Shelley Wood

June 22, 2013

CHICAGO, Illinois — Worrisome new results from Israel hint that gains seen in life expectancy over the past 50 years are likely to be attenuated by rising obesity rates among adolescents [1]. More worrying still, even higher body-mass-index (BMI) levels within the "normal" range in teens were associated with midlife mortality, according to an analysis linking the medical database of the Israeli defense force with the national death registry.

Presenting the results here at the American Diabetes Association 2013 Scientific Sessions, Dr Gilad Twig (Chaim Sheba Medical Center, Tel-Hashomer, Israel) stressed that the analysis looked only at all deaths unrelated to military service so could not single out deaths from CVD or other causes. But because military service is mandatory in Israel, and all conscripts must undergo a physical exam at the time of recruitment, the analysis provide a unique snapshot of the health and longevity of more than two million young men and women (age 16–20) over the past 40 years.

Fighting Obesity

As Twig showed here, his analysis included 2.16 million adolescent males (60%) and females, who had a mean age of 17.4 at the time of their first military medical tests and an overall prevalence of overweight and obesity of 11.7% at the time of recruitment.

The primary outcome for the study was mortality before the age of 50: this was seen in 1.21% of males and <1% of females.

Compared with mortality among conscripts whose BMIs put them in the 25th to 50th percentile, mortality for recruits in higher percentiles for BMI increased continuously up the BMI spectrum.

In men, being underweight (BMI <18.5) was associated with a significant 11% increase in mortality before age 50, while being overweight (BMI 25–29.9) and obese (BMI >30) were associated with increased risks of 40% and 88%, respectively.

A similar pattern was seen in women (increases of 11%, 44%, and 105% for underweight, overweight, and obese, respectively), although the relative risk ratios were not statistically significant for the underweight group.

Not-So-‘Normal’ BMI?

Next investigators tried to examine BMI levels within the "normal range" (18.5–24.9) to see if there were any mid-life mortality signals within this accepted-as-healthy weight range. They found, to their surprise, that BMIs even within the 50th to 70th percentile range were associated with small but significant increases in mortality risk.

"This pretty much corresponds to a BMI value between 20.5 and 22 during adolescence," Twig said. "This increased risk in mortality was seen in both males and females, indicating that BMI well within the normal range can be associated with increased mortality."

Twig et al then looked at mortality curves for normal-weight males born in the 1950s, '60s, '70s, and '80s. And while the length of follow-up is obviously different for the younger vs older groups, the survival curves for these normal-BMI males clearly become "shallower," Twig noted, the later they were born. In a multivariate analysis that looked at risk of death according to decade of birth, Twig and colleagues saw declining hazard ratios for mortality among subjects born in the 1960s, '70s, and '80s, compared with those born in the 1950s. Both findings are consistent with other studies showing that life expectancies have been steadily increasing, he explained.

When investigators ran the same analysis for military recruits who were obese at the time of their baseline exam, they saw a different pattern. Regardless of what decade they were born, recruits who were obese at the time of their first medical exam showed no separation of the survival curves as compared with conscripts born in the 1950s. In a multivariate analysis looking at hazard ratios for death, this one among overweight and obese subjects combined, born in successive decades, using the 1950s as a reference, Twig and his coinvestigators showed that mortality risks are actually increasing with each decade.

"If you are obese, there is no benefit [to] being born in a later decade," Twig stated.

Obesity is a known risk factor for cardiovascular mortality, but studies typically look at middle-aged or elderly subjects, with mortality typically assessed beginning in the seventh decade of life, Twig observed. Studies also tend to consider all patients within the normal-BMI category as "homogenously normal . . . seriously limiting our ability to ask whether the entire normal range is indeed homogenous."

The current analysis suggests that BMI in adolescence, even within the currently considered normal range, may be a risk factor for all-cause mortality in mid-life, Twig concluded.

"Midlife mortality rates among overweight and obese adolescents did not decrease in the last 40 years, and preadulthood obesity is expected to attenuate the progressive increase in life expectancy," he added. "More sensitive measures are needed to identify such at-risk adolescents for either medical diagnosis and/or intervention."

An Evolving Understanding of BMI

Commenting on the study for heartwire , Dr Rhonda Bentley-Lewis (Massachusetts General Hospital, Boston) stressed that because the study did not report causes of mortality, it's impossible to link BMI levels to cause of death.

That said, "The fact that we are seeing more overweight and obesity among adolescents is a major health concern nationally and internationally, and the implications of that I don't think have been fully examined," she said. "These data definitely begin to introduce an understanding of what the future implications are with respect to mortality."

The question of whether higher levels within the normal-BMI range in adolescents may actually prove problematic warrants more study, she continued. Worth keeping in mind, she noted, is the evolving understanding of glucose levels as a continuum, suggesting that there is no specific value that can serve as a threshold, such that any level below that figure equals no risk.

"[Twig] may be beginning to uncover similar findings with respect to BMI; I'm just not sure that the data were complete enough to be able to speak to that, but that's a very fascinating and concerning question. It's hard enough to get our patients down to that normal range, and now, if we are starting to tease out [levels of risk] within the normal range, will that be discouraging? Will it be empowering? It's hard to say."

Twig et al disclosed grant support from the Talpiot Medical Leadership Program. Twig declined to be interviewed, citing restrictions around data from the Israel Defense Force Registry.

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