Individuals with ‘Metabolically healthy obesity’ are actually not healthy

Are people with metabolically healthy obesity really healthy? A prospective cohort study of 381,363 UK Biobank participants

Literature - Zhou Z, Macpherson J, Gray SR et al. - Diabetologia. 2021 Jun 10. doi: 10.1007/s00125-021-05484-6.

Introduction and methods

Obesity is associated with the development of metabolic dysfunctions such as hypertension, dyslipidemia, elevated blood glucose, insulin resistance and systemic inflammation [1]. However, a subset of people with obesity have a normal metabolic profile. These people are sometimes referred to as having ‘metabolically healthy obesity’ [2,3]. Studies have shown mixed result on whether people with metabolically healthy obesity have an increased risk of ASCVD and all-cause mortality [4-6]. This study used data from the UK Biobank to determine the association of metabolically healthy obesity with ASCVD, HF, diabetes, respiratory diseases and all-cause mortality.

The UK biobank is a prospective cohort study which included 502,493 participants from the general population in the UK [7]. A total of 381,363 participants who were not underweight and had complete data on height, weight, BP and blood-based biomarkers were included in the analysis of this study. Metabolic health was defined as a binary condition using BP, CRP, triacylglycerols, LDL-c, HDL-c and HbA1c. Cutt-off values to define metabolically healthy were adapted from another study [8]. Fulfillment of at least 4 out of 6 criteria was considered metabolically healthy and a BMI ≥30 kg/m² was classified as obese. Participants were categorized as having metabolically healthy non-obesity (reference group, n=208 625, 54.7%), metabolically healthy obesity (n=25 103, 9.2%), metabolically unhealthy non-obesity (n=78 259, 20.5%), or metabolically unhealthy obesity (n=59 376, 15.6%). Investigated outcomes were incident diabetes and incident and fatal ASCVD, HF and respiratory diseases. Median follow-up was 11.2 (IQR 10.3-11.9) years.

Main results

  • Participants with metabolically healthy obesity had higher rates of incident diabetes, (HR 4.32, 95%CI 3.83-4.89), ASCVD (HR 1.18, 95%CI 1.10-1.27), MI (HR 1.23, 95% CI 1.11-1.37), stroke (HR 1.10, 95%CI 1.01-1.21), HF (HR 1.76, 95%CI 1.61-1.92), respiratory diseases (HR 1.28, 95%CI 1.24-1.33) and COPD (HR 1.19, 95%CI 1.11-1.28), compared with participants with metabolically healthy non-obesity.
  • Participants with metabolically unhealthy obesity had generally the highest rates of CV and respiratory outcomes, followed by participants with metabolically unhealthy non-obesity and metabolically healthy obesity, with the exception for incident and fatal HF, and incident respiratory diseases. Participants with metabolically healthy obesity had higher rates for these outcomes than participants with metabolically unhealthy non-obesity.
  • All-cause mortality was higher in participants with metabolically healthy obesity, compared with participants with metabolically healthy non-obesity (HR 1.22, 95%CI 1.14-1.31).
  • Participants with metabolically healthy obesity had higher rates of diabetes (HR 2.06, 95% CI 1.77-2.40), HF (HR 1.60, 95%CI 1.45-1.75) and respiratory diseases (HR 1.20, 95% CI 1.16-1.25) compared to participants without obesity (regardless whether they were metabolically healthy or unhealthy). In addition all-cause mortality (HR 1.12, 95%CI 1.04-1.21) and HF mortality rates (HR 1.44, 95% CI 1.09, 1.89) were significantly higher in participants with metabolically healthy obesity, than in participants without obesity.


People with metabolically healthy obesity had a significantly higher risk of diabetes, ASCVD, HF, respiratory diseases and all-cause mortality, compared with people with metabolically healthy non-obesity. Based on these results, the authors concluded that ‘Using the label ‘metabolically healthy’ to describe this group in clinical medicine is misleading and therefore should be avoided’.


1. Kim SH, Abbasi F, ReavenGM (2004) Impact of degree of obesity on surrogate estimates of insulin resistance. Diabetes Care 27(8): 1998–2002.

2. Stefan N, Häring H-U, Hu FB, Schulze MB (2013) Metabolically healthy obesity: epidemiology, mechanisms, and clinical implications. Lancet Diabetes Endocrinol 1(2):152–162.

3. Hinnouho G-M, Czernichow S, Dugravot A, Batty GD, Kivimaki M, Singh-Manoux A (2013)Metabolically healthy obesity and risk of mortality: does the definition of metabolic health matter? Diabetes Care 36(8):2294–2300.

4. Hamer M, Stamatakis E (2012) Metabolically healthy obesity and risk of all-cause and cardiovascular disease mortality. J Clin Endocrinol Metab 97(7):2482–2488.

5. Ärnlöv J, Ingelsson E, Sundström J, Lind L (2010) Impact of body mass index and the metabolic syndrome on the risk of cardiovascular disease and death in middle-aged men. Circulation 121(2):230–236.

6. Twig G, Afek A, Derazne E et al (2014) Diabetes risk among overweight and obese metabolically healthy young adults. Diabetes Care 37(11):2989–2995.

7. Sudlow C, Gallacher J, Allen N et al (2015) UK Biobank: an open access resource for identifying the causes of a wide range of complex diseases of middle and old age. PLoS Med 12(3):e1001779.

8. van Vliet-Ostaptchouk JV,NuotioM-L, Slagter SN et al (2014) The prevalence of metabolic syndrome and metabolically healthy obesity in Europe: a collaborative analysis of ten large cohort studies. BMC Endocr Disord 14(1):9

Find this article online at Diabetologia.

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