In addition to the slew of reports highlighting methodologic factors that could account for the metabolically healthy obesity effect (see: Evolution of a controversy), recent years have seen the publication of more studies, distinguished by their large size and methodologic approach, demonstrating an increased risk for poor health outcomes in the metabolically healthy obese.
One was published in the European Heart Journal, and included data from around 18,000 people from the EPIC cohort . The study authors defined metabolically healthy obese people as those who had fewer than three metabolic syndrome components and based their analyses only on a single BMI measurement. Nevertheless, they found a significantly increased risk for coronary heart disease (CHD) among metabolically healthy obese people versus healthy normal-weight people, albeit less elevated than that observed in those with the metabolic syndrome.
“Something that people forget is that if you look at all the meta-analyses in the last few years, they all quite clearly show that for the so-called healthy obesity category you don’t see a null effect,” says Hamer. “There is an elevated risk of mortality, it’s just not as high as the unhealthy obese.”
Of note, the researchers did a supplemental analysis in which they defined being metabolically healthy as having no metabolic syndrome components, and found this to be “qualitatively similar” to the main analysis, with the healthy obese by this definition still having an increased risk.
Another study was published in September this year, and involved 3.5 million UK residents from The Health Improvement Network . Again, this study used baseline BMI and so could not account for changes over time; however, it used a relatively strict definition of metabolic health, being the absence of diabetes, hyperlipidemia, and hypertension. Again, it showed an increased risk for CHD, and also for heart failure, among metabolically healthy overweight or obese people relative to those of normal weight.
In addition, two Mendelian randomization analyses published this year supported a direct effect of obesity on metabolic risk, with genetically determined increases in BMI or visceral adiposity associated with type 2 diabetes and CHD [3, 4]. And some researchers have broadened the focus beyond diabetes, CHD, and mortality, with a recent large study showing an increased risk for chronic kidney disease among overweight and obese adults without any components of the metabolic syndrome .
So, after years of controversy and heated debate, is a consensus finally emerging?
“I think it’s definitely going towards the side that you can’t really be healthy and obese,” says Hamer. “I think the most convincing argument is about this issue of stability, and the whole concept of people that are obese and healthy are probably the ones that have only just crossed the line and become obese.”
This issue is illustrated by large studies showing that metabolically healthy obese people are at an increased risk for developing metabolic abnormalities over time. Also, Hamer’s group published a study based on the English Longitudinal Study of Ageing cohort in which they found that metabolically healthy obesity based on one clinical assessment was protective against mortality. But when based on two clinical assessments 4 years apart, so accounting for people who moved between study groups over time, healthy obesity became a risk factor .
Hamer now believes that healthy obesity is a relatively brief transitional state. “I think especially in the last few years, there’ve been some really good studies that have shown that if you have this weight history then you can show that actually it’s much more powerful than just having data from a single time-point,” he says.
Notable among these was the aforementioned research conducted in the participants of the Nurses’ Health Studies and the Health Professionals Follow-Up Study, which found that the paradoxical protective effect of overweight against mortality was reversed by using the highest BMI over a 16-year period, rather than the baseline BMI .
Another, relatively unexplored, complicating factor is that the studies supporting or refuting the concept of metabolically healthy obesity use definitions, whether of obesity or of metabolic health, that are based on standard clinical thresholds. But Hamer points out that the supposedly healthy obese will often have elevated levels of risk factors relative to healthy nonobese people even if they are not classified as having metabolic abnormalities – a systolic blood pressure of 142 mmHg is little different to one of 138 mmHg, yet the former is classified as hypertension and the latter is not.
“Often that gets missed because you simply just lump people into the binary category that’s meeting the threshold,” says Hamer. “If you were to use the continuous data then it’s a slightly different story.”
On top of that are measurement issues, such as masked hypertension and white-coat hypertension, and of single blood glucose measurements underestimating  – or perhaps overstating  – the prevalence of diabetes.
“It’s a difficult area,” Hamer observes. “There’s a lot of issues with it.”
Nevertheless, the latest flurry of publications seems to have swayed most people against the metabolically healthy obesity concept, although dietician Pam Dyson (University of Oxford, UK) concedes that a minority will still argue in favor of it, as she experienced at the 2017 ADA conference. “But certainly if you go to most obesity conferences there are very few people who will stand up and say: no, it’s okay to be overweight,” she says.
But what impact has all this controversy had beyond the rarified world of the scientific literature? Clearly the concepts of fit–fat and metabolically healthy obesity have seeped into mainstream media, which could, in theory, give people cause to assume that their weight is of no particular issue as long as their general health remains good. But in practice, this theoretical risk is probably eclipsed by the problems caused by people’s demonstrable tendency to not actually realize when they are overweight and therefore not view themselves as being at risk for poor health [12, 13]. Combined with this is the influence of local cultural norms on people’s perception of their weight , plus the propensity for overweight to spread through social networks , all suggesting that people’s perception of themselves and what constitutes a healthy weight is the larger barrier to overweight and obese people seeking help to control their weight.
Dyson says: “I think we’ve normalised overweight and obesity, and the majority of the population is overweight or obese, and because of that I think people feel they’re healthy overweight as long as they’re able to carry out their normal activities. It’s when something goes wrong they start to worry.”
And by the time something does go wrong, most people have been overweight or obese for many years, with all the attendant risks, and by the time symptoms of poor health prompt them to seek medical advice they may have irreversible damage.
“Most people have had high blood glucose for about 10 years before they start to get symptoms of diabetes, and it’s been doing harm for 10 years without their knowledge,” says Dyson. “You just don’t know if their blood glucose is higher than normal – there’s just no way of telling without a blood test.”
And, expanding the focus away from cardiometabolic outcomes, Hamer adds that even if obese people do remain in relatively good metabolic health, the excess weight still impacts on other aspects of their health, such as physical function.
“Because of the excess weight you’re carrying, it has, you can imagine, quite detrimental effects on your joints because you have to bear that extra weight,” he says, citing a study from his team that showed a large physical function decline in obese people over 20 years of follow-up, irrespective of their metabolic health .
“I think there’s other interesting elements – health outcomes – to consider that are simply driven by obesity regardless of the metabolic side,” says Hamer.
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