Mechanisms in endocrinology: Are metabolically healthy obese individuals really healthy?

European Journal of Endocrinology

Volumn 171, Issue 6, 2014, Pages R209-R219

  Blüher, Matthias ^a  

^a UNIVERSITY OF LEIPZIG   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

AGE DISTRIBUTION; AGING; BARIATRIC SURGERY; BEHAVIOR; CARDIOMETABOLIC RISK; CARDIOVASCULAR DISEASE; CHRONIC PAIN; COMORBIDITY; DYSLIPIDEMIA; ENVIRONMENTAL FACTOR; EPIDEMIC; FITNESS; HEALTH STATUS; HUMAN; HYPERTENSION; LIFESTYLE; METABOLIC DISORDER; METABOLICALLY HEALTHY OBESITY; MORTALITY; NEOPLASM; NON INSULIN DEPENDENT DIABETES MELLITUS; OBESITY; OSTEOARTHRITIS; PHENOTYPE; PREVALENCE; PSYCHOLOGICAL ASPECT; PSYCHOSOMATIC DISORDER; PUBLIC HEALTH PROBLEM; RESPIRATORY TRACT DISEASE; REVIEW; RISK FACTOR; SEX DIFFERENCE; SKIN DISEASE; SOCIAL ASPECT; WEIGHT REDUCTION; ANIMAL; BODY MASS; CLASSIFICATION; HEALTH; INSULIN RESISTANCE; METABOLISM; MOTOR ACTIVITY; NOMENCLATURE;

ANIMALS; BODY MASS INDEX; HEALTH; HUMANS; INSULIN RESISTANCE; MOTOR ACTIVITY; OBESITY; PHENOTYPE; PHYSICAL FITNESS; TERMINOLOGY AS TOPIC;

EID: 84911981373     PISSN: 08044643     EISSN: 1479683X     Source Type: Journal    
DOI: 10.1530/EJE-14-0540     Document Type: Review

References (71)

1. Pischon T, Boeing H, Hoffmann K, Bergmann M, Schulze MB, Overvad K, van der Schouw YT, Spencer E, Moons KG, Tjonneland A et al. General and abdominal adiposity and risk of death in Europe. New England Journal of Medicine 2008 359 2105-2120. (doi:10.1056/NEJMoa0801891)
2. Adams KF, Schatzkin A, Harris TB, Kipnis V, Mouw T, Ballard-Barbash R, Hollenbeck A & Leitzmann MF. Overweight, obesity, and mortality in a large prospective cohort of persons 50 to 71 years old. New England Journal of Medicine 2006 355 763-778. (doi:10.1056/NEJMoa055643)
3. Hossain P, Kawar B & El Nahas M. Obesity and diabetes in the developing world - a growing challenge. New England Journal of Medicine 2007 356 213-215. (doi:10.1056/NEJMp068177)
4. Finucane MM, Stevens GA, Cowan MJ, Danaei G, Lin JK, Paciorek CJ, Singh GM, Gutierrez HR, Lu Y, Bahalim AN et al. National, regional, and global trends in body-mass index since 1980: systematic analysis of health examination surveys and epidemiological studies with 960 country-years and 9·1 million participants. Lancet 2011 377 557-567. (doi:10.1016/S0140-6736(10)62037-5)
5. Mokdad AH, Ford ES, Bowman BA, Dietz WH, Vinicor F, Bales VS & Marks JS. Prevalence of obesity, diabetes, and obesity-related health risk factors, 2001. Journal of the American Medical Association 2003 289 76-79.
6. Hu FB, Willett WC, Li T, Stampfer MJ, Colditz GA & Manson JE. Adiposity as compared with physical activity in predicting mortality among women. New England Journal of Medicine 2004 351 2694-2703. (doi:10.1056/NEJMoa042135)
7. Guh DP, Zhang W, Bansback N, Amarsi Z, Birmingham CL & Anis AH. The incidence of co-morbidities related to obesity and overweight: a systematic review and meta-analysis. BMC Public Health 2009 9 88. (doi:10.1186/1471-2458-9-88)
8. Look AHEAD Research Group, Wing RR, Bolin P, Brancati FL, Bray GA, Clark JM, Coday M, Crow RS, Curtis JM, Egan CM et al. Cardiovascular effects of intensive lifestyle intervention in type 2 diabetes. New England Journal of Medicine 2013 369 145-154. (doi:10.1056/NEJMoa1212914)
9. Wadden TA. Treatment of obesity by moderate and severe caloric restriction. Results of clinical research trials. Annals of Internal Medicine 1993 119 688-693. (doi:10.7326/0003-4819-119-7-Part-2-199310011-00012)
10. Sharma AM & Kushner RF. A proposed clinical staging system for obesity. International Journal of Obesity 2009 33 289-295. (doi:10.1038/ijo.2009.2)
11. Blüher M. Are there still healthy obese patients? Current Opinion in Endocrinology, Diabetes, and Obesity 2012 19 341-346. (doi:10.1007/s00125-011-2109-5)
12. Blüher M. Predisposition - obesity phenotype. Deutsche Medizinische Wochenschrift 2014 139 1116-1120. (doi:10.1055/s-0034-1369942)
13. van Vliet-Ostaptchouk JV, Nuotio ML, Slagter SN, Doiron D, Fischer K, Foco L, Gaye A, Gögele M, Heier M, Hiekkalinna T et al. The prevalence of metabolic syndrome and metabolically healthy obesity in Europe: a collaborative analysis of ten large cohort studies. BMC Endocrine Disorders 2014 14 9. (doi:10.1186/1472-6823-14-9)
14. Stefan N, Häring HU, Hu FB & Schulze MB. Metabolically healthy obesity: epidemiology, mechanisms, and clinical implications. Lancet. Diabetes & Endocrinology 2013 1 152-162. (doi:10.1016/S2213-8587(13)70062-7)
15. Stefan N, Kantartzis K, Machann J, Schick F, Thamer C, Rittig K, Balletshofer B, Machicao F, Fritsche A & Häring HU. Identification and characterization of metabolically benign obesity in humans. Archives of Internal Medicine 2008 168 1609-1616. (doi:10.1038/oby.2011.142)
16. Kantartzis K, Machann J, Schick F, Rittig K, Machicao F, Fritsche A, Häring HU & Stefan N. Effects of a lifestyle intervention in metabolically benign and malign obesity. Diabetologia 2011 54 864-868. (doi:10.1007/s00125-010-2006-3)
17. 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. International Journal of Obesity 2006 30 1529-1534. (doi:10.1038/sj.ijo.0803304)
18. 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. (doi:10.1007/s00125-008-1038-4)
19. Arsenault BJ, Côté M, Cartier A, Lemieux I, Després JP, Ross R, Earnest CP, Blair SN & Church TS. Effect of exercise training on cardiometabolic risk markers among sedentary, but metabolically healthy overweight or obese post-menopausal women with elevated blood pressure. Atherosclerosis 2009 207 530-533. (doi:10.1016/j.atherosclerosis.2009.05.009)
20. Janiszewski PM & Ross R. Effects of weight loss among metabolically healthy obese men and women. Diabetes Care 2010 33 1957-1959. (doi:10.2337/dc10-0547)
21. Morkedal B, Vatten LJ, Romundstad PR, Laugsand LE & Janszky I. Risk of myocardial infarction and heart failure among metabolically healthy but obese individuals: HUNT (Nord-Trøndelag Health Study), Norway. Journal of the American College of Cardiology 2014 63 1071-1078. (doi:10.1016/j.jacc.2013.11.035)
22. Hamer M & Stamatakis E. Metabolically healthy obesity and risk of all-cause and cardiovascular disease mortality. Journal of Clinical Endocrinology and Metabolism 2012 97 2482-2488. (doi:10.1210/jc.2011-3475)
23. Kuk JL & Ardern CI. Are metabolically normal but obese individuals at lower risk for all-cause mortality? Diabetes Care 2009 32 2297-2299. (doi:10.2337/dc09-0574)
24. Stefan N, Fritsche A & Häring HU. Mechanisms explaining the relationship between metabolically healthy obesity and cardiovascular risk. Journal of the American College of Cardiology 2014 63 2748-2749. (doi:10.1016/j.jacc.2014.01.079)
25. Karelis AD. Metabolically healthy but obese individuals. Lancet 2008 372 1281-1283. (doi:10.1016/S0140-6736(08)61531-7)
26. Perseghin G. Is a nutritional therapeutic approach unsuitable for metabolically healthy but obese women? Diabetologia 2008 51 1567-1569. (doi:10.1007/s00125-008-1077-x)
27. Clinical guidelines on the identification, evaluation, and treatment of overweight and obesity in adults - the evidence report. National Institutes of Health; 2005. Obesity Research 27 6 51S-209S. (doi:10.1002/j.1550-8528.1998.tb00690.x)
28. Pajunen P, Kotronen A, Korpi-Hyövälti E, Keinänen-Kiukaanniemi S, Oksa H, Niskanen L, Saaristo T, Saltevo JT, Sundvall J, Vanhala M et al. Metabolically healthy and unhealthy obesity phenotypes in the general population: the FIN-D2D Survey. BMC Public Health 2011 11 754. (doi:10.1186/1471-2458-11-754)
29. Velho S, Paccaud F, Waeber G, Vollenweider P & Marques-Vidal P. Metabolically healthy obesity: different prevalences using different criteria. European Journal of Clinical Nutrition 2010 64 1043-1051. (doi:10.1038/ejcn.2010.114)
30. Blüher M. The distinction of metabolically 'healthy' from 'unhealthy' obese individuals. Current Opinion in Lipidology 2010 21 38-43. (doi:10.1097/MOL.0b013e3283346ccc)
31. World Health Organization (WHO). Obesity: preventing and managing the global epidemic. Report of a WHO consultation. World Health Organization Technical Report Series 2000 894 1-253.
32. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. 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). Journal of the American Medical Association 2001 285 2486-2497. (doi:10.1001/jama.285.19.2486)
33. Durward CM, Hartman TJ & Nickols-Richardson SM. All-cause mortality risk of metabolically healthy obese individuals in NHANES III. Journal of Obesity 2012 2012 460321. (doi:10.1155/2012/460321)
34. Arnlöv J, Ingelsson E, Sundström 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. (doi:10.1161/CIRCULATIONAHA.109.887521)
35. Bo S, Musso G, Gambino R, Villois P, Gentile L, Durazzo M, Cavallo-Perin P & Cassader M. Prognostic implications for insulin-sensitive and insulin-resistant normal-weight and obese individuals from a population-based cohort. American Journal of Clinical Nutrition 2012 96 962-969. (doi:10.3945/ajcn.112.040006)
36. Calori G, Lattuada G, Piemonti L, Garancini MP, Ragogna F, Villa M, Mannino S, Crosignani P, Bosi E, Luzi L et al. Prevalence, metabolic features, and prognosis of metabolically healthy obese Italian individuals: the Cremona Study. Diabetes Care 2011 34 210-215. (doi:10.2337/dc10-0665)
37. Hinnouho GM, Czernichow S, Dugravot A, Batty GD, Kivimaki M & Singh-Manoux A. Metabolically healthy obesity and risk of mortality: does the definition of metabolic health matter? Diabetes Care 2013 36 2294-2300. (doi:10.2337/dc12-1654)
38. Klöting N, Fasshauer M, Dietrich A, Kovacs P, Schön MR, Kern M, Stumvoll M & Blüher M. Insulin sensitive obesity. American Journal of Physiology. Endocrinology and Metabolism 2010 299 E506-E515. (doi:10.1152/ajpendo.00586.2009)
39. Kantartzis K, Thamer C, Peter A, Machann J, Schick F, Schraml C, Königsrainer A, Königsrainer I, Kröber S, Niess A et al. High cardiorespiratory fitness is an independent predictor of the reduction in liver fat during a lifestyle intervention in non-alcoholic fatty liver disease. Gut 2009 58 1281-1288. (doi:10.1136/gut.2008.151977)
40. Bell LM, Byrne S, Thompson A, Ratnam N, Blair E, Bulsara M, Jones TW & Davis EA. Increasing body mass index z-score is continuously associated with complications of overweight in children, even in the healthy range. Journal of Clinical Endocrinology and Metabolism 2007 92 517-522. (doi:10.1210/jc.2006-1714)
41. Prince RL, Kuk JL, Ambler KA, Dhaliwal J & Ball GD. Predictors of metabolically healthy obesity in children. Diabetes Care 2014 37 1462-1468. (doi:10.2337/dc13-1697)
42. Bonora E, Kiechl S, Willeit J, Oberhollenzer F, Egger G, Targher G, Alberiche M, Bonadonna RC & Muggeo M. Prevalence of insulin resistance in metabolic disorders: the Bruneck Study. Diabetes 1998 47 1643-1649. (doi:10.2337/diabetes.47.10.1643)
43. Hwang LC, Bai CH, Sun CA & Chen CJ. Prevalence of metabolically healthy obesity and its impacts on incidences of hypertension, diabetes and the metabolic syndrome in Taiwan. Asia Pacific Journal of Clinical Nutrition 2012 21 227-233.
44. Cherqaoui R, Kassim TA, Kwagyan J, Freeman C, Nunlee-Bland G, Ketete M, Xu S & Randall OS. The metabolically healthy but obese phenotype in African Americans. Journal of Clinical Hypertension 2012 14 92-96. (doi:10.1111/j.1751-7176.2011.00565.x)
45. Geetha L, Deepa M, Anjana RM & Mohan V. Prevalence and clinical profile of metabolic obesity and phenotypic obesity in Asian Indians. Journal of Diabetes Science and Technology 2011 5 439-446. (doi:10.1177/193229681100500235)
46. Shea JL, Randell EW & Sun G. The prevalence of metabolically healthy obese subjects defined by BMI and dual-energy X-ray absorptiometry. Obesity 2011 19 624-630. (doi:10.1038/oby.2010.174)
47. Soriguer F, Gutiérrez-Repiso C, Rubio-Martín E, Garcíá-Fuentes E, Almaraz MC, Colomo N, Esteva de Antonio I, de Adana MS, Chaves FJ, Morcillo S et al. Metabolically healthy but obese, a matter of time? Findings from the prospective Pizarra study Journal of Clinical Endocrinology and Metabolism 2013 98 2318-2325. (doi:10.1210/jc.2012-4253)
48. Muscelli E, Camastra S, Gastaldelli A, Natali A, Masoni A, Pecori N & Ferrannini E. Influence of duration of obesity on the insulin resistance of obese non-diabetic patients. International Journal of Obesity and Related Metabolic Disorders 1998 22 262-267. (doi:10.1038/sj.ijo.0800580)
49. Arthur FK, Adu-Frimpong M, Osei-Yeboah J, Mensah FO & Owusu L. The prevalence of metabolic syndrome and its predominant components among pre-and postmenopausal Ghanaian women. BMC Research Notes 2013 6 446. (doi:10.1186/1756-0500-6-446)
50. Appleton SL, Seaborn CJ, Visvanathan R, Hill CL, Gill TK, Taylor AW, Adams R & North West Adelaide Health Study Team. Diabetes and cardiovascular disease outcomes in the metabolically healthy obese phenotype: a cohort study. Diabetes Care 2013 36 2388-2394. (doi:10.2337/dc12-1971)
51. Lee DC, Sui X, Church TS, Lee IM & Blair SN. Associations of cardiorespiratory fitness and obesity with risks of impaired fasting glucose and type 2 diabetes in men. Diabetes Care 2009 32 257-262. (doi:10.2337/dc08-1377)
52. Thomas EL, Parkinson JR & Frost GS. The missing risk: MRI and MRS phenotyping of abdominal adiposity and ectopic fat. Obesity 2012 20 76-87. (doi:10.1038/oby.2011.142)
53. Ortega FB, Lee DC, Katzmarzyk PT, Ruiz JR, Sui X, Church TS & Blair SN. The intriguing metabolically healthy but obese phenotype: cardiovascular prognosis and role of fitness. European Heart Journal 2013 34 389-397. (doi:10.1093/eurheartj/ehs174)
54. Dvorak RV, DeNino WF & Ades PA. Phenotypic characteristics associated with insulin resistance in metabolically obese but normal-weight young women. Diabetes 1999 48 2210-2214. (doi:10.2337/diabetes.48.11.2210)
55. Kim JY, van de Wall E, Laplante M, Azzara A, Trujillo ME, Hofmann SM, Schraw T, Durand JL, Li H, Li G et al. Obesity-associated improvements in metabolic profile through expansion of adipose tissue. Journal of Clinical Investigation 2007 117 2621-2637. (doi:10.1172/JCI31021)
56. Kusminski CM, Holland WL, Sun K, Park J, Spurgin SB, Lin Y, Askew GR, Simcox JA, McClain DA, Li C et al. MitoNEET-driven alterations in adipocyte mitochondrial activity reveal a crucial adaptive process that preserves insulin sensitivity in obesity. Nature Medicine 2012 18 1539-1549. (doi:10.1038/nm.2899)
57. 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 1127-1139. (doi:10.1007/s00125-007-0640-1)
58. Sell H, Blüher M, Klöting N, Schlich R, Willems M, Ruppe F, Knoefel WT, Dietrich A, Fielding BA, Arner P et al. Adipose dipeptidyl peptidase-4 and obesity: correlation with insulin resistance and depot-specific release from adipose tissue in vivo and in vitro. Diabetes Care 2013 36 4083-4090. (doi:10.2337/dc13-0496)
59. Hardy OT, Perugini RA, Nicoloro SM, Gallagher-Dorval K, Puri V, Straubhaar J & Czech MP. Body mass index-independent inflammation in omental adipose tissue associated with insulin resistance in morbid obesity. Surgery for Obesity and Related Diseases 2011 7 60-67. (doi:10.1016/j.soard.2010.05.013)
60. Hectors TL, Vanparys C, van der Ven K, Martens GA, Jorens PG, Van Gaal LF, Covaci A, De Coen W & Blust R. Environmental pollutants and type 2 diabetes: a review of mechanisms that can disrupt β cell function. Diabetologia 2011 54 1273-1290. (doi:10.1007/s00125-011-2109-5)
61. Flint HJ, Scott KP, Louis P & Duncan SH. The role of the gut microbiota in nutrition and health. Nature Reviews. Gastroenterology and Hepatology 2012 9 577-589. (doi:10.1038/nrgastro.2012.156)
62. Liu J, Musani SK, Bidulescu A, Carr JJ, Wilson JG, Taylor HA & Fox CS. Fatty liver, abdominal adipose tissue and atherosclerotic calcification in African Americans: the Jackson Heart Study. Atherosclerosis 2012 224 521-525. (doi:10.1016/j.atherosclerosis.2012.07.042)
63. Sung KC, Jeong WS, Wild SH & Byrne CD. Combined influence of insulin resistance, overweight/obesity, and fatty liver as risk factors for type 2 diabetes. Diabetes Care 2012 35 717-722. (doi:10.2337/dc11-1853)
64. Stefan N & Häring HU. Circulating fetuin-A and free fatty acids interact to predict insulin resistance in humans. Nature Medicine 2013 19 394-395. (doi:10.1038/nm.3116)
65. Klöting N, Graham TE, Berndt J, Kralisch S, Kovacs P, Wason CJ, Fasshauer M, Schön MR, Stumvoll M, Blüher M et al. Serum retinol-binding protein is more highly expressed in visceral than in subcutaneous adipose tissue and is a marker of intra-abdominal fat mass. Cell Metabolism 2007 6 79-87. (doi:10.1016/j.cmet.2007.06.002)
66. Sjöström L, Narbro K, Sjöström CD, Karason K, Larsson B, Wedel H, Lystig T, Sullivan M, Bouchard C, Carlsson B et al. Effects of bariatric surgery on mortality in Swedish Obese Subjects. New England Journal of Medicine 2007 357 741-752. (doi:10.1056/NEJMoa066254)
67. Sjöström L. Review of the key results from the Swedish Obese Subjects (SOS) trial - a prospective controlled intervention study of bariatric surgery. Journal of Internal Medicine 2013 273 219-234. (doi:10.1111/joim.12012)
68. Sesti G, Folli F, Perego L, Hribal ML & Pontiroli AE. Effects of weight loss in metabolically healthy obese subjects after laparoscopic adjustable gastric banding and hypocaloric diet. PLoS ONE 2011 6 e17737. (doi:10.1371/journal.pone.0017737)
69. Kuk JL, Ardern CI, Church TS, Sharma AM, Padwal R, Sui X & Blair SN. Edmonton obesity staging system: association with weight history and mortality risk. Applied Physiology, Nutrition, and Metabolism 2011 36 570-576. (doi:10.1139/h11-058)
70. Padwal RS, Pajewski NM, Allison DB & Sharma AM. Using the Edmonton obesity staging system to predict mortality in a population-representative cohort of people with overweight and obesity. Canadian Medical Association Journal 2011 183 E1059-E1066. (doi:10.1503/cmaj.110387)
71. Gill RS, Karmali S & Sharma AM. The potential role of the Edmonton obesity staging system in determining indications for bariatric surgery. Obesity Surgery 2011 21 1947-1949. (doi:10.1007/s11695-011-0533-8)