Weight change, weight fluctuation, and mortality.

OBJECTIVE: To examine the relation between weight change and weight fluctuation (cycling) and mortality in middle-aged men. METHODS: A prospective study of 5608 men aged 40 to 59 years at screening, drawn from one general practice in each of 24 British towns. Changes in weight observed during a 12- to 14-year period were related to mortality during the subsequent 8 years. RESULTS: There were 943 deaths from all causes: 458 cardiovascular disease (CVD) and 485 non-CVD deaths. Those with stable weight or weight gain had the lowest total, CVD, and non-CVD mortality. Sustained weight loss or weight fluctuation (loss-gain or gain-loss) showed a significantly higher mortality risk than stable weight even after adjustment for lifestyle variables (relative risk [95% confidence interval], 1.60 [1.32-1.95], 1.50 [1.17-1.91], and 1.63 [1.24-2.14], respectively). Adjustment or exclusion of men with preexisting disease markedly attenuated the increased risk of CVD and total mortality associated with sustained weight loss and weight gain-weight loss. In long-term nonsmokers, any weight loss since screening was associated with an increased risk of mortality, but this was markedly attenuated by adjustment for preexisting disease. Recent ex-smokers showed the most marked increase in mortality associated with sustained weight loss. CONCLUSIONS: The increased mortality in middle-aged men with sustained weight loss and weight fluctuation (cycling) is determined to a major extent by disadvantageous lifestyle factors and preexisting disease. The evidence suggests that weight loss and weight fluctuation (cycling) in these men does not directly increase the risk of death.

In vitro mononuclear cell production of tumour necrosis factor-alpha and weight loss.

OBJECTIVE: Elevated tumour necrosis factor-alpha (TNF-alpha) production in adipose tissue has been associated with obesity. We investigated whether mononuclear cell production of TNF-alpha decreased with weight loss in an obese population. RESEARCH METHODS AND PROCEDURES: Seventeen obese patients with type 2 diabetes (BMI 32.5+/-0.9 kg/m(2)) and 33 obese, non-diabetic controls (BMI 31.2+/-0.5 kg/m(2)) underwent 12 weeks of 30% total energy restriction (6622+/-84 KJ per day). Every 4 weeks, weight and blood pressure were measured and fasting venous blood was analysed for lipid, glucose and insulin concentrations. At the beginning and end of energy restriction, mononuclear cells were isolated from whole blood and TNF-alpha production measured by ELSIA. RESULTS: TNF-alpha production was not associated with the degree of adiposity but was higher in diabetic subjects (P<0.04). There was a reduction after energy restriction (281+/-43 to 182+/-30 pg/ml, P<0.05) however the presence of type 2 diabetes did not influence the magnitude of this change. Plasma glucose and insulin levels decreased after weight loss in all subjects and weak correlations were found with TNF-alpha concentrations (r=0.3, P<0.05). CONCLUSIONS: We conclude that maximal production of TNF-alpha from mononuclear cells decreases with energy restriction and is weakly associated with plasma glucose and insulin concentrations in obese patients.

The effect of high-, moderate-, and low-fat diets on weight loss and cardiovascular disease risk factors.

Over 60% of Americans are overweight and a number of popular diets have been advocated, often without evidence, to alleviate this public health hazard. This study was designed to investigate the effects of several diets on weight loss, serum lipids, and other cardiovascular disease risk factors. One hundred men and women followed one of four dietary programs for 1 year: a moderate-fat (MF) program without calorie restriction (28 patients); a low-fat (LF) diet (phase I) (16) ; a MF, calorie-controlled (phase II) diet (38 patients); and a high-fat (HF) diet (18 subjects) [corrected]. Weight, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), homocysteine (Ho), and lipoprotein(a) [Lp(a)], were measured every 4th month. The TC/HDL-C ratio was calculated and fibrinogen levels were measured at baseline and after one year. The MF diet resulted in a 2.6% (NS) decrease in weight compared with 18.4% (p=0.045) decrease in patients on phase I, 12.6% (p=0.0085) decrease in patients on phase II, and 13.7% (p=0.025) decrease in those on the HF diet. TC was reduced by 5% (NS) in the MF group, 39.1% (p=0.0005) in the phase I group, and 30.4% (p=0.0001) in the phase II group. HF group had a 4.3% (NS) increase in TC. LDL-C was reduced by 6.1% (NS) on MF, 52.0% (p=0.0001) on phase I, and 38.8% (p=0.0001) on phase II. Patients on HF had a 6.0% (NS) increase in LDL-C. There were nonsignificant reductions in HDL-C in those on MF (-1.5%) and HF (-5.8%). Patients on phase I showed an increase in HDL-C of 9.0% (NS), while those on phase II diet had a 3.6% increase (NS) in HDL-C. TC/HDL-C increased (9.8%) only in patients following the high-fat diets (NS). Patients on MF had a 5.3% (NS) reduction in TC/HDL-C, while those on LF had significant reductions on the phase I ( -45.8%; p=0.0001) diet and phase II diet (-34.7%; p=0.0001). TG levels increased on both the MF (1.0%) and HF (5.5%) diets, although neither was statistically significant. People following the phase I and II diets showed reductions of 37.3% and 36.9%, respectively. Ho levels increased by 9.7% when people followed the MF diet and by 12.4% when they followed the HF diet. Patients following the phase I and phase II diets showed reductions of 13.6% and 14.6%, respectively. Only those following phase II diets showed a tendency toward significant improvement (p=0.061). Lp(a) levels increased by 4.7% following the MF (NS) diet and by 31.0% (NS) on the HF diet. Patients following phase I showed a 7.4% (NS) reduction and a 10.8% reduction (NS) following phase II. Fibrinogen levels increased only in individuals following HF diets (11.9%), while patients following MF (-0.6%), phase I (-11.0%), and phase II (-6.3%) diets showed nonsignificant reductions in fibrinogen. Patients on MF demonstrated nonsignificant reductions in weight, LDL-C, TC, HDL-C, TC/HDL-C ratios, and fibrinogen and nonsignificant increases in TGs, Lp(a), and homocysteine. There was significant weight loss in patients on phase I and II and HF diets after 1 year. Reductions in TC, LDL-C, TGs, and TC/HDL ratios were significant only in patients either following a LF diet or a MF, calorically reduced diet. Only patients following HF diets showed a worsening of each cardiovascular disease risk factor (LDL-C, TG, TC, HDL-C, TC/HDL ratio, Ho, Lp(a), and fibrinogen), despite achieving statistically significant weight loss. Copyright 2002 CHF, Inc.

Body composition changes following laparoscopic gastric banding for morbid obesity.

Most reports of outcome following obesity surgery report weight and co-morbidity changes only. We studied body composition changes in 17 adult patients (15 F, 2 M, age 43+/-2 years, range 28-58 years), with morbid obesity (initial BMI 40.4+/-4.9 kg/m(2), range 34.7-48.8) who were managed surgically by laparoscopically inserting an adjustable gastric band. Body composition was studied before and after surgery (mean interval of 909+/-51 days, range 441-1155 days) using anthropometry (abdominal circumference, AC, sum of four skinfold thicknesses, SFSUM), whole-body potassium counting (TBK), in vivo neutron activation analysis total body nitrogen (TBProtein) and whole-body dual-energy ray absorptiometry (total body percent fat TBF%, and total body bone mineral density TBBMD). weight loss over the study period was 23.4+/-2.5 kg. ( p<0.0003) with an AC reduction of 20.0+/-4.5 cm ( p<0.008). Both SFSUM and TBF% were significantly reduced ( p<0.02 and p<0.0005 respectively). Both TBK and TBProtein after normalization for sex and height, were significantly ( p<0.0054 and p<0.001 respectively) reduced, but the ratio of loss of fat mass to fat-free mass, at 4.4:1 was usual for weight loss, and there was no significant changes in the ratio of potassium to protein. TBBMD, after normalization relative to a young same sex adult, was not significantly changed. In this group of patients, most of the substantial weight loss over a 2- to 3-year period was due to loss of fat mass, with relatively less reduction in the components of fat-free mass. Adjustable laparoscopic gastric banding induces fat loss without significant other deleterious effects on body composition.

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.

Skeletal muscle metabolism in overweight and post-overweight women: an isometric exercise study using (31)P magnetic resonance spectroscopy.

OBJECTIVE: To investigate whether skeletal muscle anaerobic metabolism, oxidative metabolism or metabolic economy during controlled sub-maximal and near-maximal exercises is altered in overweight women after diet-induced weight reduction, and whether these parameters are different between normal-weight, obesity-prone and normal-weight obesity-resistant women with similar physical fitness levels. DESIGN: A prospective weight loss study of overweight women and their comparison with never overweight controls. SUBJECTS: Thirty overweight, nondiabetic, premenopausal women and 28 never overweight controls were included in this analysis. All were participating in a longitudinal investigation of the role of energy metabolism in the etiology of obesity.The overweight women were recruited specifically to have a positive family history of obesity and have a body mass index (BMI) between 27 and 30 kg/m(2) and were studied in the overweight state and after reduction to a normal weight. The never-overweight controls were recruited specifically to have no personal and family history of obesity and were group matched with the weight-reduced post-overweight subjects in terms of premenopausal status, age, BMI, race and sedentary lifestyle. MEASUREMENTS: All testing was performed following one month of weight maintenance and during the follicular phase of the menstrual cycle. Hydrostatic weighing was performed to measure body composition and a whole-body maximal oxygen uptake (VO(2max)) test was done to measure aerobic fitness. (31)P MRS was used to determine ATP production from oxidative phosphorylation (OxPhos), 'anaerobic' glycolysis (AnGly), and creatine kinase (CK), as well as muscle metabolic economy. The time constant of ADP (TC(ADP)), V(PCr) (ie the initial rate of PCr resynthesis following exercise), and Q(max) (ie the apparent maximal oxidative ATP production rate) were also calculated as additional markers of mitochondrial function. RESULTS: Diet-induced weight loss did not have any effects on the anaerobic metabolism markers (AnGly and CK). The aerobic metabolism markers calculated from the initial recovery data (OxPhos and V(PCr)) were unaffected by diet-induced weight loss. However, diet-induced weight loss resulted in improvements in the TC(ADP) and Q(max) in the post-overweight state as compared to their overweight state. There were no differences in any of the anaerobic (AnGly and CK) or oxidative metabolism markers (OxPhos, V(PCr), Q(max) and TC(ADP)) between the post-overweight and control groups. CONCLUSIONS: Once the overweight women were reduced to a normal-weight state, their skeletal muscle energy metabolism and economy was similar to the never overweight control women. In overweight women, oxidative metabolism or mitochondrial function may be limited by blood flow to the muscle following the cessation of exercise.

Effect of weight loss on insulin sensitivity and intramuscular long-chain fatty acyl-CoAs in morbidly obese subjects.

Increases in intramyocellular long-chain fatty acyl-CoAs (LCACoA) have been implicated in the pathogenesis of insulin resistance in skeletal muscle. To test this hypothesis, we measured muscle (vastus lateralis) LCACoA content and insulin action in morbidly obese patients (n = 11) before and after weight loss (gastric bypass surgery). The intervention produced significant weight loss (142.3 +/- 6.8 vs. 79.6 +/- 4.1 kg for before versus after surgery, respectively). Fasting insulin decreased by approximately 84% (23.3 +/- 3.8 vs. 3.8 +/- 0.5 mU/ml), and insulin sensitivity, as determined by minimal model, increased by approximately 360% (1.2 +/- 0.3 vs. 4.1 +/- 0.5 min(-1). [ micro U/kg(-1)]) indicating enhanced insulin action. Muscle palmityl CoA (16:0; 0.54 +/- 0.08 vs. 0.35 +/- 0.04 nmol/g wet wt) concentration decreased by approximately 35% (P < 0.05) with weight loss, whereas stearate CoA (18:0; -17%; 0.65 +/- 0.05 vs. 0.54 +/- 0.03 nmol/g wet wt) and linoleate CoA (18:2; -30%; 2.47 +/- 0.27 vs. 1.66 +/- 0.19 nmol/g wet wt) were also reduced (P < 0.05). There were no statistically significant declines in muscle palmitoleate CoA (16:1), oleate CoA (18:1), or total LCACoA content. These data suggest that a reduction in intramuscular LCACoA content may be responsible, at least in part, for the enhanced insulin action observed with weight loss in obese individuals.

Interest in healthy diet and physical activity interventions peripartum among female partners of active duty military.

Overweight and obesity among soldiers and their dependents have increased over the last decade, mirroring rates in the general population. In general, few programs that result in sustained weight loss have been evaluated, although effective interventions could have clear health and cost benefits for the military. For women, the postpartum period represents a "teachable moment" to promote healthy diet and exercise behaviors related to weight loss, but the attitudes and preferences for weight-loss interventions in this population are unknown. With a view to developing a weight-loss intervention tailored to this population, we surveyed 161 peripartum women at a military base to assess their interests and preferences. Eighty-six percent were dependents. Despite their youth, more than one-third reported entering pregnancy overweight or obese. Interest was high for interventions that promote physical activity and facilitate social interaction. Based on these results, a postpartum exercise intervention is being designed for female partners of active duty soldiers.