Does "Metabolically Healthy Obesity" Exist?

Obesity is strongly associated with metabolic alterations and negative health outcomes including diabetes, cardiovascular disease, and some types of cancer (1, 2, 3, 4).  Excess body fat is one of the primary causes of preventable health problems and mortality in the United States and many other affluent nations, ranking in importance with cigarette smoking and physical inactivity.  Obesity is thought to contribute to disease via the metabolic disturbances it causes, including excess glucose and lipids in the circulation, dysregulated hormone activity including insulin and leptin, and inflammatory effects.  This immediately raises two questions:

1. Does metabolically healthy obesity exist?
2. If so, are metabolically healthy obese people at an elevated risk of disease and death?

Does metabolically healthy obesity exist?

Yes.  Several papers have documented that about 10-20 percent of obese people are "metabolically healthy", depending on how that is defined and what population is examined (5, 6, 7).  Metabolically, these people are often indistinguishable from lean, healthy people, and they even appear metabolically healthier than a subset of lean people who are considered "metabolically obese".

Do metabolically healthy obese people have an elevated risk of disease and death?

If we believe that we can measure obesity-related health risk using established metrics such as lipids, glucose, insulin, and blood pressure, then obese people that appear healthy by these measures shouldn't have an elevated risk of disease.  This makes good sense, but it was challenged by two recent studies that had a big impact both in the media and the scientific community (8, 9).  The studies measured diabetes and heart disease risk in metabolically unhealthy vs. healthy obese, both concluding that even metabolically healthy obese people are at an elevated risk of disease*.

This conclusion provoked a backlash from some researchers, including Dr. Arya Sharma of the University of Alberta (8), a major proponent of the metabolically healthy obesity concept.  Dr. Sharma pointed out that the studies' definition of "metabolically healthy" allowed subjects to have metabolic risk factors (up to one in the diabetes study, and up to two in the cardiovascular disease study), and therefore that they were not truly metabolically healthy (9).

The main counter-evidence he presents is his own research, including a 2011 paper that examined long-term mortality risk among overweight and obese US adults according to the number of health-related risk factors they exhibit (10).  These presence or absence of these risk factors places each individual into one of five categories, which collectively form the Edmonton Obesity Staging System (EOSS) for evaluating the need for medical intervention:

Stage 0: No apparent risk factors (e.g., blood pressure, serum lipid and fasting
glucose levels within normal range), physical symptoms, psychopathology,
functional limitations and/or impairment of well-being related to obesity. 

Stage 1: Presence of obesity-related subclinical risk factors (e.g., borderline
hypertension, impaired fasting glucose levels, elevated levels of liver
enzymes), mild physical symptoms (e.g. dyspnea on moderate exertion,
occasional aches and pains, fatigue), mild psychopathology, mild
functional limitations and/or mild impairment of well-being. 

Stage 2: Presence of established obesity-related chronic disease (e.g.,
hypertension, type 2 diabetes, sleep apnea, osteoarthritis), moderate
limitations in activities of daily living and/or well-being. 

Stage 3: Established end-organ damage such as myocardial infarction, heart
failure, stroke, significant psychopathology, significant functional
limitations and/or impairment of well-being. 

Stage 4: Severe (potentially end-stage) disabilities from obesity-related chronic
diseases, severe disabling psychopathology, severe functional limitations
and/or severe impairment of well-being.

The paper is simple but quite meaty, and I could spend several posts discussing the data and implications.  I'm going to try to stay focused for today however.  I think the findings of the paper are fairly well summarized by the following graph, showing survival over time among overweight and obese people at EOSS stages 0-3.  In this graph, the faster a line drops, the faster the people in that group died:

What you can see is that among overweight/obese people with no established risk factors (EOSS stage 0), mortality over time is low (and not significantly different from lean people).  People with elevated risk factors (EOSS stage 3) die at a rapid rate, and everyone else is in between.  The paper showed that any way you slice and dice the data, whether you look only at overweight people, only at obese people, or only at severely obese people, the conclusion is the same: risk factors are the main predictor of mortality, not fatness itself.

This is why Dr. Sharma argues passionately that obesity itself is not a major rationale for treatment in a person who exhibits no established risk factors.  That being said, this study looked at mortality, not morbidity  (disease itself) as the other studies did.  It's possible that this explains part of the discrepancy-- some of the "metabolically healthy" obese people in Dr. Sharma's study could be sick but not dead.

Another important finding of Dr. Sharma's study lurks in the supplemental materials.  These data show that although some obese people do fall into the apparently healthy EOSS stage 0 classification, this only applies to less than 10 percent.  About 20 percent fall into EOSS stages 0 and 1 combined, meaning they are minimally impaired.  The other 80 percent of obese US adults have "established obesity-related chronic disease", "established end-organ damage", or "severe (possibly end-stage) disabilities".

One finding that was consistent across all three studies is that disease risk increases with body fatness, on average.  Metabolically healthy obesity exists and is fairly common, but it's not typical.

Conclusions

Here are my tentative conclusions:

1. Obesity remains a major cause of disease and mortality in industrialized nations.
2. Metabolically healthy obesity exists, although it only represents about 10-20 percent of obese people.
3. Metabolically healthy obese people are probably not at an elevated risk of death.
4. Metabolically healthy obese may or may not be at an elevated risk of obesity-related disease relative to lean healthy people, depending on how one defines "metabolically healthy".  
5. Metabolically healthy obese are at a lower risk of disease than metabolically unhealthy obese. 
6. Genetics, diet, and lifestyle probably determine who will be metabolically healthy vs. unhealthy at any given level of body fatness.  I believe it's possible to reduce health risks at any level of body fatness by living wisely, although losing fat is preferable if possible, mostly because it improves metabolic health in the majority of obese people.

* Both studies found that metabolically healthy obese people are at a reduced risk of disease compared to metabolically unhealthy obese, but still at a higher risk level than metabolically healthy lean people.  Both studies also confirmed that obese people have a much higher risk of diabetes and heart attack than lean people on average.