Weight References

One of the principles of size acceptance is that weight loss is not always beneficial, that it often leads to weight cycling and disordered eating behaviors, and that weight instability may be more harmful than a higher but more stable weight, especially if the stable weight is accompanied by good fitness.

Here is a quick list of abstracts of various studies related to the chances of long-term weight loss maintenance, the risks of weight loss and weight cycling, and the Health At Every Size® alternative. After each citation is a PubMed ID Number (PMID), which has a link to the study's abstract.

If you run across other studies you think I should add, you can email the abstract (in the body of the email, not as an attachment) to me at kmom AT plus-size-pregnancy dot ORG and I'll review it for addition.


General Weight Loss Overviews

Am Psychol. 2007 Apr;62(3):220-33. Medicare's search for effective obesity treatments: diets are not the answer. Mann T, Tomiyama AJ, Westling E, Lew AM, Samuels B, Chatman J.  PMID: 17469900  Full text at: http://mann.bol.ucla.edu/files/Diets_don%27t_work.pdf
The prevalence of obesity and its associated health problems have increased sharply in the past 2 decades. New revisions to Medicare policy will allow funding for obesity treatments of proven efficacy. The authors review studies of the long-term outcomes of calorie-restricting diets to assess whether dieting is an effective treatment for obesity. These studies show that one third to two thirds of dieters regain more weight than they lost on their diets, and these studies likely underestimate the extent to which dieting is counterproductive because of several methodological problems, all of which bias the studies toward showing successful weight loss maintenance. In addition, the studies do not provide consistent evidence that dieting results in significant health improvements, regardless of weight change. In sum, there is little support for the notion that diets lead to lasting weight loss or health benefits.
Can Fam Physician. 2012 May;58(5):517-23. The downside of weight loss: realistic intervention in body-weight trajectory. Bosomworth NJ.   PMID: 22586192  Free full text at: http://www.cfp.ca/content/58/5/517.long
OBJECTIVE: To explore the reasons why long-term weight loss is seldom achieved and to evaluate the consequences of various weight trajectories, including stability, loss, and gain. QUALITY OF EVIDENCE: Studies evaluating population weight metrics were mainly observational. Level I evidence was available to evaluate the influence of weight interventions on mortality and quality of life. MAIN MESSAGE: Sustained weight loss is achieved by a small percentage of those intending to lose weight. Mortality is lowest in the high-normal and overweight range. The safest body-size trajectory is stable weight with optimization of physical and metabolic fitness. With weight loss there is evidence for lower mortality in those with obesity-related comorbidities. There is also evidence for improved health-related quality of life in obese individuals who lose weight. Weight loss in the healthy obese, however, is associated with increased mortality. CONCLUSION: Weight loss is advisable only for those with obesity-related comorbidities. Healthy obese people wishing to lose weight should be informed that there might be associated risks. A strategy that leads to a stable body mass index with optimized physical and metabolic fitness at any size is the safest weight intervention option.
Nutr J. 2010 Jul 20;9:30. Validity of claims made in weight management research: a narrative review of dietetic articles. Aphramor L. PMID: 20646282  Full text at:  http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2916886/
BACKGROUND: The best available evidence demonstrates that conventional weight management has a high long-term failure rate. The ethical implications of continued reliance on an energy deficit approach to weight management are under-explored. METHODS: A narrative literature review of journal articles in The Journal of Human Nutrition and Dietetics from 2004 to 2008. RESULTS: Although the energy deficit approach to weight management has a high long-term failure rate it continues to dominate research in the field. In the current research agenda, controversies and complexities in the evidence base are inadequately discussed, and claims about the likely success of weight management misrepresent available evidence. CONCLUSIONS: Dietetic literature on weight management fails to meet the standards of evidence based medicine. Research in the field is characterised by speculative claims that fail to accurately represent the available data. There is a corresponding lack of debate on the ethical implications of continuing to promote ineffective treatment regimes and little research into alternative non-weight centred approaches. An alternative health at every size approach is recommended.
Int J Obes (Lond). 2005 Oct;29(10):1153-67. Systematic review of long-term weight loss studies in obese adults: clinical significance and applicability to clinical practice. Douketis JD, Macie C, Thabane L, Williamson DF. PMID: 15997250


BACKGROUND: Obesity is a common health problem that requires a long-term care approach. We systematically reviewed long-term (> or =2 y) studies investigating dietary/lifestyle, pharmacologic, and surgical weight loss methods to assess (1) weight loss efficacy, defined by absolute weight loss and the proportion of subjects with > or =5% weight loss, (2) effects of weight loss on cardiovascular risk factors, and (3) applicability of findings from studies to everyday clinical practice. METHODS: The MEDLINE, HealthSTAR, and the Cochrane Controlled Trials databases were searched for studies investigating the long-term efficacy of weight loss methods in overweight and obese adults. Data were extracted for (i) weight loss after 1 y (pharmacologic studies only), 2 y, 3 y, and 4 y, (ii) proportion of subjects with > or =5% weight loss at the end of follow-up, and (iii) changes (end-of follow-up minus baseline values) in blood lipids, fasting blood glucose, and systolic and diastolic blood pressure. RESULTS: Dietary/lifestyle therapy provides <5 kg weight loss after 2-4 y, pharmacologic therapy provides 5-10 kg weight loss after 1-2 y, and surgical therapy provides 25-75 kg weight loss after 2-4 y. Weight loss of > or =5% baseline weight is not consistently associated with improvements in cardiovascular risk factors and these benefits appear to be intervention specific and occur mainly in people with concomitant cardiovascular risk factors. Weight loss studies have methodologic limitations that restrict the applicability of findings to unselected obese people assessed in everyday clinical practice. These limitations include an inadequate study duration, large proportions of subjects lost to follow-up, a lack of an appropriate usual care group, and a lack of reporting of outcomes in high-risk subgroups. CONCLUSIONS: Dietary/lifestyle and pharmacologic weight loss interventions provide modest weight loss, and may improve markers of cardiovascular risk factors although these benefits occur mainly in patients with cardiovascular risks. Studies investigating weight loss have methodologic limitations that restrict the applicability of findings to obese patients assessed in clinical practice.
Med Sci Sports Exerc. 1999 Aug;31(8):1129-34. How effective are traditional dietary and exercise interventions for weight loss?  Miller WC. PMID: 10449014
Health care professionals have used restrictive dieting and exercise intervention strategies in an effort to combat the rising prevalence of obesity in affluent countries. In spite of these efforts, the prevalence of obesity continues to rise. This apparent ineffectiveness of diet and exercise programming to reduce obesity has caused many health care providers, obesity researchers, and lay persons to challenge the further use of diet and exercise for the sole purpose of reducing body weight in the obese. The purposes of this paper were to examine the history and effectiveness of diet and exercise in obesity therapy and to determine the best future approach for health promotion in the obese population. A brief survey of the most popular dieting techniques used over the past 40 yr shows that most techniques cycle in and out of popularity and that many of these techniques may be hazardous to health. Data from the scientific community indicate that a 15-wk diet or diet plus exercise program produces a weight loss of about 11 kg with a 60-80% maintenance after 1 yr. Although long-term follow-up data are meager, the data that do exist suggest almost complete relapse after 3-5 yr. The paucity of data provided by the weight-loss industry has been inadequate or inconclusive. Those who challenge the use of diet and exercise solely for weight control purposes base their position on the absence of weight-loss effectiveness data and on the presence of harmful effects of restrictive dieting. Any intervention strategy for the obese should be one that would promote the development of a healthy lifestyle. The outcome parameters used to evaluate the success of such an intervention should be specific to chronic disease risk and symptomatologies and not limited to medically ambiguous variables like body weight or body composition.
Ned Tijdschr Geneeskd. 2013;157(29):A6017. [The mediocre results of dieting]. Langeveld M, de Vries JH. PMID: 23859104
Diets involving a reduction in caloric intake are frequently prescribed for the treatment of obesity, but their long-term efficacy is questionable. We considered a calorie restricted diet successful if the weight loss was ≥ 5% after at least 3 years follow up. From published data, calculating a definitive percentage of successful cases is difficult because of the way data are presented and because loss to follow-up is not corrected for in many studies. Judging by the best data available, the success rate is very low. Most individuals will regain weight and sometimes even more than they lost in the first place. The mechanisms driving this weight increase are a decrease in energy expenditure and an increased appetite which is mediated by factors such as leptin. If the first attempt to lose weight fails, the advice to go on a diet should not be endlessly repeated; stabilizing the individual's weight would probably be a more realistic goal.
Clinical Psychology Review. 1991;11(6):729-780. doi: 10.1016/0272-7358(91)90128-H Confronting the failure of behavioral and dietary treatments for obesity. Garner, David M.; Wooley, Susan C.
Questions the appropriateness of behavioral and dietary treatments of obesity in light of overwhelming evidence that they are ineffective in producing lasting weight loss. The stigmatization of obesity, the overstatement of health risks, and the pervasive influence of the lucrative diet industry have maintained public demand for dietary treatment. However, much evidence suggests that maintenance of high but stable weight is safer than weight fluctuation. Alternative nondieting approaches aimed at improving the physical and psychological well-being of the obese individual should be given priority over dietary treatments as a subject of research.
Long-Term Success of Weight Loss

Int J Obes Relat Metab Disord. 2000 Sep;24(9):1107-10. Can anyone successfully control their weight? Findings of a three year community-based study of men and women. Crawford D, Jeffery RW, French SA. PMID: 11033978
This study examined the prevalence, distribution and correlates of successful weight loss and successful weight maintenance over three years in a community-based sample of 854 subjects aged 20-45 at baseline. More than half (53.7%) of the participants in the study gained weight within the first twelve months, only one in four (24.5%) successfully avoided weight gain over three years, and less than one in twenty (4.6%) lost and maintained weight successfully. The findings underscore the importance of current public health efforts to prevent weight gain, and suggest that without much greater efforts to promote and support weight control the prevalence of obesity will continue to rise.
Int J Obes. 1989;13 Suppl 2:39-46. Treatment of obesity by very low calorie diet, behavior therapy, and their combination: a five-year perspective. Wadden TA, Sternberg JA, Letizia KA, Stunkard AJ, Foster GD. PMID: 2613427
Seventy-six obese women with a mean age of 42.1 years and weight of 106.0 kg were randomly assigned to one of three treatments: (a) very low calorie diet alone; (b) behavior therapy alone; or their combination (i.e. combined treatment). Weight losses for the three conditions at the end of treatment were 13.1, 13.0, and 16.8 kg, respectively, with losses for combined treatment significantly greater than those for the two other conditions. Weight losses 1 year after treatment were 4.7, 6.6, and 10.6 kg, respectively. A significantly greater percentage of subjects in the behavior therapy alone (36 percent) and combined treatment conditions (32 percent) maintained their full end-of-treatment weight losses than in the very low calorie diet alone condition (5 percent). Five years after treatment, a majority of subjects in all three conditions had returned to their pretreatment weight, and 55 percent of the total sample had received additional weight reduction therapy. The short and long term effects of treatment are discussed in terms of their implications for practice and research.
Int J Obes. 1989;13(2):123-36. Long-term follow-up of behavioral treatment for obesity: patterns of weight regain among men and women. Kramer FM, Jeffery RW, Forster JL, Snell MK. PMID: 2663745
Maintenance of weight loss continues to be a critical concern in behavioral treatment programs. Problems with the acquisition and/or application of behavioral skills are a likely contributor to relapse. However, biological models, especially the hypothesis of a body weight setpoint, are being offered increasingly as alternative explanations for maintenance failure. Within the context of these sometimes opposing viewpoints the present study describes long-term weight outcomes for 114 men and 38 women assessed annually for 4 or 5 years following completion of a 15 week behavioral weight loss program. Although significant mean weight loss was evident at long-term follow-up, a negatively accelerating pattern of weight regain was the predominant outcome. Less than 3 percent of the subjects were at or below their posttreatment weight on all follow-up visits. Consistent sex differences were found, with women having better weight loss maintenance than men. Implications and potential future directions are discussed.
J Nutr Educ Behav. 2005 Jul-Aug;37(4):203-5. The National Weight Control Registry: a critique. Ikeda J, Amy NK, Ernsberger P, Gaesser GA, Berg FM, Clark CA, Parham ES, Peters P.   PMID: 16029691
This article is a critique of the claim that the National Weight Control Registry provides data showing that a significant number of adults in the United States have achieved permanent weight loss. We believe that promoting calorie-restricted dieting for the purpose of weight loss is misleading and futile. We advocate the adoption of a health-at-every-size (HAES) approach to weight management, focusing on the achievement and maintenance of lifestyle changes that improve metabolic indicators of health.
J Am Diet Assoc. 2005 May;105(5 Suppl 1):S63-6. Weight maintenance: what's missing? Hill JO, Thompson H, Wyatt H.  PMID: 15867898
Obesity has reached epidemic proportions in the United States, but there are few proven strategies for either preventing further weight gain or producing permanent weight loss. Our first priority should be to prevent the gradual weight gain experienced by much of the population. Although this will require less behavior change than producing and maintaining weight loss, helping Americans make and sustain the behavior changes needed to prevent gradual weight increases will be challenging. Because approximately 65% of Americans are already overweight or obese, we must also develop effective strategies to help achieve and maintain an amount of weight loss that improves their health and quality of life. Our real challenge is not in helping people lose weight but in helping them keep it off. Many programs have been shown to produce weight loss but few, if any, have been successful in maintenance of weight loss. Our challenge is in understanding how to help people keep off the weight they can lose in several ways.
Dieting, Weight Cycling and Long-Term Weight Gain

Obes Res. 2004 Feb;12(2):267-74. Weight cycling and the risk of developing type 2 diabetes among adult women in the United States. Field AE, Manson JE, Laird N, Williamson DF, Willett WC, Colditz GA.  PMID: 14981219
OBJECTIVE: To assess the role of weight cycling independent of BMI and weight change in predicting the risk of developing type 2 diabetes. RESEARCH METHODS AND PROCEDURES: A six-year follow-up of 46,634 young and middle-aged women in the Nurses' Health Study II was conducted. Women who had intentionally lost > or = 20 lbs at least three times between 1989 and 1993 were classified as severe weight cyclers. Women who had intentionally lost > or = 10 lbs at least three times were classified as mild weight cyclers. The outcome was physician-diagnosed type 2 diabetes. RESULTS: Between 1989 and 1993, approximately 20% of the women were mild weight cyclers, and 1.6% were severe weight cyclers. BMI in 1993 was positively associated with weight-cycling status (p < 0.001). During 6 years of follow-up (1993 to 1999), 418 incident cases of type 2 diabetes were documented. BMI in 1993 had a strong association with the risk of developing diabetes. Compared with women with a BMI between 17 and 22 kg/m(2), those with a BMI between 25 and 29.9 kg/m(2) were approximately seven times more likely to develop diabetes, and those with a BMI > or = 35 kg/m(2) were 63 times more likely to be diagnosed with type 2 diabetes. After adjustment for BMI, neither mild (relative risk = 1.11, 95% confidence interval, 0.89 to 1.37) nor severe (relative risk = 1.39, 95% confidence interval, 0.90 to 2.13) weight cycling predicted risk of diabetes. DISCUSSION: Weight cycling was strongly associated with BMI, but it was not independently predictive of developing type 2 diabetes.
Int J Obes Relat Metab Disord. 2002 Jul;26(7):969-72. Prevalence and correlates of large weight gains and losses. Jeffery RW, McGuire MT, French SA.  PMID: 12080451  Free full text at: http://www.nature.com/ijo/journal/v26/n7/full/0802015a.html
OBJECTIVE: To examine the prevalence and correlates of large weight gains and losses over a 3 y period in a heterogeneous population of participants in a study of weight gain prevention. DESIGN AND MEASURES: Analyses based on a cohort of 823 participants in a weight gain prevention study whose weight was measured on at least two of four annual examinations. RESULTS: Weight gains and losses of >or=5% body weight over 1 y were observed in 9.3 and 15% of the population, respectively. Weight gains among those initially losing weight were significantly greater (3.9 kg) than among those experiencing stable weight (0.8 kg) or a large weight gain (1.5 kg) over the following 2 y. Cumulative weight changes over 3 y were -2.6, 1.0 and 7.6 kg among large loss, weight stable and large gain groups, respectively. Large weight loss was more common in smokers, large gains were more common in younger people and in those with a more extensive weight loss history, and stable weight was observed more often in individuals with less extensive histories of weight loss. CONCLUSION: The high prevalence of large short-term weight gains and losses in this heterogeneous population, their apparent resistance to short-term reversal, and the strength of their relationship to longer-term weight trends suggest that rapid weight change over relatively short time intervals is a phenomenon that deserves more research attention. Short periods of rapid weight gain may contribute importantly to rapidly rising obesity rates.
J Am Diet Assoc. 2007 Mar;107(3):448-55. Why does dieting predict weight gain in adolescents? Findings from project EAT-II: a 5-year longitudinal study. Neumark-Sztainer D, Wall M, Haines J, Story M, Eisenberg ME.   PMID: 17324664 
OBJECTIVE: Dieting has been found to predict weight gain in adolescents, but reasons for this association remain unclear. This study aimed to explore potential mechanisms by which dieting predicts weight gain over time in adolescents. DESIGN: Population-based, 5-year longitudinal study. PARTICIPANTS: Adolescents (n=2,516) from diverse ethnic and socioeconomic backgrounds who completed Project EAT (Eating Among Teens) surveys in 1999 (Time 1) and 2004 (Time 2). MAIN OUTCOME MEASURE: Body mass index (BMI) change over 5 years. STATISTICAL ANALYSIS: Multiple regressions were used to examine associations between Time 1 dieting and Time 2 binge eating, breakfast consumption, fruit and vegetable intake, and physical activity. Associations were then examined between these behaviors and BMI change. Finally, to test for mediating effects, associations between dieting and BMI change were examined with and without the inclusion of these behaviors, and regression coefficients were compared. RESULTS: In female adolescents, dieting predicted increased binge eating (P<0.001) and decreased breakfast consumption (P=0.030). In male adolescents, dieting predicted increased binge eating (P<0.001), decreased physical activity (P=0.006), and a trend toward decreased breakfast consumption (P=0.064). These behaviors were also associated with increases in BMI. The association between dieting and BMI increase was weakened, but still remained significant, after binge eating, breakfast consumption, fruit/vegetable intake, and physical activity were included in the model being tested. Thus, the longitudinal association between dieting and BMI increase was partially mediated by these behaviors. CONCLUSIONS: In part, dieting may lead to weight gain via the long-term adoption of behavioral patterns that are counterproductive to weight management.
Clin Nutr. 2011 Dec;30(6):718-23. doi: 10.1016/j.clnu.2011.06.009. Epub 2011 Jul 20. Weight cycling is associated with body weight excess and abdominal fat accumulation: a cross-sectional study. Cereda E, Malavazos AE, Caccialanza R, Rondanelli M, Fatati G, Barichella M. PMID: 21764186


BACKGROUND & AIMS: To investigate the association between history of multiple weight loss diets followed by weight regain, namely weight cycling (WCy), and both body weight excess and abdominal fat accumulation. METHODS: A one-day cross-sectional survey ("Obesity-Day") including 914 participants (605F:309M). Anthropometric variables (body mass index [BMI], waist circumference [WC] and waist-to-height ratio [WtHR]), covariates and WCy (≥ 5 intentional weight loss episodes of ≥ 5 kg followed by rapid return to pre-diet or higher body weight) were assessed by a self-administered questionnaire, interview and physical examination. RESULTS: Data on central fat accumulation (by WC and WtHR) were available in a representative sub-group (n = 600). WCy was reported by 119 participants (13.0%) of total population and by 79 (13.2%) of those with available data on central fat accumulation. At multivariable linear regressions WCy was independently associated with higher BMI (P = .004), WC (P = .011) and WtHR (P = .008). Sensitivity analyses, performed after excluding those being on a diet at the time of assessment, confirmed these findings. CONCLUSIONS: A history of WCy appears related to body weight excess and abdominal fat accumulation. These findings support the importance of designing adequate weight loss programs to achieve long-term weight maintenance and to prevent undesirable and unhealthy weight accumulation.
Int J Obes (Lond). 2012 Mar;36(3):456-64. doi: 10.1038/ijo.2011.160. Epub 2011 Aug 9. Does dieting make you fat? A twin study. Pietiläinen KH, Saarni SE, Kaprio J, Rissanen A. PMID: 21829159
OBJECTIVE: To investigate whether the paradoxical weight gain associated with dieting is better related to genetic propensity to weight gain than to the weight loss episodes themselves. SUBJECTS: Subjects included 4129 individual twins from the population-based FinnTwin16 study (90% of twins born in Finland 1975-1979). Weight and height were obtained from longitudinal surveys at 16, 17, 18 and 25 years, and number of lifetime intentional weight loss (IWL) episodes of more than 5 kg at 25 years. RESULTS: IWLs predicted accelerated weight gain and risk of overweight. The odds of becoming overweight (body mass index (BMI)≥ 25 kg m(-2)) by 25 years were significantly greater in subjects with one (OR 1.8, 95% CI 1.3-2.6, and OR 2.7, 1.7-4.3 in males and females, respectively), or two or more (OR 2.0, 1.3-3.3, and OR 5.2, 3.2-8.6, in males and females, respectively), IWLs compared with subjects with no IWL. In MZ pairs discordant for IWL, co-twins with at least one IWL were 0.4 kg m(-2) (P=0.041) heavier at 25 years than their non-dieting co-twins (no differences in baseline BMIs). In DZ pairs, co-twins with IWLs gained progressively more weight than non-dieting co-twins (BMI difference 1.7 kg m(-2) at 16 years and 2.2 kg m(-2) at 25 years, P<0.001). CONCLUSION: Our results suggest that frequent IWLs reflect susceptibility to weight gain, rendering dieters prone to future weight gain. The results from the MZ pairs discordant for IWLs suggest that dieting itself may induce a small subsequent weight gain, independent of genetic factors.
Int J Obes. 1990 Apr;14(4):303-10. Weight cycling and fat distribution. Rodin J, Radke-Sharpe N, Rebuffé-Scrive M, Greenwood MR. PMID: 2361807
Interest in factors that promote a more abdominal fat distribution has arisen because a higher waist-to-hip circumference ratio (WHR) has been linked to several major health risks, such as cardiovascular disease and diabetes. In the present study we asked whether weight variability, produced by repeated cycles of weight gain and loss, influenced fat distribution toward a more abdominal pattern in premenopausal women. It was found that a higher WHR was significantly associated with a higher degree of weight cycling, controlling for age and parity. A significant association between BMI and WHR was found only in those subjects who were weight cyclers. In addition, number of pregnancies was also associated with a higher WHR. These findings suggest that repeated bouts of weight loss and regain may promote abdominal adiposity and consequently, may contribute to long-term health risks.
Weight Cycling and Disease

Am J Epidemiol. 2007 Oct 1;166(7):752-9. Epub 2007 Jul 5. Body size, weight cycling, and risk of renal cell carcinoma among postmenopausal women: the Women's Health Initiative (United States). Luo J, Margolis KL, Adami HO, Lopez AM, Lessin L, Ye W; Women's Health Initiative Investigators. PMID: 17615089  Full text at: http://aje.oxfordjournals.org/content/166/7/752.long


Although obesity is an established risk factor for renal cell carcinoma, the possible effect of central adiposity and long-term variation in weight has yet to be established. The authors studied 140,057 women aged 50-79 years enrolled in the Women's Health Initiative in the United States to examine the role of obesity, especially abdominal obesity, and weight cycling in relation to risk of renal cell carcinoma among postmenopausal women. Cox models were used to estimate relative risks and their corresponding 95% confidence intervals. During an average of 7.7 years of follow-up through September 12, 2005, a total of 269 incident cases of renal cell carcinoma were identified. Central adiposity, as indicated by waist-to-hip ratio, was an important risk factor for developing renal cell carcinoma (highest vs. lowest quartile: relative risk = 1.8, 95% confidence interval: 1.2, 2.5; p for trend = 0.0003). Moreover, women who had experienced weight cycling more than 10 times were at 2.6 times (95% confidence interval: 1.6, 4.2) increased risk compared with women whose weight was stable. Results add evidence that obesity, particularly central adiposity, is associated with an increased risk of renal cell carcinoma among postmenopausal women. Furthermore, they indicate that weight cycling is independently associated with further increased risk of this malignancy.
Eur J Cancer. 2013 Aug;49(12):2717-26. doi: 10.1016/j.ejca.2013.03.015. Epub 2013 Apr 11. Impact of weight change and weight cycling on risk of different subtypes of endometrial cancer. Nagle CM, Marquart L, Bain CJ, O'Brien S, Lahmann PH, Quinn M, Oehler MK, Obermair A, Spurdle AB, Webb PM; Australian National Endometrial Cancer Study Group. PMID: 23583438
AIM: Obesity is an established risk factor for endometrial cancer. Associations tend to be stronger for the endometrioid subtype. The role of adult weight change and weight cycling is uncertain. Our study aimed to determine whether there is an association between different adult weight trajectories, weight cycling and risk of endometrial cancer overall, and by subtype. METHODS: We analysed data from the Australian National Endometrial Cancer study, a population-based case-control study that collected self-reported information on height, weight at three time points (age 20, maximum and 1 year prior to diagnosis [recent]), intentional weight loss/regain (weight cycling) from 1398 women with endometrial cancer and 1538 controls. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using multivariable logistic regression analysis. RESULTS: Relative to women who maintained a stable weight during adulthood, greater weight gain after the age of 20 was associated with increased risk of endometrial cancer (OR for gain 40+kg all subtypes 5.3, 95% CI 3.9-7.3; endometrioid 6.5, 95% CI 4.7-9.0). The strongest associations were observed among women who were continually overweight from the age of 20 (all subtypes OR 3.6, 95% CI 2.6-5.0). Weight cycling was associated with increased risk, particularly among women who had ever been obese (OR 2.9 95% CI 1.8-4.7), with ~3-fold risks seen for both endometrioid and non-endometrioid tumour subtypes. Women who had intentionally lost weight and maintained that weight loss were not at increased risk. CONCLUSION: These results suggest that higher adult weight gain, and perhaps weight cycling, independently increase the risk of endometrial cancer, however women who lost weight and kept that weight off were not at increased risk.
Cancer Causes Control. 2010 Feb;21(2):223-36. doi: 10.1007/s10552-009-9453-5. Epub 2009 Oct 23. Intentional weight loss and risk of lymphohematopoietic cancers. De Roos AJ, Ulrich CM, Ray RM, Mossavar-Rahmani Y, Rosenberg CA, Caan BJ, Thomson CA, McTiernan A, LaCroix AZ. PMID: 19851877
OBJECTIVES: We hypothesized that intentional weight loss may be associated with development of lymphohematopoietic cancers, based on observations of immune suppression following weight loss in short-term studies. METHODS: At the baseline of the Women's Health Initiative Observational Study (1994-1998), participants reported information about intentional weight loss episodes in the past 20 years. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) among 81,219 women for associations between past intentional weight loss and risk of developing non-Hodgkin lymphoma (NHL), leukemia, and multiple myeloma during an average 9.9 years of follow-up. RESULTS: The risk of NHL was associated with having lost a large maximum amount of weight (> or =50 pounds, HR = 1.68, 95% CI 1.13-2.50). NHL risk also varied by the frequency of intentional weight loss; women had increased risk if they lost 50 pounds or more > or =3 times (HR = 1.97, 95% CI 0.93-4.16; p trend by frequency = 0.09) or 20-49 pounds > or =3 times (HR = 1.55, 95% CI 1.00-2.40; p trend = 0.05), but there was no risk associated with smaller amounts of weight loss (10-19 pounds > or =3 times, HR = 0.78, 95% CI 0.46-1.33). These associations persisted with adjustment for body mass index at different ages. We observed non-significant associations of similar magnitude for multiple myeloma, but past intentional weight loss episodes were not associated with leukemia. CONCLUSION: Further assessment of intentional weight loss as a possible risk factor for lymphomas may provide insight into the etiology of these cancers.
Gallbladder Disease

Arch Intern Med. 2006 Nov 27;166(21):2369-74. Weight cycling and risk of gallstone disease in men. Tsai CJ, Leitzmann MF, Willett WC, Giovannucci EL. PMID: 17130391


BACKGROUND: The long-term effect of repeated intentional weight loss and weight regain on the risk of gallstone disease in men is not clear. METHODS: Participants in the Health Professionals Follow-up Study provided information on intentional weight loss during the previous 4 years in 1992. Weight cyclers were men who had intentional weight loss and weight regain. Men free of gallstone disease at baseline were followed from 1992 to 2002. On biennial questionnaires the participants reported newly diagnosed gallstone disease. RESULTS: During 264,760 person-years of follow-up we ascertained 1222 cases of symptomatic gallstones. We examined the effect of weight cycling on the risk of gallstone disease. The multivariate relative risk of weight cyclers, compared with weight maintainers, after adjusting for potential confounding variables, including body mass index, was 1.11 (95% confidence interval [CI], 0.94-1.31) in light cyclers, 1.18 (95% CI, 0.97-1.43) in moderate cyclers, and 1.42 (95% CI, 1.11-1.81) in severe cyclers. We further examined the effect of number of cycling episodes. Among weight cyclers, the relative risk associated with having more than 1 weight cycle, compared with weight maintainers, was 1.10 (95% CI, 0.88-1.37) in light cyclers, 1.28 (95% CI, 1.03-1.59) in moderate cyclers, and 1.51 (95% CI, 1.13-2.02) in severe cyclers. CONCLUSIONS: Our findings suggest that weight cycling, independent of body mass index, may increase the risk of gallstone disease in men. Larger weight fluctuation and more weight cycles are associated with greater risk.
Ann Intern Med. 1999 Mar 16;130(6):471-7. Long-term weight patterns and risk for cholecystectomy in women. Syngal S, Coakley EH, Willett WC, Byers T, Williamson DF, Colditz GA. PMID: 10075614


BACKGROUND: Obesity and rapid weight loss in obese persons are known risk factors for gallstones. However, the effect of intentional, long-term, moderate weight changes on the risk for gallstones is unclear. OBJECTIVE: To study long-term weight patterns in a cohort of women and to examine the relation between weight pattern and risk for cholecystectomy. DESIGN: Prospective cohort study. SETTING: 11 U.S. states. PARTICIPANTS: 47,153 female registered nurses who did not undergo cholecystectomy before 1988. MEASUREMENTS: Cholecystectomy between 1988 and 1994 (ascertained by patient self-report). RESULTS: During the exposure period (1972 to 1988), there was evidence of substantial variation in weight due to intentional weight loss during adulthood. Among cohort patients, 54.9% reported weight cycling with at least one episode of intentional weight loss associated with regain. Of the total cohort, 20.1% were light cyclers (5 to 9 lb of weight loss and gain), 18.8% were moderate cyclers (10 to 19 lb of weight loss and gain), and 16.0% were severe cyclers (> or = 20 lb of weight loss and gain). Net weight gain without cycling occurred in 29.3% of women; net weight loss without cycling was the least common pattern (4.6%). Only 11.1% of the cohort maintained weight within 5 lb over the 16-year period. In the study, 1751 women had undergone cholecystectomy between 1988 and 1994. Compared with weight maintainers, the relative risk for cholecystectomy (adjusted for body mass index, age, alcohol intake, fat intake, and smoking) was 1.20 (95% CI, 0.96 to 1.50) among light cyclers, 1.31 among moderate cyclers (CI, 1.05 to 1.64), and 1.68 among severe cyclers (CI, 1.34 to 2.10). CONCLUSION: Weight cycling was highly prevalent in this large cohort of middle-aged women. The risk for cholecystectomy associated with weight cycling was substantial, independent of attained relative body weight.
Cardiovascular Disease and Associated Risk Factors

J Hum Hypertens. 2005 Jan;19(1):61-7. Associations of short-term weight changes and weight cycling with incidence of essential hypertension in the EPIC-Potsdam Study. Schulz M, Liese AD, Boeing H, Cunningham JE, Moore CG, Kroke A. PMID: 15343355


The aim of this study was to examine the relationships of short-term weight gain, weight loss, and weight cycling on the odds of developing hypertension. Normotensive middle-aged German men and women (n=12,362) of the European Prospective Investigation into Cancer and Nutrition-Potsdam Study were assigned to categories of 2-year short-term weight changes that were self-reported to have occurred prior to recruitment into the study (gain only, loss only, weight cycling, stable). After 2 years of follow-up after recruitment, 180 cases of incident essential hypertension were identified. In logistic regression models, odds ratios were estimated for the associations between short-term weight changes and risk of developing hypertension. Obesity status (BMI>or=30 or BMI<30 kg/m2) modified the associations between short-term weight change and incidence of diagnosed hypertension. Among obese individuals, short-term weight gain occurring during the 2 years prior to recruitment (OR=2.79, 95% CI 1.19-6.56), weight loss (OR=6.74, 95% CI 2.58-17.6) and weight cycling (OR=4.29, 95% CI 1.55-11.9) were strongly positively associated with incident hypertension, adjusted for age and gender, compared to obese individuals with short-term stable weight. No significant associations between short-term weight changes and risk of diagnosed hypertension were detected among non-obese individuals. Short-term weight changes appeared to present strong risk factors for developing hypertension among obese individuals. The effect seen for weight cycling supports the hypothesis that weight cycling increases the risk of hypertension. The finding for short-term weight loss may be explained by subsequent weight regain and needs further investigation.
J Gerontol A Biol Sci Med Sci. 2013 Jun;68(6):691-8. doi: 10.1093/gerona/gls236. Epub 2012 Nov 26. Cardiometabolic risk after weight loss and subsequent weight regain in overweight and obese postmenopausal women. Beavers DP, Beavers KM, Lyles MF, Nicklas BJ. PMID: 23183902
BACKGROUND: Little is known about the effect of intentional weight loss and subsequent weight regain on cardiometabolic risk factors in older adults. The objective of this study was to determine how cardiometabolic risk factors change in the year following significant intentional weight loss in postmenopausal women, and if observed changes were affected by weight and fat regain. METHODS: Eighty, overweight and obese, older women (age = 58.8±5.1 years) were followed through a 5-month weight loss intervention and a subsequent 12-month nonintervention period. Body weight/composition and cardiometabolic risk factors (blood pressure; total, high-density lipoprotein, and low-density lipoprotein cholesterol; triglycerides; fasting glucose and insulin; and Homeostatic Model Assessment of Insulin Resistance) were analyzed at baseline, immediately postintervention, and 6- and 12-months postintervention. RESULTS: Average weight loss during the 5-month intervention was 11.4±4.1kg and 31.4% of lost weight was regained during the 12-month follow-up. On average, all risk factor variables were significantly improved with weight loss but regressed toward baseline values during the year subsequent to weight loss. Increases in total cholesterol, triglycerides, glucose, insulin, and Homeostatic Model Assessment of Insulin Resistance during the postintervention follow-up were significantly (p < .05) associated with weight and fat mass regain. Among women who regained weight, model-adjusted total cholesterol (205.8±4.0 vs 199.7±2.9mg/dL), low-density lipoprotein cholesterol (128.4±3.4 vs 122.7±2.4mg/dL), insulin (12.6±0.7 vs 11.4±0.7mg/dL), and Homeostatic Model Assessment of Insulin Resistance (55.8±3.5 vs 50.9±3.7mg/dL) were higher at follow-up compared with baseline. CONCLUSIONS: For postmenopausal women, even partial weight regain following intentional weight loss is associated with increased cardiometabolic risk. Conversely, maintenance of or continued weight loss is associated with sustained improvement in the cardiometabolic profile.
N Engl J Med. 1991 Jun 27;324(26):1839-44. Variability of body weight and health outcomes in the Framingham population. Lissner L, Odell PM, D'Agostino RB, Stokes J 3rd, Kreger BE, Belanger AJ, Brownell KD. PMID: 2041550  Full text can be found here.
BACKGROUND: Fluctuation in body weight is a common phenomenon, due in part to the high prevalence of dieting. In this study we examined the associations between variability in body weight and health end points in subjects participating in the Framingham Heart Study, which involves follow-up examinations every two years after entry. METHODS: The degree of variability of body weight was expressed as the coefficient of variation of each subject's measured body-mass-index values at the first eight biennial examinations during the study and on their recalled weight at 25 years of age. Using the 32-year follow-up data, we analyzed total mortality, mortality from coronary heart disease, and morbidity due to coronary heart disease and cancer in relation to intraindividual variation in body weight, including only end points that occurred after the 10th biennial examination. We used age-adjusted proportional-hazards regression for the data analysis. RESULTS: Subjects with highly variable body weights had increased total mortality (P = 0.005 for men, P = 0.01 for women), mortality from coronary heart disease (P = 0.009 for men, P = 0.009 for women), and morbidity due to coronary heart disease (P = 0.0009 for men, P = 0.006 for women). Using a multivariate analysis that also controlled for obesity, trends in weight over time, and five indicators of cardiovascular risk, we found that the positive associations between fluctuations in body weight and end points related to mortality and coronary heart disease could not be attributed to these potential confounding factors. The relative risks of these end points in subjects whose weight varied substantially, as compared with those whose weight was relatively stable, ranged from 1.27 to 1.93. CONCLUSIONS: Fluctuations in body weight may have negative health consequences, independent of obesity and the trend of body weight over time.
Int J Obes Relat Metab Disord. 1997 Mar;21(3):217-23. Weight variability and incident disease in older women: the Iowa Women's Health Study. French SA, Folsom AR, Jeffery RW, Zheng W, Mink PJ, Baxter JE. PMID: 9080261
OBJECTIVE: To evaluate the association between weight variability and disease incidence in women. DESIGN: Prospective cohort study, following women from 1986 through 1992. METHODS: A population-based sample of 33834 women aged 55-69 y, free of cancer and heart disease, completed a mail-based survey that included self-reported body weights at ages 18, 30, 40, 50 y, and currently. Weight variability was defined as (1) the root mean square error around the slope of weighton age (RMSE); and (2) categorical measures of weight change. Outcome measures were incidence of myocardial infarction (MI); stroke; diabetes; breast, endometrial, lung, or other cancer; total and hip fractures. RESULTS: Adjusted relative risks of MI, stroke, diabetes, and hip fracture increased with increasing weight variability. The age and body mass index-adjusted relative risks (RR) for highest vs lowest quartile of RMSE were: MI: 2.03; stroke: 1.61; diabetes: 1.42; breast cancer: 0.85; endometrial cancer: 0.88; lung cancer: 1.70; other cancer: 0.93; total fractures: 1.15; hip fractures: 1.45. The strongest associations between weight change categories and disease were for diabetes (RR compared to small gain/stable weight: large cycle, 1.72; small cycle, 1.55; large gain, 1.80; weight loss, 1.91; other pattern, 1.55). Large weight cycles were associated with higher risk of MI (RR = 1.89) and stroke (RR = 1.71). CONCLUSIONS: These findings are consistent with previous studies and suggest that weight variability is associated with higher risk of developing chronic diseases.

Neurology. 2013 Apr 30;80(18):1677-83. doi: 10.1212/WNL.0b013e3182904cee. Epub 2013 Apr 10.
Body weight variability in midlife and risk for dementia in old age. Ravona-Springer R, Schnaider-Beeri M, Goldbourt U. PMID: 23576627
OBJECTIVE: To analyze the relationship between body weight variability and dementia more than 3 decades later. METHODS: The measurement of body weight variability was based on 3 successive weight recordings taken from over 10,000 apparently healthy tenured working men participating in the Israel Ischemic Heart Disease study, in which cardiovascular risk factors and clinical status were assessed in 1963, 1965, and 1968, when subjects were 40-70 years of age. Groups of men were stratified according to quartiles of SD of weight change among 3 measurements (1963/1965/1968): ≤ 1.15 kg, 1.16-1.73 kg, 1.74-2.65 kg, and ≥ 2.66 kg. The prevalence of dementia was assessed more than 36 years later in approximately one-sixth of them who survived until 1999/2000 (minimum age 76 years) and underwent cognitive evaluation (n = 1,620). RESULTS: Survivors' dementia prevalence rates were 13.4%, 18.4%, 20.1%, and 19.2% in the first to fourth quartiles of weight change SD, respectively (p for trend = 0.034). Compared to the first quartile of weight change SD and adjusted for diabetes mellitus, body height, and socioeconomic status, a multivariate analysis demonstrated that the odds ratio for dementia was 1.42 (95% confidence interval [CI] 0.95-2.13), 1.59 (95% CI 1.05-2.37), and 1.74 (95% CI 1.14-2.64) in quartiles 2-4 of weight change SD respectively. This relationship was independent of the direction of weight changes. CONCLUSION: Midlife variations in weight may antecede late-life dementia.
Weight Loss and Mortality
*It should be noted that it is difficult to determine the relationship between weight loss and mortality because of the difficulty in disentangling the effects of intentional weight loss from that due to disease. Some studies indicate weight loss is beneficial to longevity, the following studies suggest it is harmful, and other studies are equivocal. Thus, the relationship between intentional weight loss and mortality has yet to be clearly defined.
J Intern Med. 2002 Jul;252(1):70-8. The enigma of increased non-cancer mortality after weight loss in healthy men who are overweight or obese. Nilsson PM, Nilsson JA, Hedblad B, Berglund G, Lindgärde F.   PMID: 12074741
OBJECTIVE: To study effects on non-cancer mortality of observational weight loss in middle-aged men stratified for body mass index (BMI), taking a wide range of possible confounders into account. DESIGN: Prospective, population based study. SETTING: Male population of Malmö, Sweden. PARTICIPANTS: In all 5722 men were screened twice with a mean time interval of 6 years in Malmö, southern Sweden. They were classified according to BMI category at baseline (<21, 22-25, overweight: 26-30, and obesity: 30+ kg m(-2)) and weight change category until second screening (weight stable men defined as having a baseline BMI +/- 0.1 kg m(-2) year-1 at follow-up re-screening). MAIN OUTCOME MEASURES: Non-cancer mortality calculated from national registers during 16 years of follow-up after the second screening. Data from the first year of follow-up were excluded to avoid bias by mortality caused by subclinical disease at re-screening. RESULTS: The relative risk (RR; 95% CI) for non-cancer mortality during follow-up was higher in men with decreasing BMI in all subgroups: RR 2.64 (1.46-4.71, baseline BMI <21 kg m(-2)), 1.39 (0.98-1.95, baseline BMI 22-25 kg m(-2)), and 1.71 (1.18-2.47, baseline BMI 26+ kg m(-2)), using BMI-stable men as reference group. Correspondingly, the non-cancer mortality was also higher in men with increasing BMI, but only in the obese group (baseline BMI 26+ kg m(-2)) with RR 1.86 (1.31-2.65). In a subanalysis, nonsmoking obese (30+ kg m(-2)) men with decreased BMI had an increased non-cancer mortality compared with BMI-stable obese men (Fischer's test: P=0.001). The mortality risk for nonsmoking overweight men who increased their BMI compared with BMI-stable men was also significant (P=0.006), but not in corresponding obese men (P=0.094). CONCLUSIONS. Weight loss in self-reported healthy but overweight middle-aged men, without serious disease, is associated with an increased non-cancer mortality, which seems even more pronounced in obese, nonsmoking men, as compared with corresponding but weight-stable men. The explanation for these observational findings is still enigmatic but could hypothetically be because of premature ageing effects causing so-called weight loss of involution.
Int J Obes (Lond). 2010 Apr;34(4):760-9. doi: 10.1038/ijo.2009.274. Epub 2010 Jan 12. Combined effects of weight loss and physical activity on all-cause mortality of overweight men and women. Østergaard JN, Grønbaek M, Schnohr P, Sørensen TI, Heitmann BL. PMID: 20065967
OBJECTIVE: To estimate the excess deaths associated with weight loss in combination with leisure time physical activity among overweight or obese people. DESIGN: Prospective cohort study. SUBJECTS: In two consecutive examinations in 1976-1978 and 1981-1983, 11 135 people participated in the Copenhagen City Heart Study. Of these, 3078 overweight or obese participants lost weight or remained weight stable from 1976-1978 to 1981-1983, and were without pre-existing diagnosis of diabetes, stroke, ischaemic heart disease or cancer in 1981-1983. They were followed up until 2007 in the Danish Civil Registration System, with a <0.2% loss to follow-up only. MEASUREMENTS: The following measurements were taken: body mass index (BMI) and physical activity in 1976-1978 and 1981-1983 and hazard ratio (HR) of mortality during 53 976 person-years of follow-up. RESULTS: Of the initially overweight or obese subjects who either lost weight or remained weight stable, 2060 died. Overall, weight loss was associated with excess mortality when compared with weight stability. Weight loss was associated with a higher mortality among those who became physically inactive, compared with those who remained active while losing weight (men: HR 2.25, 95% confidence interval 1.31-3.84; women: 1.43, 1.07-1.91). However, losing weight while remaining physically active was still associated with excess mortality when compared with those who were weight stable and initially active (men: 1.72, 1.27-2.34; women: 1.57, 1.06-2.31). Among those who remained physically inactive, weight loss seemed associated with excess mortality when compared with weight loss among those who became active, although not statistically significant (men: 2.00, 0.94-4.29; women: 1.40, 0.82-2.39). Finally, weight loss among those who became physically active was not associated with excess mortality when compared with those who were weight stable and initially inactive (men: 1.12, 0.61-2.07; women: 1.19, 0.58-2.43). CONCLUSION: Weight loss among the overweight or obese seemed hazardous to survival. However, weight loss seemed less hazardous to survival among those who remained physically active or those who became active.
Nutr Res Rev. 2009 Jun;22(1):93-108. doi: 10.1017/S0954422409990035. A review and meta-analysis of the effect of weight loss on all-cause mortality risk. Harrington M, Gibson S, Cottrell RC. PMID: 19555520


Overweight and obesity are associated with increased morbidity and mortality, although the range of body weights that is optimal for health is controversial. It is less clear whether weight loss benefits longevity and hence whether weight reduction is justified as a prime goal for all individuals who are overweight (normally defined as BMI>25 kg/m2). The purpose of the present review was to examine the evidence base for recommending weight loss by diet and lifestyle change as a means of prolonging life. An electronic search identified twenty-six eligible prospective studies that monitored subsequent mortality risk following weight loss by lifestyle change, published up to 2008. Data were extracted and further analysed by meta-analysis, giving particular attention to the influence of confounders. Moderator variables such as reason for weight loss (intentional, unintentional), baseline health status (healthy, unhealthy), baseline BMI (normal, overweight, obese), method used to estimate weight loss (measured weight loss, reported weight loss) and whether models adjusted for physical activity (adjusted data, unadjusted data) were used to classify subgroups for separate analysis. Intentional weight loss per se had a neutral effect on all-cause mortality (relative risk (RR) 1.01; P = 0.89), while weight loss which was unintentional or ill-defined was associated with excess risk of 22 to 39 %. Intentional weight loss had a small benefit for individuals classified as unhealthy (with obesity-related risk factors) (RR 0.87 (95 % CI 0.77, 0.99); P = 0.028), especially unhealthy obese (RR 0.84 (95 % CI 0.73, 0.97); P = 0.018), but appeared to be associated with slightly increased mortality for healthy individuals (RR 1.11 (95 % CI 1.00, 1.22); P = 0.05), and for those who were overweight but not obese (RR 1.09 (95 % CI 1.02, 1.17); P = 0.008). There was no evidence for weight loss conferring either benefit or risk among healthy obese. In conclusion, the available evidence does not support solely advising overweight or obese individuals who are otherwise healthy to lose weight as a means of prolonging life. Other aspects of a healthy lifestyle, especially exercise and dietary quality, should be considered. However, well-designed intervention studies are needed clearly to disentangle the influence of physical activity, diet strategy and body composition, in order to define appropriate advice to those populations that might be expected to benefit.
Int J Cardiol. 2012 Dec 15;162(1):20-6. doi: 10.1016/j.ijcard.2011.09.039. Epub 2011 Oct 29. Inverse relation of body weight and weight change with mortality and morbidity in patients with type 2 diabetes and cardiovascular co-morbidity: An analysis of the PROactive study population. Doehner W, Erdmann E, Cairns R, Clark AL, Dormandy JA, Ferrannini E, Anker SD. PMID: 22037349
CONTEXT: Although weight reduction is a recommended goal in type 2 diabetes mellitus (T2DM), weight loss is linked to impaired survival in patients with some chronic cardiovascular diseases. OBJECTIVE: To assess the association of weight and weight change with mortality and non-fatal cardiovascular outcomes (hospitalisation, myocardial infarction and stroke) in T2DM patients with cardiovascular co-morbidity and the effect of pioglitazone-induced weight change on mortality. SETTING AND PARTICIPANTS: We assessed in a post hoc analysis body weight and weight change in relation to outcome in 5202 patients from the PROactive trial population who had T2DM and evidence of pre-existing cardiovascular disease. Patients were randomized to treatment with pioglitazone or placebo in addition to their concomitant glucose-lowering and cardiovascular medication. Mean follow up was 34.5 months. MAIN OUTCOME MEASURE: The impact of body weight and body weight change on all-cause mortality, cardiovascular mortality, on non-fatal cardiovascular events and on hospitalisation. RESULTS: The lowest mortality was seen in patients with BMI 30-35kg/m(2) at baseline. In comparison to this (reference group), patients in the placebo group with BMI <22kg/m(2) (Hazard Ratio (95% confidence intervals) 2.96 [1.27 to 6.86]; P=0.012) and BMI 22 to 25kg/m(2) (HR 1.88 [1.11 to 3.21]; P=0.019) had a higher all-cause mortality. Weight loss was associated with increased total mortality (HR per 1% body weight: 1.13 [1.11 to 1.16]; P<0.0001), with increased cardiovascular mortality, all-cause hospitalisation and the composite of death, myocardial infarction and stroke.Weight loss of ≥7.5% body weight (seen in 18.3% of patients) was the strongest cut-point to predict impaired survival (multivariable adjusted HR 4.42 [3.30 to 5.94]. Weight gain was not associated with increased mortality. Weight gain in patients treated with pioglitazone (mean+4.0±6.1kg) predicted a better prognosis (HR per 1% weight gain: 0.96 [0.92 to 1.00] P=0.037) compared to patients without weight gain. CONCLUSION: Among patients with T2DM and cardiovascular co-morbidity, overweight and obese patients had a lower mortality compared to patients with normal weight. Weight loss but not weight gain was associated with increased mortality and morbidity. There may be an "obesity paradox" in patients with type 2 diabetes and cardiovascular risk. 
Am J Med. 2011 Oct;124(10):924-30. doi: 10.1016/j.amjmed.2011.04.018. Epub 2011 Jul 26. The obesity paradox and weight loss. Myers J, Lata K, Chowdhury S, McAuley P, Jain N, Froelicher V. PMID: 21798508


BACKGROUND: An "obesity paradox," in which overweight and obese individuals with established cardiovascular disease have a better prognosis than normal weight subjects, has been reported in a number of clinical cohorts, but little is known about the effects of weight loss on the obesity paradox and its association with health outcomes. METHODS: Weight was determined in 3834 men at the time of a clinically referred exercise test and again during a clinical evaluation a mean of 7 years later. The associations among weight changes, baseline fitness, and other risk markers with cardiovascular and all-cause mortality were determined by Cox proportional hazards analysis. RESULTS: During the follow-up period, 314 subjects died (72 of cardiovascular causes). In a multivariate analysis (including baseline weight, weight change, exercise capacity, and cardiovascular disease), weight gain was associated with lower mortality and weight loss was associated with higher mortality (4% higher per pound lost per year, P<.001) compared with stable weight. For all-cause mortality, the relative risks for the no change, weight gain, and weight loss groups were 1.0 (referent), 0.64 (95% confidence interval, 0.50-0.83), and 1.49 (95% confidence interval, 1.17-1.89), respectively (P<.001). Those who died and exhibited weight loss had a significantly higher prevalence of deaths due to cancer and cardiovascular causes. CONCLUSION: Weight loss was related to higher mortality and weight gain was related to lower mortality when compared with stable weight. The obesity paradox in our sample is explained in part by a combination of non-volitional weight loss related to occult disease and a protective effect of weight gain.
Int J Obes (Lond). 2010 Jun;34(6):1044-50. doi: 10.1038/ijo.2010.41. Epub 2010 Mar 9. Weight loss from maximum body weight and mortality: the Third National Health and Nutrition Examination Survey Linked Mortality File. Ingram DD, Mussolino ME. PMID: 20212495  Source: Office of Analysis and Epidemiology, Centers for Disease Control and Prevention, National Center for Health Statistics, Hyattsville, MD 20782, USA.
OBJECTIVE: The aim of this longitudinal study is to examine the relationship between weight loss from maximum body weight, body mass index (BMI), and mortality in a nationally representative sample of men and women. DESIGN: Longitudinal cohort study. SUBJECTS: In all, 6117 whites, blacks, and Mexican-Americans 50 years and over at baseline who survived at least 3 years of follow-up, from the Third National Health and Nutrition Examination Survey Linked Mortality Files (1988-1994 with passive mortality follow-up through 2000), were included. MEASUREMENTS: Measured body weight and self-reported maximum body weight obtained at baseline. Weight loss (maximum body weight minus baseline weight) was categorized as <5%, 5-<15%, and >or=15%. Maximum BMI (reported maximum weight (kg)/measured baseline height (m)(2)) was categorized as healthy weight (18.5-24.9), overweight (25.0-29.9), and obese (>or=30.0). RESULTS: In all, 1602 deaths were identified. After adjusting for age, race, smoking, health status, and preexisting illness, overweight men with weight loss of 15% or more, overweight women with weight loss of 5-<15%, and women in all BMI categories with weight loss of 15% or more were at increased risk of death from all causes compared with those in the same BMI category who lost <5%; hazard ratios ranged from 1.46 to 2.70. Weight loss of 5-<15% reduced risk of death from cardiovascular diseases among obese men. CONCLUSIONS: Weight loss of 15% or more from maximum body weight is associated with increased risk of death from all causes among overweight men and among women regardless of maximum BMI.
Gend Med. 2009 Dec;6(4):575-86. doi: 10.1016/j.genm.2009.12.003. Weight loss and mortality: a gender-specific analysis of the Tromsø study. Wilsgaard T, Jacobsen BK, Mathiesen EB, Njølstad I. PMID: 20114008


BACKGROUND: Weight loss has been associated with increased mortality, but findings have been inconsistent. OBJECTIVE: The aim of this study was to examine the association between weight loss and mortality, with a focus on gender differences. METHODS: This was a population-based cohort study in northern Norway of adults, aged 20 to 54 years in 1979, who participated in 2 or 3 consecutive health surveys in 1979-80, 1986-87, and 1994-95. Weight and height were measured at each survey. The Cox proportional hazards regression model was used to estimate hazard ratios for mortality between levels of body mass index (BMI) change during 11 years of follow-up. Participants with prior cardiovascular disease or cancer, or incident cancer within the first 2 years of follow-up, were excluded, as were participants who were pregnant, had missing data, or did not give written consent. RESULTS: A total of 4881 men and 5051 women participated in the present study. The mean age at start of follow-up was 50.8 years (range, 35-70 years) in men and 49.2 years (range, 35-65 years) in women. In men, weight loss was associated with increased all-cause, cardiovascular, and noncardiovascular mortality. The hazard ratio for men for all-cause mortality with a 10-year BMI decrease of 2 kg/m(2) versus a BMI increase of 1 kg/m(2) was 2.09 (95% CI, 1.56-2.81). The association was not significantly modified by initial BMI, age, smoking status, or self-reported attempts of weight loss, or by exclusion of subjects with self-reported poor health, diabetes mellitus, high blood pressure, or high alcohol intake. In women, no association between BMI change and mortality was observed. However, in the subgroup of women who reported no weight-loss attempts, BMI change was significantly associated with mortality risk (P = 0.022). CONCLUSIONS: In this study of a Norwegian population, weight loss was associated with excess mortality in men in all subgroups of weight-loss attempts, daily smoking, and overweight. In women, the only significant effect of BMI change on mortality was observed in those who reported no weight-loss attempts. The observed findings could not be explained by preexisting disease.
Nutr Rev. 2008 Jul;66(7):375-86. doi: 10.1111/j.1753-4887.2008.00047.x.  Intentional weight loss and mortality among initially healthy men and women. Simonsen MK, Hundrup YA, Obel EB, Grønbaek M, Heitmann BL. PMID: 18667013
Most prospective observational studies suggest that weight loss increases the risk of premature death among obese individuals. This is surprising because clinical studies show that weight loss generally leads to overall improvements in cardiovascular risk factors. It is sometimes argued that the increased mortality observed with weight loss must depend on confounding or poor study designs. This review was conducted to summarize results from studies on intentional weight loss and mortality among healthy individuals, while carefully considering the designs and problems in these studies. Evaluation criteria with a rating scale were developed. Of the studies evaluated, two found decreased mortality with intentional weight loss, three found increased mortality, and four found no significant associations between intentional weight loss and total mortality. Thus, it is still not possible for health authorities to make secure recommendations on intentional weight loss. More studies designed to specifically address this issue are warranted.
Weight Cycling and Mortality
*Again, it should be noted that it is difficult to tease out the relationship between weight loss, weight cycling and mortality. It's hard to disentangle the consequences of intentional weight loss vs. disease-related weight loss, and some researchers use disingenuous statistical sleights of hand to blunt the potential impact of weight cycling. Thus, the relationship between weight cycling and mortality has yet to be clearly delineated too.
Eur J Epidemiol. 2007;22(10):665-73. Epub 2007 Aug 4. Weight change, weight cycling and mortality in the ERFORT Male Cohort Study. Rzehak P, Meisinger C, Woelke G, Brasche S, Strube G, Heinrich J. PMID: 17676383
OBJECTIVE: To investigate the effect of weight change and weight fluctuations on all-cause-mortality in men. METHODS: Within a prospective population-based cohort of 1,160 men aged 40-59 years at recruitment, complete weight change patterns from baseline and three follow-up examinations during a period of 15 years of follow-up was used to categorize the 505 men into stable obese, stable non-obese, weight gain, weight loss and weight fluctuation groups. For these men (age range: 55-74 years at start time of survival analysis) further survival was analyzed during the subsequent 15 years. RESULTS: Overall, 183 deaths were observed among the 505 men. Only weight fluctuations had a clear significant impact on all-cause mortality. Adjusted hazard rate ratio (HRR (95%-CI)) was 1.86 (1.31-2.66) after adjustment for age group, pre-existing cardiovascular disease or diabetes mellitus, smoking and socio-economic status. The risk rate due to weight loss was borderline significant (HRR = 1.81 (0.99-3.31)). Risk of death due to weight gain (HRR = 1.15 (0.70-1.88)) or stable obesity (HRR = 1.16 (0.69-1.94)), however, were not significantly increased compared to men staying non-obese for the first 15 years after cohort recruitment. CONCLUSION: Weight fluctuations are a major risk factor for all-cause mortality in middle aged men. Moreover, stable obesity does not increase further mortality in men aged 55-74 years in long-term follow-up.
Int J Obes Relat Metab Disord. 1996 Aug;20(8):704-9. Weight variability and mortality: the Iowa Women's Health Study. Folsom AR, French SA, Zheng W, Baxter JE, Jeffery RW. PMID: 8856391
OBJECTIVE: To evaluate the association between weight variability and risk of mortality in women. DESIGN: Prospective cohort study, 1986-1991. SUBJECTS: Participants were a population-based sample of 33,760 Iowa women aged 55-69 y, free of cancer and heart disease, who completed a mailed questionnaire including self-reported weight at ages 18, 30, 40, 50 y, and currently. Weight variability was defined by (1) a measure of deviation from the linear regression of each woman's five weights on age (the root mean squared error, RMSE) and (2) categories of weight gain or loss. MEASUREMENTS: All-cause (n = 1068) and cause-specific mortality. RESULTS: After adjustment for age and the regression slope of weight on age, women who displayed higher weight variability (RMSE) over their adult years had an increased subsequent 6-y mortality. The relative risks of death for increasing quartiles of RMSE were 1.00 (referent), 1.17, 1.45 and 1.82 (ptrend < 0.001). Positive linear trends were seen across quartiles of RMSE for cardiovascular disease, cancer, and for non-cancer/non-cardiovascular deaths. These associations were attenuated increasingly with (1) statistical adjustment for body mass index, waist-to-hip ratio, smoking, education level, physical activity, alcohol intake, marital status and hormone replacement therapy; (2) further adjustment for diabetes and hypertension; and (3) exclusion of women in poor or fair health in 1986. Even so, with all adjustments, relative risks of coronary heart disease mortality for increasing quartiles of RMSE were 1.00 (referent), 1.22, 1.63 and 1.67 (ptrend = 0.049). Using the categorical approach, age-adjusted risks of death were highest in women who had a largeweight loss (> 10%) or a large cycle of weight change (> or = 10% loss-gain or gain-loss), compared with women who had a stable weight (within 5%). Adjustment for covariates attenuated these relative risks. CONCLUSIONS: Women who displayed greater weight variability in adulthood had an increased risk of dying in later life, especially from coronary heart disease. However, to a considerable degree this association seems to be due to other unhealthy characteristics and pre-existing disease among those displaying increased weight variability.
Int J Obes Relat Metab Disord. 1995 Dec;19(12):862-8. Changes in body weight in relation to mortality in 6441 European middle-aged men: the Seven Countries Study. Peters ET, Seidell JC, Menotti A, Arayanis C, Dontas A, Fidanza F, Karvonen M, Nedeljkovic S, Nissinen A, Buzina R, et al. PMID: 8963353
OBJECTIVES: To study the relation between changes in body weight and subsequent mortality. DESIGN: Prospective follow-up study. SETTING: Population study. SUBJECTS: 6441 men aged 40-59 y at baseline participating in the European cohorts of the Seven Countries Study. The men were divided into groups depending on their weight pattern ascertained from three weight measurements with intervals of 5 years. They were also divided in quartiles according to the degree of weight variability. MAIN OUTCOME MEASURES: All-cause and cause-specific mortality during 15 years following the last weight measurement. Deaths occurring during the first 5 years of follow-up were excluded. RESULTS: Significantly elevated hazard ratios (RR) for death from all causes (RR = 1.3; 95% confidence interval (CI): 1.2-1.5), all cardiovascular diseases (RR = 1.2; 95% CI: 1.0-1.5) and other causes (RR = 1.6; 95% CI: 1.2-2.2) were found for men with a decreasing weight compared with men with a constant weight. A fluctuating weight was associated with an increased risk of all cause mortality (RR = 1.2; 95% CI: 1.0-1.4), coronary heart disease (RR = 1.5; 95% CI: 1.0-1.9) and myocardial infarction (RR = 1.5; 95% CI: 1.0-2.2). The group of men with an increasing body weight also had elevated hazard ratios for dying from coronary heart disease and myocardial infarction, but these were only significant when the total 15-year follow-up was analyzed. The risks of dying from all-causes, cardiovascular disease, cancer and other causes were increased in the upper quartile versus the lower quartile of weight variability. CONCLUSIONS: The results of the present study show that a decreasing and a fluctuating body weight are associated with increased mortality. An average increase of 7 kg body weight was associated with an elevated risk of dying from coronary heart disease and myocardial infarction. Lowest mortality in these middle-aged men was found in those who maintained a constant body weight.
Negative Psychological Consequences of Dieting

J Am Diet Assoc. 1996 Jun;96(6):589-92; quiz 593-4. Psychological consequences of food restriction. Polivy J.   PMID: 8655907
A review of the literature and research on food restriction indicates that inhibiting food intake has consequences that may not have been anticipated by those attempting such restriction. Starvation and self-imposed dieting appear to result in eating binges once food is available and in psychological manifestations such as preoccupation with food and eating, increased emotional responsiveness and dysphoria, and distractibility. Caution is thus advisable in counseling clients to restrict their eating and diet to lose weight, as the negative sequelae may outweigh the benefits of restraining one's eating. Instead, healthful, balanced eating without specific food restrictions should be recommended as a long-term strategy to avoid the perils of restrictive dieting.
J Am Diet Assoc. 2004;104:1589-1592. Body Image of Chronic Dieters: Lowered Appearance Evaluation and Body Satisfaction. Gingras J, Fitzpatrick J, McCargar L. Full text at: http://www.ryerson.ca/~jgingras/pdf/body_image_chronic_dieters.pdf
This study was conducted to determine the body image of a group of female chronic dieters. Participants were asked to complete a body image questionnaire, and their results were compared with age- and sex-matched reference norms. Chronic dieters possessed significantly lower appearance evaluation, lower body satisfaction, and higher self-classified vs actual body weight compared with reference norms. Body image dissatisfaction may prevent individuals from incorporating beneficial lifestyle behaviors, and thus it is important to address body image dissatisfaction with chronic dieters for the best chance at improving health, regardless of body size.
Obes Surg. 2007 Mar;17(3):391-9. Psychological distress in morbid obesity in relation to weight history. Petroni ML, Villanova N, Avagnina S, Fusco MA, Fatati G, Compare A, Marchesini G; QUOVADIS Study Group. PMID: 17546849
BACKGROUND: Very few data are available on psychological distress in morbidly obese subjects in relation to the history of their weight. In subjects with childhood obesity, psychological distress might be better than in adult-onset obesity, because of progressive adaptation to the social stigma. METHODS: Psychological distress was tested in relation to BMI at age 20 years (BMI-20), weight history and somatic co-morbidities in 632 treatment-seeking, morbidly obese participants from the QUOVADIS cohort (130 men, 502 women; mean age 45.5 years). The number of dieting attempts/year, BMI increase and cumulative BMI loss since age 20 were calculated as weight cycling parameters. The Symptom Check List-90 (SCL-90), the Psychological General Well-Being (PGWB), the Binge-Eating Scale, and the ORWELL-97 questionnaire were used to score psychometry and health-related quality of life (HRQL). Complications were quantitatively assessed by a modified Charlson's score. RESULTS: BMI-20 was normal in 35% of cases and >35 kg/m2 in only 14%. Psychometric scores were not different in relation to BMI-20, when corrected for age, with the exception of the General Health scale of PGWB, showing a greater distress in subjects with normal BMI-20. In most cases, the prevalence of pathological results of questionnaires showed a J-shaped curve, with participants with normal BMI-20 or those with Class II-III obesity in early adulthood having the highest prevalence of psychological/psychiatric distress and poor HRQL. Weight cycling was a risk factor for binge-eating, depression and interpersonal sensitivity in SCL-90, whereas somatic co-morbidities adversely affected most SCL-90 and all PGWB scales. CONCLUSION: Weight cycling and somatic co-morbidities, but not age of onset of obesity, are the main factors negatively influencing psychological health in treatment-seeking, morbidly obese subjects.
Negative Effects of Fat Shaming Public Health Campaigns

Int J Obes (Lond). 2013 Jun;37(6):774-82. doi: 10.1038/ijo.2012.156. Epub 2012 Sep 11.
Fighting obesity or obese persons? Public perceptions of obesity-related health messages.
Puhl R, Peterson JL, Luedicke J.  PMID: 22964792
OBJECTIVE: This study examined public perceptions of obesity-related public health media campaigns with specific emphasis on the extent to which campaign messages are perceived to be motivating or stigmatizing. METHOD: In summer 2011, data were collected online from a nationally representative sample of 1014 adults. Participants viewed a random selection of 10 (from a total of 30) messages from major obesity public health campaigns from the United States, the United Kingdom and Australia, and rated each campaign message according to positive and negative descriptors, including whether it was stigmatizing or motivating. Participants also reported their familiarity with each message and their intentions to comply with the message content. RESULTS: Participants responded most favorably to messages involving themes of increased fruit and vegetable consumption, and general messages involving multiple health behaviors. Messages that have been publicly criticized for their stigmatizing content received the most negative ratings and the lowest intentions to comply with message content. Furthermore, messages that were perceived to be most positive and motivating made no mention of the word 'obesity' at all, and instead focused on making healthy behavioral changes without reference to body weight. CONCLUSION: These findings have important implications for framing messages in public health campaigns to address obesity, and suggest that certain types of messages may lead to increased motivation for behavior change among the public, whereas others may be perceived as stigmatizing and instill less motivation to improve health.
J Bioeth Inq. 2013 Mar;10(1):49-57. doi: 10.1007/s11673-012-9412-9. Epub 2013 Jan 4. Primum non nocere: obesity stigma and public health. Vartanian LR, Smyth JM. PMID: 23288439
Several recent anti-obesity campaigns appear to embrace stigmatization of obese individuals as a public health strategy. These approaches seem to be based on the fundamental assumptions that (1) obesity is largely under an individual's control and (2) stigmatizing obese individuals will motivate them to change their behavior and will also result in successful behavior change. The empirical evidence does not support these assumptions: Although body weight is, to some degree, under individuals' personal control, there are a range of biopsychosocial barriers that make weight regulation difficult. Furthermore, there is accumulating evidence that stigmatizing obese individuals decreases their motivation to diet, exercise, and lose weight. Public health campaigns should focus on facilitating behavioral change, rather than stigmatizing obese people, and should be grounded in the available empirical evidence. Fundamentally, these campaigns should, first, do no harm.
Am J Prev Med. 2013 Jul;45(1):36-48. doi: 10.1016/j.amepre.2013.02.010. Public reactions to obesity-related health campaigns: a randomized controlled trial. Puhl R, Luedicke J, Lee Peterson J. PMID: 23790987
BACKGROUND: Despite numerous obesity-related health campaigns throughout the U.S., public perceptions of these campaigns have not been formally assessed. In addition, several recent publicized campaigns have come under criticism in the popular media for reinforcing stigmatization of obese people. Thus, research in this area is warranted...The data were collected online in summer 2012 from a nationally representative sample of American adults (N=1085). INTERVENTION: Participants were randomly assigned to view 10 obesity-related health campaigns that were pretested and publicly criticized as being stigmatizing of obese people, or 10 campaigns that contained more-neutral content...RESULTS: Stigmatizing campaigns were no more likely to instill motivation for improving lifestyle behaviors among participants than campaigns that were more neutral (OR=1.095, 95% CI=0.736, 1.630). Stigmatizing campaigns were also rated as inducing less self-efficacy (adjusted mean difference = -0.171 SD, 95% CI= -0.266, -0.076) and having less-appropriate visual content compared to less stigmatizing campaigns (adjusted difference in probability = -0.092, 95% CI= -0.124, -0.059). These findings remained consistent regardless of participants' body weight, and were generally consistent across sociodemographic predictors. CONCLUSIONS: This study highlights the need for careful selection of language and visual content used in obesity-related health campaigns, and provides support for efforts to portray obese people in a nonstigmatizing manner.
Health At Every Size® Paradigm

Nutr J. 2011 Jan 24;10:9. Weight science: evaluating the evidence for a paradigm shift. Bacon L, Aphramor L. PMID: 21261939 Full text: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3041737/
Current guidelines recommend that "overweight" and "obese" individuals lose weight through engaging in lifestyle modification involving diet, exercise and other behavior change. This approach reliably induces short term weight loss, but the majority of individuals are unable to maintain weight loss over the long term and do not achieve the putative benefits of improved morbidity and mortality. Concern has arisen that this weight focus is not only ineffective at producing thinner, healthier bodies, but may also have unintended consequences, contributing to food and body preoccupation, repeated cycles of weight loss and regain, distraction from other personal health goals and wider health determinants, reduced self-esteem, eating disorders, other health decrement, and weight stigmatization and discrimination. This concern has drawn increased attention to the ethical implications of recommending treatment that may be ineffective or damaging. A growing trans-disciplinary movement called Health at Every Size (HAES) challenges the value of promoting weight loss and dieting behavior and argues for a shift in focus to weight-neutral outcomes. Randomized controlled clinical trials indicate that a HAES approach is associated with statistically and clinically relevant improvements in physiological measures (e.g., blood pressure, blood lipids), health behaviors (e.g., eating and activity habits, dietary quality), and psychosocial outcomes (such as self-esteem and body image), and that HAES achieves these health outcomes more successfully than weight loss treatment and without the contraindications associated with a weight focus. This paper evaluates the evidence and rationale that justifies shifting the health care paradigm from a conventional weight focus to HAES.
J Am Diet Assoc. 2005 Jun;105(6):929-36. Size acceptance and intuitive eating improve health for obese, female chronic dieters. Bacon L, Stern JS, Van Loan MD, Keim NL.  PMID: 15942543
OBJECTIVE: Examine a model that encourages health at every size as opposed to weight loss. The health at every size concept supports homeostatic regulation and eating intuitively (ie, in response to internal cues of hunger, satiety, and appetite). DESIGN: Six-month, randomized clinical trial; 2-year follow-up. SUBJECTS: White, obese, female chronic dieters, aged 30 to 45 years (N=78). SETTING: Free-living, general community. INTERVENTIONS: Six months of weekly group intervention (health at every size program or diet program), followed by 6 months of monthly aftercare group support. MAIN OUTCOME MEASURES: Anthropometry (weight, body mass index), metabolic fitness (blood pressure, blood lipids), energy expenditure, eating behavior (restraint, eating disorder pathology), and psychology (self-esteem, depression, body image). Attrition, attendance, and participant evaluations of treatment helpfulness were also monitored. STATISTICAL ANALYSIS PERFORMED: Analysis of variance. RESULTS: Cognitive restraint decreased in the health at every size group and increased in the diet group, indicating that both groups implemented their programs. Attrition (6 months) was high in the diet group (41%), compared with 8% in the health at every size group. Fifty percent of both groups returned for 2-year evaluation. Health at every size group members maintained weight, improved in all outcome variables, and sustained improvements. Diet group participants lost weight and showed initial improvement in many variables at 1 year; weight was regained and little improvement was sustained. CONCLUSIONS: The health at every size approach enabled participants to maintain long-term behavior change; the diet approach did not. Encouraging size acceptance, reduction in dieting behavior, and heightened awareness and response to body signals resulted in improved health risk indicators for obese women.
The Benefits of Exercise Without Weight Loss 

Cochrane Database Syst Rev. 2006 Oct 18;(4):CD003817. Exercise for overweight or obesity. Shaw K, Gennat H, O'Rourke P, Del Mar C.  PMID: 17054187
BACKGROUND: Clinical trials have shown that exercise in adults with overweight or obesity can reduce bodyweight. There has been no quantitative systematic review of this in The Cochrane Library. OBJECTIVES: To assess exercise as a means of achieving weight loss in people with overweight or obesity, using randomised controlled clinical trials. SEARCH STRATEGY: Studies were obtained from computerised searches of multiple electronic bibliographic databases. The last search was conducted in January 2006. SELECTION CRITERIA: Studies were included if they were randomised controlled trials that examined body weight change using one or more physical activity intervention in adults with overweight or obesity at baseline and loss to follow-up of participants of less than 15%. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial quality and extracted data. MAIN RESULTS: The 43 studies included 3476 participants. Although significant heterogeneity in some of the main effects' analyses limited ability to pool effect sizes across some studies, a number of pooled effect sizes were calculated. When compared with no treatment, exercise resulted in small weight losses across studies. Exercise combined with diet resulted in a greater weight reduction than diet alone (WMD -1.1 kg; 95% confidence interval (CI) -1.5 to -0.6). Increasing exercise intensity increased the magnitude of weight loss (WMD -1.5 kg; 95% CI -2.3 to -0.7). There were significant differences in other outcome measures such as serum lipids, blood pressure and fasting plasma glucose. Exercise as a sole weight loss intervention resulted in significant reductions in diastolic blood pressure (WMD -2 mmHg; 95% CI -4 to -1), triglycerides (WMD -0.2 mmol/L; 95% CI -0.3 to -0.1) and fasting glucose (WMD -0.2 mmol/L; 95% CI -0.3 to -0.1). Higher intensity exercise resulted in greater reduction in fasting serum glucose than lower intensity exercise (WMD -0.3 mmol/L; 95% CI -0.5 to -0.2). No data were identified on adverse events, quality of life, morbidity, costs or on mortality. AUTHORS' CONCLUSIONS: The results of this review support the use of exercise as a weight loss intervention, particularly when combined with dietary change. Exercise is associated with improved cardiovascular disease risk factors even if no weight is lost.
Diabetes Care. 2004 Jan;27(1):83-8. Exercise capacity and body composition as predictors of mortality among men with diabetes. Church TS, Cheng YJ, Earnest CP, Barlow CE, Gibbons LW, Priest EL, Blair SN.  PMID: 14693971

Abstract: http://care.diabetesjournals.org/content/27/1/83.abstract  Free full text at:   http://care.diabetesjournals.org/content/27/1/83.full.pdf+html
OBJECTIVE—To quantify the relation of fitness to mortality among men with diabetes, adjusted for BMI and within levels of BMI. RESEARCH DESIGN AND METHODS—In this observational cohort study, we calculated all-cause death rates in men with diabetes across quartiles of fitness and BMI categories. Study participants were 2,196 men with diabetes (average age 49.3 years, SD 9.5) who underwent a medical examination, including a maximal exercise test, during 1970 to 1995, with mortality follow-up to 31 December 1996. RESULTS—We identified 275 deaths during 32,161 person-years of observation. Risk of all-cause mortality was inversely related to fitness. For example, in the fully adjusted model, the risk of mortality was 4.5 (2.6–7.6), 2.8 (1.6–4.7), and 1.6 (0.93–2.76) for the first, second, and third fitness quartiles, respectively, with the fourth quartile (highest fitness level) as the referent (P for trend <0.0001). There was no significant trend across BMI categories for mortality after adjustment for fitness. Similar results were found when the fitness-mortality relation was examined within levels of body composition. In normal-weight men with diabetes, the relative risks of mortality were 6.6 (2.8–15.0), 3.2 (1.4–7.0), and 2.2 (1.1–4.6) for the first, second, and third quartiles of fitness, respectively, as compared with the fourth quartile (P for trend <0.0001). We found similar results in the overweight and obese weight categories. CONCLUSIONS—There was a steep inverse gradient between fitness and mortality in this cohort of men with documented diabetes, and this association was independent of BMI.
Diabetes Metab. 2010 Nov;36(5):346-51. Epub 2010 Aug 2. Physical exercise for the prevention and treatment of type 2 diabetes. Sanz C, Gautier JF, Hanaire H.   PMID: 20675173
The prevalence of type 2 diabetes is rapidly increasing worldwide, yet its primary prevention and treatment are still a challenge. The objectives of this review are to assess the effects of exercise on the prevention of type 2 diabetes in high-risk individuals and on glycaemic control in type 2 diabetic patients. Considering the available reports, there is unequivocal and strong evidence that physical exercise can prevent or delay progression to type 2diabetes in subjects with impaired glucose tolerance. Also, lifestyle interventions, including diet and physical exercise, can result in a reduction of around 50% in diabetes incidence that persists even after the individual lifestyle counselling has stopped. In addition, short-term randomized studies have confirmed that physical training based on endurance and/or resistance exercises can also improve blood glucose control in type 2 diabetics with a mean glycated haemoglobin decrease of 0.6%. Thus, physical exercise should be part of any therapeutic strategy to slow the development of type 2 diabetes in high-risk individuals and to improve glucose control in type 2 diabetes.
Curr Opin Lipidol. 2010 Feb;21(1):1-7. Cardiorespiratory fitness and metabolic risk factors in obesity. Hamer M, O'Donovan G.  PMID: 19770655
PURPOSE OF REVIEW: An increase in cardiorespiratory fitness (CRF) through exercise training appears to partly ameliorate the health hazards of obesity and a number of mechanisms might explain the potential benefits. We review recent evidence about the relationships between CRF, exercise training and metabolic risk factors in obesity. RECENT FINDINGS: Epidemiological data have shown that the anti-inflammatory effects of exercise could be an important mechanism in explaining cardio-protective effects of physical activity. Emerging evidence suggests that exercise training reduces markers of inflammation and improves glucose control in obesity, independent of weight loss. Novel mechanisms appear to involve exercise-induced changes in CD14+CD16+ cell populations, expression of toll-like receptors, and key changes in the metabolic regulation of visceral white adipose tissue. Other promising recent research has focused on exercise-induced signalling pathways governing glucose metabolism, such as insulin receptor substrate and Akt substrate. Using novel imaging techniques, studies have demonstrated exercise-induced improvements in lipoprotein subfraction particle size, and reduction in visceral adipose tissue and liver fat, independent of weight loss. These effects appear to be mostly restricted to interventions consisting of relatively high doses of exercise or exercise combined with calorie restriction, although further work is required to elucidate the dose-response relationships. SUMMARY: Physical activity and the pursuit of physical fitness are important in the treatment of obesity because exercise training can improve a number of metabolic risk factors independent of weight loss. Thus exercise can provide important health benefits irrespective of weight loss in obese and overweight individuals.
J Appl Physiol. 2005 Sep;99(3):1220-5. Epub 2005 Apr 28. Exercise without weight loss is an effective strategy for obesity reduction in obese individuals with and without Type 2 diabetes. Lee S, Kuk JL, Davidson LE, Hudson R, Kilpatrick K, Graham TE, Ross R. PMID: 15860689  Free full text at:  http://jap.physiology.org/content/99/3/1220.abstract
It is unclear whether chronic exercise without caloric restriction or weight loss is a useful strategy for obesity reduction in obese men with and without Type 2 diabetes (T2D). We examined the effects of exercise without weight loss on total and regional adiposity and skeletal muscle mass and composition in lean men and in obese men with and without T2D. Twenty-four men participated in 13 wk of supervised aerobic exercise, five times per week for 60 min at a moderate intensity (approximately 60% peak oxygen uptake). Total and regional body composition was measured by magnetic resonance imaging. Skeletal muscle composition was determined using computed tomography. Cardiorespiratory fitness was assessed using a graded maximal treadmill test. Body weight did not change within any group in response to exercise (P > 0.1). Significant reductions in total, abdominal subcutaneous, and visceral fat were observed within each group (P < 0.01). The reduction in total and abdominal subcutaneous fat was not different (P > 0.1) between groups; however, the reduction in visceral fat was greater (P < 0.01) in the obese and T2D groups by comparison to the lean group. A significant (P < 0.01) increase in total skeletal muscle, high-density muscle area, and mean muscle attenuation was observed independent of group, and these changes were not different between groups (P > 0.1). Accordingly, whole body fat-to-muscle ratio was increased (P < 0.01) independent of groups. In conclusion, regular exercise without weight loss is associated with a substantial reduction in total and visceral fat and in skeletal muscle lipid in both obesity and T2D.
Diabetes Care. 2012 Jun;35(6):1347-54. doi: 10.2337/dc11-1859. Epub 2012 Mar 7. Changes in physical fitness predict improvements in modifiable cardiovascular risk factors independently of bodyweight loss in subjects with type 2 diabetes participating in the Italian Diabetes and Exercise Study (IDES). Balducci S, Zanuso S, Cardelli P, Salvi L, Mazzitelli G, Bazuro A, Iacobini C, Nicolucci A, Pugliese G; Italian Diabetes Exercise Study (IDES) Investigators. PMID: 22399699
...RESEARCH DESIGN AND METHODS: Sedentary patients with type 2 diabetes (n = 606) were enrolled in 22 outpatient diabetes clinics and randomized to twice-a-week supervised aerobic and resistance training plus exercise counseling versus counseling alone for 12 months. Baseline to end-of-study changes in cardiorespiratory fitness, strength, and flexibility, as assessed by Vo(2max) estimation, a 5-8 maximal repetition test, and a hip/trunk flexibility test, respectively, were calculated in the whole cohort, and multiple regression analyses were applied to assess the relationship with cardiovascular risk factors. RESULTS: Changes in Vo(2max), upper and lower body strength, and flexibility were significantly associated with the variation in the volume of physical activity, HbA(1c), BMI, waist circumference, high-sensitivity C-reactive protein (hs-CRP), coronary heart disease (CHD) risk score, and inversely, HDL cholesterol. Changes in fitness predicted improvements in HbA(1c), waist circumference, HDL cholesterol, hs-CRP, and CHD risk score, independent of study arm, BMI, and in case of strength, also waist circumference. CONCLUSIONS: Physical activity/exercise-induced increases in fitness, particularly muscular, predict improvements in cardiovascular risk factors in subjects with type 2 diabetes independently of weight loss, thus indicating the need for targeting fitness in these individuals, particularly in subjects who struggle to lose weight.
Circulation. 2011 Dec 6;124(23):2483-90. doi: 10.1161/CIRCULATIONAHA.111.038422.  Long-term effects of changes in cardiorespiratory fitness and body mass index on all-cause and cardiovasculardisease mortality in men: the Aerobics Center Longitudinal Study. Lee DC, Sui X, Artero EG, Lee IM, Church TS, McAuley PA, Stanford FC, Kohl HW 3rd, Blair SN. PMID: 22144631


...METHODS AND RESULTS: We examined the independent and combined associations of changes in fitness and BMI with all-cause and cardiovascular disease (CVD) mortality in 14 345 men (mean age 44 years) with at least 2 medical examinations. Fitness, in metabolic equivalents (METs), was estimated from a maximal treadmill test. BMI was calculated using measured weight and height. Changes in fitness and BMI between the baseline and last examinations over 6.3 years were classified into loss, stable, or gain groups. During 11.4 years of follow-up after the last examination, 914 all-cause and 300 CVD deaths occurred. The hazard ratios (95% confidence intervals) of all-cause and CVD mortality were 0.70 (0.59-0.83) and 0.73 (0.54-0.98) for stable fitness, and 0.61 (0.51-0.73) and 0.58 (0.42-0.80) for fitness gain, respectively, compared with fitness loss in multivariable analyses including BMI change. Every 1-MET improvement was associated with 15% and 19% lower risk of all-cause and CVD mortality, respectively. BMI change was not associated with all-cause or CVD mortality after adjusting for possible confounders and fitness change. In the combined analyses, men who lost fitness had higher all-cause and CVD mortality risks regardless of BMI change. CONCLUSIONS: Maintaining or improving fitness is associated with a lower risk of all-cause and CVD mortality in men. Preventing age-associated fitness loss is important for longevity regardless of BMI change.

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