“Metabolically healthy obesity”: What is it and why does it matter (to all of us)?

By Angela Meadows

Obesity – the condition where a body is carrying  above an optimal amount of body fat – is associated with an increased risk of developing a number of metabolic illnesses, including diabetes, hypertension, and heart disease. However, it is worth remembering that bodies naturally come in a range of shapes and sizes and that weight alone is not a guaranteed indicator of health – heavier people are not necessarily ‘unhealthy’ and thin people are not necessarily ‘healthy’. And in the last 15 years, scientists have become interested in a sub-group of heavier people who do not exhibit the metabolic abnormalities often associated with obesity, a phenomenon known as ‘metabolically healthy obesity’ (MHO).

There are a range of measures that can define metabolic health, including abdominal adiposity, insulin sensitivity, blood pressure, blood levels of certain lipids, such as triglycerides and HDL cholesterol, and chemical molecules associated with inflammation. Because there is no agreed upon definition of MHO, understanding the biology and long-term health implications of the phenomenon can be complicated. Some studies have measured all of these things and some just a few. Some have defined MHO as having no risk factors (low abdominal adiposity, normal blood pressure, good insulin sensitivity, and so on), whereas others may allow one or even two risk factors and still classify somebody as MHO. Some studies have used different tests to measure the same thing, and others have used the same test, but defined ‘healthy’ and ‘unhealthy’ using different cut-offs. However, it is possible to draw some conclusions from the growing body of literature in this area.

While numbers vary between individual studies, larger studies suggest that approximately 30–45% of people who are ‘obese’ by BMI standards appear to be metabolically healthy. Additionally, approximately 20–25% of people who fall into the ‘normal weight’ category have risk factors that classify them as ‘metabolically unhealthy’.

However, there has been some question as to whether MHO is a stable protective condition, or merely an interim stage on a pathway to deteriorating health. A recent systematic review of MHO studies by Roberson and colleagues identified 15 cohort studies that compared long-term health outcomes between MHO and ‘metabolically healthy normal weight (MHNW) – that is, individuals with similarly low risk factors but belonging in different BMI categories. Follow-up periods ranged from 4 to 30 years.  And the outcome was pretty conclusive. The vast majority of studies looking at increased risk of death from any cause, death from cardiovascular disease, or new cases of cardiovascular disease (with sample sizes of 96,000 to 100,000 people for each outcome) found absolutely no difference in outcomes between MHO and MHNW individuals. Those that did find increased risk in heavier people tended to be the smaller studies and all failed to control their results for at least one of the most important known confounders: fitness levels and/or socioeconomic status. Another meta-analysis of long-term outcomes in MHO also published in 2014, did report higher risks with longer follow-up, has been subject to criticism over its methods (see Annals of Internal Medicine 2014, 160(7), 513-516).

In terms of future research, then, two of the main issues needed to provide a definitive answer on the stability of the MHO condition are, first, the need for a standardised definition of MHO, and second, appropriately controlling outcome data for known confounds (smoking, socioeconomic status, fitness).  But in terms of health recommendations, we do not need to wait for that answer.

Although not included in the Roberson et al systematic review, a number of major studies compared not only MHO and MHNW, but also metabolically abnormal obese (MAO) and metabolically abnormal normal-weight (MANW) participants. Importantly, the larger studies consistently show that individuals who are ‘metabolically healthy’ fare better than those who are not, regardless of their weight; see for example, this one and this one. We know from 50 years of research that it is almost impossible for the majority of people to lose weight and keep it off long-term.  The human body has numerous mechanisms that will resist weight reduction, and this is consistent with findings from reviews of diet studies with longer-term follow-up. But it is possible to improve metabolic health without weight loss. Although genetics probably plays a larger role in the development or otherwise of metabolic risk factors, several health behaviours have been shown to improve long-term health outcomes, irrespective of weight status.

For example, according to one study of nearly 12,000 people, those who didn’t smoke, who engaged in moderate exercise a few times a week, didn’t drink to excess, and who got at least five servings of fruits and vegetables a day, seemed to have the best health outcomes, regardless of which BMI category they fell into. In fact, the link between fitness levels and long-term health outcomes is now so strong, that perhaps policy makers should be focussing public health messages on physical activity rather than weight loss to maximise population health.