Characterizing the profile of obese patients who are metabolically healthy

International Journal of Obesity

Volumn 35, Issue 7, 2011, Pages 971-981

  Primeau, V ^a   Coderre, L ^b,c   Karelis, A D ^b,d   Brochu, M ^e,f   Lavoie, M E ^b,c   Messier, V ^c   Sladek, R ^g,h,i   Rabasa Lhoret, R ^a,b,c,j  

^a CENTRE HOSPITALIER DE L UNIVERSITÉ DE MONTRÉAL   (Canada)

^b UNIVERSITÉ DE MONTRÉAL   (Canada)

^c CLIN RESEARCH INSTITUTE OF MONTREAL   (Canada)

^d UNIVERSITÉ DU QUÉBEC À MONTRÉAL   (Canada)

^e UNIVERSITÉ DE SHERBROOKE   (Canada)

^f UNIVERSITY INSTITUTE OF GERIATRICS OF SHERBROOKE   (Canada)

^g MCGILL UNIVERSITY   (Canada)

^h MCGILL UNIVERSITY   (Canada)

ⁱ MCGILL UNIVERSITY   (Canada)

^j Montreal Diabetes Research Center MDRC   (Canada)

more..

Author keywords

body composition; cardiovascular diseases; insulin sensitivity; metabolic risk factors; metabolically healthy but obese

Indexed keywords

ADIPONECTIN; APOLIPOPROTEIN B; GHRELIN; HIGH DENSITY LIPOPROTEIN CHOLESTEROL; TRIACYLGLYCEROL;

ADIPOSE TISSUE; ARTERIAL WALL THICKNESS; BIOCHEMISTRY; BODY COMPOSITION; BODY FAT DISTRIBUTION; BODY MASS; CALORIC INTAKE; CARDIOPULMONARY FUNCTION; CARDIOVASCULAR RISK; ENERGY EXPENDITURE; GENE EXPRESSION; HUMAN; HYPERINSULINEMIA; INFLAMMATION; INSULIN RESISTANCE; INSULIN SENSITIVITY; METABOLIC DISORDER; NON INSULIN DEPENDENT DIABETES MELLITUS; OBESITY; PRIORITY JOURNAL; REVIEW; SOCIAL PSYCHOLOGY; TISSUE METABOLISM; WEIGHT REDUCTION;

CANADA; ENERGY METABOLISM; FEMALE; HEALTH STATUS; HUMANS; HYPERTENSION; INSULIN RESISTANCE; MALE; OBESITY;

EID: 79960226240     PISSN: 03070565     EISSN: 14765497     Source Type: Journal    
DOI: 10.1038/ijo.2010.216     Document Type: Review

References (89)

1. Flegal KM, Carroll MD, Ogden CL, Curtin LR. Prevalence and trends in obesity among US adults, 1999-2008. JAMA 2010; 303: 235-241.
2. Lau DC, Douketis JD, Morrison KM, Hramiak IM, Sharma AM, Ur E. 2006 Canadian clinical practice guidelines on the management and prevention of obesity in adults and children (summary). CMAJ 2007; 176: S1-S13.
3. Despres JP, Lemieux I, Bergeron J, Pibarot P, Mathieu P, Larose E et al. Abdominal obesity and the metabolic syndrome: contribution to global cardiometabolic risk. Arterioscler Thromb Vasc Biol 2008; 28: 1039-1049.
4. 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. (Pubitemid 28445355)
5. 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. (Pubitemid 27386301)
6. Bluher M. The distinction of metabolically 'healthy' from 'unhealthy' obese individuals. Curr Opin Lipidol 2010; 21: 38-43.
7. 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. (Pubitemid 32322976)
8. Karelis AD. Metabolically healthy but obese individuals. Lancet 2008; 372: 1281-1283.
9. 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. (Pubitemid 41058189)
10. Karelis AD, St-Pierre DH, Conus F, Rabasa-Lhoret R, Poehlman ET. Metabolic and body composition factors in subgroups of obesity: what do we know? J Clin Endocrinol Metab 2004; 89: 2569-2575. (Pubitemid 38766333)
11. 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. (Pubitemid 44271734)
12. Sims EA. Are there persons who are obese, but metabolically healthy? Metabolism 2001; 50: 1499-1504. (Pubitemid 34007425)
13. 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.
14. Lynch LA, O'Connell JM, Kwasnik AK, Cawood TJ, O'Farrelly C, O'Shea DB. Are natural killer cells protecting the metabolically healthy obese patient? Obesity (Silver Spring) 2009; 17: 601-605.
15. 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.
16. Weiss R, Taksali SE, Dufour S, Yeckel CW, Papademetris X, Cline G et al. The 'obese insulin-sensitive' adolescent: importance of adiponectin and lipid partitioning. J Clin Endocrinol Metab 2005; 90: 3731-3737. (Pubitemid 41014349)
17. Andres R. Effect of obesity on total mortality. Int J Obes 1980; 4: 381-386. (Pubitemid 10006809)
18. Sims EA. Characterization of the syndromes of obesity. In: Brodoff BN, Bleicher SJ (eds). Diabetes Mellitus and Obesity. Williams & Wilkins: Baltimore, 1982, pp 219-226.
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.
20. 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. (Pubitemid 47219439)
21. Karelis AD, Rabasa-Lhoret R. Inclusion of C-reactive protein in the identification of metabolically healthy but obese (MHO) individuals. Diabetes Metab 2008; 34: 183-184.
22. Shin MJ, Hyun YJ, Kim OY, Kim JY, Jang Y, Lee JH. Weight loss effect on inflammation and LDL oxidation inmetabolically healthy but obese (MHO) individuals: low inflammation and LDL oxidation in MHO women. Int J Obes (London) 2006; 30: 1529-1534. (Pubitemid 44470202)
23. 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) final report. Circulation 2002; 106: 3143-3421.
24. 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: 39-48. (Pubitemid 47016245)
25. Park YW, Zhu S, Palaniappan L, Heshka S, Carnethon MR, Heymsfield SB. The metabolic syndrome: prevalence and associated risk factor findings in the US population from the Third National Health and Nutrition Examination Survey, 1988-1994. Arch Intern Med 2003; 163: 427-436. (Pubitemid 36241019)
26. Genelhu VA, Celoria BM, Duarte SF, Cabello PH, Francischetti EA. Not all obese subjects of multiethnic origin are at similar risk for developing hypertension and type-2 diabetes. Eur J Intern Med 2009; 20: 289-295.
27. McLaughlin T, Deng A, Yee G, Lamendola C, Reaven G, Tsao PS et al. Inflammation in subcutaneous adipose tissue: relationship to adipose cell size. Diabetologia 2010; 53: 369-377.
28. Despres JP, Cartier A, Cote M, Arsenault BJ. The concept of cardiometabolic risk: bridging the fields of diabetology and cardiology. Ann Med 2008; 40: 514-523.
29. Jennings CL, Lambert EV, Collins M, Joffe Y, Levitt NS, Goedecke JH. Determinants of insulin-resistant phenotypes in normalweight and obese Black African women. Obesity (Silver Spring) 2008; 16: 1602-1609. (Pubitemid 351915104)
30. Messier V, Karelis AD, Robillard ME, Bellefeuille P, Brochu M, Lavoie JM et al. Metabolically healthy but obese individuals: relationship with hepatic enzymes. Metabolism 2010; 59: 20-24.
31. Fabbrini E, Magkos F, Mohammed BS, Pietka T, Abumrad NA, Patterson BWet al. Intrahepatic fat, not visceral fat, is linked with metabolic complications of obesity. Proc Natl Acad Sci USA 2009; 106: 15430-15435.
32. Magkos F, Fabbrini E, Mohammed BS, Patterson BW, Klein S. Increased whole-body adiposity without a concomitant increase in liver fat is not associated with augmented metabolic dysfunction. Obesity (Silver Spring) 2010; 18: 1510-1515.
33. D'Adamo E, Cali AM, Weiss R, Santoro N, Pierpont B, Northrup V et al. Central role of fatty liver in the pathogenesis of insulin resistance in obese adolescents. Diabetes Care 2010; 33: 1817-1822.
34. Brochu M, Mathieu ME, Karelis AD, Doucet E, Lavoie ME, Garrel D et al. Contribution of the lean body mass to insulin resistance in postmenopausal women with visceral obesity: a MONET study. Obesity (Silver Spring) 2008; 16: 1085-1093. (Pubitemid 351620466)
35. Karelis AD, Tousignant B, Nantel J, Proteau-Labelle M, Malita FM, St-Pierre DH et al. Association of insulin sensitivity and muscle strength in overweight and obese sedentary postmenopausal women. Appl Physiol Nutr Metab 2007; 32: 297-301.
36. Succurro E, Marini MA, Frontoni S, Hribal ML, Andreozzi F, Lauro R et al. Insulin secretion in metabolically obese, but normal weight, and in metabolically healthy but obese individuals. Obesity (Silver Spring) 2008; 16: 1881-1886.
37. Abbasi F, Chu JW, Lamendola C, McLaughlin T, Hayden J, Reaven GM et al. Discrimination between obesity and insulin resistance in the relationship with adiponectin. Diabetes 2004; 53: 585-590. (Pubitemid 38270626)
38. St-Pierre DH, Karelis AD, Coderre L,Malita F, Fontaine J,Mignault D et al. Association of acylated and nonacylated ghrelin with insulin sensitivity in overweight and obese postmenopausal women. J Clin Endocrinol Metab 2007; 92: 264-269. (Pubitemid 46067542)
39. Elisha B, Karelis AD, Imbeault P, Rabasa-Lhoret R. Effect of acute hyperinsulinemia on total and high molecular weight adiponectin concentration in metabolically healthy but obese postmenopausal women: a Montreal Ottawa New Emerging Team study (MONET). Diabetes Metab 2010; 36: 319-321.
40. Lihn AS, Bruun JM, He G, Pedersen SB, Jensen PF, Richelsen B. Lower expression of adiponectin mRNA in visceral adipose tissue in lean and obese subjects. Mol Cell Endocrinol 2004; 219: 9-15. (Pubitemid 38638516)
41. Kim CS, Park HS, Kawada T, Kim JH, Lim D, Hubbard NE et al. Circulating levels of MCP-1 and IL-8 are elevated in human obese subjects and associated with obesity-related parameters. Int J Obes (London) 2006; 30: 1347-1355. (Pubitemid 44306516)
42. Wu X, Motoshima H, Mahadev K, Stalker TJ, Scalia R, Goldstein BJ. Involvement of AMP-activated protein kinase in glucose uptake stimulated by the globular domain of adiponectin in primary rat adipocytes. Diabetes 2003; 52: 1355-1363. (Pubitemid 36666188)
43. Yamauchi T, Kamon J, Ito Y, Tsuchida A, Yokomizo T, Kita S et al. Cloning of adiponectin receptors that mediate antidiabetic metabolic effects. Nature 2003; 423: 762-769. (Pubitemid 36735700)
44. Kojima M, Hosoda H, Date Y, Nakazato M, Matsuo H, Kangawa K. Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature 1999; 402: 656-660. (Pubitemid 129516334)
45. Wren AM, Seal LJ, Cohen MA, Brynes AE, Frost GS, Murphy KG et al. Ghrelin enhances appetite and increases food intake in humans. J Clin Endocrinol Metab 2001; 86: 5992.
46. Marzullo P, Verti B, Savia G,Walker GE, Guzzaloni G, Tagliaferri M et al. The relationship between active ghrelin levels and human obesity involves alterations in resting energy expenditure. J Clin Endocrinol Metab 2004; 89: 936-939. (Pubitemid 38269914)
47. St-Pierre DH, Karelis AD, Cianflone K, Conus F, Mignault D, Rabasa-Lhoret R et al. Relationship between ghrelin and energy expenditure in healthy young women. J Clin Endocrinol Metab 2004; 89: 5993-5997. (Pubitemid 39628405)
48. Bornfeldt KE, Arnqvist HJ, Dahlkvist HH, Skottner A, Wikberg JE. Receptors for insulin-like growth factor-I in plasma membranes isolated from bovine mesenteric arteries. Acta Endocrinol (Copenh) 1988; 117: 428-434. (Pubitemid 18096237)
49. Cook NR, Buring JE, Ridker PM. The effect of including C-reactive protein in cardiovascular risk prediction models for women. Ann Intern Med 2006; 145: 21-29. (Pubitemid 46780601)
50. 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. (Pubitemid 43872603)
51. Bouhours-Nouet N, Dufresne S, de Casson FB, Mathieu E, Douay O, Gatelais F et al. High birth weight and early postnatal weight gain protect obese children and adolescents from truncal adiposity and insulin resistance: metabolically healthy but obese subjects? Diabetes Care 2008; 31: 1031-1036.
52. Swinburn BA, Nyomba BL, Saad MF, Zurlo F, Raz I, Knowler WC et al. Insulin resistance associated with lower rates of weight gain in Pima Indians. J Clin Invest 1991; 88: 168-173.
53. Eckel RH. Insulin resistance: an adaptation for weight maintenance. Lancet 1992; 340: 1452-1453.
54. Ravussin E, Swinburn BA. Metabolic predictors of obesity: cross-sectional versus longitudinal data. Int J Obes Relat Metab Disord 1993; 17 (Suppl 3): S28-S31; discussion S41-22. (Pubitemid 24008317)
55. Riou M, Karelis AD, Messier L, Garrel D, Prud'homme D, Rabasa-Lhoret R. Metabolically healthy but obese individual do not present a specific medical history: A MONET study. J Endocardiol 2008; 1: 89-96.
56. McAuley KA, Williams SM, Mann JI, Goulding A, Chisholm A, Wilson N et al. Intensive lifestyle changes are necessary to improve insulin sensitivity: a randomized controlled trial. Diabetes Care 2002; 25: 445-452. (Pubitemid 41103334)
57. Muscelli E, Camastra S, Catalano C, Galvan AQ, Ciociaro D, Baldi S et al. Metabolic and cardiovascular assessment in moderate obesity: effect of weight loss. J Clin Endocrinol Metab 1997; 82: 2937-2943. (Pubitemid 27385652)
58. Janiszewski PM, Ross R. Effects of weight loss among metabolically healthy obese men and women. Diabetes Care 2010; 33: 1957-1959.
59. McLaughlin T, Abbasi F, Lamendola C, Liang L, Reaven G, Schaaf P et al. Differentiation between obesity and insulin resistance in the association with C-reactive protein. Circulation 2002; 106: 2908-2912. (Pubitemid 35424740)
60. Arsenault BJ, Rana JS, Lemieux I, Despres JP, Wareham NJ, Kastelein JJ et al. Physical activity, the Framingham risk score and risk of coronary heart disease in men and women of the EPIC-Norfolk study. Atherosclerosis 2010; 209: 261-265.
61. 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.
62. Heiss G, Sharrett AR, Barnes R, Chambless LE, Szklo M, Alzola C. Carotid atherosclerosis measured by B-mode ultrasound in populations: associations with cardiovascular risk factors in the ARIC study. Am J Epidemiol 1991; 134: 250-256.
63. O'Leary DH, Polak JF, Kronmal RA, Manolio TA, Burke GL, Wolfson Jr SK. Carotid-artery intima and media thickness as a risk factor for myocardial infarction and stroke in older adults. Cardiovascular Health Study Collaborative Research Group. N Engl J Med 1999; 340: 14-22. (Pubitemid 29024679)
64. Lee JW, Lee HR, Shim JY, Im JA, Kim SH, Choi H et al. Viscerally obese women with normal body weight have greater brachialankle pulse wave velocity than nonviscerally obese women with excessive body weight. Clin Endocrinol 2007; 66: 572-578. (Pubitemid 46434946)
65. St-Pierre AC, Cantin B, Mauriege P, Bergeron J, Dagenais GR, Despres JP et al. Insulin resistance syndrome, body mass index and the risk of ischemic heart disease. CMAJ 2005; 172: 1301-1305. (Pubitemid 40745071)
66. Arnlov J, Ingelsson E, Sundstrom J, Lind L. Impact of body mass index and the metabolic syndrome on the risk of cardiovascular disease and death in middle-aged men. Circulation 2010; 121: 230-236.
67. Kuk JL, Ardern CI. Are metabolically normal but obese individuals at lower risk for all-cause mortality? Diabetes Care 2009; 32: 2297-2299.
68. Shea MK, Houston DK, Nicklas BJ, Messier SP, Davis CC, Miller ME et al. The effect of randomization to weight loss on total mortality in older overweight and obese adults: the ADAPT Study. J Gerontol A Biol Sci Med Sci 2010; 65: 519-525.
69. 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: 753-761. (Pubitemid 47295642)
70. 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: 741-752. (Pubitemid 47295641)
71. 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) 2010; 18: 911-917.
72. Brook CG, Lloyd JK. Adipose cell size and glucose tolerance in obese children and effects of diet. Arch Dis Child 1973; 48: 301-304.
73. Hirsch J, Knittle JL. Cellularity of obese and nonobese human adipose tissue. Fed Proc 1970; 29: 1516-1521.
74. Salans LB, Cushman SW, Weismann RE. Studies of human adipose tissue. Adipose cell size and number in nonobese and obese patients. J Clin Invest 1973; 52: 929-941.
75. Stern JS, Batchelor BR, Hollander N, Cohn CK, Hirsch J. Adiposecell size and immunoreactive insulin levels in obese and normalweight adults. Lancet 1972; 2: 948-951.
76. Krotkiewski M, Bjorntorp P, Sjostrom L, Smith U. Impact of obesity on metabolism in men and women. Importance of regional adipose tissue distribution. J Clin Invest 1983; 72: 1150-1162. (Pubitemid 14212633)
77. McLaughlin T, Sherman A, Tsao P, Gonzalez O, Yee G, Lamendola C et al. Enhanced proportion of small adipose cells in insulin-resistant vs insulin-sensitive obese individuals implicates impaired adipogenesis. Diabetologia 2007; 50: 1707-1715. (Pubitemid 47036653)
78. Gavrilova O, Marcus-Samuels B, Graham D, Kim JK, Shulman GI, Castle AL et al. Surgical implantation of adipose tissue reverses diabetes in lipoatrophic mice. J Clin Invest 2000; 105: 271-278. (Pubitemid 30094446)
79. Tarcin O, Bajaj M, Akalin S. Insulin resistance, adipocyte biology, and thiazolidinediones: a review. Metab Syndr Relat Disord 2007; 5: 103-115. (Pubitemid 46954295)
80. Medina-Gomez G, Gray SL, Yetukuri L, Shimomura K, Virtue S, Campbell M et al. PPAR gamma 2 prevents lipotoxicity by controlling adipose tissue expandability and peripheral lipid metabolism. PLoS Genet 2007; 3: e64.
81. Pasarica M, Mashtalir N, McAllister EJ, Kilroy GE, Koska J, Permana P et al. Adipogenic human adenovirus Ad-36 induces commitment, differentiation, and lipid accumulation in human adipose-derived stem cells. Stem Cells 2008; 26: 969-978.
82. Rogers PM, Mashtalir N, Rathod MA, Dubuisson O, Wang Z, Dasuri K et al. Metabolically favorable remodeling of human adipose tissue by human adenovirus type 36. Diabetes 2008; 57: 2321-2331.
83. Dhurandhar NV, Israel BA, Kolesar JM, Mayhew GF, Cook ME, Atkinson RL. Increased adiposity in animals due to a human virus. Int J Obes Relat Metab Disord 2000; 24: 989-996. (Pubitemid 30618118)
84. Dhurandhar NV, Whigham LD, Abbott DH, Schultz-Darken NJ, Israel BA, Bradley SM et al. Human adenovirus Ad-36 promotes weight gain in male rhesus and marmoset monkeys. J Nutr 2002; 132: 3155-3160.
85. Pasarica M, Shin A, Yu M, Yang HM, Rathod M, Jen C et al. Human Adenovirus 36 induces adiposity, increases insulin sensitivity, and alters hypothalamic monoamines in rats. Obesity 2006; 11: 1905-1913. (Pubitemid 46121920)
86. Rome S, Clement K, Rabasa-Lhoret R, Loizon E, Poitou C, Barsh GS et al. Microarray profiling of human skeletal muscle reveals that insulin regulates approximately 800 genes during a hyperinsulinemic clamp. J Biol Chem 2003; 278: 18063-18068. (Pubitemid 36799418)
87. MacLaren R, Cui W, Simard S, Cianflone K. Influence of obesity and insulin sensitivity on insulin signaling genes in human omental and subcutaneous adipose tissue. J Lipid Res 2008; 49: 308-323. (Pubitemid 351213615)
88. Westerbacka J, Corner A, Kannisto K, Kolak M, Makkonen J, Korsheninnikova E et al. Acute in vivo effects of insulin on gene expression in adipose tissue in insulin-resistant and insulinsensitive subjects. Diabetologia 2006; 49: 132-140. (Pubitemid 43151624)
89. 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.