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Open questions about metabolically normal obesity

International Journal of Obesity volume 34, pages S18–S23 (2010)Cite this article

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Abstract

Subsets of obese subjects without any cardiometabolic risk factors have been repeatedly described. This raises questions whether obesity ‘per se’ enhances the risk for cardiovascular or metabolic diseases and whether healthy obese subjects would benefit from a medical treatment. In order to answer these questions, as a first step, an expert consensus should be reached for the definition of metabolic normality. In fact, up to now, different parameters related to the metabolic syndrome and/or to insulin sensitivity have been utilized across studies. Once an agreement is reached, population-based studies should be undertaken to establish the incidence of metabolic normality among obese subjects. Furthermore, many other parameters such as age, sex, race, fat distribution and physical activity should be monitored to obtain results representative of a general population. Longitudinal studies aimed at investigating the evolution of the cardiometabolic profile of healthy obese subjects are also needed. In conclusion, data from the literature strongly suggest that a regular surveillance of the cardiometabolic parameters and a prevention of any further weight gain should be applied to healthy obese individuals, whereas possible benefits of a weight loss treatment are still a matter of debate.

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References

  1. Hubert HB, Feinleib M, McNamara PM, Castelli WP . Obesity as an independent risk factor for cardiovascular disease: a 26-year follow-up of participants in the Framingham Heart Study. Circulation 1983; 67: 968–977.

    Article  CAS  Google Scholar 

  2. Calle EE, Thun MJ, Petrelli JM, Rodriguez C, Heath Jr CW . Body-mass index and mortality in a prospective cohort of US adults. N Engl J Med 1999; 341: 1097–1105.

    Article  CAS  Google Scholar 

  3. Must A, Spadano J, Coakley EH, Field AE, Colditz G, Dietz WH . The disease burden associated with overweight and obesity. JAMA 1999; 282: 1523–1529.

    Article  CAS  Google Scholar 

  4. Ferrannini E, Natali A, Bell P, Cavallo-Perin P, Lalic N, Mingrone G . Insulin resistance and hypersecretion in obesity. European Group for the Study of Insulin Resistance (EGIR). J Clin Invest 1997; 100: 1166–1173.

    Article  CAS  Google Scholar 

  5. Brochu M, Tchernof A, Dionne IJ, Sites CK, Eltabbakh GH, Sims EA et al. What are the physical characteristics associated with a normal metabolic profile despite a high level of obesity in postmenopausal women? J Clin Endocrinol Metab 2001; 86: 1020–1025.

    CAS  PubMed  Google Scholar 

  6. Karelis AD, Faraj M, Bastard JP, St-Pierre DH, Brochu M, Prud′homme D et al. The metabolically healthy but obese individual presents a favorable inflammation profile. J Clin Endocrinol Metab 2005; 90: 4145–4150.

    Article  CAS  Google Scholar 

  7. McLaughlin T, Allison G, Abbasi F, Lamendola C, Reaven G . Prevalence of insulin resistance and associated cardiovascular disease risk factors among normal weight, overweight, and obese individuals. Metabolism 2004; 53: 495–499.

    Article  CAS  Google Scholar 

  8. McLaughlin T, Abbasi F, Lamendola C, Reaven G . Heterogeneity in the prevalence of risk factors for cardiovascular disease and type 2 diabetes mellitus in obese individuals: effect of differences in insulin sensitivity. Arch Intern Med 2007; 167: 642–648.

    Article  CAS  Google Scholar 

  9. Bonora E, Kiechl S, Willeit J, Oberhollenzer F, Egger G, Targher G et al. Prevalence of insulin resistance in metabolic disorders: the Bruneck Study. Diabetes 1998; 47: 1643–1649.

    Article  CAS  Google Scholar 

  10. Bonora E, Kiechl S, Willeit J, Oberhollenzer F, Egger G, Meigs JB et al. Insulin resistance as estimated by homeostasis model assessment predicts incident symptomatic cardiovascular disease in caucasian subjects from the general population: the Bruneck study. Diabetes Care 2007; 30: 318–324.

    Article  Google Scholar 

  11. Reaven G . All obese individuals are not created equal: insulin resistance is the major determinant of cardiovascular disease in overweight/obese individuals. Diab Vasc Dis Res 2005; 2: 105–112.

    Article  Google Scholar 

  12. Iacobellis G, Ribaudo MC, Zappaterreno A, Iannucci CV, Leonetti F . Prevalence of uncomplicated obesity in an Italian obese population. Obes Res 2005; 13: 1116–1122.

    Article  Google Scholar 

  13. Karelis AD, Brochu M, Rabasa-Lhoret R . Can we identify metabolically healthy but obese individuals (MHO)? Diabetes Metab 2004; 30: 569–572.

    Article  CAS  Google Scholar 

  14. Stefan N, Kantartzis K, Machann J, Schick F, Thamer C, Rittig K et al. Identification and characterization of metabolically benign obesity in humans. Arch Intern Med 2008; 168: 1609–1616.

    Article  Google Scholar 

  15. Marini MA, Succurro E, Frontoni S, Hribal ML, Andreozzi F, Lauro R et al. Metabolically healthy but obese women have an intermediate cardiovascular risk profile between healthy nonobese women and obese insulin-resistant women. Diabetes Care 2007; 30: 2145–2147.

    Article  Google Scholar 

  16. Matsuda M, DeFronzo RA . Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglycemic insulin clamp. Diabetes Care 1999; 22: 1462–1470.

    Article  CAS  Google Scholar 

  17. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC . Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985; 28: 412–419.

    Article  CAS  Google Scholar 

  18. Katz A, Nambi SS, Mather K, Baron AD, Follmann DA, Sullivan G et al. Quantitative insulin sensitivity check index: a simple, accurate method for assessing insulin sensitivity in humans. J Clin Endocrinol Metab 2000; 85: 2402–2410.

    Article  CAS  Google Scholar 

  19. Wildman RP, Muntner P, Reynolds K, McGinn AP, Rajpathak S, Wylie-Rosett J et al. The obese without cardiometabolic risk factor clustering and the normal weight with cardiometabolic risk factor clustering: prevalence and correlates of 2 phenotypes among the US population (NHANES 1999–2004). Arch Intern Med 2008; 168: 1617–1624.

    Article  Google Scholar 

  20. Kuk JL, Ardern CI . Are metabolically normal but obese individuals at lower risk for all-cause mortality? Diabetes Care 2009; 32: 2297–2299.

    Article  Google Scholar 

  21. Perseghin G, Ghosh S, Gerow K, Shulman GI . Metabolic defects in lean nondiabetic offspring of NIDDM parents: a cross-sectional study. Diabetes 1997; 46: 1001–1009.

    Article  CAS  Google Scholar 

  22. Messier V, Karelis AD, Prud′homme D, Primeau V, Brochu M, Rabasa-Lhoret R . Identifying metabolically healthy but obese individuals in sedentary postmenopausal women. Obesity (Silver Spring) 2009; 18: 911–917.

    Article  Google Scholar 

  23. Pataky Z, Bobbioni-Harsch E, Makoundou V, Carpentier A, Golay A . Does metabolically normal obesity exist? Obesity Facts 2009; 2 (Suppl 2): 48.

    Google Scholar 

  24. Fox CS, Heard-Costa N, Cupples LA, Dupuis J, Vasan RS, Atwood LD . Genome-wide association to body mass index and waist circumference: the Framingham Heart Study 100 K project. BMC Med Genet 2007; 8 (Suppl 1): S18.

    Article  Google Scholar 

  25. Kunnas T, Lahtio R, Kortelainen ML, Kalela A, Nikkari ST . Gln27Glu variant of Beta2-adrenoceptor gene affects male type fat accumulation in women. Lipids Health Dis 2009; 8: 43.

    Article  Google Scholar 

  26. Peeters AV, Beckers S, Verrijken A, Mertens I, Roevens P, Peeters PJ et al. Association of SIRT1 gene variation with visceral obesity. Hum Genet 2008; 124: 431–436.

    Article  CAS  Google Scholar 

  27. Levine JA, Eberhardt NL, Jensen MD . Role of nonexercise activity thermogenesis in resistance to fat gain in humans. Science 1999; 283: 212–214.

    Article  CAS  Google Scholar 

  28. Choh AC, Demerath EW, Lee M, Williams KD, Towne B, Siervogel RM et al. Genetic analysis of self-reported physical activity and adiposity: the Southwest Ohio Family Study. Public Health Nutr 2009; 12: 1052–1060.

    Article  Google Scholar 

  29. Dumke CL, Rhodes JS, Garland Jr T, Maslowski E, Swallow JG, Wetter AC et al. Genetic selection of mice for high voluntary wheel running: effect on skeletal muscle glucose uptake. J Appl Physiol 2001; 91: 1289–1297.

    Article  CAS  Google Scholar 

  30. Dabelea D, Hanson RL, Lindsay RS, Pettitt DJ, Imperatore G, Gabir MM et al. Intrauterine exposure to diabetes conveys risks for type 2 diabetes and obesity: a study of discordant sibships. Diabetes 2000; 49: 2208–2211.

    Article  CAS  Google Scholar 

  31. Gallou-Kabani C, Junien C . Nutritional epigenomics of metabolic syndrome: new perspective against the epidemic. Diabetes 2005; 54: 1899–1906.

    Article  CAS  Google Scholar 

  32. Jennings CL, Lambert EV, Collins M, Joffe Y, Levitt NS, Goedecke JH . Determinants of insulin-resistant phenotypes in normal-weight and obese Black African women. Obesity (Silver Spring) 2008; 16: 1602–1609.

    Article  Google Scholar 

  33. Diamant M, Lamb HJ, van de Ree MA, Endert EL, Groeneveld Y, Bots ML et al. The association between abdominal visceral fat and carotid stiffness is mediated by circulating inflammatory markers in uncomplicated type 2 diabetes. J Clin Endocrinol Metab 2005; 90: 1495–1501.

    Article  CAS  Google Scholar 

  34. O'Connell J, Lynch L, Cawood TJ, Kwasnik A, Nolan N, Geoghegan J et al. The relationship of omental and subcutaneous adipocyte size to metabolic disease in severe obesity. PLoS One 2010; 5: e9997.

    Article  Google Scholar 

  35. Drolet R, Belanger C, Fortier M, Huot C, Mailloux J, Legare D et al. Fat depot-specific impact of visceral obesity on adipocyte adiponectin release in women. Obesity (Silver Spring) 2009; 17: 424–430.

    Article  CAS  Google Scholar 

  36. Aguilar-Salinas CA, Garcia EG, Robles L, Riano D, Ruiz-Gomez DG, Garcia-Ulloa AC et al. High adiponectin concentrations are associated with the metabolically healthy obese phenotype. J Clin Endocrinol Metab 2008; 93: 4075–4079.

    Article  CAS  Google Scholar 

  37. Szendroedi J, Roden M . Ectopic lipids and organ function. Curr Opin Lipidol 2009; 20: 50–56.

    Article  CAS  Google Scholar 

  38. McLaren L, Godley J, MacNairn IA . Social class, gender, and time use: implications for the social determinants of body weight? Health Rep 2009; 20: 65–73.

    PubMed  Google Scholar 

  39. Karelis AD, Fontaine J, Rabasa-Lhoret R, Prud′homme D, Doucet E, Blanchard C et al. Psychosocial profile of the metabolically healthy but obese postmenopausal woman. Diabetes Metab 2006; 32: 90–91.

    Article  CAS  Google Scholar 

  40. Kyrou I, Chrousos GP, Tsigos C . Stress, visceral obesity, and metabolic complications. Ann N Y Acad Sci 2006; 1083: 77–110.

    Article  CAS  Google Scholar 

  41. Meigs JB, Wilson PW, Fox CS, Vasan RS, Nathan DM, Sullivan LM et al. Body mass index, metabolic syndrome, and risk of type 2 diabetes or cardiovascular disease. J Clin Endocrinol Metab 2006; 91: 2906–2912.

    Article  CAS  Google Scholar 

  42. Janssen I, Katzmarzyk PT, Ross R . Duration of overweight and metabolic health risk in American men and women. Ann Epidemiol 2004; 14: 585–591.

    Article  Google Scholar 

  43. Muscelli E, Camastra S, Gastaldelli A, Natali A, Masoni A, Pecori N et al. Influence of duration of obesity on the insulin resistance of obese non-diabetic patients. Int J Obes Relat Metab Disord 1998; 22: 262–267.

    Article  CAS  Google Scholar 

  44. Robinson MR, Scheuermann-Freestone M, Leeson P, Channon KM, Clarke K, Neubauer S et al. Uncomplicated obesity is associated with abnormal aortic function assessed by cardiovascular magnetic resonance. J Cardiovasc Magn Reson 2008; 10: 10.

    Article  Google Scholar 

  45. Oflaz H, Ozbey N, Mantar F, Genchellac H, Mercanoglu F, Sencer E et al. Determination of endothelial function and early atherosclerotic changes in healthy obese women. Diabetes Nutr Metab 2003; 16: 176–181.

    CAS  PubMed  Google Scholar 

  46. Berrahmoune H, Herbeth B, Samara A, Marteau JB, Siest G, Visvikis-Siest S . Five-year alterations in BMI are associated with clustering of changes in cardiovascular risk factors in a gender-dependant way: the Stanislas study. Int J Obes (Lond) 2008; 32: 1279–1288.

    Article  CAS  Google Scholar 

  47. Shin MJ, Hyun YJ, Kim OY, Kim JY, Jang Y, Lee JH . Weight loss effect on inflammation and LDL oxidation in metabolically healthy but obese (MHO) individuals: low inflammation and LDL oxidation in MHO women. Int J Obes (Lond) 2006; 30: 1529–1534.

    Article  CAS  Google Scholar 

  48. Karelis AD, Messier V, Brochu M, Rabasa-Lhoret R . Metabolically healthy but obese women: effect of an energy-restricted diet. Diabetologia 2008; 51: 1752–1754.

    Article  CAS  Google Scholar 

  49. Rzehak P, Meisinger C, Woelke G, Brasche S, Strube G, Heinrich J . Weight change, weight cycling and mortality in the ERFORT Male Cohort Study. Eur J Epidemiol 2007; 22: 665–673.

    Article  Google Scholar 

  50. Olson MB, Kelsey SF, Bittner V, Reis SE, Reichek N, Handberg EM et al. Weight cycling and high-density lipoprotein cholesterol in women: evidence of an adverse effect: a report from the NHLBI-sponsored WISE study. Women′s Ischemia Syndrome Evaluation Study Group. J Am Coll Cardiol 2000; 36: 1565–1571.

    Article  CAS  Google Scholar 

  51. Karelis AD, Brochu M, Rabasa-Lhoret R . Can we identify metabolically healthy but obese individuals (MHO)? Diabetes Metab 2004; 30: 569–572.

    Article  CAS  Google Scholar 

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  1. Department of Community Medicine, Service of Therapeutic Education for Chronic Diseases, WHO Collaborating Centre, University Hospitals of Geneva and University of Geneva, Geneva, Switzerland

    Z Pataky, E Bobbioni-Harsch & A Golay

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Correspondence to E Bobbioni-Harsch.

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Pataky, Z., Bobbioni-Harsch, E. & Golay, A. Open questions about metabolically normal obesity. Int J Obes 34 (Suppl 2), S18–S23 (2010). https://doi.org/10.1038/ijo.2010.235

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