What is metabolically healthy obesity?

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Metabolically healthy obesity (MHO) refers to a subset of people with a BMI ≥30 who display a relatively normal metabolic profile and a reduced risk of disease when compared to people with a BMI ≥30 who have the more typical profile of increased cardiometabolic risk, which is referred to as metabolically unhealthy obesity (MUO).[1][2] Basically, people with MHO don’t seem to have increased cardiometabolic risk despite their elevated BMI.

While the general concept of MHO is clear, standardized criteria have yet to be defined. In fact, more than 30 different definitions of MHO have been used in the scientific literature.[3] Most definitions are based on the criteria for metabolic syndrome outlined by the National Cholesterol Education Program Adult Treatment Panel III,[4] with the presence of 2 or less of the 5 metabolic syndrome components commonly qualifying as MHO.

Consequently, MHO is a misnomer of sorts — people with MHO are typically not truly healthy; they just have fewer cardiometabolic abnormalities than their MUO peers. People with MHO may lack certain cardiometabolic risk factors,[5] but still generally have a higher risk of cardiovascular disease,[6][7] type 2 diabetes,[8] nonalcoholic fatty liver disease,[9][10] and all-cause mortality[5][11][12] than people who are metabolically healthy and have a normal BMI.

To cast further doubt on the seemingly benign nature of MHO, evidence suggests that MHO is not a stable condition and 30%–50% of people with MHO transition to MUO after 4 to 20 years of follow-up.[3] In a large prospective cohort study published in 2018, only about 15% of women with MHO at baseline remained metabolically healthy over 20 years of follow-up.[13]

Lastly, several observational studies have found that increased liver fat is a crucial risk factor for cardiometabolic disease and is associated with an increased risk of transitioning from MHO to MUO;[14][15][16][17] however, very few studies have considered liver fat as part of the criteria for MHO.

In sum, MHO is a misleading term on the basis of the common criteria used to classify it. People with MHO may be at a lower risk of cardiometabolic disease than people with MUO, but their risk is still higher than that of people who are metabolically healthy and have a normal BMI. Additionally, people with MHO commonly transition to MUO over time. As such, just like people with MUO, obesity treatment is indicated for people with MHO to improve long-term health outcomes.[1]

References
1.^Blüher MMetabolically Healthy Obesity.Endocr Rev.(2020-05-01)
2.^April-Sanders AK, Rodriguez CJMetabolically Healthy Obesity Redefined.JAMA Netw Open.(2021-05-03)
3.^Smith GI, Mittendorfer B, Klein SMetabolically healthy obesity: facts and fantasies.J Clin Invest.(2019-10-01)
4.^Grundy SM, Cleeman JI, Daniels SR, Donato KA, Eckel RH, Franklin BA, Gordon DJ, Krauss RM, Savage PJ, Smith SC Jr, Spertus JA, Costa F, American Heart Association, National Heart, Lung, and Blood InstituteDiagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute Scientific StatementCirculation.(2005 Oct 25)
6.^Grégoire Fauchier, Arnaud Bisson, Alexandre Bodin, Julien Herbert, Carl Semaan, Denis Angoulvant, Pierre Henri Ducluzeau, Gregory Y H Lip, Laurent FauchierMetabolically healthy obesity and cardiovascular events: A nationwide cohort studyDiabetes Obes Metab.(2021 Jul 12)
7.^Ma LZ, Sun FR, Wang ZT, Tan L, Hou XH, Ou YN, Dong Q, Yu JT, Tan LMetabolically healthy obesity and risk of stroke: a meta-analysis of prospective cohort studies.Ann Transl Med.(2021-Feb)
10.^Chen TP, Lin WY, Chiang CH, Shen TH, Huang KC, Yang KCMetabolically healthy obesity and risk of non-alcoholic fatty liver disease severity independent of visceral fat.J Gastroenterol Hepatol.(2021-Oct)
11.^Zhou Z, Macpherson J, Gray SR, Gill JMR, Welsh P, Celis-Morales C, Sattar N, Pell JP, Ho FKAre people with metabolically healthy obesity really healthy? A prospective cohort study of 381,363 UK Biobank participants.Diabetologia.(2021-09)
14.^Hashimoto Y, Hamaguchi M, Fukuda T, Ohbora A, Kojima T, Fukui MFatty liver as a risk factor for progression from metabolically healthy to metabolically abnormal in non-overweight individuals.Endocrine.(2017-Jul)
16.^Ampuero J, Aller R, Gallego-Durán R, Crespo J, Calleja JL, García-Monzón C, Gómez-Camarero J, Caballería J, Lo Iacono O, Ibañez L, García-Samaniego J, Albillos A, Francés R, Fernández-Rodríguez C, Diago M, Soriano G, Andrade RJ, Latorre R, Jorquera F, Morillas RM, Escudero D, Estévez P, Guerra MH, Augustín S, Banales JM, Aspichueta P, Benlloch S, Rosales JM, Salmerón J, Turnes J, Romero Gómez M,Significant fibrosis predicts new-onset diabetes mellitus and arterial hypertension in patients with NASH.J Hepatol.(2020-07)
17.^Chang Y, Jung HS, Yun KE, Cho J, Ahn J, Chung EC, Shin H, Ryu SMetabolically healthy obesity is associated with an increased risk of diabetes independently of nonalcoholic fatty liver disease.Obesity (Silver Spring).(2016-09)