Lesser Degrees of Excess Weight Do Not Increase Mortality

Miriam E. Tucker

January 01, 2013

Severe obesity is associated with an increased risk for death from all causes, but lesser amounts of excess weight either do not increase the risk or may be protective, according to the results of a systematic review and meta-analysis.

The findings were published in the January 2, 2013, issue of JAMA by Katherine M. Flegal, PhD, from the National Center for Health Statistics, Centers for Disease Control and Prevention, Hyattsville, Maryland, and colleagues.

In an accompanying editorial, Steven B. Heymsfield, MD, and William T. Cefalu, MD, both from the Pennington Biomedical Research Center, New Orleans, Louisiana, caution against relying on weight alone to stratify risk.

The analysis used body mass index (BMI) categories drawn up by the National Heart Lung and Blood Institute (NHLBI) as follows: underweight, BMI less than 18.5 kg/m2; normal weight, BMI from 18.5 to less than 25 kg/m2; overweight, BMI from 25 to less than 30 kg/m2; and obese, BMI of 30 kg/m2 or more). The category for obesity was further subdivided into grade 1 (BMI, 30 to <35 kg/m2), grade 2 (BMI, 35 to <40 kg/m2), and grade 3 (BMI, 40 kg/m2 or more) obesity.

The researchers analyzed 97 published studies, identified through PubMed and EMBASE searches, of which 41 were from the United States or Canada and 37 were from Europe. Others were from Australia (7 studies), China/Taiwan (4 studies), Japan (2 studies), Brazil (2 studies), Israel (2 studies), India (1 study), and Mexico (1 study).

In all, the studies included more than 2.88 million participants and more than 270,000 deaths. All of them investigated the relationship between BMI and all-cause mortality and provided hazard ratios (HRs) for standard BMI categories (although some used slightly different ranges for the lowest BMI categories).

Compared with the normal-weight group, the HR for the overweight group was 0.94, with a 95% confidence interval of 0.91 to 0.96. For all grades of obesity together, the HR was 1.18 (95% CI, 1.12 - 1.25), but when the obesity categories were broken down separately, grade 1 was not associated with increased all-cause mortality (HR, 0.95; 95% CI, 0.88 - 1.01).

Obesity grades 2 and 3, in contrast, were associated with greater mortality risk, with an HR of 1.29 for the 2 grades combined (95% CI, 1.18 - 1.41).

"Relative to normal weight, obesity (all grades) and grades 2 and 3 obesity were both associated with significantly higher all-cause mortality. Grade 1 obesity was not associated with higher mortality, suggesting that the excess mortality in obesity may predominantly be due to elevated mortality at higher BMI levels. Overweight was associated with significantly lower all-cause mortality," the authors write.

In a subsequent analysis that excluded 34 studies that were considered possibly overadjusted (ie, adjusted for factors such as hypertension that are considered to be part of the causal pathway between obesity and mortality) and 10 studies that were considered possibly underadjusted (ie, neglected to adjust for factors such as age, sex or smoking), results for the remaining 53 adequately adjusted studies did not significantly alter the results.

Moreover, an analyses of contributors to heterogeneity, including study adjustment levels, whether BMI data were measured or self-reported, age group, and slight differences in BMI categorization, did not reveal a significant effect of heterogeneity on the overall meta-analysis conclusions.

Fits in With Previous Studies

Dr. Flegal and colleagues note that their findings are consistent with previous studies that have also shown lower mortality among overweight and moderately obese patients. Possible explanations also have included earlier presentation of heavier patients for medical care and increased likelihood of receiving aggressive risk factor treatment, cardioprotective metabolic effects of increased body fat, and beneficial effects of higher metabolic reserves.

In their accompanying editorial, Dr. Heymsfield and Dr. Cefalu comment that relying on weight alone is not enough, as individuals with the same BMI can differ widely from one another in factors affecting health and mortality.

"Sole use of BMI as a health risk phenotype aggregates people with substantial differences in nutritional status, disability, disease, and mortality risk together into similar BMI categories," they point out.

Recognizing that, the NHLBI also recommends using the additional marker of waist circumference to help quantify risk, they note.

In addition, the NHLBI's classification of normal as a BMI between 18.5 and 25 kg/m2 obscures the fact that people with a BMI between 18.5 and 22 kg/m2 have been found to have higher mortality than those with a BMI between 22 and 25 kg/m2. Lumping them together raises the mortality rate for the normal-weight group, which could explain why their observed mortality is similar to grade 1 obesity.

However, the editorialists also point out that there does appear to be a protective effect of the overweight or low-obesity BMI categories for people chronic conditions such as heart disease, diabetes, and older age — the so-called "obesity paradox."

"Even in the absence of chronic disease, small excess amounts of adipose tissue may provide needed energy reserves during acute catabolic illnesses, have beneficial mechanical effects with some types of traumatic injuries, and convey other salutary effects that need to be investigated," they add.

Clinically, this means that "[n]ot all patients classified as being overweight or having grade 1 obesity, particularly those with chronic diseases, can be assumed to require weight loss treatment. Establishing BMI is only the first step toward a more comprehensive risk evaluation," Dr. Heymsfield and Dr. Cefalu conclude.

The authors have disclosed no relevant financial relationships. Dr. Heymsfield has reported serving as a consultant to EISIA Inc and Merck & Co, serving on an advisory board for Tanita Medical, having travel expenses paid by the Korean Society for the Study of Obesity, and receiving retirement payments from Merck & Co. Dr. Cefalu has reported serving on advisory boards or as a consultant to Halozyme, Lexicon, Intarcia, AstraZeneca, sanofi, and Johnson & Johnson and receiving grants from Johnson & Johnson, AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKline, Mannkind, Merck & Co, Lilly, Amylin, and Intarcia.

JAMA. 2013;309:71-82.