title: Metabolically healthy obesity and risk of mortality: does the definition of metabolic health matter?
abstract: OBJECTIVE
  To assess the association of a "metabolically healthy obese" phenotype with mortality using five definitions of metabolic health.
  
  
  METHODS
  Adults (n = 5,269; 71.7% men) aged 39-62 years in 1991 through 1993 provided data on BMI and metabolic health, defined using data from the Adult Treatment Panel-III (ATP-III); criteria from two studies; and the Matsuda and homeostasis model assessment (HOMA) indices. Cross-classification of BMI categories and metabolic status (healthy/unhealthy) created six groups. Cox proportional hazards regression models were used to analyze associations with all-cause and cardiovascular disease (CVD) mortality during a median follow-up of 17.7 years.
  
  
  RESULTS
  A total of 638 individuals (12.1% of the cohort) were obese, of whom 9-41% were metabolically healthy, depending on the definition. Regardless of the definition, compared with metabolically healthy, normal-weight individuals, both the metabolically healthy obese (hazard ratios [HRs] ranged from 1.81 [95% CI 1.16-2.84] for ATP-III to 2.30 [1.13-4.70] for the Matsuda index) and the metabolically abnormal obese (HRs ranged from 1.57 [1.08-2.28] for the Matsuda index to 2.05 [1.44-2.92] for criteria defined in a separate study) had an increased risk of mortality. The only exception was the lack of excess risk using the HOMA criterion for the metabolically healthy obese (1.08; 0.67-1.74). Among the obese, the risk of mortality did not vary as a function of metabolic health apart from when using the HOMA criterion (1.93; 1.15-3.22). Similar results were obtained for cardiovascular mortality.
  
  
  CONCLUSIONS
  For most definitions of metabolic health, both metabolically healthy and unhealthy obese patients carry an elevated risk of mortality.
authors: INSERM, Centre for Research in Epidemiology and Population Health, Hôpital Paul Brousse, Villejuif Cedex, France. guy-marino.hinnouho@inserm.fr
authors: Guy-Marino
authors: GM
authors: Hinnouho
authors: Sébastien
authors: S
authors: Czernichow
authors: Aline
authors: A
authors: Dugravot
authors: G David
authors: GD
authors: Batty
authors: Mika
authors: M
authors: Kivimaki
authors: Archana
authors: A
authors: Singh-Manoux
mesh_terms: D000328:Adult; D015992:Body Mass Index; D005260:Female; D006262:Health / Q000145:classification; D006706:Homeostasis; D006801:Humans; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D009765:Obesity / Q000378:metabolism* / Q000401:mortality*; D016016:Proportional Hazards Models; D012306:Risk; D006113:United Kingdom / Q000453:epidemiology
references: Int J Epidemiol. 2005 Apr;34(2):251-6
references: 15576467
references: Circulation. 2010 Jan 19;121(2):230-6
references: 20038741
references: Diabetes Care. 2006 Jul;29(7):1697-9
references: 16801605
references: J Clin Endocrinol Metab. 2001 Mar;86(3):1020-5
references: 11238480
references: N Engl J Med. 2007 Jan 18;356(3):213-5
references: 17229948
references: Diabetes Metab. 2004 Dec;30(6):569-72
references: 15671927
references: Diabetologia. 2008 Sep;51(9):1752-4
references: 18504546
references: CRC Crit Rev Clin Lab Sci. 1973 Aug;4(2):101-45
references: 4583188
references: J Clin Endocrinol Metab. 2012 Jul;97(7):2482-8
references: 22508708
references: JAMA. 2001 May 16;285(19):2486-97
references: 11368702
references: Diabetes. 1998 Oct;47(10):1643-9
references: 9753305
references: Lancet. 2011 Feb 12;377(9765):557-67
references: 21295846
references: Arch Intern Med. 2008 Aug 11;168(15):1609-16
references: 18695074
references: J Clin Endocrinol Metab. 2006 Aug;91(8):2906-12
references: 16735483
references: Diabetes Care. 2011 Jan;34(1):210-5
references: 20937689
references: Arch Intern Med. 2008 Aug 11;168(15):1617-24
references: 18695075
references: Diabetes Care. 2007 Aug;30(8):2145-7
references: 17507694
references: Diabetes Care. 2009 Dec;32(12):2297-9
references: 19729521
references: JAMA. 2004 Jun 16;291(23):2847-50
references: 15199035
references: Diabetes Metab. 2008 Apr;34(2):183-4
references: 18329310
references: N Engl J Med. 2006 Aug 24;355(8):763-78
references: 16926275
references: Int J Obes (Lond). 2011 Jul;35(7):971-81
references: 20975726
references: Diabetes Care. 1999 Sep;22(9):1462-70
references: 10480510
references: Am J Physiol Endocrinol Metab. 2008 Mar;294(3):E607-14
references: 18182465
references: Diabetes Care. 2004 Jun;27(6):1487-95
references: 15161807
references: Lancet. 2008 Oct 11;372(9646):1281-3
references: 18929889
references: World Health Organ Tech Rep Ser. 2000;894:i-xii, 1-253
references: 11234459
references: Diabetologia. 1985 Jul;28(7):412-9
references: 3899825
references: J Clin Invest. 1997 Sep 1;100(5):1166-73
references: 9303923
references: Obes Rev. 2011 Sep;12(9):680-7
references: 21521449
references: Diabetologia. 2007 Aug;50(8):1707-15
references: 17549449
references: Metabolism. 2001 Dec;50(12):1499-504
references: 11735101
references: Obesity (Silver Spring). 2010 May;18(5):911-7
references: 19851302