Biexponential model for predicting weight loss after gastric surgery for obesity.

BACKGROUND: Following gastric restrictive surgery, morbidly obese patients rarely achieve their ideal body weight defined by Metropolitan Life tables. The final body weight will depend on the initial body composition because there will be greater weight loss from fat than lean body mass. The purpose of this study was to develop a mathematical model that accurately estimates the rate and extent of weight loss following gastric bypass surgery. METHODS: Patients underwent gastric bypass followed by intensive medical therapy and serial bioelectrical impedance analysis (BIA) body composition measurements. Differential equations were derived to model weight loss. RESULTS: weight loss in the fat and lean body compartments followed monoexponential decay kinetics with differing rate constants. Total body weight loss (W(T)) at time t was W(T) = k(f)(k(f) - k(l)) (W(f(o))e(-k(f)t) + W(l(o))e(-k(l)t)), where W(fo) and W(lo) are the initial fat and lean body masses determined by BIA and k(f) and k(l) are the rate constants for the fat and lean compartments, respectively. Following surgically induced weight loss, k(f) = 7.61 +/- 1.27 x 10(-2), and k(l) = -0.93 +/- 0.13 x 10(-2), with the ratio of residual sum of the squares to the total sum of the squares of 98.8%. CONCLUSION: Accurate prediction of weight loss depends on the initial fat and lean compartment mass since each of these loses weight at a different rate and to a different extent. When these effects are accounted for, the total body weight loss can be accurately predicted for any given time following surgery.

Intentional weight loss, blood lipids and coronary morbidity and mortality.

PURPOSE OF REVIEW: Although weight reduction has been recommended to reduce cardiovascular risk, studies on the association between weight loss and coronary morbidity and mortality show conflicting results. This review summarizes findings from large studies examining this issue and accentuates the importance of carrying out additional well-designed research. RECENT FINDINGS: Many observational studies report that weight loss in older men and women is associated with increased cardiovascular morbidity and mortality. Recent studies suggest that this association may arise from the confounding effect of preexisting disease. Many studies do not report whether weight loss is intentional or unintentional. Unintentional weight loss may mask beneficial changes in cardiovascular risk due to intentional weight loss. In addition to issues related to the cause of weight loss, use of reported rather than measured weight may bias the results of large studies. However, one recent observational study with a methodology aimed at overcoming these limitations found that individuals who intentionally lost weight experienced a decreased coronary risk. SUMMARY: Weight reduction in overweight individuals is not universally associated with good health. This is true even if the weight loss results in normal body mass index. Reports of increased coronary risk associated with intentional weight loss may be explained by comorbidities that are also associated with weight loss. Individuals who are overweight and at high coronary risk may benefit from professionally supervised dieting and avoiding regain of lost weight. Clinical trials on cardiovascular outcomes in individuals who lose weight under supervised dieting are needed to assess this recommendation definitively.

Debilitating diarrhoea and weight loss due to colitis in two RA patients treated with leflunomide.

Diarrhoea and weight loss are frequently reported adverse events in rheumatoid arthritis (RA) patients receiving the disease-modifying antirheumatic drug (DMARD) leflunomide. According to the available literature these side effects occur mostly during the first 6 months of treatment, are rather mild and rarely lead to treatment withdrawal. In this report, we describe the clinical, endoscopic and histologic findings in two RA patients with severe diarrhoea and important weight loss more than 12 months after starting treatment with leflunomide. In both cases the symptoms were caused by colitis, but one had ulcerative and the other microscopic colitis. Despite treatment with budesonide the complaints only improved after withdrawal of leflunomide, making a causal relationship between this drug and the pathogenesis of colitis probable. The heterogeneous histopathological findings in these two patients, however, do not allow us to draw any definitive conclusions about the mechanism by which leflunomide causes diarrhoea and weight loss in RA patients. We conclude that persistent diarrhoea or weight loss in patients taking leflunomide can be more serious than what is previously reported in the literature. In such cases leflunomide treatment should be stopped and an endoscopic examination of the colon is recommended. Given the long half-life of this drug a washout procedure with cholestyramine should be considered whenever the problem is severe or persistent.

Effects of behavioral therapy on weight loss in overweight and obese patients with schizophrenia or schizoaffective disorder.

BACKGROUND: obesity is common in persons with schizophrenia. Besides its adverse health effects, obesity reduces quality of life and contributes to the social stigma of schizophrenia. METHOD: This 14-week, multicenter, open-label, rater-blinded, randomized study evaluated the effects of a group-based behavioral treatment (BT) for weight loss in overweight and obese stable patients with DSM-IV schizophrenia or schizoaffective disorder who had been switched from olanzapine to risperidone. Participants were randomly assigned to receive BT or usual clinical care (UC). BT included 20 sessions during which patients were taught to reduce caloric intake. In UC, patients were encouraged to lose weight but received no special advice about weight reduction. The primary outcome measure was change in body weight. RESULTS: Seventy-two patients were enrolled. The mean +/- SD weight loss at endpoint was significant in both groups (p < .05) and numerically greater in patients receiving BT than in those receiving UC (-2.0 +/- 3.79 and -1.1 +/- 3.11 kg, respectively). More patients in the BT group than in the UC group had lost > or = 5% of their body weight at endpoint (26.5% [9/34] and 10.8% [4/37], respectively; p = .082). A post hoc analysis of patients attending at least 1 BT session showed that significantly more patients in the BT than the UC group had lost > or = 5% of their body weight at endpoint (32.1% [9/28] vs. 10.8% [4/37], respectively, p = .038) and at week 14 (complete population; 40.9% [9/22] and 14.3% [4/28], respectively, p = .027). CONCLUSION: BT may be an effective method for weight reduction in patients with chronic psychotic illness.

Serum leptin, IGF-I and insulin levels in preterm infants receiving parenteral nutrition during the first week of life.

Leptin is involved in the regulation of body weight through a feedback signal between adipose tissue and the satiety center, to decrease food intake and increase energy expenditure. Newborn infants experience physiological weight loss during the first week of life. The leptin level may be decreased to enhance food intake and to decrease energy expenditure for physiological adaptation during early postnatal days. Insulin-like growth factor-I (IGF-I) and insulin are involved in the regulation of perinatal growth. Leptin might be interrelated with IGF-I or insulin, since both of these have adipogenic and somatotropic effects. We therefore hypothesized that leptin, IGF-I and insulin would be decreased during the first week of life, concurrently with physiological weight loss. Thirty preterm AGA infants (birth weight 1.574+/-313 g; GA 31.9+/-2.2 wk) were studied. All infants received parenteral nutrition from the third day after birth. Leptin was significantly decreased during the first week of life, and insulin was significantly increased at day 7 vs. day 1 and day 3. IGF-I did not change during the first week of life. Leptin was positively correlated with body weight (r = 0.368, p<0.01), body mass index (r = 0.267, p<0.05), and serum IGF-I (r = 0.330, p <0.01), but not with serum insulin. The percent of weight reduction during the first week of life was not correlated with the percent of leptin reduction during the first week of life. In conclusion, leptin was significantly decreased and positively correlated with body weight and IGF-I during the first week of life. Changes of leptin and insulin might be related to postnatal adaptation in metabolism, but the exact role of leptin, IGF-I and insulin in postnatal physiological weight loss is not clear.

Relationship between cholesteryl ester transfer protein and atherogenic lipoprotein profile in morbidly obese women.

OBJECTIVE: obesity is associated with increased morbidity and mortality from atherosclerotic disease. Lipid abnormalities contribute to the increased relative risk in obese subjects. Cholesteryl ester transfer protein (CETP) mass is increased in these patients and might mediate the atherogenic lipoprotein pattern observed in obesity. METHODS AND RESULTS: Twenty-one morbidly obese, middle-aged, female subjects participated in this prospective study. Subjects were examined before and 1 year after surgical treatment. Fat mass was determined by body impedance analysis; CETP mass, by ELISA; CETP activity, by exogenous substrate assay; and LDL particle diameter, by gradient gel electrophoresis. Mean weight loss after 1 year was 28.7 kg; mean fat mass loss was 22.6 kg. Mean CETP mass decreased from 1.81 to 1.32 microg/mL (P=0.008); mean CETP activity decreased from 244 to 184 nmol x mL(-1) x h(-1) (P=0.004); and in parallel, the mean diameter of LDL particles increased (256.8 to 258.4 A, P=0.04). CONCLUSIONS: We conclude that weight loss is associated with a pronounced decrease in CETP mass and activity and a consistent increase in LDL particle diameter. After 1 year of this prospective study in morbidly obese subjects undergoing weight loss by surgical treatment, it has been determined that some features of the atherogenic lipoprotein profile can be reversed.

Comparison of high-fat and high-protein diets with a high-carbohydrate diet in insulin-resistant obese women.

AIMS/HYPOTHESIS: A diet low in saturated fatty acids and rich in wholegrains, vegetables and fruit is recommended in order to reduce the risk of obesity, cardiovascular disease and type 2 diabetes mellitus. However there is widespread interest in high-fat ("Atkins Diet") and high-protein ("Zone Diet") alternatives to the conventional high-carbohydrate, high-fibre approach. We report on a randomised trial that compared these two alternative approaches with a conventional diet in overweight insulin-resistant women. METHODS: Ninety-six normoglycaemic, insulin-resistant women (BMI >27 kg/m(2)) were randomised to one of three dietary interventions: a high-carbohydrate, high-fibre (HC) diet, the high-fat (HF) Atkins Diet, or the high-protein (HP) Zone Diet. The experimental approach was designed to mimic what might be achieved in clinical practice: the recommendations involved advice concerning food choices and were not prescriptive in terms of total energy. There were supervised weight loss and weight maintenance phases (8 weeks each), but there was no contact between the research team and the participants during the final 8 weeks of the study. Outcome was assessed in terms of body composition and indicators of cardiovascular and diabetes risk. RESULTS: Body weight, waist circumference, triglycerides and insulin levels decreased with all three diets but, apart from insulin, the reductions were significantly greater in the HF and HP groups than in the HC group. These observations suggest that the popular diets reduced insulin resistance to a greater extent than the standard dietary advice did. When compared with the HC diet, the HF and HP diets were shown to produce significantly (p<0.01) greater reductions in several parameters, including weight loss (HF -2.8 kg, HF -2.7 kg), waist circumference (HF -3.5 cm, HF -2.7 cm) and triglycerides (HF -0.30 mmol/l, HF -0.22 mmol/l). LDL cholesterol decreased in individuals on the HC and HP diets, but tended to fluctuate in those on the HF diet to the extent that overall levels were significantly lower in the HP group than in the HF group (-0.28 mmol/l, 95% CI 0.04-0.52, p=0.02). Of those on the HF diet, 25% showed a >10% increase in LDL cholesterol, whereas this occurred in only 13% of subjects on the HC diet and 3% of those on the HP diet. CONCLUSIONS/INTERPRETATION: In routine practice a reduced-carbohydrate, higher protein diet may be the most appropriate overall approach to reducing the risk of cardiovascular disease and type 2 diabetes. To achieve similar benefits on a HC diet, it may be necessary to increase fibre-rich wholegrains, legumes, vegetables and fruits, and to reduce saturated fatty acids to a greater extent than appears to be achieved by implementing current guidelines. The HF approach appears successful for weight loss in the short term, but lipid levels should be monitored. The potential deleterious effects of the diet in the long term remain a concern.

Topiramate: long-term maintenance of weight loss induced by a low-calorie diet in obese subjects.

OBJECTIVE: To examine the safety and efficacy of topiramate (TPM) for maintaining weight following a low-calorie diet. RESEARCH METHODS AND PROCEDURES: Obese subjects (30 < or = BMI < 50 kg/m(2)) 18 to 75 years old received a low-calorie diet for 8 weeks. Those who lost > or =8% of their initial weight received TPM (96 or 192 mg/d) or placebo; all were on a lifestyle modification plan. Sixty weeks of medication were planned. Sponsor ended study early to develop a new controlled-release formulation with the potential to enhance tolerability and simplify dosing in this patient population. Efficacy was analyzed in subjects who completed 44 weeks of treatment before study termination. RESULTS: Of the 701 subjects enrolled, 80% lost > or =8% of their initial body weight and were randomized; 293 were analyzed for efficacy. Most withdrawals were due to premature termination of the study. Subjects receiving TPM lost 15.4% (96 mg/d) and 16.5% (192 mg/d) of their enrollment weight by week 44, compared with 8.9% in the placebo group (p < 0.001). Subjects on TPM continued to lose weight after the run-in, whereas those on placebo regained weight. Significantly more TPM subjects lost 5%, 10%, or 15% of their randomization weight than placebo. Most adverse events were related to the central nervous system. DISCUSSION: During a treatment period of 44 weeks, TPM was generally well tolerated, and subjects maintained weight loss initially achieved by a low-calorie diet-and produced additional clinically significant weight loss beyond that achieved by a low-calorie diet.