NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.

Feingold KR, Anawalt B, Boyce A, et al., editors. Endotext [Internet]. South Dartmouth (MA):, Inc.; 2000-.

Cover of Endotext

Endotext [Internet].

Show details

Clinical Problems Caused by Obesity

, M.D., PhD, , MD, PhD, FRCP, , MD, PHD, , MD, FRCP, and , MD, FRCP.

Author Information

Last Update: January 11, 2018.


Obesity constitutes a worldwide epidemic with prevalence rates which are increasing in most Western societies and in the developing world. By 2025, if this trend continues, the global obesity prevalence will reach 18% in men and exceed 21% in women. Furthermore, it is now well-established that obesity (depending on the degree, duration, and distribution of the excess weight/adipose tissue) can progressively cause and/or exacerbate a wide spectrum of co-morbidities, including type 2 diabetes mellitus, hypertension, dyslipidemia, cardiovascular disease, non-alcoholic fatty liver disease, reproductive dysfunction, respiratory abnormalities, psychiatric conditions, and even increase the risk for certain types of cancer. This chapter presents an overview of these links focusing on the most common obesity-related co-morbidities.


During the past few decades, the prevalence rates of obesity [defined as body mass index (BMI) over 30 kg/m2] have been increasing at a rapid pace in both Western societies and the developing world (1), reaching 641 million adults being obese in 2014 [266 million men and 375 million women], compared to 105 million adults in 1975 [34 million men and 71 million women] (2). Notably, if this trend persists, the global obesity prevalence is predicted to rise to 18% in men and surpass 21% in women by 2025 (2). Overall, obesity can be considered a chronic relapsing and progressive disease (3) and a leading risk factor for global deaths. Furthermore, alarming trends of weight gain have also been documented for children and adolescents, undermining the present and future health status of the population (4-7). To highlight the related threat to public health, the World Health Organization (WHO) declared obesity a global epidemic, also stressing that in many cases it remains an under-recognized problem of the public health agenda (1, 8, 9).

Depending on the degree and duration of weight gain, obesity can progressively cause and/or exacerbate a wide spectrum of co-morbidities, including type 2 diabetes mellitus (T2DM), hypertension, dyslipidemia, cardiovascular disease (CVD), liver dysfunction, respiratory and musculoskeletal disorders, sub-fertility, psychosocial problems, and certain types of cancer (Figure 1).

Figure 1. Co-Morbidities Associated with Overweight and Obesity.

Image clin-prblms-obesity_figure1-1024x699.jpg

These chronic diseases have been shown to have strong correlations with BMI, and closely follow the prevalence patterns of excessive body weight in all studied populations (10, 11). Notably, the risk of developing a number of obesity-related co-morbidities rises exponentially with increasing BMI over 30 kg/m2, which is further associated with a graded increase in the relative risk of premature death, primarily from CVD (9, 10, 12). For individuals with BMI between 25 and 29.9 kg/m2 (pre-obesity) the risk of premature mortality is weaker and appears to be influenced mainly by fat distribution (Figure 2). Indeed, fat accumulation intra-abdominally and subcutaneously around the abdomen (central, abdominal, visceral, android, upper body or apple-shaped obesity) is associated with higher risk for cardiometabolic diseases, independent of BMI (13, 14). On the other hand, fat accumulation in the subcutaneous regions of hips, thighs and lower trunk (gluteofemoral, peripheral, gynoid, lower body or pear-shaped obesity) is considered less harmful or even protective against cardiometabolic complications (13, 15-17).

Figure 2. Relationship Between Body Mass Index (BMI) and Mortality (data from Calle et al. NEJM 1999 (12)).

Image clin-prblms-obesity_figure2-1024x891.jpg

Notably, individuals of certain ethnic backgrounds, regardless of the country of residence, are predisposed to central/abdominal obesity and more vulnerable to obesity-related complications (18-21). Indeed, studies in South Asian, Japanese, and Chinese populations have demonstrated significantly higher risk for insulin resistance, T2DM and CVD compared to matched overweight/obese Caucasians (22-24). Accordingly, rigorous cut-off points have been proposed for weight management among these populations, diagnosing obesity with BMI thresholds as low as 25 kg/m2 and defining central obesity based on ethnicity specific cut-off values of waist circumference (22-27).

In any case, obesity should be recognized by the treating physician as a key risk factor for the health of the patient, and appropriate weight loss treatments should be offered to patients with obesity, independently of other related co-morbidities (28-30). Weight management is crucial and should be suggested promptly even when these individuals are otherwise healthy (e.g. metabolically healthy patients with obesity) to prevent and/or delay the onset of obesity-related complications. Interestingly, recent advances in treatment options for CVD risk factors and acute coronary syndromes are now offering improved cardio-protection outcomes and appear to prolong life expectancy in patients with obesity. Indeed, epidemiologic data support the notion that, in developed societies increasing numbers of these patients are expected to live more than previously predicted, despite failing to reduce their excessive body weight (31, 32). As such, it is estimated that growing and progressively ageing populations in Western societies will continue to develop an increasing burden of obesity-related disease, including complications (e.g. chronic liver disease, respiratory or mobility problems) which were previously under-diagnosed or under-expressed due to earlier mortality (expansion of obesity-related morbidity) (31, 33, 34). Subsequently, the economic impact of obesity on health care costs is profound and will continue to increase, while the additional indirect costs (e.g. absence from work, reduced productivity and disability benefits) are also substantial. National surveys in the UK have shown that obesity is directly responsible for almost 7% of the overall morbidity and mortality, with a direct cost to the Neational Health System (NHS) that currently exceeds five billion pounds per year and could potentially rise to more than nine billion pounds by 2050 (35-37).

Childhood obesity also poses a significant burden due to a spectrum of complications both in the short term and later in life, highlighting the need for early intervention and prevention of obesity in children and adolescents (5, 38, 39). It should be noted that the absolute BMI is not an appropriate screen index to identify children with elevated body fat mass since BMI normative values differ based on age and gender. Hence, in the pediatric population BMI should be plotted on the Centers for Disease Control and Prevention’s percentile curves to identify the corresponding BMI percentile category ( [obesity in children and adolescents will be reviewed in detail in the EndoText chapter dedicated to Pediatric Obesity].


In this chapter, we have discussed major disorders/diseases that are associated with obesity and are caused, at least in part, by adipose tissue accumulation. These include disturbances of glucose metabolism, manifestations of the metabolic syndrome, non-alcoholic fatty liver disease, gallbladder disease, osteoarthritis, obstructive sleep apnea, and various types of cancer, as well as unfavorable outcomes regarding reproduction, stress levels, and psychiatric disorders.

In clinical practice it should be noted that individuals with obesity often vary significantly regarding clinical manifestations of obesity-related morbidity, and it appears that patterns of lipid partitioning are a major determinant of their metabolic profile (65). Distribution of body fat plays an important role in this context (65, 641). As such, visceral accumulation of excess body fat is shown to be strongly associated with most of the obesity-related disorders including insulin resistance (642), and T2DM (643), as well as with all-cause mortality (644). On the other hand, increased subcutaneous fat depots can even have protective metabolic effects (645-647). Although not all previous studies have shown an independent effect of the subcutaneous abdominal fat on insulin sensitivity (646) and controversial findings have also been reported (648), data suggest that an expanded fat mass, particularly of subcutaneous adipose tissue, may function as a sink for glucose uptake and triglyceride accumulation resulting in compensatory improvement of insulin sensitivity (647). In agreement with this hypothesis, it has been shown that enabling a massive expansion of the subcutaneous adipose tissue mass in the ob/ob mouse model potently counteracts the development of insulin resistance associated with excess caloric intake (649). Importantly, evidence from rodent models of obesity and research into the genetic basis of human obesity have started to provide novel insight into the predisposition to weight gain and the pathophysiology of obesity-associated co-morbidity [rodent models of obesity and the genetics of obesity in humans will be reviewed in detail in the corresponding EndoText chapters].

In conclusion, obesity constitutes a complex, multifactorial disease associated with a wide spectrum of comorbidities due to both a deleterious endocrine/metabolic profile of the expanded/accumulated adipose tissue, and an increased physical burden imposed on various body sites/organs. Thus, even in cases of “metabolically healthy” obese individuals (presenting with a predominantly female type of fat distribution and absence of metabolic abnormalities) multiple other parameters and the risk of long-term adverse outcomes (e.g. risk of CVD, osteoarthritis, disability, psychological comorbidity) need to be seriously considered when discussing the benefits of various weight management interventions (28, 650, 651).


  1. James WP. Obesity-a modern pandemic: the burden of disease. Endocrinol Nutr. 2013;60 Suppl 1:3-6.
  2. Collaboration NCDRF. Trends in adult body-mass index in 200 countries from 1975 to 2014: a pooled analysis of 1698 population-based measurement studies with 19.2 million participants. Lancet. 2016;387(10026):1377-96.
  3. Bray GA, Kim KK, Wilding JPH, World Obesity F. Obesity: a chronic relapsing progressive disease process. A position statement of the World Obesity Federation. Obes Rev. 2017;18(7):715-23.
  4. Collaboration NCDRF. Worldwide trends in body-mass index, underweight, overweight, and obesity from 1975 to 2016: a pooled analysis of 2416 population-based measurement studies in 128.9 million children, adolescents, and adults. Lancet. 2017;390(10113):2627-42.
  5. Barton M. Childhood obesity: a life-long health risk. Acta Pharmacol Sin. 2012;33(2):189-93.
  6. Gupta N, Goel K, Shah P, Misra A. Childhood obesity in developing countries: epidemiology, determinants, and prevention. Endocr Rev. 2012;33(1):48-70.
  7. Santo Domingo L, Scheimann AO. Overview of the epidemiology and management of childhood obesity. Minerva Pediatr. 2012;64(6):607-13.
  8. James WP. WHO recognition of the global obesity epidemic. Int J Obes (Lond). 2008;32 Suppl 7:S120-6.
  9. World Health Organization G. Obesity: preventing and managing the global epidemic: Report of a WHO Consultation. 2004.
  10. Pi-Sunyer X. The medical risks of obesity. Postgrad Med. 2009;121(6):21-33.
  11. World Health Organization G. World Health Organization. Comparative Quantification of Health Risks: Global and Regional Burden of Disease Attributable to Selected Major Risk Factors. 2004.
  12. Calle EE, Thun MJ, Petrelli JM, Rodriguez C, Heath CW, Jr. Body-mass index and mortality in a prospective cohort of U.S. adults. N Engl J Med. 1999;341(15):1097-105.
  13. Cameron AJ, Magliano DJ, Soderberg S. A systematic review of the impact of including both waist and hip circumference in risk models for cardiovascular diseases, diabetes and mortality. Obes Rev. 2013;14(1):86-94.
  14. Klein S, Allison DB, Heymsfield SB, Kelley DE, Leibel RL, Nonas C, et al. Waist circumference and cardiometabolic risk: a consensus statement from shaping America's health: Association for Weight Management and Obesity Prevention; NAASO, the Obesity Society; the American Society for Nutrition; and the American Diabetes Association. Diabetes Care. 2007;30(6):1647-52.
  15. Kwon H, Kim D, Kim JS. Body Fat Distribution and the Risk of Incident Metabolic Syndrome: A Longitudinal Cohort Study. Sci Rep. 2017;7(1):10955.
  16. Manolopoulos KN, Karpe F, Frayn KN. Gluteofemoral body fat as a determinant of metabolic health. Int J Obes (Lond). 2010;34(6):949-59.
  17. Snijder MB, Zimmet PZ, Visser M, Dekker JM, Seidell JC, Shaw JE. Independent and opposite associations of waist and hip circumferences with diabetes, hypertension and dyslipidemia: the AusDiab Study. Int J Obes Relat Metab Disord. 2004;28(3):402-9.
  18. Wells JC. Ethnic variability in adiposity, thrifty phenotypes and cardiometabolic risk: addressing the full range of ethnicity, including those of mixed ethnicity. Obes Rev. 2012;13 Suppl 2:14-29.
  19. El-Sayed AM, Scarborough P, Galea S. Ethnic inequalities in obesity among children and adults in the UK: a systematic review of the literature. Obes Rev. 2011;12(5):e516-34.
  20. James WP. Assessing obesity: are ethnic differences in body mass index and waist classification criteria justified? Obes Rev. 2005;6(3):179-81.
  21. James WP, Rigby N, Leach R. Obesity and the metabolic syndrome: the stress on society. Ann N Y Acad Sci. 2006;1083:1-10.
  22. Barnett AH, Dixon AN, Bellary S, Hanif MW, O'Hare J P, Raymond NT, et al. Type 2 diabetes and cardiovascular risk in the UK south Asian community. Diabetologia. 2006;49(10):2234-46.
  23. consultation We. Appropriate body-mass index for Asian populations and its implications for policy and intervention strategies. Lancet. 2004;363(9403):157-63.
  24. Misra A, Khurana L. Obesity-related non-communicable diseases: South Asians vs White Caucasians. Int J Obes (Lond). 2011;35(2):167-87.
  25. Alberti KG, Eckel RH, Grundy SM, Zimmet PZ, Cleeman JI, Donato KA, et al. Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation. 2009;120(16):1640-5.
  26. Huxley R, Barzi F, Stolk R, Caterson I, Gill T, Lam TH, et al. Ethnic comparisons of obesity in the Asia-Pacific region: protocol for a collaborative overview of cross-sectional studies. Obes Rev. 2005;6(3):193-8.
  27. Lear SA, Humphries KH, Kohli S, Birmingham CL. The use of BMI and waist circumference as surrogates of body fat differs by ethnicity. Obesity (Silver Spring). 2007;15(11):2817-24.
  28. Kramer CK, Zinman B, Retnakaran R. Are metabolically healthy overweight and obesity benign conditions?: A systematic review and meta-analysis. Ann Intern Med. 2013;159(11):758-69.
  29. Kyrou I, Kumar S. Weight Management in Overweight and Obese Patients With Type 2 Diabetes Mellitus Br J Diabetes Vasc Dis. 2010(10):274-83.
  30. Tsigos C, Hainer V, Basdevant A, Finer N, Fried M, Mathus-Vliegen E, et al. Management of obesity in adults: European clinical practice guidelines. Obes Facts. 2008;1(2):106-16.
  31. Alley DE, Chang VW. The changing relationship of obesity and disability, 1988-2004. Jama. 2007;298(17):2020-7.
  32. Reynolds SL, Saito Y, Crimmins EM. The impact of obesity on active life expectancy in older American men and women. Gerontologist. 2005;45(4):438-44.
  33. Reuser M, Bonneux LG, Willekens FJ. Smoking kills, obesity disables: a multistate approach of the US Health and Retirement Survey. Obesity (Silver Spring). 2009;17(4):783-9.
  34. Walter S, Kunst A, Mackenbach J, Hofman A, Tiemeier H. Mortality and disability: the effect of overweight and obesity. Int J Obes (Lond). 2009;33(12):1410-8.
  35. Allender S, Rayner M. The burden of overweight and obesity-related ill health in the UK. Obes Rev. 2007;8(5):467-73.
  36. Health Do. Healthy Lives, Healthy People: A call to action on obesity in England. 2011.
  37. Scarborough P, Bhatnagar P, Wickramasinghe KK, Allender S, Foster C, Rayner M. The economic burden of ill health due to diet, physical inactivity, smoking, alcohol and obesity in the UK: an update to 2006-07 NHS costs. J Public Health (Oxf). 2011;33(4):527-35.
  38. Daniels SR. Complications of obesity in children and adolescents. Int J Obes (Lond). 2009;33 Suppl 1:S60-5.
  39. Park MH, Falconer C, Viner RM, Kinra S. The impact of childhood obesity on morbidity and mortality in adulthood: a systematic review. Obes Rev. 2012;13(11):985-1000.
  40. ADA. Standards of medical care in diabetes--2014. Diabetes Care. 2014;37 Suppl 1:S14-80.
  41. Field AE, Coakley EH, Must A, Spadano JL, Laird N, Dietz WH, et al. Impact of overweight on the risk of developing common chronic diseases during a 10-year period. Arch Intern Med. 2001;161(13):1581-6.
  42. Krug EG. Trends in diabetes: sounding the alarm. Lancet. 2016;387(10027):1485-6.
  43. Yates T, Khunti K. Epidemiology: The diabetes mellitus tsunami: worse than the 'Spanish flu' pandemic? Nat Rev Endocrinol. 2016;12(7):377-8.
  44. Astrup A, Finer N. Redefining type 2 diabetes: 'diabesity' or 'obesity dependent diabetes mellitus'? Obes Rev. 2000;1(2):57-9.
  45. Smyth S, Heron A. Diabetes and obesity: the twin epidemics. Nat Med. 2006;12(1):75-80.
  46. Chan JM, Rimm EB, Colditz GA, Stampfer MJ, Willett WC. Obesity, fat distribution, and weight gain as risk factors for clinical diabetes in men. Diabetes Care. 1994;17(9):961-9.
  47. 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):481-6.
  48. Schienkiewitz A, Schulze MB, Hoffmann K, Kroke A, Boeing H. Body mass index history and risk of type 2 diabetes: results from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam Study. Am J Clin Nutr. 2006;84(2):427-33.
  49. Wannamethee SG, Shaper AG. Weight change and duration of overweight and obesity in the incidence of type 2 diabetes. Diabetes Care. 1999;22(8):1266-72.
  50. Kautzky-Willer A, Handisurya A. Metabolic diseases and associated complications: sex and gender matter! Eur J Clin Invest. 2009;39(8):631-48.
  51. Regitz-Zagrosek V, Lehmkuhl E, Weickert MO. Gender differences in the metabolic syndrome and their role for cardiovascular disease. Clin Res Cardiol. 2006;95(3):136-47.
  52. Norhammar A, Schenck-Gustafsson K. Type 2 diabetes and cardiovascular disease in women. Diabetologia. 2013;56(1):1-9.
  53. Ehm MG, Karnoub MC, Sakul H, Gottschalk K, Holt DC, Weber JL, et al. Genomewide search for type 2 diabetes susceptibility genes in four American populations. Am J Hum Genet. 2000;66(6):1871-81.
  54. Karastergiou K. The Interplay Between Sex, Ethnicity, and Adipose Tissue Characteristics. Curr Obes Rep. 2015;4(2):269-78.
  55. Temneanu OR, Trandafir LM, Purcarea MR. Type 2 diabetes mellitus in children and adolescents: a relatively new clinical problem within pediatric practice. J Med Life. 2016;9(3):235-9.
  56. Alberti G, Zimmet P, Shaw J, Bloomgarden Z, Kaufman F, Silink M. Type 2 diabetes in the young: the evolving epidemic: the international diabetes federation consensus workshop. Diabetes Care. 2004;27(7):1798-811.
  57. Fazeli Farsani S, van der Aa MP, van der Vorst MM, Knibbe CA, de Boer A. Global trends in the incidence and prevalence of type 2 diabetes in children and adolescents: a systematic review and evaluation of methodological approaches. Diabetologia. 2013;56(7):1471-88.
  58. Liese AD, D'Agostino RB, Jr., Hamman RF, Kilgo PD, Lawrence JM, Liu LL, et al. The burden of diabetes mellitus among US youth: prevalence estimates from the SEARCH for Diabetes in Youth Study. Pediatrics. 2006;118(4):1510-8.
  59. Despres JP. Intra-abdominal obesity: an untreated risk factor for Type 2 diabetes and cardiovascular disease. J Endocrinol Invest. 2006;29(3 Suppl):77-82.
  60. Pi-Sunyer FX. The epidemiology of central fat distribution in relation to disease. Nutr Rev. 2004;62(7 Pt 2):S120-6.
  61. Kouli GM, Panagiotakos DB, Kyrou I, Georgousopoulou EN, Chrysohoou C, Tsigos C, et al. Visceral adiposity index and 10-year cardiovascular disease incidence: The ATTICA study. Nutr Metab Cardiovasc Dis. 2017;27(10):881-9.
  62. Ashwell M, Gunn P, Gibson S. Waist-to-height ratio is a better screening tool than waist circumference and BMI for adult cardiometabolic risk factors: systematic review and meta-analysis. Obes Rev. 2012;13(3):275-86.
  63. Schneider HJ, Glaesmer H, Klotsche J, Bohler S, Lehnert H, Zeiher AM, et al. Accuracy of anthropometric indicators of obesity to predict cardiovascular risk. J Clin Endocrinol Metab. 2007;92(2):589-94.
  64. Bjorntorp P. "Portal" adipose tissue as a generator of risk factors for cardiovascular disease and diabetes. Arteriosclerosis. 1990;10(4):493-6.
  65. Weiss R. Fat distribution and storage: how much, where, and how? Eur J Endocrinol. 2007;157 Suppl 1:S39-45.
  66. Montague CT, O'Rahilly S. The perils of portliness: causes and consequences of visceral adiposity. Diabetes. 2000;49(6):883-8.
  67. Yang X, Smith U. Adipose tissue distribution and risk of metabolic disease: does thiazolidinedione-induced adipose tissue redistribution provide a clue to the answer? Diabetologia. 2007;50(6):1127-39.
  68. Bjorntorp P, Rosmond R. Neuroendocrine abnormalities in visceral obesity. Int J Obes Relat Metab Disord. 2000;24 Suppl 2:S80-5.
  69. Kyrou I, Chrousos GP, Tsigos C. Stress, visceral obesity, and metabolic complications. Ann N Y Acad Sci. 2006;1083:77-110.
  70. Seckl JR, Morton NM, Chapman KE, Walker BR. Glucocorticoids and 11beta-hydroxysteroid dehydrogenase in adipose tissue. Recent Prog Horm Res. 2004;59:359-93.
  71. Reaven GM. Insulin resistance: the link between obesity and cardiovascular disease. Med Clin North Am. 2011;95(5):875-92.
  72. Najjar SM, Yang Y, Fernstrom MA, Lee SJ, Deangelis AM, Rjaily GA, et al. Insulin acutely decreases hepatic fatty acid synthase activity. Cell Metab. 2005;2(1):43-53.
  73. Isken F, Weickert MO, Tschop MH, Nogueiras R, Mohlig M, Abdelrahman A, et al. Metabolic effects of diets differing in glycaemic index depend on age and endogenous glucose-dependent insulinotrophic polypeptide in mice. Diabetologia. 2009;52(10):2159-68.
  74. Schenk S, Davidson CJ, Zderic TW, Byerley LO, Coyle EF. Different glycemic indexes of breakfast cereals are not due to glucose entry into blood but to glucose removal by tissue. Am J Clin Nutr. 2003;78(4):742-8.
  75. Weickert MO, Mohlig M, Koebnick C, Holst JJ, Namsolleck P, Ristow M, et al. Impact of cereal fibre on glucose-regulating factors. Diabetologia. 2005;48(11):2343-53.
  76. Clifton P. High protein diets and weight control. Nutr Metab Cardiovasc Dis. 2009;19(6):379-82.
  77. Davis JN, Alexander KE, Ventura EE, Toledo-Corral CM, Goran MI. Inverse relation between dietary fiber intake and visceral adiposity in overweight Latino youth. Am J Clin Nutr. 2009;90(5):1160-6.
  78. Due A, Toubro S, Skov AR, Astrup A. Effect of normal-fat diets, either medium or high in protein, on body weight in overweight subjects: a randomised 1-year trial. Int J Obes Relat Metab Disord. 2004;28(10):1283-90.
  79. Isken F, Klaus S, Osterhoff M, Pfeiffer AF, Weickert MO. Effects of long-term soluble vs. insoluble dietary fiber intake on high-fat diet-induced obesity in C57BL/6J mice. J Nutr Biochem. 2010;21(4):278-84.
  80. McKeown NM, Yoshida M, Shea MK, Jacques PF, Lichtenstein AH, Rogers G, et al. Whole-grain intake and cereal fiber are associated with lower abdominal adiposity in older adults. J Nutr. 2009;139(10):1950-5.
  81. Russell WR, Baka A, Bjorck I, Delzenne N, Gao D, Griffiths HR, et al. Impact of diet composition on blood glucose regulation. Crit Rev Food Sci Nutr. 2014.
  82. Weickert MO. What dietary modification best improves insulin sensitivity and why? Clin Endocrinol (Oxf). 2012;77(4):508-12.
  83. Weickert MO, Pfeiffer AF. [Preventing type 2 diabetes: what does dietary fiber achieve?]. MMW Fortschr Med. 2005;147(17):28-30.
  84. Weickert MO, Pfeiffer AF. Metabolic effects of dietary fiber consumption and prevention of diabetes. J Nutr. 2008;138(3):439-42.
  85. Weickert MO, Roden M, Isken F, Hoffmann D, Nowotny P, Osterhoff M, et al. Effects of supplemented isoenergetic diets differing in cereal fiber and protein content on insulin sensitivity in overweight humans. Am J Clin Nutr. 2012;94(2):459-71.
  86. Weickert MO. Nutritional modulation of insulin resistance. Scientifica (Cairo). 2012;2012:424780.
  87. Hession M, Rolland C, Kulkarni U, Wise A, Broom J. Systematic review of randomized controlled trials of low-carbohydrate vs. low-fat/low-calorie diets in the management of obesity and its comorbidities. Obes Rev. 2009;10(1):36-50.
  88. de Munter JS, Hu FB, Spiegelman D, Franz M, van Dam RM. Whole grain, bran, and germ intake and risk of type 2 diabetes: a prospective cohort study and systematic review. PLoS Med. 2007;4(8):e261.
  89. Schulze MB, Schulz M, Heidemann C, Schienkiewitz A, Hoffmann K, Boeing H. Fiber and magnesium intake and incidence of type 2 diabetes: a prospective study and meta-analysis. Arch Intern Med. 2007;167(9):956-65.
  90. Pi-Sunyer FX. Weight loss in type 2 diabetic patients. Diabetes Care. 2005;28(6):1526-7.
  91. Wang TJ, Larson MG, Vasan RS, Cheng S, Rhee EP, McCabe E, et al. Metabolite profiles and the risk of developing diabetes. Nat Med. 2011;17(4):448-53.
  92. Krebs M, Krssak M, Bernroider E, Anderwald C, Brehm A, Meyerspeer M, et al. Mechanism of amino acid-induced skeletal muscle insulin resistance in humans. Diabetes. 2002;51(3):599-605.
  93. Linn T, Santosa B, Gronemeyer D, Aygen S, Scholz N, Busch M, et al. Effect of long-term dietary protein intake on glucose metabolism in humans. Diabetologia. 2000;43(10):1257-65.
  94. Tremblay F, Brule S, Hee Um S, Li Y, Masuda K, Roden M, et al. Identification of IRS-1 Ser-1101 as a target of S6K1 in nutrient- and obesity-induced insulin resistance. Proc Natl Acad Sci U S A. 2007;104(35):14056-61.
  95. Tremblay F, Krebs M, Dombrowski L, Brehm A, Bernroider E, Roth E, et al. Overactivation of S6 kinase 1 as a cause of human insulin resistance during increased amino acid availability. Diabetes. 2005;54(9):2674-84.
  96. Um SH, D'Alessio D, Thomas G. Nutrient overload, insulin resistance, and ribosomal protein S6 kinase 1, S6K1. Cell Metab. 2006;3(6):393-402.
  97. Um SH, Frigerio F, Watanabe M, Picard F, Joaquin M, Sticker M, et al. Absence of S6K1 protects against age- and diet-induced obesity while enhancing insulin sensitivity. Nature. 2004;431(7005):200-5.
  98. Wolever TM, Hamad S, Gittelsohn J, Gao J, Hanley AJ, Harris SB, et al. Low dietary fiber and high protein intakes associated with newly diagnosed diabetes in a remote aboriginal community. Am J Clin Nutr. 1997;66(6):1470-4.
  99. Hattersley JG, Pfeiffer AF, Roden M, Petzke KJ, Hoffmann D, Rudovich NN, et al. Modulation of amino acid metabolic signatures by supplemented isoenergetic diets differing in protein and cereal fiber content. J Clin Endocrinol Metab. 2014;99(12):E2599-609.
  100. de Koning L, Fung TT, Liao X, Chiuve SE, Rimm EB, Willett WC, et al. Low-carbohydrate diet scores and risk of type 2 diabetes in men. Am J Clin Nutr. 2011;93(4):844-50.
  101. Sluijs I, Beulens JW, van der AD, Spijkerman AM, Grobbee DE, van der Schouw YT. Dietary intake of total, animal, and vegetable protein and risk of type 2 diabetes in the European Prospective Investigation into Cancer and Nutrition (EPIC)-NL study. Diabetes Care. 2010;33(1):43-8.
  102. Lagiou P, Sandin S, Lof M, Trichopoulos D, Adami HO, Weiderpass E. Low carbohydrate-high protein diet and incidence of cardiovascular diseases in Swedish women: prospective cohort study. Bmj. 2012;344:e4026.
  103. Levine ME, Suarez JA, Brandhorst S, Balasubramanian P, Cheng CW, Madia F, et al. Low Protein Intake Is Associated with a Major Reduction in IGF-1, Cancer, and Overall Mortality in the 65 and Younger but Not Older Population. Cell Metab. 2014;19(3):407-17.
  104. Chevalier S, Marliss EB, Morais JA, Lamarche M, Gougeon R. Whole-body protein anabolic response is resistant to the action of insulin in obese women. Am J Clin Nutr. 2005;82(2):355-65.
  105. Glynn EL, Lujan HL, Kramer VJ, Drummond MJ, DiCarlo SE, Rasmussen BB. A chronic increase in physical activity inhibits fed-state mTOR/S6K1 signaling and reduces IRS-1 serine phosphorylation in rat skeletal muscle. Appl Physiol Nutr Metab. 2008;33(1):93-101.
  106. Abdul-Ghani MA, DeFronzo RA. Pathophysiology of prediabetes. Curr Diab Rep. 2009;9(3):193-9.
  107. DeFronzo RA. Pathogenesis of type 2 diabetes mellitus. Med Clin North Am. 2004;88(4):787-835, ix.
  108. Bays H, Mandarino L, DeFronzo RA. Role of the adipocyte, free fatty acids, and ectopic fat in pathogenesis of type 2 diabetes mellitus: peroxisomal proliferator-activated receptor agonists provide a rational therapeutic approach. J Clin Endocrinol Metab. 2004;89(2):463-78.
  109. Boden G. Effects of free fatty acids (FFA) on glucose metabolism: significance for insulin resistance and type 2 diabetes. Exp Clin Endocrinol Diabetes. 2003;111(3):121-4.
  110. Weickert MO, Pfeiffer AF. Signalling mechanisms linking hepatic glucose and lipid metabolism. Diabetologia. 2006;49(8):1732-41.
  111. Roden M, Bernroider E. Hepatic glucose metabolism in humans--its role in health and disease. Best Pract Res Clin Endocrinol Metab. 2003;17(3):365-83.
  112. DeFronzo RA, Ferrannini E, Simonson DC. Fasting hyperglycemia in non-insulin-dependent diabetes mellitus: contributions of excessive hepatic glucose production and impaired tissue glucose uptake. Metabolism. 1989;38(4):387-95.
  113. Shulman GI, Rothman DL, Jue T, Stein P, DeFronzo RA, Shulman RG. Quantitation of muscle glycogen synthesis in normal subjects and subjects with non-insulin-dependent diabetes by 13C nuclear magnetic resonance spectroscopy. N Engl J Med. 1990;322(4):223-8.
  114. McGarry JD. Banting lecture 2001: dysregulation of fatty acid metabolism in the etiology of type 2 diabetes. Diabetes. 2002;51(1):7-18.
  115. Kashyap S, Belfort R, Gastaldelli A, Pratipanawatr T, Berria R, Pratipanawatr W, et al. A sustained increase in plasma free fatty acids impairs insulin secretion in nondiabetic subjects genetically predisposed to develop type 2 diabetes. Diabetes. 2003;52(10):2461-74.
  116. Cusi K, Kashyap S, Gastaldelli A, Bajaj M, Cersosimo E. Effects on insulin secretion and insulin action of a 48-h reduction of plasma free fatty acids with acipimox in nondiabetic subjects genetically predisposed to type 2 diabetes. Am J Physiol Endocrinol Metab. 2007;292(6):E1775-81.
  117. Ferrannini E, Gastaldelli A, Miyazaki Y, Matsuda M, Mari A, DeFronzo RA. beta-Cell function in subjects spanning the range from normal glucose tolerance to overt diabetes: a new analysis. J Clin Endocrinol Metab. 2005;90(1):493-500.
  118. Ferrannini E, Gastaldelli A, Miyazaki Y, Matsuda M, Pettiti M, Natali A, et al. Predominant role of reduced beta-cell sensitivity to glucose over insulin resistance in impaired glucose tolerance. Diabetologia. 2003;46(9):1211-9.
  119. Leitner DR, Fruhbeck G, Yumuk V, Schindler K, Micic D, Woodward E, et al. Obesity and Type 2 Diabetes: Two Diseases with a Need for Combined Treatment Strategies - EASO Can Lead the Way. Obes Facts. 2017;10(5):483-92.
  120. Ryan DH, Yockey SR. Weight Loss and Improvement in Comorbidity: Differences at 5%, 10%, 15%, and Over. Curr Obes Rep. 2017;6(2):187-94.
  121. Fujimoto WY, Jablonski KA, Bray GA, Kriska A, Barrett-Connor E, Haffner S, et al. Body size and shape changes and the risk of diabetes in the diabetes prevention program. Diabetes. 2007;56(6):1680-5.
  122. Knowler WC, Fowler SE, Hamman RF, Christophi CA, Hoffman HJ, Brenneman AT, et al. 10-year follow-up of diabetes incidence and weight loss in the Diabetes Prevention Program Outcomes Study. Lancet. 2009;374(9702):1677-86.
  123. Laaksonen DE, Lindstrom J, Lakka TA, Eriksson JG, Niskanen L, Wikstrom K, et al. Physical activity in the prevention of type 2 diabetes: the Finnish diabetes prevention study. Diabetes. 2005;54(1):158-65.
  124. Lindstrom J, Ilanne-Parikka P, Peltonen M, Aunola S, Eriksson JG, Hemio K, et al. Sustained reduction in the incidence of type 2 diabetes by lifestyle intervention: follow-up of the Finnish Diabetes Prevention Study. Lancet. 2006;368(9548):1673-9.
  125. Merlotti C, Morabito A, Pontiroli AE. Prevention of type 2 diabetes; a systematic review and meta-analysis of different intervention strategies. Diabetes Obes Metab. 2014.
  126. Penn L, White M, Oldroyd J, Walker M, Alberti KG, Mathers JC. Prevention of type 2 diabetes in adults with impaired glucose tolerance: the European Diabetes Prevention RCT in Newcastle upon Tyne, UK. BMC Public Health. 2009;9:342.
  127. Tuomilehto J, Lindstrom J, Eriksson JG, Valle TT, Hamalainen H, Ilanne-Parikka P, et al. Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N Engl J Med. 2001;344(18):1343-50.
  128. Reilly SM, Saltiel AR. Adapting to obesity with adipose tissue inflammation. Nat Rev Endocrinol. 2017;13(11):633-43.
  129. Rheinheimer J, de Souza BM, Cardoso NS, Bauer AC, Crispim D. Current role of the NLRP3 inflammasome on obesity and insulin resistance: A systematic review. Metabolism. 2017;74:1-9.
  130. Gregor MF, Hotamisligil GS. Inflammatory mechanisms in obesity. Annu Rev Immunol. 2011;29:415-45.
  131. Hotamisligil GS. Inflammation and metabolic disorders. Nature. 2006;444(7121):860-7.
  132. Makki K, Froguel P, Wolowczuk I. Adipose Tissue in Obesity-Related Inflammation and Insulin Resistance: Cells, Cytokines, and Chemokines. ISRN Inflamm. 2013;2013:139239.
  133. Maury E, Brichard SM. Adipokine dysregulation, adipose tissue inflammation and metabolic syndrome. Mol Cell Endocrinol. 2010;314(1):1-16.
  134. Randeva HS, Tan BK, Weickert MO, Lois K, Nestler JE, Sattar N, et al. Cardiometabolic aspects of the polycystic ovary syndrome. Endocr Rev. 2012;33(5):812-41.
  135. Sivakumar K, Bari MF, Adaikalakoteswari A, Guller S, Weickert MO, Randeva HS, et al. Elevated fetal adipsin/acylation-stimulating protein (ASP) in obese pregnancy: novel placental secretion via Hofbauer cells. J Clin Endocrinol Metab. 2013;98(10):4113-22.
  136. von Loeffelholz C, Mohlig M, Arafat AM, Isken F, Spranger J, Mai K, et al. Circulating vaspin is unrelated to insulin sensitivity in a cohort of nondiabetic humans. Eur J Endocrinol. 2013;162(3):507-13.
  137. Weickert MO, Hodges P, Tan BK, Randeva HS. Neuroendocrine and endocrine dysfunction in the hyperinsulinemic PCOS patient: the role of metformin. Minerva Endocrinol. 2012;37(1):25-40.
  138. Bobbert T, Rochlitz H, Wegewitz U, Akpulat S, Mai K, Weickert MO, et al. Changes of adiponectin oligomer composition by moderate weight reduction. Diabetes. 2005;54(9):2712-9.
  139. von Loeffelholz C, Mohlig M, Arafat AM, Isken F, Spranger J, Mai K, et al. Circulating vaspin is unrelated to insulin sensitivity in a cohort of nondiabetic humans. Eur J Endocrinol. 2010;162(3):507-13.
  140. Mohlig M, Weickert MO, Ghadamgadai E, Machlitt A, Pfuller B, Arafat AM, et al. Adipocyte fatty acid-binding protein is associated with markers of obesity, but is an unlikely link between obesity, insulin resistance, and hyperandrogenism in polycystic ovary syndrome women. Eur J Endocrinol. 2007;157(2):195-200.
  141. Mohlig M, Freudenberg M, Bobbert T, Ristow M, Rochlitz H, Weickert MO, et al. Acetylsalicylic acid improves lipid-induced insulin resistance in healthy men. J Clin Endocrinol Metab. 2006;91(3):964-7.
  142. Kyrou I, Mattu HS, Chatha K, Randeva HS. Fat hormones, adipokines. in: J.C. Schisler, C.H. Lang, M.S. Willis (Eds.) Endocrinology of the heart in health and disease. Academic Press. 2017:167–205
  143. Libby P. Inflammation in atherosclerosis. Nature. 2002;420(6917):868-74.
  144. Rocha VZ, Libby P. Obesity, inflammation, and atherosclerosis. Nat Rev Cardiol. 2009;6(6):399-409.
  145. Samad F, Ruf W. Inflammation, obesity, and thrombosis. Blood. 2013;122(20):3415-22.
  146. Shoelson SE, Lee J, Goldfine AB. Inflammation and insulin resistance. J Clin Invest. 2006;116(7):1793-801.
  147. Lee J. Adipose tissue macrophages in the development of obesity-induced inflammation, insulin resistance and type 2 diabetes. Arch Pharm Res. 2013;36(2):208-22.
  148. Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel RL, Ferrante AW, Jr. Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest. 2003;112(12):1796-808.
  149. Xu H, Barnes GT, Yang Q, Tan G, Yang D, Chou CJ, et al. Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J Clin Invest. 2003;112(12):1821-30.
  150. Carey AL, Febbraio MA. Interleukin-6 and insulin sensitivity: friend or foe? Diabetologia. 2004;47(7):1135-42.
  151. Wellen KE, Hotamisligil GS. Obesity-induced inflammatory changes in adipose tissue. J Clin Invest. 2003;112(12):1785-8.
  152. Tilg H, Moschen AR. Adipocytokines: mediators linking adipose tissue, inflammation and immunity. Nat Rev Immunol. 2006;6(10):772-83.
  153. Yudkin JS. Inflammation, obesity, and the metabolic syndrome. Horm Metab Res. 2007;39(10):707-9.
  154. Alessi MC, Juhan-Vague I. PAI-1 and the metabolic syndrome: links, causes, and consequences. Arterioscler Thromb Vasc Biol. 2006;26(10):2200-7.
  155. Ernst E, Resch KL. Fibrinogen as a cardiovascular risk factor: a meta-analysis and review of the literature. Ann Intern Med. 1993;118(12):956-63.
  156. Kannel WB, Wolf PA, Castelli WP, D'Agostino RB. Fibrinogen and risk of cardiovascular disease. The Framingham Study. Jama. 1987;258(9):1183-6.
  157. Nieuwdorp M, Stroes ES, Meijers JC, Buller H. Hypercoagulability in the metabolic syndrome. Curr Opin Pharmacol. 2005;5(2):155-9.
  158. Davalos D, Akassoglou K. Fibrinogen as a key regulator of inflammation in disease. Semin Immunopathol. 2012;34(1):43-62.
  159. Woodward M, Lowe GD, Rumley A, Tunstall-Pedoe H, Philippou H, Lane DA, et al. Epidemiology of coagulation factors, inhibitors and activation markers: The Third Glasgow MONICA Survey. II. Relationships to cardiovascular risk factors and prevalent cardiovascular disease. Br J Haematol. 1997;97(4):785-97.
  160. Duncan BB, Schmidt MI, Chambless LE, Folsom AR, Carpenter M, Heiss G. Fibrinogen, other putative markers of inflammation, and weight gain in middle-aged adults--the ARIC study. Atherosclerosis Risk in Communities. Obes Res. 2000;8(4):279-86.
  161. Chen R, Yan J, Liu P, Wang Z, Wang C. Plasminogen activator inhibitor links obesity and thrombotic cerebrovascular diseases: The roles of PAI-1 and obesity on stroke. Metab Brain Dis. 2017;32(3):667-73.
  162. Juhan-Vague I, Pyke SD, Alessi MC, Jespersen J, Haverkate F, Thompson SG. Fibrinolytic factors and the risk of myocardial infarction or sudden death in patients with angina pectoris. ECAT Study Group. European Concerted Action on Thrombosis and Disabilities. Circulation. 1996;94(9):2057-63.
  163. Matsuzawa Y. The metabolic syndrome and adipocytokines. FEBS Lett. 2006;580(12):2917-21.
  164. Mertens I, Ballaux D, Funahashi T, Matsuzawa Y, Van der Planken M, Verrijken A, et al. Inverse relationship between plasminogen activator inhibitor-I activity and adiponectin in overweight and obese women. Interrelationship with visceral adipose tissue, insulin resistance, HDL-chol and inflammation. Thromb Haemost. 2005;94(6):1190-5.
  165. Shimomura I, Funahashi T, Takahashi M, Maeda K, Kotani K, Nakamura T, et al. Enhanced expression of PAI-1 in visceral fat: possible contributor to vascular disease in obesity. Nat Med. 1996;2(7):800-3.
  166. Kaji H. Adipose Tissue-Derived Plasminogen Activator Inhibitor-1 Function and Regulation. Compr Physiol. 2016;6(4):1873-96.
  167. Creely SJ, McTernan PG, Kusminski CM, Fisher f M, Da Silva NF, Khanolkar M, et al. Lipopolysaccharide activates an innate immune system response in human adipose tissue in obesity and type 2 diabetes. Am J Physiol Endocrinol Metab. 2007;292(3):E740-7.
  168. Lehrke M, Lazar MA. Inflamed about obesity. Nat Med. 2004;10(2):126-7.
  169. Cousin B, Andre M, Casteilla L, Penicaud L. Altered macrophage-like functions of preadipocytes in inflammation and genetic obesity. J Cell Physiol. 2001;186(3):380-6.
  170. Cousin B, Munoz O, Andre M, Fontanilles AM, Dani C, Cousin JL, et al. A role for preadipocytes as macrophage-like cells. Faseb J. 1999;13(2):305-12.
  171. Clement K, Langin D. Regulation of inflammation-related genes in human adipose tissue. J Intern Med. 2007;262(4):422-30.
  172. Ferrante AW, Jr. Obesity-induced inflammation: a metabolic dialogue in the language of inflammation. J Intern Med. 2007;262(4):408-14.
  173. Schaffler A, Scholmerich J, Salzberger B. Adipose tissue as an immunological organ: Toll-like receptors, C1q/TNFs and CTRPs. Trends Immunol. 2007;28(9):393-9.
  174. Stolarczyk E. Adipose tissue inflammation in obesity: a metabolic or immune response? Curr Opin Pharmacol. 2017;37:35-40.
  175. Reaven GM. Banting lecture 1988. Role of insulin resistance in human disease. Diabetes. 1988;37(12):1595-607.
  176. Kaplan NM. The deadly quartet. Upper-body obesity, glucose intolerance, hypertriglyceridemia, and hypertension. Arch Intern Med. 1989;149(7):1514-20.
  177. Kassi E, Pervanidou P, Kaltsas G, Chrousos G. Metabolic syndrome: definitions and controversies. BMC Med. 2011;9:48.
  178. World Health Organization G. Definition, Diagnosis, and Classification of Diabetes Mellitus and its Complications: Report of a WHO Consultation. . 1999.
  179. Ford ES, Li C, Zhao G. Prevalence and correlates of metabolic syndrome based on a harmonious definition among adults in the US. J Diabetes. 2010;2(3):180-93.
  180. Kahn R, Buse J, Ferrannini E, Stern M. The metabolic syndrome: time for a critical appraisal. Joint statement from the American Diabetes Association and the European Association for the Study of Diabetes. Diabetologia. 2005;48(9):1684-99.
  181. Pi-Sunyer X. The metabolic syndrome: how to approach differing definitions. Med Clin North Am. 2007;91(6):1025-40, vii.
  182. Mottillo S, Filion KB, Genest J, Joseph L, Pilote L, Poirier P, et al. The metabolic syndrome and cardiovascular risk a systematic review and meta-analysis. J Am Coll Cardiol. 2010;56(14):1113-32.
  183. Alberti KG, Zimmet PZ. Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus provisional report of a WHO consultation. Diabet Med. 1998;15(7):539-53.
  184. Balkau B, Charles MA. Comment on the provisional report from the WHO consultation. European Group for the Study of Insulin Resistance (EGIR). Diabet Med. 1999;16(5):442-3.
  185. Expert-Panel. 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):2486-97.
  186. Alberti KG, Zimmet P, Shaw J. The metabolic syndrome--a new worldwide definition. Lancet. 2005;366(9491):1059-62.
  187. IDF. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. 2006.
  188. Hara K, Matsushita Y, Horikoshi M, Yoshiike N, Yokoyama T, Tanaka H, et al. A proposal for the cutoff point of waist circumference for the diagnosis of metabolic syndrome in the Japanese population. Diabetes Care. 2006;29(5):1123-4.
  189. Oka R, Kobayashi J, Yagi K, Tanii H, Miyamoto S, Asano A, et al. Reassessment of the cutoff values of waist circumference and visceral fat area for identifying Japanese subjects at risk for the metabolic syndrome. Diabetes Res Clin Pract. 2008;79(3):474-81.
  190. Zhou BF. Predictive values of body mass index and waist circumference for risk factors of certain related diseases in Chinese adults--study on optimal cut-off points of body mass index and waist circumference in Chinese adults. Biomed Environ Sci. 2002;15(1):83-96.
  191. Grundy SM. Metabolic syndrome: a multiplex cardiovascular risk factor. J Clin Endocrinol Metab. 2007;92(2):399-404.
  192. de Zeeuw D, Bakker SJ. Does the metabolic syndrome add to the diagnosis and treatment of cardiovascular disease? Nat Clin Pract Cardiovasc Med. 2008;5 Suppl 1:S10-4.
  193. Gale EA. The myth of the metabolic syndrome. Diabetologia. 2005;48(9):1679-83.
  194. Preiss D, Sattar N. Metabolic syndrome: collapsing under its own weight? Diabet Med. 2009;26(5):457-9.
  195. Reaven GM. The metabolic syndrome: requiescat in pace. Clin Chem. 2005;51(6):931-8.
  196. Sattar N. Why metabolic syndrome criteria have not made prime time: a view from the clinic. Int J Obes (Lond). 2008;32 Suppl 2:S30-4.
  197. Sattar N, McConnachie A, Shaper AG, Blauw GJ, Buckley BM, de Craen AJ, et al. Can metabolic syndrome usefully predict cardiovascular disease and diabetes? Outcome data from two prospective studies. Lancet. 2008;371(9628):1927-35.
  198. Simmons RK, Alberti KG, Gale EA, Colagiuri S, Tuomilehto J, Qiao Q, et al. The metabolic syndrome: useful concept or clinical tool? Report of a WHO Expert Consultation. Diabetologia. 2010;53(4):600-5.
  199. Borch-Johnsen K, Wareham N. The rise and fall of the metabolic syndrome. Diabetologia. 2010;53(4):597-9.
  200. Vassallo P, Driver SL, Stone NJ. Metabolic Syndrome: An Evolving Clinical Construct. Prog Cardiovasc Dis. 2016;59(2):172-7.
  201. Diehl AM, Day C. Cause, Pathogenesis, and Treatment of Nonalcoholic Steatohepatitis. N Engl J Med. 2017;377(21):2063-72.
  202. Rinella ME. Nonalcoholic fatty liver disease: a systematic review. JAMA. 2015;313(22):2263-73.
  203. Chalasani N, Younossi Z, Lavine JE, Diehl AM, Brunt EM, Cusi K, et al. The diagnosis and management of non-alcoholic fatty liver disease: practice Guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association. Hepatology. 2012;55(6):2005-23.
  204. Fabbrini E, Sullivan S, Klein S. Obesity and nonalcoholic fatty liver disease: biochemical, metabolic, and clinical implications. Hepatology. 2010;51(2):679-89.
  205. Masuoka HC, Chalasani N. Nonalcoholic fatty liver disease: an emerging threat to obese and diabetic individuals. Ann N Y Acad Sci. 2013;1281:106-22.
  206. Qureshi K, Abrams GA. Metabolic liver disease of obesity and role of adipose tissue in the pathogenesis of nonalcoholic fatty liver disease. World J Gastroenterol. 2007;13(26):3540-53.
  207. Smith BW, Adams LA. Nonalcoholic fatty liver disease and diabetes mellitus: pathogenesis and treatment. Nat Rev Endocrinol. 2011;7(8):456-65.
  208. Williams KH, Shackel NA, Gorrell MD, McLennan SV, Twigg SM. Diabetes and nonalcoholic Fatty liver disease: a pathogenic duo. Endocr Rev. 2013;34(1):84-129.
  209. Zelman S. The liver in obesity. AMA Arch Intern Med. 1952;90(2):141-56.
  210. Ludwig J, Viggiano TR, McGill DB, Oh BJ. Nonalcoholic steatohepatitis: Mayo Clinic experiences with a hitherto unnamed disease. Mayo Clin Proc. 1980;55(7):434-8.
  211. Brunt EM. Nonalcoholic steatohepatitis. Semin Liver Dis. 2004;24(1):3-20.
  212. Brunt EM. Pathology of nonalcoholic fatty liver disease. Nat Rev Gastroenterol Hepatol. 2010;7(4):195-203.
  213. Brunt EM, Tiniakos DG. Histopathology of nonalcoholic fatty liver disease. World J Gastroenterol. 2010;16(42):5286-96.
  214. Matteoni CA, Younossi ZM, Gramlich T, Boparai N, Liu YC, McCullough AJ. Nonalcoholic fatty liver disease: a spectrum of clinical and pathological severity. Gastroenterology. 1999;116(6):1413-9.
  215. Kleiner DE, Brunt EM, Van Natta M, Behling C, Contos MJ, Cummings OW, et al. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology. 2005;41(6):1313-21.
  216. European Association for the Study of the L, European Association for the Study of D, European Association for the Study of O. EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease. Diabetologia. 2016;59(6):1121-40.
  217. McPherson S, Stewart SF, Henderson E, Burt AD, Day CP. Simple non-invasive fibrosis scoring systems can reliably exclude advanced fibrosis in patients with non-alcoholic fatty liver disease. Gut. 2010;59(9):1265-9.
  218. Musso G, Gambino R, Cassader M, Pagano G. Meta-analysis: natural history of non-alcoholic fatty liver disease (NAFLD) and diagnostic accuracy of non-invasive tests for liver disease severity. Ann Med. 2011;43(8):617-49.
  219. Farrell GC, Wong VW, Chitturi S. NAFLD in Asia--as common and important as in the West. Nat Rev Gastroenterol Hepatol. 2013;10(5):307-18.
  220. Vernon G, Baranova A, Younossi ZM. Systematic review: the epidemiology and natural history of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in adults. Aliment Pharmacol Ther. 2011;34(3):274-85.
  221. Angulo P. GI epidemiology: nonalcoholic fatty liver disease. Aliment Pharmacol Ther. 2007;25(8):883-9.
  222. Estes C, Razavi H, Loomba R, Younossi Z, Sanyal AJ. Modeling the epidemic of nonalcoholic fatty liver disease demonstrates an exponential increase in burden of disease. Hepatology. 2017.
  223. Younossi ZM, Koenig AB, Abdelatif D, Fazel Y, Henry L, Wymer M. Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology. 2016;64(1):73-84.
  224. Beymer C, Kowdley KV, Larson A, Edmonson P, Dellinger EP, Flum DR. Prevalence and predictors of asymptomatic liver disease in patients undergoing gastric bypass surgery. Arch Surg. 2003;138(11):1240-4.
  225. Machado M, Marques-Vidal P, Cortez-Pinto H. Hepatic histology in obese patients undergoing bariatric surgery. J Hepatol. 2006;45(4):600-6.
  226. Giorgio V, Prono F, Graziano F, Nobili V. Pediatric non alcoholic fatty liver disease: old and new concepts on development, progression, metabolic insight and potential treatment targets. BMC Pediatr. 2013;13:40.
  227. Clark JM. The epidemiology of nonalcoholic fatty liver disease in adults. J Clin Gastroenterol. 2006;40 Suppl 1:S5-10.
  228. Anstee QM, Day CP. The genetics of NAFLD. Nat Rev Gastroenterol Hepatol. 2013;10(11):645-55.
  229. Browning JD, Szczepaniak LS, Dobbins R, Nuremberg P, Horton JD, Cohen JC, et al. Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity. Hepatology. 2004;40(6):1387-95.
  230. Sanyal AJ. Nonalcoholic fatty liver disease in the Indian subcontinent: a medical consequence of globalization? Indian J Gastroenterol. 2001;20(6):215-6.
  231. Loomba R, Chalasani N. The Hierarchical Model of NAFLD: Prognostic Significance of Histologic Features in NASH. Gastroenterology. 2015;149(2):278-81.
  232. Angulo P. Long-term mortality in nonalcoholic fatty liver disease: is liver histology of any prognostic significance? Hepatology. 2010;51(2):373-5.
  233. De Minicis S, Day C, Svegliati-Baroni G. From NAFLD to NASH and HCC: pathogenetic mechanisms and therapeutic insights. Curr Pharm Des. 2013;19(29):5239-49.
  234. Falck-Ytter Y, Younossi ZM, Marchesini G, McCullough AJ. Clinical features and natural history of nonalcoholic steatosis syndromes. Semin Liver Dis. 2001;21(1):17-26.
  235. Ratziu V, Poynard T. Assessing the outcome of nonalcoholic steatohepatitis? It's time to get serious. Hepatology. 2006;44(4):802-5.
  236. Ong JP, Younossi ZM. Epidemiology and natural history of NAFLD and NASH. Clin Liver Dis. 2007;11(1):1-16, vii.
  237. Siegel AB, Zhu AX. Metabolic syndrome and hepatocellular carcinoma: two growing epidemics with a potential link. Cancer. 2009;115(24):5651-61.
  238. Ekstedt M, Franzen LE, Mathiesen UL, Thorelius L, Holmqvist M, Bodemar G, et al. Long-term follow-up of patients with NAFLD and elevated liver enzymes. Hepatology. 2006;44(4):865-73.
  239. Soderberg C, Stal P, Askling J, Glaumann H, Lindberg G, Marmur J, et al. Decreased survival of subjects with elevated liver function tests during a 28-year follow-up. Hepatology. 2010;51(2):595-602.
  240. Caldwell SH, Crespo DM. The spectrum expanded: cryptogenic cirrhosis and the natural history of non-alcoholic fatty liver disease. J Hepatol. 2004;40(4):578-84.
  241. Maheshwari A, Thuluvath PJ. Cryptogenic cirrhosis and NAFLD: are they related? Am J Gastroenterol. 2006;101(3):664-8.
  242. Day CP, James OF. Steatohepatitis: a tale of two "hits"? Gastroenterology. 1998;114(4):842-5.
  243. Larter CZ, Chitturi S, Heydet D, Farrell GC. A fresh look at NASH pathogenesis. Part 1: the metabolic movers. J Gastroenterol Hepatol. 2010;25(4):672-90.
  244. Doulberis M, Kotronis G, Gialamprinou D, Kountouras J, Katsinelos P. Non-alcoholic fatty liver disease: An update with special focus on the role of gut microbiota. Metabolism. 2017;71:182-97.
  245. Gariani K, Philippe J, Jornayvaz FR. Non-alcoholic fatty liver disease and insulin resistance: from bench to bedside. Diabetes Metab. 2013;39(1):16-26.
  246. Moschen AR, Kaser S, Tilg H. Non-alcoholic steatohepatitis: a microbiota-driven disease. Trends Endocrinol Metab. 2013;24(11):537-45.
  247. Sun Z, Lazar MA. Dissociating fatty liver and diabetes. Trends Endocrinol Metab. 2013;24(1):4-12.
  248. Nielsen S, Guo Z, Johnson CM, Hensrud DD, Jensen MD. Splanchnic lipolysis in human obesity. J Clin Invest. 2004;113(11):1582-8.
  249. Gibbons G. Old fat, make way for new fat. Nat Med. 2005;11(7):722-3.
  250. Donnelly KL, Smith CI, Schwarzenberg SJ, Jessurun J, Boldt MD, Parks EJ. Sources of fatty acids stored in liver and secreted via lipoproteins in patients with nonalcoholic fatty liver disease. J Clin Invest. 2005;115(5):1343-51.
  251. Roden M. Mechanisms of Disease: hepatic steatosis in type 2 diabetes--pathogenesis and clinical relevance. Nat Clin Pract Endocrinol Metab. 2006;2(6):335-48.
  252. Day CP. From fat to inflammation. Gastroenterology. 2006;130(1):207-10.
  253. Li Z, Diehl AM. Innate immunity in the liver. Curr Opin Gastroenterol. 2003;19(6):565-71.
  254. Tomita K, Tamiya G, Ando S, Ohsumi K, Chiyo T, Mizutani A, et al. Tumour necrosis factor alpha signalling through activation of Kupffer cells plays an essential role in liver fibrosis of non-alcoholic steatohepatitis in mice. Gut. 2006;55(3):415-24.
  255. Nascimbeni F, Pais R, Bellentani S, Day CP, Ratziu V, Loria P, et al. From NAFLD in clinical practice to answers from guidelines. J Hepatol. 2013;59(4):859-71.
  256. Smelt AH. Triglycerides and gallstone formation. Clin Chim Acta. 2010;411(21-22):1625-31.
  257. Stinton LM, Myers RP, Shaffer EA. Epidemiology of gallstones. Gastroenterol Clin North Am. 2010;39(2):157-69, vii.
  258. Shaffer EA. Gallstone disease: Epidemiology of gallbladder stone disease. Best Pract Res Clin Gastroenterol. 2006;20(6):981-96.
  259. Marschall HU, Einarsson C. Gallstone disease. J Intern Med. 2007;261(6):529-42.
  260. Shaffer EA. Epidemiology and risk factors for gallstone disease: has the paradigm changed in the 21st century? Curr Gastroenterol Rep. 2005;7(2):132-40.
  261. Maclure KM, Hayes KC, Colditz GA, Stampfer MJ, Speizer FE, Willett WC. Weight, diet, and the risk of symptomatic gallstones in middle-aged women. N Engl J Med. 1989;321(9):563-9.
  262. Must A, Spadano J, Coakley EH, Field AE, Colditz G, Dietz WH. The disease burden associated with overweight and obesity. Jama. 1999;282(16):1523-9.
  263. 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):652-8.
  264. Tucker LE, Tangedahl TN, Newmark SR. Prevalence of gallstones in obese Caucasian American women. Int J Obes. 1982;6(3):247-51.
  265. Attili AF, Capocaccia R, Carulli N, Festi D, Roda E, Barbara L, et al. Factors associated with gallstone disease in the MICOL experience. Multicenter Italian Study on Epidemiology of Cholelithiasis. Hepatology. 1997;26(4):809-18.
  266. Kaechele V, Wabitsch M, Thiere D, Kessler AL, Haenle MM, Mayer H, et al. Prevalence of gallbladder stone disease in obese children and adolescents: influence of the degree of obesity, sex, and pubertal development. J Pediatr Gastroenterol Nutr. 2006;42(1):66-70.
  267. Mehta S, Lopez ME, Chumpitazi BP, Mazziotti MV, Brandt ML, Fishman DS. Clinical characteristics and risk factors for symptomatic pediatric gallbladder disease. Pediatrics. 2012;129(1):e82-8.
  268. Svensson J, Makin E. Gallstone disease in children. Semin Pediatr Surg. 2012;21(3):255-65.
  269. Ruhl CE, Everhart JE. Relationship of serum leptin concentration and other measures of adiposity with gallbladder disease. Hepatology. 2001;34(5):877-83.
  270. Heaton KW, Emmett PM. Insulin and gall stones. Gut. 2001;48(5):737-8.
  271. Tsai CJ, Leitzmann MF, Willett WC, Giovannucci EL. Prospective study of abdominal adiposity and gallstone disease in US men. Am J Clin Nutr. 2004;80(1):38-44.
  272. Tsai CJ, Leitzmann MF, Willett WC, Giovannucci EL. Central adiposity, regional fat distribution, and the risk of cholecystectomy in women. Gut. 2006;55(5):708-14.
  273. Dittrick GW, Thompson JS, Campos D, Bremers D, Sudan D. Gallbladder pathology in morbid obesity. Obes Surg. 2005;15(2):238-42.
  274. Tsai CJ. Steatocholecystitis and fatty gallbladder disease. Dig Dis Sci. 2009;54(9):1857-63.
  275. Yoon JH, Kim YJ, Baik GH, Kim YS, Suk KT, Kim JB, et al. The Impact of Body Mass Index as a Predictive Factor of Steatocholecystitis. Hepatogastroenterology. 2014;61(132):902-7.
  276. Liew PL, Lee WJ, Wang W, Lee YC, Chen WY, Fang CL, et al. Fatty liver disease: predictors of nonalcoholic steatohepatitis and gallbladder disease in morbid obesity. Obes Surg. 2008;18(7):847-53.
  277. Koller T, Kollerova J, Hlavaty T, Huorka M, Payer J. Cholelithiasis and markers of nonalcoholic fatty liver disease in patients with metabolic risk factors. Scand J Gastroenterol. 2012;47(2):197-203.
  278. Liu B, Balkwill A, Spencer E, Beral V. Relationship between body mass index and length of hospital stay for gallbladder disease. J Public Health (Oxf). 2008;30(2):161-6.
  279. Paajanen H, Kakela P, Suuronen S, Paajanen J, Juvonen P, Pihlajamaki J. Impact of obesity and associated diseases on outcome after laparoscopic cholecystectomy. Surg Laparosc Endosc Percutan Tech. 2012;22(6):509-13.
  280. Angelin B, Einarsson K, Ewerth S, Leijd B. Biliary lipid composition in obesity. Scand J Gastroenterol. 1981;16(8):1015-9.
  281. Mabee TM, Meyer P, DenBesten L, Mason EE. The mechanism of increased gallstone formation in obese human subjects. Surgery. 1976;79(4):460-8.
  282. Madura JA, Loomis RC, Harris RA, Grosfeld J, Tompkins RK. Relationship of obesity to bile lithogenicity in man. Ann Surg. 1979;189(1):106-11.
  283. Mathus-Vliegen EM, Van Ierland-Van Leeuwen ML, Terpstra A. Determinants of gallbladder kinetics in obesity. Dig Dis Sci. 2004;49(1):9-16.
  284. Petroni ML. Review article: gall-bladder motor function in obesity. Aliment Pharmacol Ther. 2000;14 Suppl 2:48-50.
  285. Caroli-Bosc FX, Pugliese P, Peten EP, Demarquay JF, Montet JC, Hastier P, et al. Gallbladder volume in adults and its relationship to age, sex, body mass index, body surface area and gallstones. An epidemiologic study in a nonselected population in France. Digestion. 1999;60(4):344-8.
  286. Hendel HW, Hojgaard L, Andersen T, Pedersen BH, Paloheimo LI, Rehfeld JF, et al. Fasting gall bladder volume and lithogenicity in relation to glucose tolerance, total and intra-abdominal fat masses in obese non-diabetic subjects. Int J Obes Relat Metab Disord. 1998;22(4):294-302.
  287. Palasciano G, Serio G, Portincasa P, Palmieri V, Fanelli M, Velardi A, et al. Gallbladder volume in adults, and relationship to age, sex, body mass index, and gallstones: a sonographic population study. Am J Gastroenterol. 1992;87(4):493-7.
  288. Vezina WC, Paradis RL, Grace DM, Zimmer RA, Lamont DD, Rycroft KM, et al. Increased volume and decreased emptying of the gallbladder in large (morbidly obese, tall normal, and muscular normal) people. Gastroenterology. 1990;98(4):1000-7.
  289. Chait A, Bierman EL, Albers JJ. Low-density lipoprotein receptor activity in cultured human skin fibroblasts. Mechanism of insulin-induced stimulation. J Clin Invest. 1979;64(5):1309-19.
  290. Gielkens HA, Lam WF, Coenraad M, Frolich M, van Oostayen JA, Lamers CB, et al. Effect of insulin on basal and cholecystokinin-stimulated gallbladder motility in humans. J Hepatol. 1998;28(4):595-602.
  291. Nakeeb A, Comuzzie AG, Al-Azzawi H, Sonnenberg GE, Kissebah AH, Pitt HA. Insulin resistance causes human gallbladder dysmotility. J Gastrointest Surg. 2006;10(7):940-8; discussion 8-9.
  292. Nepokroeff CM, Lakshmanan MR, Ness GC, Muesing RA, Kleinsek DA, Porter JW. Coordinate control of rat liver lipogenic enzymes by insulin. Arch Biochem Biophys. 1974;162(2):340-4.
  293. Festi D, Colecchia A, Orsini M, Sangermano A, Sottili S, Simoni P, et al. Gallbladder motility and gallstone formation in obese patients following very low calorie diets. Use it (fat) to lose it (well). Int J Obes Relat Metab Disord. 1998;22(6):592-600.
  294. Gebhard RL, Prigge WF, Ansel HJ, Schlasner L, Ketover SR, Sande D, et al. The role of gallbladder emptying in gallstone formation during diet-induced rapid weight loss. Hepatology. 1996;24(3):544-8.
  295. Kiewiet RM, Durian MF, van Leersum M, Hesp FL, van Vliet AC. Gallstone formation after weight loss following gastric banding in morbidly obese Dutch patients. Obes Surg. 2006;16(5):592-6.
  296. Li VK, Pulido N, Fajnwaks P, Szomstein S, Rosenthal R, Martinez-Duartez P. Predictors of gallstone formation after bariatric surgery: a multivariate analysis of risk factors comparing gastric bypass, gastric banding, and sleeve gastrectomy. Surg Endosc. 2009;23(7):1640-4.
  297. Li VK, Pulido N, Martinez-Suartez P, Fajnwaks P, Jin HY, Szomstein S, et al. Symptomatic gallstones after sleeve gastrectomy. Surg Endosc. 2009;23(11):2488-92.
  298. Moon RC, Teixeira AF, Ducoin C, Varnadore S, Jawad MA. Comparison of cholecystectomy cases after Roux-en-Y gastric bypass, sleeve gastrectomy, and gastric banding. Surg Obes Relat Dis. 2014;10(1):64-8.
  299. Nagem R, Lazaro-da-Silva A. Cholecystolithiasis after gastric bypass: a clinical, biochemical, and ultrasonographic 3-year follow-up study. Obes Surg. 2012;22(10):1594-9.
  300. Zapata R, Severin C, Manriquez M, Valdivieso V. Gallbladder motility and lithogenesis in obese patients during diet-induced weight loss. Dig Dis Sci. 2000;45(2):421-8.
  301. Syngal S, Coakley EH, Willett WC, Byers T, Williamson DF, Colditz GA. Long-term weight patterns and risk for cholecystectomy in women. Ann Intern Med. 1999;130(6):471-7.
  302. Uy MC, Talingdan-Te MC, Espinosa WZ, Daez ML, Ong JP. Ursodeoxycholic acid in the prevention of gallstone formation after bariatric surgery: a meta-analysis. Obes Surg. 2008;18(12):1532-8.
  303. Fuller W, Rasmussen JJ, Ghosh J, Ali MR. Is routine cholecystectomy indicated for asymptomatic cholelithiasis in patients undergoing gastric bypass? Obes Surg. 2007;17(6):747-51.
  304. Tucker ON, Fajnwaks P, Szomstein S, Rosenthal RJ. Is concomitant cholecystectomy necessary in obese patients undergoing laparoscopic gastric bypass surgery? Surg Endosc. 2008;22(11):2450-4.
  305. Hussain A, El-Hasani S. Potential Benefits of Prophylactic Cholecystectomy in Patients Undergoing Bariatric Bypass Surgery. Obes Surg. 2016;26(4):865.
  306. Ackroyd R. Population-based study of the need for cholecystectomy after obesity surgery (Br J Surg 2012; 99: 864-869). Br J Surg. 2012;99(6):870.
  307. D'Hondt M, D'Haeninck A, Penninckx F. Gallstone ileus causing perforation of the sigmoid colon. J Gastrointest Surg. 2011;15(4):701-2.
  308. Plecka Ostlund M, Wenger U, Mattsson F, Ebrahim F, Botha A, Lagergren J. Population-based study of the need for cholecystectomy after obesity surgery. Br J Surg. 2012;99(6):864-9.
  309. Warschkow R, Tarantino I, Ukegjini K, Beutner U, Guller U, Schmied BM, et al. Concomitant cholecystectomy during laparoscopic Roux-en-Y gastric bypass in obese patients is not justified: a meta-analysis. Obes Surg. 2013;23(3):397-407.
  310. Worni M, Guller U, Shah A, Gandhi M, Shah J, Rajgor D, et al. Cholecystectomy concomitant with laparoscopic gastric bypass: a trend analysis of the nationwide inpatient sample from 2001 to 2008. Obes Surg. 2012;22(2):220-9.
  311. Randi G, Franceschi S, La Vecchia C. Gallbladder cancer worldwide: geographical distribution and risk factors. Int J Cancer. 2006;118(7):1591-602.
  312. Randi G, Malvezzi M, Levi F, Ferlay J, Negri E, Franceschi S, et al. Epidemiology of biliary tract cancers: an update. Ann Oncol. 2009;20(1):146-59.
  313. Wang F, Wang B, Qiao L. Association between obesity and gallbladder cancer. Front Biosci (Landmark Ed). 2012;17:2550-8.
  314. Larsson SC, Wolk A. Obesity and the risk of gallbladder cancer: a meta-analysis. Br J Cancer. 2007;96(9):1457-61.
  315. Lauby-Secretan B, Scoccianti C, Loomis D, Grosse Y, Bianchini F, Straif K, et al. Body Fatness and Cancer--Viewpoint of the IARC Working Group. N Engl J Med. 2016;375(8):794-8.
  316. Park Y, Colditz GA. Fresh evidence links adiposity with multiple cancers. BMJ. 2017;356:j908.
  317. Kyrou I, Tsigos C. Chronic stress, visceral obesity and gonadal dysfunction. Hormones (Athens). 2008;7(4):287-93.
  318. Michalakis K, Mintziori G, Kaprara A, Tarlatzis BC, Goulis DG. The complex interaction between obesity, metabolic syndrome and reproductive axis: a narrative review. Metabolism. 2013;62(4):457-78.
  319. Tena-Sempere M. Interaction between energy homeostasis and reproduction: central effects of leptin and ghrelin on the reproductive axis. Horm Metab Res. 2013;45(13):919-27.
  320. Craig JR, Jenkins TG, Carrell DT, Hotaling JM. Obesity, male infertility, and the sperm epigenome. Fertil Steril. 2017;107(4):848-59.
  321. Legro RS. Effects of obesity treatment on female reproduction: results do not match expectations. Fertil Steril. 2017;107(4):860-7.
  322. Meldrum DR. Introduction: Obesity and reproduction. Fertil Steril. 2017;107(4):831-2.
  323. Practice Committee of the American Society for Reproductive M. Obesity and reproduction: a committee opinion. Fertil Steril. 2015;104(5):1116-26.
  324. Committee P. Obesity and reproduction: an educational bulletin. Fertil Steril. 2008;90(5 Suppl):S21-9.
  325. Tsatsanis C, Dermitzaki E, Avgoustinaki P, Malliaraki N, Mytaras V, Margioris AN. The impact of adipose tissue-derived factors on the hypothalamic-pituitary-gonadal (HPG) axis. Hormones (Athens). 2015;14(4):549-62.
  326. Chehab FF. 20 years of leptin: leptin and reproduction: past milestones, present undertakings, and future endeavors. J Endocrinol. 2014;223(1):T37-48.
  327. Vazquez MJ, Romero-Ruiz A, Tena-Sempere M. Roles of leptin in reproduction, pregnancy and polycystic ovary syndrome: consensus knowledge and recent developments. Metabolism. 2015;64(1):79-91.
  328. Bluher S, Mantzoros CS. Leptin in reproduction. Curr Opin Endocrinol Diabetes Obes. 2007;14(6):458-64.
  329. Budak E, Fernandez Sanchez M, Bellver J, Cervero A, Simon C, Pellicer A. Interactions of the hormones leptin, ghrelin, adiponectin, resistin, and PYY3-36 with the reproductive system. Fertil Steril. 2006;85(6):1563-81.
  330. Israel D, Chua S, Jr. Leptin receptor modulation of adiposity and fertility. Trends Endocrinol Metab. 2010;21(1):10-6.
  331. Arafat AM, Weickert MO, Frystyk J, Spranger J, Schofl C, Mohlig M, et al. The role of insulin-like growth factor (IGF) binding protein-2 in the insulin-mediated decrease in IGF-I bioactivity. J Clin Endocrinol Metab. 2009;94(12):5093-101.
  332. Fischer-Posovszky P, Wabitsch M, Hochberg Z. Endocrinology of adipose tissue - an update. Horm Metab Res. 2007;39(5):314-21.
  333. Haffner SM. Sex hormones, obesity, fat distribution, type 2 diabetes and insulin resistance: epidemiological and clinical correlation. Int J Obes Relat Metab Disord. 2000;24 Suppl 2:S56-8.
  334. Tchernof A, Despres JP. Sex steroid hormones, sex hormone-binding globulin, and obesity in men and women. Horm Metab Res. 2000;32(11-12):526-36.
  335. Mai K, Bobbert T, Kullmann V, Andres J, Rochlitz H, Osterhoff M, et al. Free fatty acids increase androgen precursors in vivo. J Clin Endocrinol Metab. 2006;91(4):1501-7.
  336. Hammond GL. Diverse roles for sex hormone-binding globulin in reproduction. Biol Reprod. 2011;85(3):431-41.
  337. Weaver JU, Holly JM, Kopelman PG, Noonan K, Giadom CG, White N, et al. Decreased sex hormone binding globulin (SHBG) and insulin-like growth factor binding protein (IGFBP-1) in extreme obesity. Clin Endocrinol (Oxf). 1990;33(3):415-22.
  338. Kolotkin RL, Binks M, Crosby RD, Ostbye T, Gress RE, Adams TD. Obesity and sexual quality of life. Obesity (Silver Spring). 2006;14(3):472-9.
  339. Sarwer DB, Lavery M, Spitzer JC. A review of the relationships between extreme obesity, quality of life, and sexual function. Obes Surg. 2012;22(4):668-76.
  340. Shah MB. Obesity and sexuality in women. Obstet Gynecol Clin North Am. 2009;36(2):347-60, ix.
  341. Rogers J, Mitchell GW, Jr. The relation of obesity to menstrual disturbances. N Engl J Med. 1952;247(2):53-5.
  342. Manfredi-Lozano M, Roa J, Tena-Sempere M. Connecting metabolism and gonadal function: Novel central neuropeptide pathways involved in the metabolic control of puberty and fertility. Front Neuroendocrinol. 2017.
  343. Casanueva FF, Dieguez C. Neuroendocrine regulation and actions of leptin. Front Neuroendocrinol. 1999;20(4):317-63.
  344. Frisch RE, McArthur JW. Menstrual cycles: fatness as a determinant of minimum weight for height necessary for their maintenance or onset. Science. 1974;185(4155):949-51.
  345. Holtkamp K, Mika C, Grzella I, Heer M, Pak H, Hebebrand J, et al. Reproductive function during weight gain in anorexia nervosa. Leptin represents a metabolic gate to gonadotropin secretion. J Neural Transm. 2003;110(4):427-35.
  346. Ahmed ML, Ong KK, Dunger DB. Childhood obesity and the timing of puberty. Trends Endocrinol Metab. 2009;20(5):237-42.
  347. Roa J, Garcia-Galiano D, Castellano JM, Gaytan F, Pinilla L, Tena-Sempere M. Metabolic control of puberty onset: new players, new mechanisms. Mol Cell Endocrinol. 2010;324(1-2):87-94.
  348. Wang Y. Is obesity associated with early sexual maturation? A comparison of the association in American boys versus girls. Pediatrics. 2002;110(5):903-10.
  349. Biro FM, Khoury P, Morrison JA. Influence of obesity on timing of puberty. Int J Androl. 2006;29(1):272-7; discussion 86-90.
  350. Himes JH. Examining the evidence for recent secular changes in the timing of puberty in US children in light of increases in the prevalence of obesity. Mol Cell Endocrinol. 2006;254-255:13-21.
  351. Bray GA. Obesity and reproduction. Hum Reprod. 1997;12 Suppl 1:26-32.
  352. Kok HS, van Asselt KM, van der Schouw YT, van der Tweel I, Peeters PH, Wilson PW, et al. Heart disease risk determines menopausal age rather than the reverse. J Am Coll Cardiol. 2006;47(10):1976-83.
  353. Lash MM, Armstrong A. Impact of obesity on women's health. Fertil Steril. 2009;91(5):1712-6.
  354. Metwally M, Li TC, Ledger WL. The impact of obesity on female reproductive function. Obes Rev. 2007;8(6):515-23.
  355. Lake JK, Power C, Cole TJ. Women's reproductive health: the role of body mass index in early and adult life. Int J Obes Relat Metab Disord. 1997;21(6):432-8.
  356. Rotterdam. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Hum Reprod. 2004;19(1):41-7.
  357. Kyrou I, Weickert MO, Randeva HS. Diagnosis and Management of PCOS. In: Ajjan R, (Eds), Endocrinology & Diabetes: Case Studies, Questions & Commentaries Springer. 2014.
  358. Green BB, Weiss NS, Daling JR. Risk of ovulatory infertility in relation to body weight. Fertil Steril. 1988;50(5):721-6.
  359. Grodstein F, Goldman MB, Cramer DW. Body mass index and ovulatory infertility. Epidemiology. 1994;5(2):247-50.
  360. Rich-Edwards JW, Goldman MB, Willett WC, Hunter DJ, Stampfer MJ, Colditz GA, et al. Adolescent body mass index and infertility caused by ovulatory disorder. Am J Obstet Gynecol. 1994;171(1):171-7.
  361. Jensen TK, Scheike T, Keiding N, Schaumburg I, Grandjean P. Fecundability in relation to body mass and menstrual cycle patterns. Epidemiology. 1999;10(4):422-8.
  362. Ramlau-Hansen CH, Thulstrup AM, Nohr EA, Bonde JP, Sorensen TI, Olsen J. Subfecundity in overweight and obese couples. Hum Reprod. 2007;22(6):1634-7.
  363. Pasquali R, Pelusi C, Genghini S, Cacciari M, Gambineri A. Obesity and reproductive disorders in women. Hum Reprod Update. 2003;9(4):359-72.
  364. Christopoulou-Aletra H, Papavramidou N, Pozzilli P. Obesity in the Neolithic era: a Greek female figurine. Obes Surg. 2006;16(8):1112-4.
  365. Colman ME. Obesity in the Paleolithic era? The Venus of Willendorf. Endocr Pract. 1998;4(1):58-9.
  366. Fedorcsak P, Dale PO, Storeng R, Ertzeid G, Bjercke S, Oldereid N, et al. Impact of overweight and underweight on assisted reproduction treatment. Hum Reprod. 2004;19(11):2523-8.
  367. Fedorcsak P, Storeng R, Dale PO, Tanbo T, Abyholm T. Obesity is a risk factor for early pregnancy loss after IVF or ICSI. Acta Obstet Gynecol Scand. 2000;79(1):43-8.
  368. Kumbak B, Oral E, Bukulmez O. Female obesity and assisted reproductive technologies. Semin Reprod Med. 2010;30(6):507-16.
  369. Lintsen AM, Pasker-de Jong PC, de Boer EJ, Burger CW, Jansen CA, Braat DD, et al. Effects of subfertility cause, smoking and body weight on the success rate of IVF. Hum Reprod. 2005;20(7):1867-75.
  370. Loveland JB, McClamrock HD, Malinow AM, Sharara FI. Increased body mass index has a deleterious effect on in vitro fertilization outcome. J Assist Reprod Genet. 2001;18(7):382-6.
  371. Rittenberg V, Seshadri S, Sunkara SK, Sobaleva S, Oteng-Ntim E, El-Toukhy T. Effect of body mass index on IVF treatment outcome: an updated systematic review and meta-analysis. Reprod Biomed Online. 2011;23(4):421-39.
  372. Awartani KA, Nahas S, Al Hassan SH, Al Deery MA, Coskun S. Infertility treatment outcome in sub groups of obese population. Reprod Biol Endocrinol. 2009;7:52.
  373. Dokras A, Baredziak L, Blaine J, Syrop C, VanVoorhis BJ, Sparks A. Obstetric outcomes after in vitro fertilization in obese and morbidly obese women. Obstet Gynecol. 2006;108(1):61-9.
  374. Imani B, Eijkemans MJ, Faessen GH, Bouchard P, Giudice LC, Fauser BC. Prediction of the individual follicle-stimulating hormone threshold for gonadotropin induction of ovulation in normogonadotropic anovulatory infertility: an approach to increase safety and efficiency. Fertil Steril. 2002;77(1):83-90.
  375. Wang JX, Davies M, Norman RJ. Body mass and probability of pregnancy during assisted reproduction treatment: retrospective study. Bmj. 2000;321(7272):1320-1.
  376. Balen AH, Anderson RA. Impact of obesity on female reproductive health: British Fertility Society, Policy and Practice Guidelines. Hum Fertil (Camb). 2007;10(4):195-206.
  377. Norman RJ, Noakes M, Wu R, Davies MJ, Moran L, Wang JX. Improving reproductive performance in overweight/obese women with effective weight management. Hum Reprod Update. 2004;10(3):267-80.
  378. Stang J, Huffman LG. Position of the Academy of Nutrition and Dietetics: Obesity, Reproduction, and Pregnancy Outcomes. J Acad Nutr Diet. 2016;116(4):677-91.
  379. Dixit A, Girling JC. Obesity and pregnancy. J Obstet Gynaecol. 2008;28(1):14-23.
  380. Joy S, Istwan N, Rhea D, Desch C, Stanziano G. The impact of maternal obesity on the incidence of adverse pregnancy outcomes in high-risk term pregnancies. Am J Perinatol. 2009;26(5):345-9.
  381. Bray GA. The underlying basis for obesity: relationship to cancer. J Nutr. 2002;132(11 Suppl):3451S-5S.
  382. Kulie T, Slattengren A, Redmer J, Counts H, Eglash A, Schrager S. Obesity and women's health: an evidence-based review. J Am Board Fam Med. 2011;24(1):75-85.
  383. Modesitt SC, van Nagell JR, Jr. The impact of obesity on the incidence and treatment of gynecologic cancers: a review. Obstet Gynecol Surv. 2005;60(10):683-92.
  384. Fader AN, Arriba LN, Frasure HE, von Gruenigen VE. Endometrial cancer and obesity: epidemiology, biomarkers, prevention and survivorship. Gynecol Oncol. 2009;114(1):121-7.
  385. Gunter MJ, Hoover DR, Yu H, Wassertheil-Smoller S, Rohan TE, Manson JE, et al. Insulin, insulin-like growth factor-I, and risk of breast cancer in postmenopausal women. J Natl Cancer Inst. 2009;101(1):48-60.
  386. Louie SM, Roberts LS, Nomura DK. Mechanisms linking obesity and cancer. Biochim Biophys Acta. 2013;1831(10):1499-508.
  387. Marcovecchio ML, Chiarelli F. Obesity and growth during childhood and puberty. World Rev Nutr Diet. 2013;106:135-41.
  388. Denzer C, Weibel A, Muche R, Karges B, Sorgo W, Wabitsch M. Pubertal development in obese children and adolescents. Int J Obes (Lond). 2007;31(10):1509-19.
  389. He Q, Karlberg J. Bmi in childhood and its association with height gain, timing of puberty, and final height. Pediatr Res. 2001;49(2):244-51.
  390. Karpati AM, Rubin CH, Kieszak SM, Marcus M, Troiano RP. Stature and pubertal stage assessment in American boys: the 1988-1994 Third National Health and Nutrition Examination Survey. J Adolesc Health. 2002;30(3):205-12.
  391. Laron Z. Is obesity associated with early sexual maturation? Pediatrics. 2004;113(1 Pt 1):171-2; author reply -2.
  392. Hammoud AO, Gibson M, Peterson CM, Meikle AW, Carrell DT. Impact of male obesity on infertility: a critical review of the current literature. Fertil Steril. 2008;90(4):897-904.
  393. Loret de Mola JR. Obesity and its relationship to infertility in men and women. Obstet Gynecol Clin North Am. 2009;36(2):333-46, ix.
  394. Pasquali R. Obesity and androgens: facts and perspectives. Fertil Steril. 2006;85(5):1319-40.
  395. Ghiyath Shayeb G, Bhattacharya S. Male obesity and reproductive potential. The British Journal of Diabetes & Vascular Disease 2009;9(1):7-12.
  396. Goulis DG, Tarlatzis BC. Metabolic syndrome and reproduction: I. testicular function. Gynecol Endocrinol. 2008;24(1):33-9.
  397. Sallmen M, Sandler DP, Hoppin JA, Blair A, Baird DD. Reduced fertility among overweight and obese men. Epidemiology. 2006;17(5):520-3.
  398. Jarow JP, Kirkland J, Koritnik DR, Cefalu WT. Effect of obesity and fertility status on sex steroid levels in men. Urology. 1993;42(2):171-4.
  399. Jung A, Schill WB. [Male infertility. Current life style could be responsible for infertility]. MMW Fortschr Med. 2000;142(37):31-3.
  400. Cao Y, Giovannucci E. Obesity and Prostate Cancer. Recent Results Cancer Res. 2016;208:137-53.
  401. Golabek T, Bukowczan J, Chlosta P, Powroznik J, Dobruch J, Borowka A. Obesity and prostate cancer incidence and mortality: a systematic review of prospective cohort studies. Urol Int. 2014;92(1):7-14.
  402. Vidal AC, Freedland SJ. Obesity and Prostate Cancer: A Focused Update on Active Surveillance, Race, and Molecular Subtyping. Eur Urol. 2017;72(1):78-83.
  403. Allott EH, Masko EM, Freedland SJ. Obesity and prostate cancer: weighing the evidence. Eur Urol. 2013;63(5):800-9.
  404. Freedland SJ, Platz EA. Obesity and prostate cancer: making sense out of apparently conflicting data. Epidemiol Rev. 2007;29:88-97.
  405. Hsing AW, Sakoda LC, Chua S, Jr. Obesity, metabolic syndrome, and prostate cancer. Am J Clin Nutr. 2007;86(3):s843-57.
  406. Tewari R, Rajender S, Natu SM, Dalela D, Goel A, Goel MM, et al. Diet, obesity, and prostate health: are we missing the link? J Androl. 2012;33(5):763-76.
  407. Gong Z, Neuhouser ML, Goodman PJ, Albanes D, Chi C, Hsing AW, et al. Obesity, diabetes, and risk of prostate cancer: results from the prostate cancer prevention trial. Cancer Epidemiol Biomarkers Prev. 2006;15(10):1977-83.
  408. Rodriguez C, Freedland SJ, Deka A, Jacobs EJ, McCullough ML, Patel AV, et al. Body mass index, weight change, and risk of prostate cancer in the Cancer Prevention Study II Nutrition Cohort. Cancer Epidemiol Biomarkers Prev. 2007;16(1):63-9.
  409. Wright ME, Chang SC, Schatzkin A, Albanes D, Kipnis V, Mouw T, et al. Prospective study of adiposity and weight change in relation to prostate cancer incidence and mortality. Cancer. 2007;109(4):675-84.
  410. Culp S, Porter M. The effect of obesity and lower serum prostate-specific antigen levels on prostate-cancer screening results in American men. BJU Int. 2009;104(10):1457-61.
  411. Granieri MA, Freedland SJ. The interplay between obesity and the accuracy of prostate-specific antigen (PSA) for predicting prostate cancer. BJU Int. 2013;112(4):E272.
  412. Oh JJ, Jeong SJ, Lee BK, Jeong CW, Byun SS, Hong SK, et al. Does obesity affect the accuracy of prostate-specific antigen (PSA) for predicting prostate cancer among men undergoing prostate biopsy. BJU Int. 2013;112(4):E265-71.
  413. Efstathiou JA, Bae K, Shipley WU, Hanks GE, Pilepich MV, Sandler HM, et al. Obesity and mortality in men with locally advanced prostate cancer: analysis of RTOG 85-31. Cancer. 2007;110(12):2691-9.
  414. Mistry T, Digby JE, Desai KM, Randeva HS. Obesity and prostate cancer: a role for adipokines. Eur Urol. 2007;52(1):46-53.
  415. Kyrou I, Kollia N, Panagiotakos D, Georgousopoulou E, Chrysohoou C, Tsigos C, et al. Association of depression and anxiety status with 10-year cardiovascular disease incidence among apparently healthy Greek adults: The ATTICA Study. Eur J Prev Cardiol. 2017;24(2):145-52.
  416. Atlantis E, Goldney RD, Wittert GA. Obesity and depression or anxiety. Bmj. 2009;339:b3868.
  417. Blaine B. Does depression cause obesity?: A meta-analysis of longitudinal studies of depression and weight control. J Health Psychol. 2008;13(8):1190-7.
  418. Ippoliti F, Canitano N, Businaro R. Stress and obesity as risk factors in cardiovascular diseases: a neuroimmune perspective. J Neuroimmune Pharmacol. 2013;8(1):212-26.
  419. Steptoe A, Kivimaki M. Stress and cardiovascular disease: an update on current knowledge. Annu Rev Public Health. 2013;34:337-54.
  420. Kivimaki M, Lawlor DA, Singh-Manoux A, Batty GD, Ferrie JE, Shipley MJ, et al. Common mental disorder and obesity: insight from four repeat measures over 19 years: prospective Whitehall II cohort study. Bmj. 2009;339:b3765.
  421. Kivimaki M, Batty GD, Singh-Manoux A, Nabi H, Sabia S, Tabak AG, et al. Association between common mental disorder and obesity over the adult life course. Br J Psychiatry. 2009;195(2):149-55.
  422. Vogelzangs N, Kritchevsky SB, Beekman AT, Newman AB, Satterfield S, Simonsick EM, et al. Depressive symptoms and change in abdominal obesity in older persons. Arch Gen Psychiatry. 2008;65(12):1386-93.
  423. Mooy JM, de Vries H, Grootenhuis PA, Bouter LM, Heine RJ. Major stressful life events in relation to prevalence of undetected type 2 diabetes: the Hoorn Study. Diabetes Care. 2000;23(2):197-201.
  424. Brunner EJ, Chandola T, Marmot MG. Prospective effect of job strain on general and central obesity in the Whitehall II Study. Am J Epidemiol. 2007;165(7):828-37.
  425. Chandola T, Brunner E, Marmot M. Chronic stress at work and the metabolic syndrome: prospective study. Bmj. 2006;332(7540):521-5.
  426. Serlachius A, Hamer M, Wardle J. Stress and weight change in university students in the United Kingdom. Physiol Behav. 2007;92(4):548-53.
  427. Atlantis E, Baker M. Obesity effects on depression: systematic review of epidemiological studies. Int J Obes (Lond). 2008;32(6):881-91.
  428. Gariepy G, Nitka D, Schmitz N. The association between obesity and anxiety disorders in the population: a systematic review and meta-analysis. Int J Obes (Lond). 2009;34(3):407-19.
  429. Muhlig Y, Antel J, Focker M, Hebebrand J. Are bidirectional associations of obesity and depression already apparent in childhood and adolescence as based on high-quality studies? A systematic review. Obes Rev. 2016;17(3):235-49.
  430. Onyike CU, Crum RM, Lee HB, Lyketsos CG, Eaton WW. Is obesity associated with major depression? Results from the Third National Health and Nutrition Examination Survey. Am J Epidemiol. 2003;158(12):1139-47.
  431. Petry NM, Barry D, Pietrzak RH, Wagner JA. Overweight and obesity are associated with psychiatric disorders: results from the National Epidemiologic Survey on Alcohol and Related Conditions. Psychosom Med. 2008;70(3):288-97.
  432. Scott KM, Bruffaerts R, Simon GE, Alonso J, Angermeyer M, de Girolamo G, et al. Obesity and mental disorders in the general population: results from the world mental health surveys. Int J Obes (Lond). 2008;32(1):192-200.
  433. Simon GE, Von Korff M, Saunders K, Miglioretti DL, Crane PK, van Belle G, et al. Association between obesity and psychiatric disorders in the US adult population. Arch Gen Psychiatry. 2006;63(7):824-30.
  434. Zhao G, Ford ES, Dhingra S, Li C, Strine TW, Mokdad AH. Depression and anxiety among US adults: associations with body mass index. Int J Obes (Lond). 2009;33(2):257-66.
  435. Preiss K, Brennan L, Clarke D. A systematic review of variables associated with the relationship between obesity and depression. Obes Rev. 2013;14(11):906-18.
  436. Herva A, Laitinen J, Miettunen J, Veijola J, Karvonen JT, Laksy K, et al. Obesity and depression: results from the longitudinal Northern Finland 1966 Birth Cohort Study. Int J Obes (Lond). 2006;30(3):520-7.
  437. Roberts RE, Deleger S, Strawbridge WJ, Kaplan GA. Prospective association between obesity and depression: evidence from the Alameda County Study. Int J Obes Relat Metab Disord. 2003;27(4):514-21.
  438. Roberts RE, Kaplan GA, Shema SJ, Strawbridge WJ. Are the obese at greater risk for depression? Am J Epidemiol. 2000;152(2):163-70.
  439. Roberts RE, Strawbridge WJ, Deleger S, Kaplan GA. Are the fat more jolly? Ann Behav Med. 2002;24(3):169-80.
  440. Crisp AH, McGuiness B. Jolly fat: relation between obesity and psychoneurosis in general population. Br Med J. 1976;1(6000):7-9.
  441. Crisp AH, Queenan M, Sittampaln Y, Harris G. 'Jolly fat' revisited. J Psychosom Res. 1980;24(5):233-41.
  442. Jansen A, Havermans R, Nederkoorn C, Roefs A. Jolly fat or sad fat? Subtyping non-eating disordered overweight and obesity along an affect dimension. Appetite. 2008;51(3):635-40.
  443. Palinkas LA, Wingard DL, Barrett-Connor E. Depressive symptoms in overweight and obese older adults: a test of the "jolly fat" hypothesis. J Psychosom Res. 1996;40(1):59-66.
  444. de Wit LM, van Straten A, van Herten M, Penninx BW, Cuijpers P. Depression and body mass index, a u-shaped association. BMC Public Health. 2009;9:14.
  445. Dixon JB, Dixon ME, O'Brien PE. Depression in association with severe obesity: changes with weight loss. Arch Intern Med. 2003;163(17):2058-65.
  446. Karlsson J, Taft C, Sjostrom L, Torgerson JS, Sullivan M. Psychosocial functioning in the obese before and after weight reduction: construct validity and responsiveness of the Obesity-related Problems scale. Int J Obes Relat Metab Disord. 2003;27(5):617-30.
  447. Larsen JK, Geenen R, van Ramshorst B, Brand N, de Wit P, Stroebe W, et al. Psychosocial functioning before and after laparoscopic adjustable gastric banding: a cross-sectional study. Obes Surg. 2003;13(4):629-36.
  448. Schowalter M, Benecke A, Lager C, Heimbucher J, Bueter M, Thalheimer A, et al. Changes in depression following gastric banding: a 5- to 7-year prospective study. Obes Surg. 2008;18(3):314-20.
  449. Vage V, Solhaug JH, Viste A, Bergsholm P, Wahl AK. Anxiety, depression and health-related quality of life after jejunoileal bypass: a 25-year follow-up study of 20 female patients. Obes Surg. 2003;13(5):706-13.
  450. Zeller MH, Modi AC, Noll JG, Long JD, Inge TH. Psychosocial functioning improves following adolescent bariatric surgery. Obesity (Silver Spring). 2009;17(5):985-90.
  451. Legenbauer T, De Zwaan M, Benecke A, Muhlhans B, Petrak F, Herpertz S. Depression and anxiety: their predictive function for weight loss in obese individuals. Obes Facts. 2009;2(4):227-34.
  452. Tsigos C, Kyrou I, Kassi E, Chrousos GP. Stress, Endocrine Physiology and Pathophysiology. In: De Groot LJ, Chrousos G, Dungan K, Feingold KR, Grossman A, Hershman JM, et al., editors. Endotext. South Dartmouth (MA)2000.
  453. Bose M, Olivan B, Laferrere B. Stress and obesity: the role of the hypothalamic-pituitary-adrenal axis in metabolic disease. Curr Opin Endocrinol Diabetes Obes. 2009;16(5):340-6.
  454. Chrousos GP. Stress and disorders of the stress system. Nat Rev Endocrinol. 2009;5(7):374-81.
  455. Dallman MF. Stress-induced obesity and the emotional nervous system. Trends Endocrinol Metab. 2010;21(3):159-65.
  456. Holmes ME, Ekkekakis P, Eisenmann JC. The physical activity, stress and metabolic syndrome triangle: a guide to unfamiliar territory for the obesity researcher. Obes Rev. 2010;11(7):492-507.
  457. Kyrou I, Tsigos C. Stress hormones: physiological stress and regulation of metabolism. Curr Opin Pharmacol. 2009;9(6):787-93.
  458. Kyrou I, Tsigos C. Stress mechanisms and metabolic complications. Horm Metab Res. 2007;39(6):430-8.
  459. Kyrou I, Randeva HS, Tsigos C. Chapter 35 - Stress, insulin resistance and type 2 diabetes; in Stress: Neuroendocrinology and Neurobiology; Handbook of Stress, Volume 2, ed Fink G., Elsevier 2017.
  460. Adam TC, Epel ES. Stress, eating and the reward system. Physiol Behav. 2007;91(4):449-58.
  461. Anagnostis P, Athyros VG, Tziomalos K, Karagiannis A, Mikhailidis DP. Clinical review: The pathogenetic role of cortisol in the metabolic syndrome: a hypothesis. J Clin Endocrinol Metab. 2009;94(8):2692-701.
  462. Bjorntorp P. Do stress reactions cause abdominal obesity and comorbidities? Obes Rev. 2001;2(2):73-86.
  463. Rosmond R, Dallman MF, Bjorntorp P. Stress-related cortisol secretion in men: relationships with abdominal obesity and endocrine, metabolic and hemodynamic abnormalities. J Clin Endocrinol Metab. 1998;83(6):1853-9.
  464. Gangwisch JE. Epidemiological evidence for the links between sleep, circadian rhythms and metabolism. Obes Rev. 2009;10 Suppl 2:37-45.
  465. Motivala SJ, Tomiyama AJ, Ziegler M, Khandrika S, Irwin MR. Nocturnal levels of ghrelin and leptin and sleep in chronic insomnia. Psychoneuroendocrinology. 2009;34(4):540-5.
  466. Arafat AM, Weickert MO, Adamidou A, Otto B, Perschel FH, Spranger J, et al. The impact of insulin-independent, glucagon-induced suppression of total ghrelin on satiety in obesity and type 1 diabetes mellitus. J Clin Endocrinol Metab. 2013;98(10):4133-42.
  467. Sarem Z, Bumke-Vogt C, Mahmoud AM, Assefa B, Weickert MO, Adamidou A, et al. Glucagon Decreases IGF-1 Bioactivity in Humans, Independently of Insulin, by Modulating Its Binding Proteins. J Clin Endocrinol Metab. 2017;102(9):3480-90.
  468. Strine TW, Mokdad AH, Balluz LS, Gonzalez O, Crider R, Berry JT, et al. Depression and anxiety in the United States: findings from the 2006 Behavioral Risk Factor Surveillance System. Psychiatr Serv. 2008;59(12):1383-90.
  469. Friedman KE, Ashmore JA, Applegate KL. Recent experiences of weight-based stigmatization in a weight loss surgery population: psychological and behavioral correlates. Obesity (Silver Spring). 2008;16 Suppl 2:S69-74.
  470. Hasnain M, Vieweg WV. Weight considerations in psychotropic drug prescribing and switching. Postgrad Med. 2013;125(5):117-29.
  471. Malone M, Alger-Mayer SA, Anderson DA. Medication associated with weight gain may influence outcome in a weight management program. Ann Pharmacother. 2005;39(7-8):1204-8.
  472. Calle EE. Obesity and cancer. Bmj. 2007;335(7630):1107-8.
  473. 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):1625-38.
  474. Calle EE, Teras LR, Thun MJ. Obesity and mortality. N Engl J Med. 2005;353(20):2197-9.
  475. Eliassen AH, Colditz GA, Rosner B, Willett WC, Hankinson SE. Adult weight change and risk of postmenopausal breast cancer. Jama. 2006;296(2):193-201.
  476. Hjartaker A, Langseth H, Weiderpass E. Obesity and diabetes epidemics: cancer repercussions. Adv Exp Med Biol. 2008;630:72-93.
  477. Pischon T, Nothlings U, Boeing H. Obesity and cancer. Proc Nutr Soc. 2008;67(2):128-45.
  478. Reeves GK, Pirie K, Beral V, Green J, Spencer E, Bull D. Cancer incidence and mortality in relation to body mass index in the Million Women Study: cohort study. Bmj. 2007;335(7630):1134.
  479. Thygesen LC, Gronbaek M, Johansen C, Fuchs CS, Willett WC, Giovannucci E. Prospective weight change and colon cancer risk in male US health professionals. Int J Cancer. 2008;123(5):1160-5.
  480. Arnold M, Pandeya N, Byrnes G, Renehan PAG, Stevens GA, Ezzati PM, et al. Global burden of cancer attributable to high body-mass index in 2012: a population-based study. Lancet Oncol. 2015;16(1):36-46.
  481. Kyrgiou M, Kalliala I, Markozannes G, Gunter MJ, Paraskevaidis E, Gabra H, et al. Adiposity and cancer at major anatomical sites: umbrella review of the literature. BMJ. 2017;356:j477.
  482. Park Y, Colditz GA. Diabetes and adiposity: a heavy load for cancer. Lancet Diabetes Endocrinol. 2017.
  483. Gallagher EJ, LeRoith D. Epidemiology and molecular mechanisms tying obesity, diabetes, and the metabolic syndrome with cancer. Diabetes Care. 2013;36 Suppl 2:S233-9.
  484. Wolin KY, Carson K, Colditz GA. Obesity and cancer. Oncologist. 2010;15(6):556-65.
  485. Bianchini F, Kaaks R, Vainio H. Weight control and physical activity in cancer prevention. Obes Rev. 2002;3(1):5-8.
  486. Berrington de Gonzalez A, Spencer EA, Bueno-de-Mesquita HB, Roddam A, Stolzenberg-Solomon R, Halkjaer J, et al. Anthropometry, physical activity, and the risk of pancreatic cancer in the European prospective investigation into cancer and nutrition. Cancer Epidemiol Biomarkers Prev. 2006;15(5):879-85.
  487. Friedenreich C, Cust A, Lahmann PH, Steindorf K, Boutron-Ruault MC, Clavel-Chapelon F, et al. Anthropometric factors and risk of endometrial cancer: the European prospective investigation into cancer and nutrition. Cancer Causes Control. 2007;18(4):399-413.
  488. Wang Y, Jacobs EJ, Patel AV, Rodriguez C, McCullough ML, Thun MJ, et al. A prospective study of waist circumference and body mass index in relation to colorectal cancer incidence. Cancer Causes Control. 2008;19(7):783-92.
  489. World Cancer Research Fund / American Institute for Cancer Research. Food, Nutrition, Physical Activity, and the Prevention of Cancer: a Global Perspective. Washington DC: AICR. 2007.
  490. The new WCRF/AICR report: Food, Nutrition, Physical Activity and the Prevention of Cancer: A Global Perspective Nutrition Bulletin. 2008;33(1):26-32.
  491. Wiseman M. The second World Cancer Research Fund/American Institute for Cancer Research expert report. Food, nutrition, physical activity, and the prevention of cancer: a global perspective. Proc Nutr Soc. 2008;67(3):253-6.
  492. Peltonen M, Carlsson LM. Body Fatness and Cancer. N Engl J Med. 2016;375(20):2007-8.
  493. 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):753-61.
  494. Sjostrom L, Gummesson A, Sjostrom CD, Narbro K, Peltonen M, Wedel H, et al. Effects of bariatric surgery on cancer incidence in obese patients in Sweden (Swedish Obese Subjects Study): a prospective, controlled intervention trial. Lancet Oncol. 2009;10(7):653-62.
  495. 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):741-52.
  496. Renehan AG, Roberts DL, Dive C. Obesity and cancer: pathophysiological and biological mechanisms. Arch Physiol Biochem. 2008;114(1):71-83.
  497. 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):569-78.
  498. Arnold M, Jiang L, Stefanick ML, Johnson KC, Lane DS, LeBlanc ES, et al. Duration of Adulthood Overweight, Obesity, and Cancer Risk in the Women's Health Initiative: A Longitudinal Study from the United States. PLoS Med. 2016;13(8):e1002081.
  499. Bjorge T, Engeland A, Tverdal A, Smith GD. Body mass index in adolescence in relation to cause-specific mortality: a follow-up of 230,000 Norwegian adolescents. Am J Epidemiol. 2008;168(1):30-7.
  500. Engeland A, Bjorge T, Tverdal A, Sogaard AJ. Obesity in adolescence and adulthood and the risk of adult mortality. Epidemiology. 2004;15(1):79-85.
  501. Carmichael AR, Bates T. Obesity and breast cancer: a review of the literature. Breast. 2004;13(2):85-92.
  502. Kroenke CH, Chen WY, Rosner B, Holmes MD. Weight, weight gain, and survival after breast cancer diagnosis. J Clin Oncol. 2005;23(7):1370-8.
  503. Haydon AM, Macinnis RJ, English DR, Giles GG. Effect of physical activity and body size on survival after diagnosis with colorectal cancer. Gut. 2006;55(1):62-7.
  504. Meyerhardt JA, Catalano PJ, Haller DG, Mayer RJ, Benson AB, 3rd, Macdonald JS, et al. Influence of body mass index on outcomes and treatment-related toxicity in patients with colon carcinoma. Cancer. 2003;98(3):484-95.
  505. Meyerhardt JA, Niedzwiecki D, Hollis D, Saltz LB, Mayer RJ, Nelson H, et al. Impact of body mass index and weight change after treatment on cancer recurrence and survival in patients with stage III colon cancer: findings from Cancer and Leukemia Group B 89803. J Clin Oncol. 2008;26(25):4109-15.
  506. Sinicrope FA, Foster NR, Sargent DJ, O'Connell MJ, Rankin C. Obesity is an independent prognostic variable in colon cancer survivors. Clin Cancer Res. 2010;16(6):1884-93.
  507. Amy NK, Aalborg A, Lyons P, Keranen L. Barriers to routine gynecological cancer screening for White and African-American obese women. Int J Obes (Lond). 2006;30(1):147-55.
  508. Arndt V, Sturmer T, Stegmaier C, Ziegler H, Dhom G, Brenner H. Patient delay and stage of diagnosis among breast cancer patients in Germany -- a population based study. Br J Cancer. 2002;86(7):1034-40.
  509. Cui Y, Whiteman MK, Flaws JA, Langenberg P, Tkaczuk KH, Bush TL. Body mass and stage of breast cancer at diagnosis. Int J Cancer. 2002;98(2):279-83.
  510. Reeves MJ, Newcomb PA, Remington PL, Marcus PM, MacKenzie WR. Body mass and breast cancer. Relationship between method of detection and stage of disease. Cancer. 1996;77(2):301-7.
  511. Berriel Diaz M, Herzig S, Schafmeier T. Biological Mechanisms for the Effect of Obesity on Cancer Risk: Experimental Evidence. Recent Results Cancer Res. 2016;208:219-42.
  512. Iyengar NM, Gucalp A, Dannenberg AJ, Hudis CA. Obesity and Cancer Mechanisms: Tumor Microenvironment and Inflammation. J Clin Oncol. 2016;34(35):4270-6.
  513. Iyengar NM, Hudis CA, Dannenberg AJ. Obesity and cancer: local and systemic mechanisms. Annu Rev Med. 2015;66:297-309.
  514. Park J, Morley TS, Kim M, Clegg DJ, Scherer PE. Obesity and cancer--mechanisms underlying tumour progression and recurrence. Nat Rev Endocrinol. 2014;10(8):455-65.
  515. Ferguson RD, Gallagher EJ, Scheinman EJ, Damouni R, LeRoith D. The epidemiology and molecular mechanisms linking obesity, diabetes, and cancer. Vitam Horm. 2013;93:51-98.
  516. Calle EE, Kaaks R. Overweight, obesity and cancer: epidemiological evidence and proposed mechanisms. Nat Rev Cancer. 2004;4(8):579-91.
  517. Niemann HH. Structural basis of MET receptor dimerization by the bacterial invasion protein InlB and the HGF/SF splice variant NK1. Biochim Biophys Acta. 2013;1834(10):2195-204.
  518. Roberts DL, Dive C, Renehan AG. Biological mechanisms linking obesity and cancer risk: new perspectives. Annu Rev Med. 2010;61:301-16.
  519. Khandwala HM, McCutcheon IE, Flyvbjerg A, Friend KE. The effects of insulin-like growth factors on tumorigenesis and neoplastic growth. Endocr Rev. 2000;21(3):215-44.
  520. Le Roith D. Regulation of proliferation and apoptosis by the insulin-like growth factor I receptor. Growth Horm IGF Res. 2000;10 Suppl A:S12-3.
  521. van Kruijsdijk RC, van der Wall E, Visseren FL. Obesity and cancer: the role of dysfunctional adipose tissue. Cancer Epidemiol Biomarkers Prev. 2009;18(10):2569-78.
  522. Bray GA. Medical consequences of obesity. J Clin Endocrinol Metab. 2004;89(6):2583-9.
  523. Neogi T, Zhang Y. Epidemiology of osteoarthritis. Rheum Dis Clin North Am. 2013;39(1):1-19.
  524. Kulkarni K, Karssiens T, Kumar V, Pandit H. Obesity and osteoarthritis. Maturitas. 2016;89:22-8.
  525. Blagojevic M, Jinks C, Jeffery A, Jordan KP. Risk factors for onset of osteoarthritis of the knee in older adults: a systematic review and meta-analysis. Osteoarthritis Cartilage. 2010;18(1):24-33.
  526. Felson DT, Anderson JJ, Naimark A, Walker AM, Meenan RF. Obesity and knee osteoarthritis. The Framingham Study. Ann Intern Med. 1988;109(1):18-24.
  527. Gelber AC, Hochberg MC, Mead LA, Wang NY, Wigley FM, Klag MJ. Body mass index in young men and the risk of subsequent knee and hip osteoarthritis. Am J Med. 1999;107(6):542-8.
  528. Hart DJ, Doyle DV, Spector TD. Incidence and risk factors for radiographic knee osteoarthritis in middle-aged women: the Chingford Study. Arthritis Rheum. 1999;42(1):17-24.
  529. Lee R, Kean WF. Obesity and knee osteoarthritis. Inflammopharmacology. 2012;20(2):53-8.
  530. Wluka AE, Lombard CB, Cicuttini FM. Tackling obesity in knee osteoarthritis. Nat Rev Rheumatol. 2013;9(4):225-35.
  531. Toivanen AT, Heliovaara M, Impivaara O, Arokoski JP, Knekt P, Lauren H, et al. Obesity, physically demanding work and traumatic knee injury are major risk factors for knee osteoarthritis--a population-based study with a follow-up of 22 years. Rheumatology (Oxford). 2010;49(2):308-14.
  532. Anderson JJ, Felson DT. Factors associated with osteoarthritis of the knee in the first national Health and Nutrition Examination Survey (HANES I). Evidence for an association with overweight, race, and physical demands of work. Am J Epidemiol. 1988;128(1):179-89.
  533. Berenbaum F, Sellam J. Obesity and osteoarthritis: what are the links? Joint Bone Spine. 2008;75(6):667-8.
  534. Murphy L, Schwartz TA, Helmick CG, Renner JB, Tudor G, Koch G, et al. Lifetime risk of symptomatic knee osteoarthritis. Arthritis Rheum. 2008;59(9):1207-13.
  535. Carman WJ, Sowers M, Hawthorne VM, Weissfeld LA. Obesity as a risk factor for osteoarthritis of the hand and wrist: a prospective study. Am J Epidemiol. 1994;139(2):119-29.
  536. Gelber AC. Obesity and hip osteoarthritis: the weight of the evidence is increasing. Am J Med. 2003;114(2):158-9.
  537. Grotle M, Hagen KB, Natvig B, Dahl FA, Kvien TK. Obesity and osteoarthritis in knee, hip and/or hand: an epidemiological study in the general population with 10 years follow-up. BMC Musculoskelet Disord. 2008;9:132.
  538. Karlson EW, Mandl LA, Aweh GN, Sangha O, Liang MH, Grodstein F. Total hip replacement due to osteoarthritis: the importance of age, obesity, and other modifiable risk factors. Am J Med. 2003;114(2):93-8.
  539. Lievense AM, Bierma-Zeinstra SM, Verhagen AP, van Baar ME, Verhaar JA, Koes BW. Influence of obesity on the development of osteoarthritis of the hip: a systematic review. Rheumatology (Oxford). 2002;41(10):1155-62.
  540. Oliveria SA, Felson DT, Cirillo PA, Reed JI, Walker AM. Body weight, body mass index, and incident symptomatic osteoarthritis of the hand, hip, and knee. Epidemiology. 1999;10(2):161-6.
  541. Felson DT, Zhang Y, Anthony JM, Naimark A, Anderson JJ. Weight loss reduces the risk for symptomatic knee osteoarthritis in women. The Framingham Study. Ann Intern Med. 1992;116(7):535-9.
  542. Christensen R, Bartels EM, Astrup A, Bliddal H. Effect of weight reduction in obese patients diagnosed with knee osteoarthritis: a systematic review and meta-analysis. Ann Rheum Dis. 2007;66(4):433-9.
  543. Springer BD, Carter JT, McLawhorn AS, Scharf K, Roslin M, Kallies KJ, et al. Obesity and the role of bariatric surgery in the surgical management of osteoarthritis of the hip and knee: a review of the literature. Surg Obes Relat Dis. 2017;13(1):111-8.
  544. Gill RS, Al-Adra DP, Shi X, Sharma AM, Birch DW, Karmali S. The benefits of bariatric surgery in obese patients with hip and knee osteoarthritis: a systematic review. Obes Rev. 2011;12(12):1083-9.
  545. Messier SP. Obesity and osteoarthritis: disease genesis and nonpharmacologic weight management. Med Clin North Am. 2009;93(1):145-59, xi-xii.
  546. Teichtahl AJ, Wang Y, Wluka AE, Cicuttini FM. Obesity and knee osteoarthritis: new insights provided by body composition studies. Obesity (Silver Spring). 2008;16(2):232-40.
  547. Finkelstein EA, Chen H, Prabhu M, Trogdon JG, Corso PS. The relationship between obesity and injuries among U.S. adults. Am J Health Promot. 2007;21(5):460-8.
  548. Cooper C, Snow S, McAlindon TE, Kellingray S, Stuart B, Coggon D, et al. Risk factors for the incidence and progression of radiographic knee osteoarthritis. Arthritis Rheum. 2000;43(5):995-1000.
  549. Duclos M. Osteoarthritis, obesity and type 2 diabetes: The weight of waist circumference. Ann Phys Rehabil Med. 2016;59(3):157-60.
  550. Francisco V, Perez T, Pino J, Lopez V, Franco E, Alonso A, et al. Biomechanics, obesity, and osteoarthritis. The role of adipokines: When the levee breaks. J Orthop Res. 2017.
  551. Thijssen E, van Caam A, van der Kraan PM. Obesity and osteoarthritis, more than just wear and tear: pivotal roles for inflamed adipose tissue and dyslipidaemia in obesity-induced osteoarthritis. Rheumatology (Oxford). 2015;54(4):588-600.
  552. Gabay O, Hall DJ, Berenbaum F, Henrotin Y, Sanchez C. Osteoarthritis and obesity: experimental models. Joint Bone Spine. 2008;75(6):675-9.
  553. Gegout PP, Francin PJ, Mainard D, Presle N. Adipokines in osteoarthritis: friends or foes of cartilage homeostasis? Joint Bone Spine. 2008;75(6):669-71.
  554. Livshits G, Zhai G, Hart DJ, Kato BS, Wang H, Williams FM, et al. Interleukin-6 is a significant predictor of radiographic knee osteoarthritis: The Chingford Study. Arthritis Rheum. 2009;60(7):2037-45.
  555. Pottie P, Presle N, Terlain B, Netter P, Mainard D, Berenbaum F. Obesity and osteoarthritis: more complex than predicted! Ann Rheum Dis. 2006;65(11):1403-5.
  556. Sandell LJ. Obesity and osteoarthritis: is leptin the link? Arthritis Rheum. 2009;60(10):2858-60.
  557. Tobin AM, Ahern T, Rogers S, Collins P, O'Shea D, Kirby B. The dermatological consequences of obesity. Int J Dermatol. 2013;52(8):927-32.
  558. Mathur AN, Goebel L. Skin findings associated with obesity. Adolesc Med State Art Rev. 2011;22(1):146-56, ix.
  559. Scheinfeld NS. Obesity and dermatology. Clin Dermatol. 2004;22(4):303-9.
  560. Shipman AR, Millington GW. Obesity and the skin. Br J Dermatol. 2011;165(4):743-50.
  561. Yosipovitch G, DeVore A, Dawn A. Obesity and the skin: skin physiology and skin manifestations of obesity. J Am Acad Dermatol. 2007;56(6):901-16; quiz 17-20.
  562. Garcia Hidalgo L. Dermatological complications of obesity. Am J Clin Dermatol. 2002;3(7):497-506.
  563. Karimi K, Lindgren TH, Koch CA, Brodell RT. Obesity as a risk factor for malignant melanoma and non-melanoma skin cancer. Rev Endocr Metab Disord. 2016;17(3):389-403.
  564. McClean KM, Kee F, Young IS, Elborn JS. Obesity and the lung: 1. Epidemiology. Thorax. 2008;63(7):649-54.
  565. O'Donnell CP, Holguin F, Dixon AE. Pulmonary physiology and pathophysiology in obesity. J Appl Physiol (1985). 2010;108(1):197-8.
  566. Parameswaran K, Todd DC, Soth M. Altered respiratory physiology in obesity. Can Respir J. 2006;13(4):203-10.
  567. Sebastian JC. Respiratory physiology and pulmonary complications in obesity. Best Pract Res Clin Endocrinol Metab. 2013;27(2):157-61.
  568. Salome CM, King GG, Berend N. Physiology of obesity and effects on lung function. J Appl Physiol (1985). 2010;108(1):206-11.
  569. Adams JP, Murphy PG. Obesity in anaesthesia and intensive care. Br J Anaesth. 2000;85(1):91-108.
  570. Jones RL, Nzekwu MM. The effects of body mass index on lung volumes. Chest. 2006;130(3):827-33.
  571. Schachter LM, Peat JK, Salome CM. Asthma and atopy in overweight children. Thorax. 2003;58(12):1031-5.
  572. Sin DD, Jones RL, Man SF. Obesity is a risk factor for dyspnea but not for airflow obstruction. Arch Intern Med. 2002;162(13):1477-81.
  573. Hakala K, Mustajoki P, Aittomaki J, Sovijarvi AR. Effect of weight loss and body position on pulmonary function and gas exchange abnormalities in morbid obesity. Int J Obes Relat Metab Disord. 1995;19(5):343-6.
  574. Morgan WK, Reger RB. Rise and fall of the FEV(1). Chest. 2000;118(6):1639-44.
  575. Womack CJ, Harris DL, Katzel LI, Hagberg JM, Bleecker ER, Goldberg AP. Weight loss, not aerobic exercise, improves pulmonary function in older obese men. J Gerontol A Biol Sci Med Sci. 2000;55(8):M453-7.
  576. Bottai M, Pistelli F, Di Pede F, Carrozzi L, Baldacci S, Matteelli G, et al. Longitudinal changes of body mass index, spirometry and diffusion in a general population. Eur Respir J. 2002;20(3):665-73.
  577. Wang ML, McCabe L, Petsonk EL, Hankinson JL, Banks DE. Weight gain and longitudinal changes in lung function in steel workers. Chest. 1997;111(6):1526-32.
  578. Cook NR, Hebert PR, Satterfield S, Taylor JO, Buring JE, Hennekens CH. Height, lung function, and mortality from cardiovascular disease among the elderly. Am J Epidemiol. 1994;139(11):1066-76.
  579. Schunemann HJ, Dorn J, Grant BJ, Winkelstein W, Jr., Trevisan M. Pulmonary function is a long-term predictor of mortality in the general population: 29-year follow-up of the Buffalo Health Study. Chest. 2000;118(3):656-64.
  580. Pelosi P, Croci M, Ravagnan I, Tredici S, Pedoto A, Lissoni A, et al. The effects of body mass on lung volumes, respiratory mechanics, and gas exchange during general anesthesia. Anesth Analg. 1998;87(3):654-60.
  581. Pelosi P, Croci M, Ravagnan I, Vicardi P, Gattinoni L. Total respiratory system, lung, and chest wall mechanics in sedated-paralyzed postoperative morbidly obese patients. Chest. 1996;109(1):144-51.
  582. Waltemath CL, Bergman NA. Respiratory compliance in obese patients. Anesthesiology. 1974;41(1):84-5.
  583. Harik-Khan RI, Wise RA, Fleg JL. The effect of gender on the relationship between body fat distribution and lung function. J Clin Epidemiol. 2001;54(4):399-406.
  584. Carey IM, Cook DG, Strachan DP. The effects of adiposity and weight change on forced expiratory volume decline in a longitudinal study of adults. Int J Obes Relat Metab Disord. 1999;23(9):979-85.
  585. Ochs-Balcom HM, Grant BJ, Muti P, Sempos CT, Freudenheim JL, Trevisan M, et al. Pulmonary function and abdominal adiposity in the general population. Chest. 2006;129(4):853-62.
  586. Chen Y, Rennie D, Cormier YF, Dosman J. Waist circumference is associated with pulmonary function in normal-weight, overweight, and obese subjects. Am J Clin Nutr. 2007;85(1):35-9.
  587. Crummy F, Piper AJ, Naughton MT. Obesity and the lung: 2. Obesity and sleep-disordered breathing. Thorax. 2008;63(8):738-46.
  588. Franssen FM, O'Donnell DE, Goossens GH, Blaak EE, Schols AM. Obesity and the lung: 5. Obesity and COPD. Thorax. 2008;63(12):1110-7.
  589. Malhotra A, Hillman D. Obesity and the lung: 3. Obesity, respiration and intensive care. Thorax. 2008;63(10):925-31.
  590. Mancuso P. Obesity and lung inflammation. J Appl Physiol (1985). 2010;108(3):722-8.
  591. Santamaria F, Montella S, Pietrobelli A. Obesity and pulmonary disease: unanswered questions. Obes Rev. 2012;13(9):822-33.
  592. Sin DD, Sutherland ER. Obesity and the lung: 4. Obesity and asthma. Thorax. 2008;63(11):1018-23.
  593. Senaratna CV, Perret JL, Lodge CJ, Lowe AJ, Campbell BE, Matheson MC, et al. Prevalence of obstructive sleep apnea in the general population: A systematic review. Sleep Med Rev. 2017;34:70-81.
  594. Romero-Corral A, Caples SM, Lopez-Jimenez F, Somers VK. Interactions between obesity and obstructive sleep apnea: implications for treatment. Chest. 2010;137(3):711-9.
  595. Johns MW. A new method for measuring daytime sleepiness: the Epworth sleepiness scale. Sleep. 1991;14(6):540-5.
  596. Netzer NC, Stoohs RA, Netzer CM, Clark K, Strohl KP. Using the Berlin Questionnaire to identify patients at risk for the sleep apnea syndrome. Ann Intern Med. 1999;131(7):485-91.
  597. Kahal H, Kyrou I, Tahrani AA, Randeva HS. Obstructive sleep apnoea and polycystic ovary syndrome: A comprehensive review of clinical interactions and underlying pathophysiology. Clin Endocrinol (Oxf). 2017;87(4):313-9.
  598. Seetho IW, Wilding JP. Screening for obstructive sleep apnoea in obesity and diabetes--potential for future approaches. Eur J Clin Invest. 2013;43(6):640-55.
  599. Iber C, Ancoli-Israel S, Chesson ALJ, Quan SF. The AASM Manual for the Scoring of Sleep and Associated Events: Rules, Terminology and Technical Specifications. Westchester, IL: American Academy of Sleep Medicine. 2007.
  600. Sleep-related breathing disorders in adults: recommendations for syndrome definition and measurement techniques in clinical research. The Report of an American Academy of Sleep Medicine Task Force. Sleep. 1999;22(5):667-89.
  601. Gottlieb DJ, Whitney CW, Bonekat WH, Iber C, James GD, Lebowitz M, et al. Relation of sleepiness to respiratory disturbance index: the Sleep Heart Health Study. Am J Respir Crit Care Med. 1999;159(2):502-7.
  602. Veasey SC. Obstructive sleep apnea: re-evaluating our index of severity. Sleep Med. 2006;7(1):5-6.
  603. Littleton SW, Mokhlesi B. The pickwickian syndrome-obesity hypoventilation syndrome. Clin Chest Med. 2009;30(3):467-78, vii-viii.
  604. Al Lawati NM, Patel SR, Ayas NT. Epidemiology, risk factors, and consequences of obstructive sleep apnea and short sleep duration. Prog Cardiovasc Dis. 2009;51(4):285-93.
  605. Young T, Palta M, Dempsey J, Skatrud J, Weber S, Badr S. The occurrence of sleep-disordered breathing among middle-aged adults. N Engl J Med. 1993;328(17):1230-5.
  606. Bonsignore MR, McNicholas WT, Montserrat JM, Eckel J. Adipose tissue in obesity and obstructive sleep apnoea. Eur Respir J. 2012;39(3):746-67.
  607. Attal P, Chanson P. Endocrine aspects of obstructive sleep apnea. J Clin Endocrinol Metab. 2010;95(2):483-95.
  608. Frey WC, Pilcher J. Obstructive sleep-related breathing disorders in patients evaluated for bariatric surgery. Obes Surg. 2003;13(5):676-83.
  609. Vgontzas AN, Tan TL, Bixler EO, Martin LF, Shubert D, Kales A. Sleep apnea and sleep disruption in obese patients. Arch Intern Med. 1994;154(15):1705-11.
  610. O'Keeffe T, Patterson EJ. Evidence supporting routine polysomnography before bariatric surgery. Obes Surg. 2004;14(1):23-6.
  611. Peppard PE, Young T, Palta M, Dempsey J, Skatrud J. Longitudinal study of moderate weight change and sleep-disordered breathing. Jama. 2000;284(23):3015-21.
  612. Flemons WW. Clinical practice. Obstructive sleep apnea. N Engl J Med. 2002;347(7):498-504.
  613. Seidell JC. Waist circumference and waist/hip ratio in relation to all-cause mortality, cancer and sleep apnea. Eur J Clin Nutr. 2010;64(1):35-41.
  614. Kawaguchi Y, Fukumoto S, Inaba M, Koyama H, Shoji T, Shoji S, et al. Different impacts of neck circumference and visceral obesity on the severity of obstructive sleep apnea syndrome. Obesity (Silver Spring). 2011;19(2):276-82.
  615. Grunstein R, Wilcox I, Yang TS, Gould Y, Hedner J. Snoring and sleep apnoea in men: association with central obesity and hypertension. Int J Obes Relat Metab Disord. 1993;17(9):533-40.
  616. Mukherjee S, Saxena R, Palmer LJ. The genetics of obstructive sleep apnoea. Respirology. 2018;23(1):18-27.
  617. Horner RL, Mohiaddin RH, Lowell DG, Shea SA, Burman ED, Longmore DB, et al. Sites and sizes of fat deposits around the pharynx in obese patients with obstructive sleep apnoea and weight matched controls. Eur Respir J. 1989;2(7):613-22.
  618. Schwab RJ, Gupta KB, Gefter WB, Metzger LJ, Hoffman EA, Pack AI. Upper airway and soft tissue anatomy in normal subjects and patients with sleep-disordered breathing. Significance of the lateral pharyngeal walls. Am J Respir Crit Care Med. 1995;152(5 Pt 1):1673-89.
  619. Shelton KE, Gay SB, Hollowell DE, Woodson H, Suratt PM. Mandible enclosure of upper airway and weight in obstructive sleep apnea. Am Rev Respir Dis. 1993;148(1):195-200.
  620. Carrera M, Barbe F, Sauleda J, Tomas M, Gomez C, Santos C, et al. Effects of obesity upon genioglossus structure and function in obstructive sleep apnoea. Eur Respir J. 2004;23(3):425-9.
  621. Ip MS, Lam B, Ng MM, Lam WK, Tsang KW, Lam KS. Obstructive sleep apnea is independently associated with insulin resistance. Am J Respir Crit Care Med. 2002;165(5):670-6.
  622. Vgontzas AN. Does obesity play a major role in the pathogenesis of sleep apnoea and its associated manifestations via inflammation, visceral adiposity, and insulin resistance? Arch Physiol Biochem. 2008;114(4):211-23.
  623. Arnardottir ES, Mackiewicz M, Gislason T, Teff KL, Pack AI. Molecular signatures of obstructive sleep apnea in adults: a review and perspective. Sleep. 2009;32(4):447-70.
  624. Phillips BG, Kato M, Narkiewicz K, Choe I, Somers VK. Increases in leptin levels, sympathetic drive, and weight gain in obstructive sleep apnea. Am J Physiol Heart Circ Physiol. 2000;279(1):H234-7.
  625. Charkoudian N, Rabbitts JA. Sympathetic neural mechanisms in human cardiovascular health and disease. Mayo Clin Proc. 2009;84(9):822-30.
  626. Shamsuzzaman AS, Gersh BJ, Somers VK. Obstructive sleep apnea: implications for cardiac and vascular disease. Jama. 2003;290(14):1906-14.
  627. Wolf J, Lewicka J, Narkiewicz K. Obstructive sleep apnea: an update on mechanisms and cardiovascular consequences. Nutr Metab Cardiovasc Dis. 2007;17(3):233-40.
  628. Tuomilehto H, Seppa J, Uusitupa M. Obesity and obstructive sleep apnea--clinical significance of weight loss. Sleep Med Rev. 2013;17(5):321-9.
  629. 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):1724-37.
  630. Greenburg DL, Lettieri CJ, Eliasson AH. Effects of surgical weight loss on measures of obstructive sleep apnea: a meta-analysis. Am J Med. 2009;122(6):535-42.
  631. Sarkhosh K, Switzer NJ, El-Hadi M, Birch DW, Shi X, Karmali S. The impact of bariatric surgery on obstructive sleep apnea: a systematic review. Obes Surg. 2013;23(3):414-23.
  632. Pillar G, Peled R, Lavie P. Recurrence of sleep apnea without concomitant weight increase 7.5 years after weight reduction surgery. Chest. 1994;106(6):1702-4.
  633. Patel SR, Hu FB. Short sleep duration and weight gain: a systematic review. Obesity (Silver Spring). 2008;16(3):643-53.
  634. Phillips BG, Hisel TM, Kato M, Pesek CA, Dyken ME, Narkiewicz K, et al. Recent weight gain in patients with newly diagnosed obstructive sleep apnea. J Hypertens. 1999;17(9):1297-300.
  635. Chung SA, Yuan H, Chung F. A systemic review of obstructive sleep apnea and its implications for anesthesiologists. Anesth Analg. 2008;107(5):1543-63.
  636. Flum DR, Belle SH, King WC, Wahed AS, Berk P, Chapman W, et al. Perioperative safety in the longitudinal assessment of bariatric surgery. N Engl J Med. 2009;361(5):445-54.
  637. Rasmussen JJ, Fuller WD, Ali MR. Sleep apnea syndrome is significantly underdiagnosed in bariatric surgical patients. Surg Obes Relat Dis. 2012;8(5):569-73.
  638. Ravesloot MJ, van Maanen JP, Hilgevoord AA, van Wagensveld BA, de Vries N. Obstructive sleep apnea is underrecognized and underdiagnosed in patients undergoing bariatric surgery. Eur Arch Otorhinolaryngol. 2012;269(7):1865-71.
  639. Nepomnayshy D, Hesham W, Erickson B, MacDonald J, Iorio R, Brams D. Sleep apnea: is routine preoperative screening necessary? Obes Surg. 2013;23(3):287-91.
  640. de Raaff CAL, Gorter-Stam MAW, de Vries N, Sinha AC, Jaap Bonjer H, Chung F, et al. Perioperative management of obstructive sleep apnea in bariatric surgery: a consensus guideline. Surg Obes Relat Dis. 2017;13(7):1095-109.
  641. Camhi SM, Katzmarzyk PT. Differences in body composition between metabolically healthy obese and metabolically abnormal obese adults. Int J Obes (Lond). 2013.
  642. Lebovitz HE, Banerji MA. Point: visceral adiposity is causally related to insulin resistance. Diabetes Care. 2005;28(9):2322-5.
  643. Seidell JC, Han TS, Feskens EJ, Lean ME. Narrow hips and broad waist circumferences independently contribute to increased risk of non-insulin-dependent diabetes mellitus. J Intern Med. 1997;242(5):401-6.
  644. Bigaard J, Frederiksen K, Tjonneland A, Thomsen BL, Overvad K, Heitmann BL, et al. Waist and hip circumferences and all-cause mortality: usefulness of the waist-to-hip ratio? Int J Obes Relat Metab Disord. 2004;28(6):741-7.
  645. Fox CS, Massaro JM, Hoffmann U, Pou KM, Maurovich-Horvat P, Liu CY, et al. Abdominal visceral and subcutaneous adipose tissue compartments: association with metabolic risk factors in the Framingham Heart Study. Circulation. 2007;116(1):39-48.
  646. Goodpaster BH, Thaete FL, Simoneau JA, Kelley DE. Subcutaneous abdominal fat and thigh muscle composition predict insulin sensitivity independently of visceral fat. Diabetes. 1997;46(10):1579-85.
  647. Virtanen KA, Iozzo P, Hallsten K, Huupponen R, Parkkola R, Janatuinen T, et al. Increased fat mass compensates for insulin resistance in abdominal obesity and type 2 diabetes: a positron-emitting tomography study. Diabetes. 2005;54(9):2720-6.
  648. Abate N, Garg A, Peshock RM, Stray-Gundersen J, Grundy SM. Relationships of generalized and regional adiposity to insulin sensitivity in men. J Clin Invest. 1995;96(1):88-98.
  649. Kim JY, van de Wall E, Laplante M, Azzara A, Trujillo ME, Hofmann SM, et al. Obesity-associated improvements in metabolic profile through expansion of adipose tissue. J Clin Invest. 2007;117(9):2621-37.
  650. Hill JO, Wyatt HR. The myth of healthy obesity. Ann Intern Med. 2013;159(11):789-90.
  651. Roberson LL, Aneni EC, Maziak W, Agatston A, Feldman T, Rouseff M, et al. Beyond BMI: The "Metabolically healthy obese" phenotype & its association with clinical/subclinical cardiovascular disease and all-cause mortality -- a systematic review. BMC Public Health. 2014;14:14.
Copyright © 2000-2019,, Inc.

This electronic version has been made freely available under a Creative Commons (CC-BY-NC-ND) license. A copy of the license can be viewed at

Bookshelf ID: NBK278973PMID: 25905207


  • PubReader
  • Print View
  • Cite this Page

Links to

Similar articles in PubMed

See reviews...See all...

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...