Maturitas
Volume 65, Issue 2 , Pages 106-111, February 2010

Predictors of chronic disease at midlife and beyond - the health risks of obesity

  • Edward J. Nejat

      Affiliations

    • Department of Obstetrics and Gynecology and Women's Health, Albert Einstein College of Medicine, NY, USA
    • ,
  • Alex J. Polotsky

      Affiliations

    • Department of Obstetrics and Gynecology and Women's Health, Albert Einstein College of Medicine, NY, USA
    • ,
  • Lubna Pal

      Affiliations

    • Department of Obstetrics, Gynecology & Reproductive Sciences, Yale University School of Medicine, 333 Cedar St., New Haven, CT, USA
    • Corresponding Author InformationCorresponding author.

Received 24 July 2009; received in revised form 3 September 2009; accepted 4 September 2009. published online 22 September 2009.

Article Outline

Abstract 

A burgeoning pandemic of obesity is well characterized. 41% of U.S. adults are projected to be obese by 2015 and obesity, a potentially modifiable risk, is emerging as a leading predictor of lifetime health. The wide spectrum of morbidities related to excess body mass includes risks for diabetes, hypertension, coronary artery disease, dyslipidemia, malignancy, venous thrombosis, degenerative joint disease, pulmonary compromise, sleep apnea, cholelithiasis, depression and overall reduced quality of life. Beyond the myriad major and minor morbidities linked to obesity, increased all-cause mortality and cardiovascular mortality is recognized in the obese. Bariatric surgery literature suggests that, in the morbidly obese, increase in the lifespan is achievable with reversal of obesity, reinforcing the realization that sequelae therein are by no means inevitable. Aggressive efforts must be targeted towards population-based strategies to educate and sensitize all generations on contributors to and sequelae of excess body mass as obesity represents one of the few modifiable factors that impact on the quantity and quality of lifespan.

Keywords: Obesity, Health risk, Morbidity, Mortality, Predictor, BMI

 

Back to Article Outline

1. Introduction 

The global obesity epidemic is advancing at an ever-accelerating pace with the United States taking an embarrassing lead [1]. Currently, 32% of U.S. adults are obese as defined by a body mass index (BMI) of greater than 30kg/m2, according to the latest National Health and Nutrition Examination Survey [2]. It is estimated that by 2015, 75% of U.S. adults will be overweight or obese (BMI of greater than 25kg/m2) and 41% will be obese [3]. Excess weight has emerged as one of the leading factors in predicting chronic disease and even death in later life [4], [5]. Accruing data identify detrimental consequences of early obesity on lifetime health; BMI greater than 25kg/m2 at age 18 was associated with an increased risk of premature death in a large cohort from the Nurses’ Health Study [6]. Notably, this effect was only partly explained by the adult BMI, implying that overweight status in early adulthood is an independent predictor of longevity. This narrative review focuses on published studies that explore the role of non-syndromic obesity as a predictor of lifetime morbidity and mortality.

Back to Article Outline

2. Epidemiology 

A substantial body of existing literature is supportive of health hazards of obesity. In order to determine an individual's risk relating to obesity however, familiarity with the concept of body mass index (BMI) and the commonly used nomenclature proposed by the World Health Organization (WHO) and the National Institutes of Health (NIH) is imperative; deteriorating categories of body weight excess are identified based on increasing BMI (Table 1).

Table 1. Categorization of body mass by body mass index [9], [70].
BMICategory
<18.5kg/m2Underweight
18.5–24.9kg/m2Normal weight
25.0–29.9kg/m2Overweight
30.0–34.9kg/m2Class I obesity
35.0–39.9kg/m2Class II obesity
≥40kg/m2Class III obesity (also referred to as severe, extreme or morbid obesity)

The WHO's latest projections from 2005 estimate approximately 1.6 billion adults (age 15+) worldwide as overweight and at least 400 million adults as obese by BMI criteria (Table 1). It is further projected that by 2015, approximately 2.3 billion adults worldwide will be overweight and more than 700 million will meet criteria for obesity [7]. These figures identify the problem of obesity as reaching pandemic proportions and underscore that underdeveloped nations are not immune to the escalating obesity epidemic.

In addition to the magnitude of body weight excess, the distribution of body fat has received considerable interest. Specifically, central or abdominal obesity has been postulated as a better predictor of overall health as compared with body mass alone [8]. The NIH in the United States defines a waist circumference (WC) of greater than 102cm for men and greater than 88cm for women as “high” and relating to enhanced health risk [9]. Interestingly, important ethnic differences in the quantum of health risk relating to the varying magnitude of central obesity have emerged; Asians are recognized to manifest metabolic burden at lesser grades of weight excess compared to other races [9]. This latter appreciation has lead to acceptance of a lesser WC threshold of 80cm beyond which central obesity is identified in Asian women. Adults who are overweight or obese (class I) and have a high WC appear to be at a greater risk for hypertension, type 2 diabetes mellitus and dyslipidemia as compared to their BMI-matched counterparts with normal WC [10]. An additional method of quantifying the degree of central obesity is by measuring the waist-to-hip ratio (WHR). A study of more than 29,000 men concluded that for men 65 and older, measures of fat distribution using the WHR may be superior to the BMI at predicting risk of coronary artery disease (CAD) [11]. A prospective cohort study of more than 44,000 women from the Nurses Health Study found that after adjusting for BMI and other known cardiac risk factors, women with a WHR of 0.88 or higher had a relative risk (RR) of 3.25 for CAD compared with women with a WHR of less than 0.72 [12].

Yet another characterization of body mass is the “ideal body weight”, a parameter identified as the weight to be aspired for by an individual at a given height. The term was derived from standard height–weight tables created by the Metropolitan Life Insurance Company in 1943 [13] and revised in 1983 [14]. Currently, these tables have fallen out of vogue as they do not provide adequate information at the extremes of height and it is it difficult to easily obtain the desired reference range. Evolution in the nomenclature for defining excess body mass has thus paralleled the increasing appreciation of adverse health implications therein.

Back to Article Outline

3. Obesity and mortality 

Evidence pointing to a shorter lifespan in the obese as compared to those of lesser body mass is recognized, and this association holds true after controlling for known causes of death. Simply put, an ostensibly “healthy” person with a large body mass is likely facing a decreased lifespan by virtue of maintaining excessive body weight alone [15]. In a prospective study with 14-year follow-up of over one million healthy nonsmokers (men and women) who were without any history of disease at enrollment, the all-cause and cardiovascular mortality were increased two-to-three fold for subjects with BMI of 30kg/m2 and above [16]. A study of over 90,000 women with an average follow-up of 7 years showed that those with BMI over 40kg/m2 appear to have as much as a two-fold increase in facing a profoundly shortened lifespan [17]. Of note is the observation that even a relatively modest deviation from the normal BMI is associated with decreased survival [18], [19]. One prospective study of over 500,000 U.S. men and women age 50–71 at enrollment identified an increased death risk in those who were overweight or obese compared to those of normal BMI [18]; the mortality risk increased by 20–40 percent when the analysis was restricted to midlife participants (age of 50 years) who had never smoked [18]. These data suggest that excessive weight may be one of the strongest, and yet modifiable, predictors of longevity at midlife! Noteworthy, this association between obesity and mortality has been described in populations across the globe. A 12 year prospective cohort study of more than 1.2 million Koreans showed that underweight, overweight and obese individuals (men and women) had higher rates of death compared with those of normal weight [19].

In an attempt to tease out the specific causes of obesity related mortality, one study found that when compared to individuals of normal weight, obesity conferred a greater than nine-fold risk of death from cardiovascular disease and an almost three-fold risk of death from some cancers (colon, breast, esophageal, uterine, ovarian, kidney and pancreatic) [20].

Back to Article Outline

4. Evidence to support causality to the association between obesity and hastened death 

While there is ample evidence to support an association between obesity and shortened lifespan, other factors, perhaps under-investigated or overlooked, may potentially explain this connection, given that the bulk of evidence is based on observational studies. Accruing data on the facilitatory implications of obesity reversal (e.g. following bariatric surgery) on mortality holds the promise of generating causal inference in support of obesity causing hastened death. Indeed, recent evidence from bariatric surgery patients suggests that if obesity is reversed, one lives longer [21]. A cleverly designed retrospective cohort study compared 7925 patients who had undergone gastric bypass surgery to the same number of severely obese non-operated controls. Patients were matched for age, sex and BMI. After a mean follow-up of 7.1 years, the adjusted long-term mortality in the surgery group was 40% lower than that observed in the control group. Cause-specific mortality due to CAD, diabetes and cancer were significantly higher in the control group. Of note and inexplicably, rates of death not caused by disease (such as accidents and suicide), was significantly higher in the surgery group [21]. It appears that this observation may conceivably represent a spurious finding, given the small numbers and a possibility of a Type I error inherently associated with multiple secondary analyses. Nonetheless, due to the potential seriousness of the implications, it is prudent to suggest and expect further studies that will refute or confirm the observed association between bariatric surgery and accidental demise.

Back to Article Outline

5. Morbidity of obesity 

Obesity is associated with increased prevalence of many health hazards (see Fig. 1 and Table 2). The following overview will focus on the studies of diabetes hypertension, CAD, dyslipidemia, malignancy, venous thrombosis and cholelithiasis [22], [23], [24], [25]. The strong association between type II diabetes and obesity is well documented. One study found that men with a BMI of 26kg/m2 (i.e. overweight per WHO and NIH criteria) had up to four-fold increase in the risk of developing diabetes when compared with men with BMI of 21kg/m2; the magnitude of this association was even more striking for women (eight-fold increase risk of diabetes in women of BMI 26kg/m2 compared to those of BMI 21kg/m2) [25]. Another study found that women with a BMI of ≥31kg/m2 (i.e. obese by WHO and NIH criteria) had a highly clinically significant 40-fold increase in the prevalence of diabetes when compared to those with BMI<22kg/m2 [22].

  • View full-size image.
  • Fig. 1. 

    Relation between BMI up to 30kg/m2 and the relative risk of type 2 diabetes, hypertension, coronary heart disease and cholelithiasis in women (A) and men (B). Reprinted with permission from Ref. [25] Copyright © 1999. Massachusetts Medical Society. All rights reserved.

Table 2. Morbidities associated with obesity.
MorbidityRepresentative data on increased risk attributable to obesity as compared with individuals of normal weight
Coronary artery diseaseAdjusted relative risk of 36 for BMI≥29kg/m2[25]
Type II diabetes mellitus and insulin resistanceType II DM: adjusted relative risk of 61 for BMI≥35kg/m2[25]
HypertensionEstimated to account for up to 26 percent of cases [24]
DyslipidemiaReduction in serum high-density-lipoprotein cholesterol of about 5 percent [23]
Venous thrombosisAdjusted relative risk of 27 for a first episode of VTE for a for BMI≥40kg/m2[71]
CholelithiasisWomen 34–59 years old: annual incidence of greater than 1% for BMI≥30kg/m2[33]
GoutAdjusted relative risk of 30 for BMI 30–34.9kg/m2[72]
StrokeAdjusted relative risk of 22 for BMI≥32kg/m2[73]
OsteoarthritisAdjusted odds ratio of 6–18 of radiographic OA at the knee for BMI≥26kg/m2[74]
Obstructive sleep apneaTwo- to four-fold increased [75]
NephrolithiasisDoubling of the risk for BMI≥30kg/m2[76]
Heart failureDoubling of the risk for BMI≥30kg/m2[77]
DepressionHigher risk for younger women with poor body image [54]

While overall obesity has also been shown to relate to insulin resistance, most evidence implicates central obesity specifically as a significant risk factor for the development of insulin resistance and type II diabetes mellitus [26]. At a mechanistic level, the relatively recently discovered link between obesity and inflammation has led to a new body of research that implicates local inflammatory factors including cytokines and C-reactive protein as potential mediators between obesity, insulin resistance and diabetes [26], [27].

Dyslipidemia, a well-quantified risk for CAD, is seen commonly in obese individuals. Data from the National Health and Nutrition Survey Examination Survey III indicate that there is a four-fold increase in the prevalence of elevated total cholesterol for women and almost six-fold for men when individuals with BMI of over 30kg/m2 were compared with their normal weight counterparts [28]. It has been postulated that this association is, in part, due to an increased production of the atherogenic very low-density lipoprotein (VLDL) particles in obese individuals [23], [29]. Alarmingly, this association of dyslipidemia and obesity is often co-incident with insulin resistance and a proinflammatory milieu, [30] prompting a definition of a relatively new entity, metabolic syndrome [31].

Obesity is a well-established risk factor for CAD [12]. Overweight and obese individuals are at increased risk for hypertension and cardiovascular sequelae [24]. In one study of 3230 U.S. men and women from the Framingham cohort, fasting blood samples were tested for cardiovascular markers. BMI was directly and significantly associated with fibrinogen, factor VII, plasminogen activator inhibitor (PAI-1) and tissue plasminogen activator (tPA) in both men and women and with von Willebrand factor (VWF) and viscosity in women. Similar associations were present between waist-to-hip ratio and the hemostatic factors. With minor exceptions for VWF and viscosity, all associations persisted after controlling for age, smoking, total and HDL cholesterol, triglycerides, glucose level, blood pressure and use of antihypertensive medication. The association between increased BMI, WHR, prothrombotic factors and impaired fibrinolysis suggests that obesity is a risk factor whose effect is mediated, in part, by a prothrombotic state. In the same study, obese individuals were found to have a higher risk for venous thrombosis, lending support to this prothrombotic hypothesis [24]. Indeed, a meta-analysis of 21 case-control and cohort studies with a total of more than 63,000 subjects found that, compared with controls, the relative risk of venous thromboembolism was 2.33 in obese patients [32].

Cholelithiasis is another co-morbidity that appears with higher frequency in the obese. A report of 90,302 women aged 34–59 from the Nurses’ Health Study found that increasing rates of cholelithiasis and/or cholecystectomy were directly correlated with increased BMI. Women with a BMI>45kg/m2 had a seven-fold increase in gallbladder disease as compared with women whose BMI was less than 24kg/m2. Remarkably, women with a BMI of greater than 45kg/m2 had a approximately 2% annual incidence of gallstones [33].

Back to Article Outline

6. Obesity … a carcinogen? 

The prevalence of certain malignancies is more common in obese men and women. In a prospective study of more than 900,000 U.S. adults, women with BMI ≥40kg/m2 had a 62% higher rate of death from malignancy when compared to their normal weight counterparts [34]. Increasing BMI was found to be significantly associated with mortality from the following malignancies: esophagus, colon and rectum, liver, gallbladder, pancreas, kidney, non-Hodgkin's lymphoma and multiple myeloma. There were significant trends of increasing risk with higher BMI for death from cancers of the stomach and prostate in men and for death from cancers of the breast, uterus, cervix, and ovary in women. This study suggests that current patterns of overweight and obesity in the United States could account for up to 14% and 20% of all deaths from cancer in men and women, respectively [34].

Obesity has long been implicated to have a causal relationship with development of endometrial cancer [35]. In a recent meta-analysis of 221 prospective datasets, 5kg/m2 increase in BMI resulted in a 59% increase in the risk of developing endometrial cancer [36]. A case-cohort study of greater than 62,000 women from the Netherlands showed that women with a BMI ≥30kg/m2 had a 4.5 times higher risk of developing endometrial cancer as compared to women with BMI between 20 and 22.9kg/m2 [37]. Furthermore, women with endometrial cancer and BMI>40kg/m2 were found to have a relative risk of death of 6.25 when compared to women with normal BMI [38].

A causal relationship between obesity and ovarian cancer has not been well established. However, one meta-analysis of 28 studies reported a positive association between obesity and ovarian cancer. Statistical significance was reached in only ten of these studies. While the authors concluded that the risk of ovarian cancer is likely related to obesity [39], this observation merits additional support by other researchers.

Intriguingly, BMI has varying effects on the incidence of breast cancer in pre- and postmenopausal women. In a recent meta-analysis of seven large prospective cohorts, premenopausal women with a BMI of greater than 31kg/m2 had a 54% increase in the risk of developing breast cancer when compared with women with a BMI of less than 21kg/m2 [40]. These findings are consistent with several earlier studies [41], [42], [43]. In contrast, studies of postmenopausal women have reported disparate results, some showing a weak positive or no association between weight and postmenopausal breast cancer risk [44], [45], [46] and some showing significant positive associations [40], [47], [48], [49].

Back to Article Outline

7. Role of reproductive senescence in “Middle Age Spread”? 

Progressive weight gain concomitant with chronological aging is well recognized in either gender. In women, this latter phenomenon is temporally tied to cessation of ovarian function concomitant with menopause transition and menopause [50] suggesting a pathophysiological role for the loss of ovarian estrogen in body mass accrual observed around menopause. While a role for lack of estrogen in the causation of midlife spread is liberally implied, the data are far from conclusive [51] and on the mechanistic level the hormonal effects of menopausal transition and menopause must be distinguished from chronological aging. Longitudinal data from the Massachusetts Women's Health Study suggest that weight increases commonly seen in middle-aged women in the United States are not caused by the menopausal transition [50]. Similarly, a paired MRI examination of 8 healthy women before and after menopause showed an increase in absolute adiposity (likely related to chronological aging) but no changes in relative fat distribution [52]. In a racially and ethnically diverse group of women aged 42–52 years enrolled in the Study of Women's Health Across the Nation (SWAN), an observational study of the menopausal transition (n=3064) over 3 years of follow-up, while increases in mean population weight (by 2.1kg±4.8 [standard deviation – SD]) and WC (by 2.2cm±5.4SD) were observed [53]; more importantly, increase in physical activity was associated with prevention and mitigation in this age related weight gain underscoring that the increase in body weight concomitant with aging (chronological and reproductive) is by no means inevitable (Table 3).

Table 3. Indications for bariatric surgery [78].
BMI>40kg/m2
BMI 35–40kg/m2 for patients with high-risk co-morbidities (hypertension, diabetes mellitus, dyslipidemia, sleep apnea)
Failed non-surgical weight loss attempts
Well-informed and motivated patient
Ability to participate in long-term follow-up

Back to Article Outline

8. Psychosocial implications of obesity and impact on quality of life (QOL) 

Obesity has been linked with higher rates of depression, particularly affecting young women with low self-esteem [54]. The largest study of social implications of obesity to date was a prospective cohort of over 10,000 U.S. men and women who were 16–24 years old at baseline. After adjusting for aptitude scores, women who were overweight completed 0.3 less years of schooling, were 20 percent less likely to be married, and had 10 percent higher rates of poverty than their normal weight counterparts [55]. More research is needed to address the issues of societal stigmatization directed at obese subjects, whether the psychological implications of obesity constitute a possible consequence or cause of these problems and whether the psychological burden ameliorates with weight loss. It is noteworthy that despite obesity being a recognized risk for depressive symptoms, a large body of literature reassuringly supports an inverse relationship between obesity and suicidal tendencies, although this relationship is by no means unequivocal [56], [57].

Back to Article Outline

9. Therapies available to combat obesity 

Lifestyle modifications including dietary manipulations and exercise, behavioral modifications, pharmacologic therapy and more recently, bariatric surgery, are strategies that have been utilized with varying success in the management of obesity. Modest weight reductions (<8kg) are described with diet [58], exercise [59], [60] or both [61], [62]. Comparable degrees of weight reduction are additionally ascribed to behavioral modifications such as setting realistic goals, stimulus control and enhancing social support [63]. Medical therapy is sometimes used in conjunction with the aforementioned conservative weight loss techniques. The most commonly used classes of medications include sympathomimetics (sibutramine, phentermine and diethylpropion), lipase inhibitors (orlistat) and antidepressants (fluoxetine and bupropion). According to a recent meta-analysis of randomized trials of pharmacologic treatments of obesity, modest weight loss (<5kg at 1 year) can be attributed to some of the available pharmacologic interventions [64]. A major drawback of conservative management of obesity is a lack of sustained weight loss in many patients following cessation of the intervention. Surgical therapy for obesity promotes weight loss by restricting caloric intake; early satiety attributable to reduction in the size of the stomach reservoir and decrease in the length of functional small bowel, or both are identified as key players in successful postoperative weight reduction. Of the available strategies for management of obesity, bariatric surgical interventions are associated with the most significant and sustainable reductions in weight [65], [66]. Success stories of improvements or even resolution of medical co-morbidities are well described sequelae to bariatric surgery [67], [68] and a reduction in mortality related to successful surgical intervention is also reported [21], [67], [69]. Procedure related complications from bariatric surgery, while dependant on the type of surgery, are relatively uncommon; a meta-analysis of 136 studies reassuringly reports a 30-day operative mortality rate of 0.1% for restrictive procedures, 0.5% for bypass procedures and 1.1% for combined procedures [65].

Back to Article Outline

10. Conclusion 

In summary, excessive body mass represents a significant health hazard, and especially so in those deemed otherwise healthy and lacking any identifiable disease or health risk [18]. The list of co-morbidities of obesity with proven causal associations is ever-increasing and excess body mass is recognized a risk factor for mortality. Of particular relevance are emerging data that identify a reversal in the health burden of obesity concomitant with successful weight loss; disease and death is thus not an inevitable sequel to body weight excess! In the morbidly obese, a reversal in increased mortality is observed after a dramatic weight loss [21]. While annihilation from surfeit of consumption may not be a pressing concern for mankind at least in the short term, concerted and collaborative efforts are desperately needed to reverse the trends within this burgeoning epidemic of obesity; excess body weight must be recognized and tackled as the single modifiable health risk, a strategy that holds potential for global health benefit.

Back to Article Outline

Contributors 

Edward J Nejat: Postdoctoral Research Fellow, Department of Obstetrics and Gynecology and Women's Health, Albert Einstein College of Medicine, NY, USA. Conducted review of literature, prepared the preliminary manuscript, obtained requisite permission for use of included figure, addressed critique provided by senior authors and finalized the manuscript.

Alex J Polotsky: Assistant Professor, Department of Obstetrics and Gynecology and Women's Health, Albert Einstein College of Medicine, NY, USA. Conducted and oversaw review of literature on the topic, involved in preparation of the preliminary manuscript, addressed critique provided by senior author and involved in finalization of the manuscript.

Lubna Pal: Assistant Professor, Department of Obstetrics, Gynecology & Reproductive Sciences, Yale University School of Medicine, CT, USA. Reviewed literature on the topic, guided the first and second authors in preparation and finalization of the manuscript.

Back to Article Outline

Competing interests/funding 

None.

Back to Article Outline

Provenance 

Commissioned and externally peer reviewed.

Back to Article Outline

References 

  1. National Center for Health Statistics, Centers for Disease Control and Prevention. Prevalence of Overweight and Obesity Among Adults: United States, 2003–2004. 2006 April 2006.
  2. Ogden CL, Carroll MD, Curtin LR, McDowell MA, Tabak CJ, Flegal KM. Prevalence of overweight and obesity in the United States, 1999–2004. JAMA. 2006;295(13):1549–1555
  3. Wang Y, Beydoun MA. The obesity epidemic in the United States—gender, age, socioeconomic, racial/ethnic, and geographic characteristics: a systematic review and meta-regression analysis. Epidemiologic Reviews. 2007;29:6–28
  4. Dietz WH, Robinson TN. Overweight Children and Adolescents. New England Journal of Medicine. 2005;352(20):2100–2109
  5. Strauss RS, Pollack HA. Epidemic Increase in Childhood Overweight, 1986–1998. JAMA. 2001;286(22):2845–2848
  6. van Dam RM, Willett WC, Manson JE, Hu FB. The relationship between overweight in adolescence and premature death in women. Ann Intern Med. 2006;145(2):91–97
  7. WHO. WHO Fact Sheet Number 311. 2006 [cited; Available from: http://www.who.int/mediacentre/factsheets/fs311/en/index.html.
  8. Larsson B, Svardsudd K, Welin L, Wilhelmsen L, Bjorntorp P, Tibblin G. Abdominal adipose tissue distribution, obesity, and risk of cardiovascular disease and death: 13 year follow up of participants in the study of men born in 1913. Br Med J (Clin Res Ed). 1984;288(6428):1401–1404
  9. Clinical Guidelines on the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults—The Evidence Report. National Institutes of Health. Obes Res. 1998;6(Suppl 2):51S–209S
  10. Janssen I, Katzmarzyk PT, Ross R. Body mass index, waist circumference, and health risk: evidence in support of current National Institutes of Health guidelines. Arch Intern Med. 2002;162(18):2074–2079
  11. Rimm EB, Stampfer MJ, Giovannucci E, Ascherio A, Spiegelman D, Colditz GA, et al. Body size and fat distribution as predictors of coronary heart disease among middle-aged and older US men. Am J Epidemiol. 1995;141(12):1117–1127
  12. Rexrode KM, Carey VJ, Hennekens CH, Walters EE, Colditz GA, Stampfer MJ, et al. Abdominal adiposity and coronary heart disease in women. JAMA. 1998;280(21):1843–1848
  13. Pai MP, Paloucek FP. The origin of the “ideal” body weight equations. Ann Pharmacother. 2000;34(9):1066–1069
  14. Himes JH, Bouchard C. Do the new Metropolitan Life Insurance weight-height tables correctly assess body frame and body fat relationships?. Am J Public Health. 1985;75(9):1076–1079
  15. Allison DB, Fontaine KR, Manson JE, Stevens J, VanItallie TB. Annual deaths attributable to obesity in the United States. JAMA. 1999;282(16):1530–1538
  16. Calle EE, Thun MJ, Petrelli JM, Rodriguez C, Heath CW. Body-mass index and mortality in a prospective cohort of U.S. adults. N Engl J Med. 1999;341(15):1097–1105
  17. McTigue K, Larson JC, Valoski A, Burke G, Kotchen J, Lewis CE, et al. Mortality and cardiac and vascular outcomes in extremely obese women. JAMA. 2006;296(1):79–86
  18. Adams KF, Schatzkin A, Harris TB, Kipnis V, Mouw T, Ballard-Barbash R, et al. Overweight, obesity, and mortality in a large prospective cohort of persons 50 to 71 years old. N Engl J Med. 2006;355(8):763–778
  19. Jee SH, Sull JW, Park J, Lee SY, Ohrr H, Guallar E, et al. Body-mass index and mortality in Korean men and women. N Engl J Med. 2006;355(8):779–787
  20. Flegal KM, Graubard BI, Williamson DF, Gail MH. Cause-specific excess deaths associated with underweight, overweight, and obesity. JAMA. 2007;298(17):2028–2037
  21. Adams TD, Gress RE, Smith SC, Halverson RC, Simper SC, Rosamond WD, et al. Long-term mortality after gastric bypass surgery. N Engl J Med. 2007;357(8):753–761
  22. Colditz GA, Willett WC, Rotnitzky A, Manson JE. Weight gain as a risk factor for clinical diabetes mellitus in women. Ann Intern Med. 1995;122(7):481–486
  23. Grundy SM, Barnett JP. Metabolic and health complications of obesity. Dis Mon. 1990;36(12):641–731
  24. Wilson PW, D’Agostino RB, Sullivan L, Parise H, Kannel WB. Overweight and obesity as determinants of cardiovascular risk: the Framingham experience. Arch Intern Med. 2002;162(16):1867–1872
  25. Willett WC, Dietz WH, Colditz GA. Guidelines for healthy weight. N Engl J Med. 1999;341(6):427–434
  26. Zeyda M, Stulnig TM. Obesity, Inflammation, and Insulin Resistance - A Mini-Review. Gerontology. 2009;
  27. Shoelson SE, Herrero L, Naaz A. Obesity, inflammation, and insulin resistance. Gastroenterology. 2007;132(6):2169–2180
  28. Brown CD, Higgins M, Donato KA, Rohde FC, Garrison R, Obarzanek E, et al. Body mass index and the prevalence of hypertension and dyslipidemia. Obes Res. 2000;8(9):605–619
  29. Ginsberg HN, Zhang YL, Hernandez-Ono A. Metabolic syndrome: focus on dyslipidemia. Obesity (Silver Spring). 2006;14(Suppl 1):41S–49S
  30. Bamba V, Rader DJ. Obesity and atherogenic dyslipidemia. Gastroenterology. 2007;132(6):2181–2190
  31. Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, And Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III). JAMA. 2001;285(19):2486–2497
  32. Ageno W, Becattini C, Brighton T, Selby R, Kamphuisen PW. Cardiovascular risk factors and venous thromboembolism: a meta-analysis. Circulation. 2008;117(1):93–102
  33. Stampfer MJ, Maclure KM, Colditz GA, Manson JE, Willett WC. Risk of symptomatic gallstones in women with severe obesity. Am J Clin Nutr. 1992;55(3):652–658
  34. Calle EE, Rodriguez C, Walker-Thurmond K, Thun MJ. Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults. N Engl J Med. 2003;348(17):1625–1638
  35. Wynder EL, Escher GC, Mantel N. An epidemiological investigation of cancer of the endometrium. Cancer. 1966;19(4):489–520
  36. Renehan AG, Tyson M, Egger M, Heller RF, Zwahlen M. Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies. Lancet. 2008;371(9612):569–578
  37. Schouten LJ, Goldbohm RA, van den Brandt PA. Anthropometry, physical activity, and endometrial cancer risk: results from the Netherlands Cohort Study. J Natl Cancer Inst. 2004;96(21):1635–1638
  38. Fader AN, Arriba LN, Frasure HE, von Gruenigen VE. Endometrial cancer and obesity: epidemiology, biomarkers, prevention and survivorship. Gynecol Oncol. 2009;114(1):121–127
  39. Olsen CM, Green AC, Whiteman DC, Sadeghi S, Kolahdooz F, Webb PM. Obesity and the risk of epithelial ovarian cancer: a systematic review and meta-analysis. Eur J Cancer. 2007;43(4):690–709
  40. van den Brandt PA, Spiegelman D, Yaun SS, Adami HO, Beeson L, Folsom AR, et al. Pooled analysis of prospective cohort studies on height, weight, and breast cancer risk. Am J Epidemiol. 2000;152(6):514–527
  41. London SJ, Colditz GA, Stampfer MJ, Willett WC, Rosner B, Speizer FE. Prospective study of relative weight, height, and risk of breast cancer. JAMA. 1989;262(20):2853–2858
  42. Trentham-Dietz A, Newcomb PA, Storer BE, Longnecker MP, Baron J, Greenberg ER, et al. Body size and risk of breast cancer. Am J Epidemiol. 1997;145(11):1011–1019
  43. Brinton LA, Swanson CA. Height and weight at various ages and risk of breast cancer. Ann Epidemiol. 1992;2(5):597–609
  44. van den Brandt PA, Dirx MJ, Ronckers CM, van den Hoogen P, Goldbohm RA. Height, weight weight change, and postmenopausal breast cancer risk: The Netherlands Cohort Study. Cancer Causes Control. 1997;8(1):39–47
  45. Vatten LJ, Kvinnsland S. Body mass index and risk of breast cancer. A prospective study of 23,826 Norwegian women. Int J Cancer. 1990;45(3):440–444
  46. den Tonkelaar I, Seidell JC, Collette HJ, de Waard F. A prospective study on obesity and subcutaneous fat patterning in relation to breast cancer in post-menopausal women participating in the DOM project. Br J Cancer. 1994;69(2):352–357
  47. Tretli S. Height and weight in relation to breast cancer morbidity and mortality. A prospective study of 570,000 women in Norway. Int J Cancer. 1989;44(1):23–30
  48. Swanson CA, Brinton LA, Taylor PR, Licitra LM, Ziegler RG, Schairer C. Body size and breast cancer risk assessed in women participating in the Breast Cancer Detection Demonstration Project. Am J Epidemiol. 1989;130(6):1133–1141
  49. Yong LC, Brown CC, Schatzkin A, Schairer C. Prospective study of relative weight and risk of breast cancer: the Breast Cancer Detection Demonstration Project follow-up study, 1979 to 1987–1989. Am J Epidemiol. 1996;143(10):985–995
  50. Crawford SL, Casey VA, Avis NE, McKinlay SM. A longitudinal study of weight and the menopause transition: results from the Massachusetts Women's Health Study. Menopause. 2000;7(2):96–104
  51. Norman RJ, Flight IH, Rees MC. Oestrogen and progestogen hormone replacement therapy for peri-menopausal and post-menopausal women: weight and body fat distribution. Cochrane Database Syst Rev 2000(2):CD001018.
  52. Franklin RM, Ploutz-Snyder L, Kanaley JA. Longitudinal changes in abdominal fat distribution with menopause. Metabolism. 2009;58(3):311–315
  53. Sternfeld B, Wang H, Quesenberry CP, Abrams B, Everson-Rose SA, Greendale GA, et al. Physical activity and changes in weight and waist circumference in midlife women: findings from the Study of Women's Health Across the Nation. Am J Epidemiol. 2004;160(9):912–922
  54. Dixon JB, Dixon ME, O’Brien PE. Depression in association with severe obesity: changes with weight loss. Arch Intern Med. 2003;163(17):2058–2065
  55. Gortmaker SL, Must A, Perrin JM, Sobol AM, Dietz WH. Social and economic consequences of overweight in adolescence and young adulthood. N Engl J Med. 1993;329(14):1008–1012
  56. Mukamal KJ, Wee CC, Miller M. BMI and Rates of Suicide in the United States: An Ecological Analysis. Obesity (Silver Spring). 2009;
  57. Mather AA, Cox BJ, Enns MW, Sareen J. Associations of obesity with psychiatric disorders and suicidal behaviors in a nationally representative sample. J Psychosom Res. 2009;66(4):277–285
  58. Dansinger ML, Tatsioni A, Wong JB, Chung M, Balk EM. Meta-analysis: the effect of dietary counseling for weight loss. Ann Intern Med. 2007;147(1):41–50
  59. Slentz CA, Duscha BD, Johnson JL, Ketchum K, Aiken LB, Samsa GP, et al. Effects of the amount of exercise on body weight, body composition, and measures of central obesity: STRRIDE—a randomized controlled study. Arch Intern Med. 2004;164(1):31–39
  60. Ballor DL, Keesey RE. A meta-analysis of the factors affecting exercise-induced changes in body mass, fat mass and fat-free mass in males and females. Int J Obes. 1991;15(11):717–726
  61. Garrow JS, Summerbell CD. Meta-analysis: effect of exercise, with or without dieting, on the body composition of overweight subjects. Eur J Clin Nutr. 1995;49(1):1–10
  62. Pavlou KN, Krey S, Steffee WP. Exercise as an adjunct to weight loss and maintenance in moderately obese subjects. Am J Clin Nutr. 1989;49(5 Suppl):1115–1123
  63. Avenell A, Broom J, Brown TJ, Poobalan A, Aucott L, Stearns SC, et al. Systematic review of the long-term effects and economic consequences of treatments for obesity and implications for health improvement. Health Technol Assess. 2004;8(21):p. iii–iv, 1–182
  64. Li Z, Maglione M, Tu W, Mojica W, Arterburn D, Shugarman LR, et al. Meta-analysis: pharmacologic treatment of obesity. Ann Intern Med. 2005;142(7):532–546
  65. Buchwald H, Avidor Y, Braunwald E, Jensen MD, Pories W, Fahrbach K, et al. Bariatric surgery: a systematic review and meta-analysis. JAMA. 2004;292(14):1724–1737
  66. Maggard MA, Shugarman LR, Suttorp M, Maglione M, Sugerman HJ, Livingston EH, et al. Meta-analysis: surgical treatment of obesity. Ann Intern Med. 2005;142(7):547–559
  67. Christou NV, Sampalis JS, Liberman M, Look D, Auger S, McLean AP, et al. Surgery decreases long-term mortality, morbidity, and health care use in morbidly obese patients. Ann Surg. 2004;240(3):416–423discussion 23–4
  68. Abu-Abeid S, Keidar A, Szold A. Resolution of chronic medical conditions after laparoscopic adjustable silicone gastric banding for the treatment of morbid obesity in the elderly. Surg Endosc. 2001;15(2):132–134
  69. Sjostrom L, Narbro K, Sjostrom CD, Karason K, Larsson B, Wedel H, et al. Effects of bariatric surgery on mortality in Swedish obese subjects. N Engl J Med. 2007;357(8):741–752
  70. Obesity: preventing and managing the global epidemic. Report of a WHO consultation. World Health Organ Tech Rep Ser. 2000;894:p. i–xii, 1–253
  71. Tsai AW, Cushman M, Rosamond WD, Heckbert SR, Polak JF, Folsom AR. Cardiovascular risk factors and venous thromboembolism incidence: the longitudinal investigation of thromboembolism etiology. Arch Intern Med. 2002;162(10):1182–1189
  72. Choi HK, Atkinson K, Karlson EW, Curhan G. Obesity, weight change, hypertension, diuretic use, and risk of gout in men: the health professionals follow-up study. Arch Intern Med. 2005;165(7):742–748
  73. Rexrode KM, Hennekens CH, Willett WC, Colditz GA, Stampfer MJ, Rich-Edwards JW, et al. A prospective study of body mass index, weight change, and risk of stroke in women. JAMA. 1997;277(19):1539–1545
  74. Hart DJ, Spector TD. The relationship of obesity, fat distribution and osteoarthritis in women in the general population: the Chingford Study. J Rheumatol. 1993;20(2):331–335
  75. Gami AS, Caples SM, Somers VK. Obesity and obstructive sleep apnea. Endocrinol Metab Clin North Am. 2003;32(4):869–894
  76. Taylor EN, Stampfer MJ, Curhan GC. Obesity, weight gain, and the risk of kidney stones. JAMA. 2005;293(4):455–462
  77. Kenchaiah S, Evans JC, Levy D, Wilson PW, Benjamin EJ, Larson MG, et al. Obesity and the risk of heart failure. N Engl J Med. 2002;347(5):305–313
  78. NIH conference. Gastrointestinal surgery for severe obesity. Consensus Development Conference Panel. Ann Intern Med. 1991;115(12):956–961

PII: S0378-5122(09)00300-4

doi:10.1016/j.maturitas.2009.09.006

Maturitas
Volume 65, Issue 2 , Pages 106-111, February 2010

Article Tools

* Image Usage & Resolution