Obesity

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Obesity is the medical condition associated with excessive stores of body fat, to the extent that it causes serious health concerns. Obesity is a major problem in today’s society, with more than 1 billion people being classed as obese worldwide.

Obesity is an increase in adipose tissue, so much so that it can cause a variety of adverse health consequences. Physical problems include high blood pressure, heart disease, some cancers and Diabetes mellitus type 2; by 2025, 300 million people are expected to suffer from obesity-related diabetes. Emotional problems including low self esteem, and depression.

There are many ways of measuring body fat but the most popular uses the body mass index (BMI), which measures the relationship between weight and height. A BMI of 30 or more puts you in the category of obese. This method is simple, but imprecise; people carrying a lot of muscle will not receive an accurate BMI measure due to muscle being heavier than fat.

Prevalence and epidemiology

Obesity is increasing in Europe.[1] In the United States, obesity is increased through 2004[2] but has been stable since[3]. Among immigrants, the incidence of obesity increases with the duration of living in the United States.[4]

Causes/etiology

See Genetics of obesity

Obesity is caused by a mix of environmental and genetic factors.[5][6] In only very few cases can obesity in humans be attributed to a single gene defect, but many genes have been found that have variants associated with an increased risk of obesity.

Obesity is associated with a state of leptin resistance, analogous to the insulin resistance seen in type 2 diabetes. Leptin, secreted by fat tissues, is a major appetite suppressor; it is secreted at high levels in obese individuals, but the hypothalamus does not respond proportionately to leptin in obese individuals.

Behavioural and environmental factors

The increase in overweight and obesity (the increase that has taken place during the 20th century and is continuing today) is most obviously due to environmental changes (in the widest sense), the most commonly discussed obesogenic factors being diet and exercise. This is not to say that no relevant obesogenic changes in the human genetic pool happened during this period, and this does not exclude epigenetic modifications of the genome. In a multi-center review of the literature on the possible causes of this secular trend, 10 other factors, including epigenetic changes and modifications in mating behaviours modulating the gene pool, were found to be equally plausible etiologic factors contributing to the epidemic.[7]

Diet and Sedentarity

While a sedentary lifestyle is involved in the development of a wide range of physical and mental ills, and obesity is associated with a more sedentary lifestyle, it is not obvious that lack of exercise is a major factor in the present obesity epidemic. In a 5.6 years follow-up study of 393 middle-aged healthy subjects, Cambridge epidemiologists demonstrated that carrying excess weight predicted a sedentary lifestyle, but that sedentary time did not predict weight gain.[8]

Other factors

Many other changes in environment and lifestyle may be involved in the increasing prevalence of obesity. Stress and depression (and associated disruptions of sleep) can lead to obesity.[9] [10][7]; changes in eating patterns may contribute [11] and cultural changes in perceptions of overweight[12] Smoking cessation has a well known effect to increase caloric intake.

The role of fetal programming,[13] [14][15] perhaps operative in the higher risk of obesity in offspring of older and/or very lean women.

Pathophysiology

The response to a meal in obesity: the insulin paradox

All consumers of refined starches, soft drinks, high-fructose corn syrups and other energy-replete products are not born equal. Obese persons, after a meal, appear to burn carbohydrates less efficiently and fat even more poorly.[16] A contribution of leptin resistance was suggested, as circulating concentrations of leptin were higher in the obese men that were the least efficient metabolisers of fat. However, the arrow of causality may be oriented in the other direction. In persons with a family history of obesity, the earliest obesogenic changes are not related to leptin, but to metabolic efficiency and to insulin status and responsiveness: subjects at increased risk of obesity oxidize carbohydrates more quickly and fat more slowly, and have lower insulin, consistent with a greater insulin sensitivity.[17] These findings contrast with those implicating obesity with the development, over the long term, of the opposite of insulin sensitivity, i.e. insulin resistance.

Magnesium Obese subjects, like type II diabetics, are magnesium deficient.[18] This deficiency is intracellular, and measuring intracellular magnesium requires techniques not yet available in routine clinical settings. Magnesium is required in more than 300 enzymatic reactions, including several that are rate-limiting in carbohydrate utilization. Insulin action depends on magnesium availability in cells and high glucose exposure leads to magnesium depletion and insulin resistance. In obese children, magnesium deficiency precedes insulin resistance[18], but how the heightened responsivity of cells to insulin, that is characteristic of the pre-obese state,[17] relates to magnesium deficiency is not known.

Oxidative stress and reductant stress

At the scale of the adipocyte, we are facing a paradox similar to the one involving insulin. Obesity may present associated with a range of abnormalities: insulin resistance, chronic inflammation, oxidative stress and a range of ills aggregating in what has been called the metabolic syndrome. It thus appears reasonable to assume that adipocytes, in obesity, are in a state of oxidative stress. However, studying obesity in isolation, it became apparent that obesity at the adipocyte level required the opposite of oxidative stress, e.g. a balance between oxidants and reductants tilted in favour of the latter.[19]

Omega-6 vs. omega-3 unsaturated fatty acids

The amount and type of fat to which adipocytes are exposed conditions their development. The amount of omega-6 fatty acids in the diet, in absolute terms as well as relative to the amounts of omega-3 fatty acids, have risen sharply since 1945 due to novel techniques to extract fat from vegetable sources. Omega-6 fatty acids, as a prostacyclin precursors, enhance cyclic AMP-dependent signaling pathways in preadipocytes and promote the development of mature adipocytes. Only by modulating the proportion of omega-6 fatty acids in the diet (without increasing total caloric intake), it is possible to cause in animals a 50% increase in body mass.[20]


Starving in a sea of plenty

In 2008, a twin study was published which carefully selected, from 2,453 young healthy twin pairs, 14 pairs that were discordant for obesity (one twin being obese, and the other not).[21] This study ruled out all genetic factors, as well as intrauterine influences and several environmental factors commonly shared amongst siblings of similar ages. The most significant changes in adipocytes were a sharp decrease in the number of mitochondria, the power plants of the cells that are involved in fat burning, and a specific decrease in their ability to oxidize (burn) three amino acids called branched-chain amino acids, that are the first amino acids to be used as fuel when other sources are unavailable. These amino acids, being poorly catabolized, were higher in the circulation; this signalled the release of higher amounts of more insulin, possibly leading to a vicious cycle. Considering metabolic pathways that were, on the contrary, up-regulated, the researchers found that numerous inflammatory cascades were overactive. The decline in the number of mitochondria remains the most important finding, which will help to design therapies addressing the fact that, in the disease of affluent civilisations par excellence, adipocytes and their energy-producing organelles, the mitochondria, are "starving in a sea of plenty".

The gut flora of the obese: the enemy within

The gut flora, which fulfills an essential symbiotic role in animal metabolism, is probably the first victim of a high-fat diet. Before one becomes obese due to dietary excesses, the trillions of micro-organisms which inhabit our intestines have already transformed into a pro-inflammatory, obesogenic organ.[22][23][24]

Treatment

See also Bariatric surgery, Drug treatments for obesity and Exercise and body weight

The mainstay of treatment for obesity is an energy-limited diet and increased exercise. In studies, diet and exercise programs have consistently produced an average weight loss of approximately 8% of total body mass (excluding study drop-outs). While not all dieters will be satisfied with this outcome, a loss of as little as 5% of body mass can create large health benefits. A more intractable therapeutic problem appears to be weight loss maintenance. Of dieters who manage to lose 10% or more of their body mass in studies, 80-95% will regain that weight within two to five years, supporting the finding that the body has various mechanisms that maintain weight at a certain set point.

A clinical practice guideline issued by the American College of Physicians in 2005 made five recommendations:[25]

  1. People with a BMI above 30 should be counseled on diet, exercise and other relevant behavioral interventions, and set a realistic goal for weight loss.
  2. If these goals are not achieved, pharmacotherapy can be offered. The patient needs to be informed of the possibility of side-effects and the unavailability of long-term safety and efficacy data.
  3. Drug therapy may consist of sibutramine, orlistat, phentermine, diethylpropion, fluoxetine, and bupropion. For more severe cases of obesity, stronger drugs such as amphetamine and methamphetamine may be used on a selective basis. Evidence is not sufficient to recommend sertraline, topiramate, or zonisamide.
  4. In patients with BMI > 40 who fail to achieve their weight loss goals (with or without medication) and who develop obesity-related complications, referral for bariatric surgery may be indicated. The patient needs to be aware of the potential complications.
  5. Those requiring bariatric surgery should be referred to high-volume referral centers, as the evidence suggests that surgeons who frequently perform these procedures have fewer complications.

A clinical practice guideline by the US Preventive Services Task Force (USPSTF) concluded that the evidence is insufficient to recommend for or against routine behavioral counseling to promote a healthy diet in unselected patients in primary care settings, but that intensive behavioral dietary counseling is recommended in those with hyperlipidemia and other known risk factors for cardiovascular and diet-related chronic disease. Intensive counseling can be delivered by primary care clinicians or by referral to other specialists, such as nutritionists or dietitians.[26][27]

Counseling

A meta-analysis of randomized controlled trials concluded that "compared with usual care, dietary counseling interventions produce modest weight losses that diminish over time."[28]

The role of genetic counseling is unclear[29]; but based on a study done of hypercholesterolemia, it is possible that genetic counseling might lead to patients preferring medication over diet therapy.[30]

The Internet offer a method to increase patient participation in their health care. A randomized controlled trial showed some benefit in a weight loss program that used the Internet.[31]

Portion control plate

A randomized controlled trial found that patients using portion control plates and log books had more weight loss and less use of hypoglycemic drugs.[32]

Drink more water

Encouraging more water drinking may help.[33]

Financial incentives

Financial incentives may help.[34]


Exercise

See Exercise and body weight

Reduction of ambient temperature

When ambient temperatures decrease below certain levels, the body must make homeostatic and adaptive adjustments to maintain optimal body temperature. Those adjustments entail increased body heat production that add to total energy expenditure. Thus, it has been hypothesized that lowering ambient temperatures in homes and workplaces will contribute to mitigation of obesogenesis.[35]

Drugs

See Drug treatments for obesity

Many drugs reduce appetite by activating serotonin 5-HT2C receptor. This may occur via:

Orlistat is an inhibitor of gastrointestinal lipase.

For patients with diabetes mellitus type 2, metformin can assist in weight loss—rather than sulfonylurea derivatives and insulin, which often lead to further weight gain. The thiazolidinediones (rosiglitazone or pioglitazone) can cause slight weight gain, but decrease the "pathologic" form of abdominal fat, and so may help obese diabetics.

Effectiveness

A systematic review found that the average weight loss after at least one year was:[38]

  • Orlistat: 2.9 kg, but with gastrointestinal side effects.
  • Sibutramine: 4.2 kg, but with raised blood pressure and pulse.
  • Rimonabant: 4.7-kg, but associated with increased psychiatric disorders. About a third of patients discontinued treatment.[39][38]

Subsequent trials show:

Bariatric surgery

Bariatric surgery (or "weight loss surgery") is the use of surgical interventions in the treatment of obesity. As every surgical intervention may lead to complications, it is regarded as a last resort when dietary modification and pharmacological treatment have proven to be unsuccessful. In the United States, Medicare will only only pay for procedures performed at approved facilities.[40]

Weight loss surgery relies on various principles. Band surgery is reversible, while bowel shortening operations are not. Some procedures can be performed laparoscopically.

  • Predominantly malabsorptive procedures Others procedures also reduce the length of bowel that food will be in contact with, directly reducing absorption (gastric bypass surgery).

In general, the malabsorptive procedures lead to more weight loss than the restrictive procedures. A meta-analysis by the American College of Physicians reports the following weight loss at 36 months:[41]

  • Biliopancreatic diversion - 53 kg
  • Roux-en-Y gastric bypass (RYGB) - 41 kg
    • Open - 42 kg
    • Laparoscopic - 38 kg
  • Adjustable gastric banding - 35 kg
  • Vertical banded gastroplasty - 32 kg

This meta-analysis does not include a more recent randomized controlled trial.[42]

Mortality

Two studies report decrease in mortality from bariatric surgery.[43][44] In the Swedish randomized controlled trial, patients with a body mass index of 34 or more for men and 38 or more for women underwent various types of bariatric surgery and were followed for a mean of 11 years. Surgery patients had 5.0% mortality while control patients had 6.3% mortality. This means 75 patients must be treated to avoid one death after 11 years (number needed to treat is 77).[43] In a Utah retrospective cohort study that followed patients for a mean of 7 years after various types of gastric bypass, surgery patients had 0.4% mortality while control patients had 0.6% mortality.[44]

Remission of diabetes

Bariatric surgery remits diabetes mellitus type 2 in more than 1 of every two people after 2 years if they are similar to the patients in the randomized controlled trial / meta-analysis by Dixon et al. (Number needed to treat is 1.7).[45] In this trial 73% of the patients who remitted their diabetes versus 13% of the patients in the control group.

Prevention

Display of calorie information on the menus or menu boards of restaurants has been proposed by the city of New York.[46]

Eating breakfast may reduce weight gain by adolescents[47]

References

  1. ↑ Kotseva K et al. (2009). "Cardiovascular prevention guidelines in daily practice: a comparison of EUROASPIRE I, II, and III surveys in eight European countries". Lancet 373: 929–40. DOI:10.1016/S0140-6736(09)60330-5. PMID 19286092. Research Blogging.
  2. ↑ Ogden CL et al. (April 2006). "Prevalence of overweight and obesity in the United States, 1999-2004". JAMA 295 (13): 1549–55. DOI:10.1001/jama.295.13.1549. PMID 16595758. Research Blogging.
  3. ↑ Ogden CL et al. (May 2008). "High body mass index for age among US children and adolescents, 2003-2006". JAMA 299: 2401–5. DOI:10.1001/jama.299.20.2401. PMID 18505949. Research Blogging.
  4. ↑ Goel MS et al. (December 2004). "Obesity among US immigrant subgroups by duration of residence". JAMA 292: 2860–7. DOI:10.1001/jama.292.23.2860. PMID 15598917. Research Blogging.
  5. ↑ Stunkard AJ et al. (1990). "The body-mass index of twins who have been reared apart". N a J Med 322: 1483–7. PMID 2336075. [e]
  6. ↑ Christakis NA, Fowler JH (2007). "The spread of obesity in a large social network over 32 years". N Engl J Med 357: 370–9. DOI:10.1056/NEJMsa066082. PMID 17652652. Research Blogging.
  7. ↑ 7.0 7.1 Keith SW et al (2006). "Putative contributors to the secular increase in obesity: exploring the roads less traveled". Int J Obes (Lond) 30: 1585–94. PMID 16801930.
  8. ↑ Ekelund U et al.(2008) Time spent being sedentary and weight gain in healthy adults: reverse or bidirectional causality? Am J Clin Nutr 88:612-7
  9. ↑ Kivimäki M et al. (2009). "Common mental disorder and obesity: insight from four repeat measures over 19 years: prospective Whitehall II cohort study". BMJ 339: b3765. DOI:10.1136/bmj.b3765. PMID 19808765. Research Blogging.
  10. ↑ Vgontzas AN et al. (2008). "Short sleep duration and obesity: the role of emotional stress and sleep disturbances". Int J Obes 32: 801-9. DOI:10.1038/ijo.2008.4. PMID 18253159. Research Blogging.
  11. ↑ Maruyama, K; et al. (2008-10-21). "The joint impact on being overweight of self reported behaviours of eating quickly and eating until full : cross sectional survey". BMJ 337: a2002. DOI:10.1136/bmj.a2002. Research Blogging.
  12. ↑ Johnson F et al. (2008). "Changing perceptions of weight in Great Britain: comparison of two population surveys". BMJ 337: a494. PMID 18617488. [e]
  13. ↑ Breier BH et al. (2001). "Fetal programming of appetite and obesity". Mol Cell Endocrinol 185: 73-9. PMID 11738796.
  14. ↑ Vickers MH et al. (2001). "Dysregulation of the adipoinsular axis -- a mechanism for the pathogenesis of hyperleptinemia and adipogenic diabetes induced by fetal programming". J Endocrinol 170: 323-32. PMID 11479129.
  15. ↑ Vickers MH et al. (2000). "Fetal origins of hyperphagia, obesity, and hypertension and postnatal amplification by hypercaloric nutrition". Am J Physiol 279: E83-7. PMID 10893326.
  16. ↑ Lopes IM et al. (2001). "Effects of leptin resistance on acute fuel metabolism after a high carbohydrate load in lean and overweight young men". J Am Coll Nutr 20: 643–8. PMID 11771681.
  17. ↑ 17.0 17.1 Giacco R et al. (2004). "Insulin sensitivity is increased and fat oxidation after a high-fat meal is reduced in normal-weight healthy men with strong familial predisposition to overweight". Int J Obes Relat Metab Disord 28: 342–8. PMID 14970841.
  18. ↑ 18.0 18.1 Takaya J et al. (2003). "Intracellular magnesium of platelets in children with diabetes and obesity". Metab Clin Exp 52: 468–71. PMID 12701060.
  19. ↑ Galinier A et al. (2006). "Adipose tissue proadipogenic redox changes in obesity". J Biol Chem 281: 12682–7. PMID 16377639. (Free full text)
  20. ↑ Massiera F et al. (2003). "Arachidonic acid and prostacyclin signaling promote adipose tissue development: a human health concern?". J Lipid Res 44: 271–9. PMID 12576509.
  21. ↑ Pietiläinen KH et al. (2008). "Global transcript profiles of fat in monozygotic twins discordant for BMI: pathways behind acquired obesity". PLoS Med 5: e51. PMID 18336063.
  22. ↑ Kalliomäki M et al. (2008). "Early differences in fecal microbiota composition in children may predict overweight". Am J Clin Nutr 87: 534–8. PMID 18326589. [e]
  23. ↑ Cani PD et al. (2008). "Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet-induced obesity and diabetes in mice". Diabetes. DOI:10.2337/db07-1403. PMID 18305141. Research Blogging.
  24. ↑ Cani PD et al. (2007). "Metabolic endotoxemia initiates obesity and insulin resistance". Diabetes 56: 1761–72. DOI:10.2337/db06-1491. PMID 17456850. Research Blogging.
  25. ↑ Snow V et al. (2005). "Pharmacologic and surgical management of obesity in primary care: a clinical practice guideline from the American College of Physicians". Ann Intern Med 142: 525-31. PMID 15809464. Fulltext.
  26. ↑ Behavioral counseling in primary care to promote a healthy diet: recommendations and rationale.. Retrieved on 2007-05-22.
  27. ↑ Pignone MP, Ammerman A, Fernandez L, et al (2003). "Counseling to promote a healthy diet in adults: a summary of the evidence for the U.S. Preventive Services Task Force". American journal of preventive medicine 24 (1): 75-92. PMID 12554027. [e]
  28. ↑ Dansinger ML et al. (2007). "Meta-analysis: the effect of dietary counseling for weight loss". Ann Intern Med 147: 41-50. PMID 17606960. [e]
  29. ↑ Marteau T et al. (2004). "Psychological impact of genetic testing for familial hypercholesterolemia within a previously aware population: a randomized controlled trial". Am J Med Genet A 128: 285–93. DOI:10.1002/ajmg.a.30102. PMID 15216550. Research Blogging.
  30. ↑ Rief W et al. (2007). "Is information on genetic determinants of obesity helpful or harmful for obese people?--A randomized clinical trial". J Gen Intern Med 22: 1553–9. DOI:10.1007/s11606-007-0353-7. PMID 17879121. Research Blogging.
  31. ↑ Hunter CM et al (2008). "Weight management using the internet a randomized controlled trial". Am J Prev Med 34: 119–26. DOI:10.1016/j.amepre.2007.09.026. PMID 18201641. Research Blogging.
  32. ↑ Pedersen SD et al. (2007). "Portion control plate for weight loss in obese patients with type 2 diabetes mellitus: a controlled clinical trial". Arch Intern Med 167: 1277–83. DOI:10.1001/archinte.167.12.1277. PMID 17592101. Research Blogging. ACP Journal Club review
  33. ↑ Muckelbauer R et al. (2009). "Promotion and provision of drinking water in schools for overweight prevention: randomized, controlled cluster trial". Pediatrics 123: e661–7. DOI:10.1542/peds.2008-2186. PMID 19336356. Research Blogging.
  34. ↑ Volpp KG et al. (December 2008). "Financial incentive-based approaches for weight loss: a randomized trial". JAMA 300: 2631–7. DOI:10.1001/jama.2008.804. PMID 19066383. Research Blogging.
  35. ↑ Hansen JC, Gilman AP, Odland JO. (2010) Is thermogenesis a significant causal factor in preventing the ‘‘globesity” epidemic?. Med Hypotheses. In press as of 16 May 2010.
  36. ↑ 36.0 36.1 Astrup A et al. (November 2008). "Effect of tesofensine on bodyweight loss, body composition, and quality of life in obese patients: a randomised, double-blind, placebo-controlled trial". Lancet 372: 1906–13. DOI:10.1016/S0140-6736(08)61525-1. PMID 18950853. Research Blogging. Cite error: Invalid <ref> tag; name "pmid18950853" defined multiple times with different content
  37. ↑ 37.0 37.1 Smith, SR; et al. (2010-07-15). "Multicenter, placebo-controlled trial of Lorcaserin for weight management". N Engl J Med 363: 245-56. DOI:10.1056/NEJMoa0909809. Retrieved on 2010-07-15. Research Blogging. Cite error: Invalid <ref> tag; name "10.1056/NEJMoa0909809" defined multiple times with different content
  38. ↑ 38.0 38.1 Rucker D et al. (2007). "Long term pharmacotherapy for obesity and overweight: updated meta-analysis". BMJ. DOI:10.1136/bmj.39385.413113.25. PMID 18006966. Research Blogging.
  39. ↑ Christensen R et al. (2007). "Efficacy and safety of the weight-loss drug rimonabant: a meta-analysis of randomised trials". Lancet 370: 1706–13. DOI:10.1016/S0140-6736(07)61721-8. PMID 18022033. Research Blogging.
  40. ↑ Bariatric Surgery. Centers for Medicare & Medicaid Services. Retrieved on 2008-06-26.
  41. ↑ Maggard MA et al. (2005). "Meta-analysis: surgical treatment of obesity". Ann. Intern. Med. 142: 547–59. PMID 15809466. [e]
  42. ↑ Nguyen, Ninh T et al. A prospective randomized trial of laparoscopic gastric bypass versus laparoscopic adjustable gastric banding for the treatment of morbid obesity: Outcomes, quality of life, and costs. Annals of Surgery. 2009;250(4):631-641. DOI:10.1097/SLA.0b013e3181b92480
  43. ↑ 43.0 43.1 Sjöström L et al. (2007). "Effects of bariatric surgery on mortality in Swedish obese subjects". N Engl J Med 357: 741-52. DOI:10.1056/NEJMoa066254. PMID 17715408. Research Blogging.
  44. ↑ 44.0 44.1 Adams TD et al. (2007). "Long-term mortality after gastric bypass surgery". N Engl J Med 357: 753-61. DOI:10.1056/NEJMoa066603. PMID 17715409. Research Blogging.
  45. ↑ Dixon JB et al. (2008). "Adjustable gastric banding and conventional therapy for type 2 diabetes: a randomized controlled trial". JAMA 299: 316–23. DOI:10.1001/jama.299.3.316. PMID 18212316. Research Blogging.
  46. ↑ Rivera R (2007) “New York City Reintroduces Calorie Rule,” The New York Times, October 25, 2007, http://www.nytimes.com/2007/10/25/nyregion/25calories.html (accessed October 26, 2007)
  47. ↑ Timlin MT et al. (2008). "Breakfast eating and weight change in a 5-year prospective analysis of adolescents: Project EAT (Eating Among Teens)". Pediatrics 121: e638-45. DOI:10.1542/peds.2007-1035. PMID 18310183. Research Blogging.
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