health. Improvements in binge eating and physical health were associated with weight loss.

Trial registration: ClinicalTrials.gov identifier: NCT01675713.     

The effect of obesity on 12-month survival following admission to intensive care: a prospective study

OBJECTIVE: Evaluate the effect of intensive care (ICU) admission body mass index (BMI) on 30-day and 12-month survival in critically ill patients and determine the impact of obesity on outcome. DESIGN: Prospective, observational cohort study. SETTING: Fourteen-bed medical and surgical ICU of a university-affiliated hospital. PATIENTS: Four hundred and ninety-three adult patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: BMI (kg/m) was calculated from height (m) and measured weight (kg) within 4 hrs of ICU admission, using the PROMED weighing device, or premorbid weight (documented in the previous month) (BMImeasured). Follow-up was for >/=12 months post-ICU admission. Time to mortality outcome, censored at 30 and 365 days (12-months), was analyzed using a log-normal accelerated failure time regression model. Predictor variables were parameterized as time ratios (TR), where TR <1 is associated with decreased survival time and TR >1 is associated with prolonged survival time. Mean (sd) age and Acute Physiology and Chronic Health Evaluation II score were 62.3 (17.5) years and 20.7(8.4), respectively; 56.0% (285 of 493) of patients were male and 60.6% (299 of 493) medical. ICU admission weight and BMImeasured (available in 433 patients) were 79.1 (22.1) kg and 27.8 (7.0) kg/m, respectively. In 16.9% (73 of 433) of patients, weight was >/=100 kg, and in 29.8% (129 of 433), BMImeasured was >/=30 kg/m. Raw intensive care, 30-day, and 12-month mortality rates were 15.2% (66 of 433), 22.3% (95 of 433), and 37.3% (159 of 433), respectively. BMImeasured was a significant determinant of mortality at 30 days (TR 1.853, 95% confidence interval 1.053-3.260, p = .032) and 12 months (TR 1.034, 95% confidence interval 1.005-1.063, p = .019). The effect of BMI on 12-month mortality was linear, such that increasing BMI was associated with decreasing mortality. CONCLUSIONS: ICU admission BMI was a determinant of short- to medium-term survival. Obesity was not associated with adverse outcomes and may be protective.     

A randomized study and open-label extension evaluating the long-term efficacy of pramlintide as an adjunct to insulin therapy in type 1 diabetes

OBJECTIVE: To assess the effect of mealtime amylin replacement with pramlintide on long-term glycemic and weight control in patients with type 1 diabetes. RESEARCH DESIGN AND METHODS: In a 52-week, double-blind, placebo-controlled, multicenter study, 480 patients with type 1 diabetes were randomized to receive preprandial injections of placebo or 30 microg pramlintide q.i.d., in addition to existing insulin regimens. At week 20, pramlintide-treated patients were re-randomized to 30 or 60 microg pramlintide q.i.d. if decreases from baseline in HbA(1c) were <1% at week 13. Of the 342 patients who completed the 52-week study, 236 individuals ( approximately 70%) elected to participate in a 1-year open-label extension in which all patients received 30 or 60 microg pramlintide q.i.d. RESULTS: Treatment with pramlintide led to a mean reduction in HbA(1c) of 0.67% from baseline to week 13 that was significantly (P < 0.0001) greater than the placebo reduction (0.16%), and a significant placebo-corrected treatment difference was sustained through week 52 (P = 0.0071). The greater HbA(1c) reduction was associated with an average weight loss, rather than weight gain, and was not accompanied by an increased overall event rate of severe hypoglycemia. In the open-label extension, mean HbA(1c) levels decreased rapidly in patients receiving pramlintide for the first time and remained at reduced levels in patients who continued pramlintide treatment. The most common adverse events reported by the pramlintide group were mild nausea and anorexia, which both occurred during the initial weeks of treatment and dissipated over time. CONCLUSIONS: Mealtime pramlintide treatment as an adjunct to insulin improved long-term glycemic control without inducing weight gain or increasing the overall risk of severe hypoglycemia in patients with type 1 diabetes.     

Revisiting leptin's role in obesity and weight loss

Maintenance of weight loss is often unsuccessful because of metabolic adaptations that conserve energy. Studies in rodents suggest that a reduction in leptin level during weight loss signals to the brain to increase feeding and decrease energy expenditure. In this issue of the JCI, Rosenbaum et al. examined this concept in obese patients who lost weight and were maintained at 10% below their initial weight (see the related article beginning on page 2583). Brain activity responses to visual food stimuli were visualized using functional MRI. Leptin levels fell during weight loss and increased brain activity in areas involved in emotional, cognitive, and sensory control of food intake. Restoration of leptin levels maintained weight loss and reversed the changes in brain activity. Thus, leptin is a critical factor linking reduced energy stores to eating behavior. Potentially, leptin therapy could sustain weight loss by overriding the tendency toward energy conservation.     

Management of overweight and obesity in adults: behavioral intervention for long-term weight loss and maintenance.

BACKGROUND: The World Health Organization has identified obesity as a global epidemic. While weight loss is a considerable challenge, long-term maintenance of weight loss is an even greater problem. AIMS: This review of the assessment and management of overweight and obesity in adults covers factors contributing to overweight and obesity, components of weight-loss management, and interventions and effects of behavioral treatment for long-term weight loss and maintenance. METHODS: A thorough search of the medical and nursing literature recorded in the MEDLINE database from 1995 to 2003 was conducted by using the keywords "overweight", "obesity", and "behavioral therapy". RESULTS: Obesity is a complex, multifaceted condition in which excessive body fat places a person at risk of multiple health problems. Excessive body fat results from energy intake that exceeds energy expenditure. CONCLUSIONS: Increasing evidence suggests that obesity is not simply a problem of will power or self-control but a complex disorder involving appetite regulation and energy metabolism that is associated with a variety of comorbid conditions. Effective strategies of weight loss require management strategies in a combined approach of dietary therapy and physical activity by using behavioral interventions.     

Metabolic rate after massive weight loss in human obesity

Resting metabolic rate, measured by the ventilated hood technique in 11 obese subjects before weight loss was 6.5 +/- 0.3 kJ/min, not significantly different from the value predicted by regression equations relating metabolic rate to body weight (established from measurements in 106 subjects). After 34.5 kg mean weight loss, and during continued dieting, resting metabolic rate fell an average of 25% to 5.0 +/- 0.18 kJ/min, significantly below that predicted for the new slimmed weight. The fall in metabolic rate, over and above that expected from weight loss alone, suggests that the slimmed obese are hypometabolic compared with subjects of the same weight who have not lost weight. The failure of the slimmed obese to maintain their weight loss is unlikely to be due solely to this excessive fall in resting metabolic rate, since they still had quantitatively higher energy expenditure than lean subjects.     

Transdermal clonidine as an adjunct to sustained-release diltiazem in the treatment of mild-to-moderate hypertension

An open-label study was conducted to evaluate the clinical safety and efficacy of transdermal clonidine as an adjunct to sustained-release (SR) diltiazem (90 mg twice daily) in mild-to-moderate hypertension. Ninety patients with a mean baseline sitting blood pressure of 154/102 mmHg were given 90 mg of diltiazem SR twice daily and transdermal placebo. After four weeks of therapy, 21 patients (23%) had trough sitting diastolic blood pressures (DBP) less than 90 mmHg and were withdrawn. Of the remaining 69 patients (DBP greater than or equal to 90 mmHg), 60 (mean blood pressure 149/98 mmHg) continued to receive 90 mg of diltiazem SR twice daily, to which was added transdermal clonidine, titrated as needed (3.5 cm2, 7.0 cm2, or 10.5 cm2) to achieve blood pressure control. During titration, 58 patients achieved DBP less than 90 mmHg, with a mean blood pressure of 133/84 mmHg. Of these patients, 54 completed an eight-week maintenance period, during which their mean blood pressure was 137/84 mmHg. No significant decrease in pulse or change from baseline in lipid profiles (high-density lipoprotein, low-density lipoprotein, apolipoprotein A-I, apolipoprotein B) was observed with combination therapy. The most frequently reported side effect during maintenance therapy was mild skin irritation at the transdermal application site. One patient was withdrawn because of contact dermatitis. Compliance with the oral twice-daily regimen was variable, with 83% of patients failing to take diltiazem SR at the prescribed dosing intervals 80% to 100% of the time. Transdermal clonidine was worn as directed by 97% of patients. It is concluded that transdermal clonidine in combination with diltiazem SR is safe and effective in the treatment of mild-to-moderate hypertension.     

Needle aspiration biopsy as an adjunct to mediastinoscopy

Conventional mediastinoscopy has a small but definite morbidity and mortality. Our continuing study was done to determine whether needle aspiration during mediastinoscopy is a safe and reliable procedure. In 14 consecutive patients having mediastinoscopy, needle aspiration biopsy was also done. There was a 100% correlation between diagnosis made by needle cytology and the final diagnosis, with neither false-positive nor false-negative results. This correlation was only 75% in the forceps biopsy group. In 90% of the cases, the cytopathologist correctly identified the final cell type. There were no complications, even in cases of superior vena caval (SVC) obstructions. The distinct advantages of the technique include high specificity, better tissue sampling, immediate availability of results, reduced morbidity, expanded indications in SVC syndromes, and higher yield than conventional punch biopsies.     

Platelet alpha-adrenergic receptors in obesity: alteration with weight loss

We studied platelet alpha-adrenergic receptor concentration and function in 19 subjects with simple obesity participating in a double-blind, controlled clinical trial of diet and anorexiants (phentermine, fenfluramine, or a combination of the two) or placebo. From wk 1 to wk 8, weight loss for the group as a whole was 4.9 +/- 0.7 kg (mean +/- SE). Concomitant with this weight loss, the platelet alpha-adrenergic receptor concentration rose from 85.7 +/- 5.8 to 113 +/- 5.8 fmol/mg protein. This increase moved the values for the obese subjects toward or beyond values in lean controls (100 +/- 10.5 fmol/mg protein). The response in the different treatment groups was similar. The receptor concentration increase was accompanied by a corresponding increase in alpha-adrenergic receptor-mediated platelet aggregation. For individual subjects the extent of weight loss over time generally correlated with percent receptor change. Altered adrenergic sensitivity occurring in obese subjects who are losing weight may have important implications in relation to external (therapeutic or inadvertent) administration of catecholamines.