Is Bigger Really Better? The Obesity Paradox

Peter H. Jones, MD

Diabetes and Health: Going the Distance

The ever-expanding waistlines of the US populace have gained much attention in the past decade, and our patients are not only aware of their own tendencies to gain weight, they are also aware of the health consequences of obesity, which include a high risk for cardiovascular disease, hypertension, and diabetes. Therefore, it’s obvious that obesity is bad and reducing weight should be a desirable objective in order to reduce morbidity and mortality. Right?

Recently, evidence has been accumulating that a higher body mass index (BMI), as compared with a “normal” BMI, actually confers a survival benefit in people with end-stage renal disease, chronic heart failure, stroke, and chronic obstructive lung disease. This has led some to suggest that this paradox—“obesity is good”—is evident only if chronic disease is present in the first place. This so-called obesity paradox, therefore, should not exist in a healthy population, in whom the evidence clearly shows that obesity confers an increase in chronic disease over time. So what is going on here? Should our healthy patients constantly strive to maintain/achieve a reasonable weight in order to prevent disease, per our admonitions, only to switch to adding weight if or when they are given a chronic disease diagnosis? The absurdity of such a message requires a closer look at some of the new data, as well as what our measure of obesity can tell us in healthy people.

“Metabolic Syndrome”

Factors BMI has been a better measure than total weight in identifying the risk of disease, regardless of gender or ethnicity. However, BMI does not consider body composition, such as percentage of fat mass versus fat-free mass (muscle), nor the location of excess fat deposits, such as visceral adiposity, which is reflected in waist circumference. Many obesity experts cite observational data that waist circumference measurements, and subsequent changes, are better predictors of incident hypertension and diabetes than is BMI. Visceral fat correlates better with metabolic abnormalities such as insulin resistance, high triglycerides, low high-density lipoprotein cholesterol (HDL-C), and increased systolic blood pressure than does subcutaneous fat, and these “metabolic syndrome” factors are actually the reason for the higher risk of diabetes, dyslipidemia, and hypertension.

Metabolically Normal Obesity?

It is important to note that a new paradox has emerged here as well: there are “metabolically normal” obese people whose BMI and total body fat are the same as “metabolically abnormal” obese people, and a recent observation from the Dallas Heart Study confirms this finding.1 The authors followed 732 obese subjects (65% women, mean age 43, mean BMI 35)without cardiovascular disease or diabetes for 7 years to determine the incidence of diabetes. A subgroup of 512 who had normal fasting glucose were followed for the incidence of pre-diabetes as well. Overall, 11.5% developed diabetes, and this was predicted by higher visceral fat mass (measured by MRI), higher fasting glucose, higher systolic blood pressure, and family history of diabetes. The risk for diabetes was independent of BMI, as well as the total and abdominal subcutaneous fat (measured by dual-energy x-ray absorptiometry). In other words, visceral fat and insulin resistance, rather than BMI and total fat, predicted the incidence of diabetes, suggesting that there are people who have dysfunctional fat and others who apparently do not. The authors speculated that people who deposit excess fat in the visceral and hepatic areas, as opposed to subcutaneous areas, are more likely to have insulin resistance, dyslipidemia, and hypertension, regardless of their BMI. The prevalence of these metabolically normal obese people is about 25% of all obese people in the United States. The reasons for this finding are probably multifactorial, with unknown genetic contributors the most likely explanation.2 We don’t know much about the long-term outcomes of these people, including whether they stay metabolically normal over time or just become abnormal at a later age, or whether other structural defects related to obesity (osteoarthritis, sleep apnea, deep vein thrombosis) have a significant impact on their comorbidity/survival.

The most plausible reason people can become obese without insulin resistance may rest in their capacity to store caloric excesses in subcutaneous fat depots rather than in the visceral region or in organs such as the liver and muscle.3 There is another paradox worth noting: the impact of cardiorespiratory fitness on cardiovascular and all-cause mortality in obese subjects, which underscores the concept that fitness, rather than BMI, determines a favorable outcome. A recent study of the “fit and fat” phenomenon from the Aerobics Center Longitudinal Study (ACLS) assessed fitness by maximal treadmill testing, along with BMI and percentage of body fat in 43,265 subjects.4 The follow-up for mortality was 14 years and 8 years for nonfatal cardiovascular events. Subjects were classified as obese based on BMI (13% of the

cohort) and percentage body fat (20% of the cohort), and were considered “metabolically healthy” if they had ≤1 metabolic syndrome criterion. Of all the obese subjects, 31% of the “BMI-obese” group and 46% of the “percentage body fat-obese” group were metabolically healthy. Overall, these metabolically normal subjects had higher levels of cardiorespiratory fitness than the metabolically abnormal obese subjects, and had 30% to 50% lower all-cause mortality and fatal/nonfatal cardiovascular events. It should be noted that all the participants in the ACLS are self-referred, and that the majority of these people were not obese, contrary to the general US population. As a result, the conclusion that one’s level of fitness, not BMI, determines disease outcome needs further confirmation.

It should be noted that the studies cited here evaluated people with BMI <45. As a result, it cannot be assumed that stage 3 obese patients (BMI >45) experience any of these “paradoxes.” With that said, these studies—plus prior evidence&mdash; permit the following conclusions about the obesity paradox to be made:

1. A higher BMI (30-40) in people with chronic disease is good and weight loss for them would not only be a bad sign, it would not be a recommended therapy, either.

2. Not all obese people are metabolically abnormal and therefore they may not have higher incidences of diabetes and hypertension.

3. Higher levels of cardiorespiratory fitness in obese subjects may be associated with better cardiometabolic status and a lower mortality, regardless of their BMI.

References

1. Neeland IJ, Turer AT, Ayers CR, et al. Dysfunctional adiposity and the risk of prediabetes and type 2 diabetes in obese adults. JAMA. 2012;308:1150-1159.

2. Wildman RP, Munter P, Reynolds K, et al. The obese without cardiometabolic risk factor clustering and the normal weight with cardiometabolic risk factor clustering: prevalence and correlates of 2 phenotypes among the US populations. (NHANES 1999-2004). Arch Intern Med. 2008;168:1617-1624.

3. Bluher M. The distinction of metabolically healthy from unhealthy obese individuals. Curr Opin Lipidol. 2010;21:38-43.

4. Ortega FB, Lee DC, Katzmarzyk PT, et al. The intriguing metabolically healthy but obese phenotype: cardiovascular prognosis and the role of fitness. Eur Heart J. 2012; doi:10.1093/euroheartj174.