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Why overweight people may be more likely to die from infections like pneumonia and sepsis

We may be vastly underestimating obesity’s toll.

Human fat cells, computer artwork.
Fat cells promote inflammation and alter hormone levels in ways that doctors now think increase the risk of disease.

As obesity rates have hit global epidemic proportions, researchers are finding new ways that excess body fat harms our health. This week, a new study adds another worry to the list: Being overweight or obese in adolescence seems to put people at a higher risk of dying from infectious diseases by middle age.

In a first-of-its-kind paper, published in the International Journal of Obesity, researchers from the Israel Defense Forces gathered data on 2.3 million people and found that even a few extra pounds early on in life was associated with an increased risk of death from infectious diseases — such as sepsis or pneumonia — before the age of 60.

“There’s been an increase in both the US and Europe of infectious diseases deaths among young and middle age adults,” said lead study author Gilad Twig, a physician from the Israel Defense Forces and professor at Sheba Medical Center in Tel Aviv. In the US, for example, researchers have found a 0.5 percent annual increase in the rate of deaths attributed to common infectious diseases among middle-aged women over the past two decades. Now Twig and his colleagues think part of that trend may be explained by the rise in obesity.

For the study, the researchers drew from a data set of 2.3 million Israelis ages 17 to 19 who were screened for fitness before starting mandatory military service between 1967 and 2010. In these military health assessments, height and weight are measured along with vision, diabetes, asthma, and other health risks.

The researchers then linked this youth data with cause of death information from the Ministry of Health, focusing in particular on the relationship between body mass index (a measure of body fat calculated by dividing one's weight by one's height squared) and deaths from infectious diseases.

Of the 2.3 million people in the study, 689 had died from infectious diseases by middle age. Among these, the researchers uncovered staggering associations with bodyweight. Obese women were at a sevenfold higher risk for infectious diseases death compared to normal-weight women, while obese men were at a 2.3-fold higher risk of infectious diseases death compared to normal-weight men.

For every unit increase in a person’s body mass index, their risk of death from an infectious disease also shot up: For men, there was a 4 percent increase in risk with every unit of BMI, and for women, a 15 percent increase.

Why might a high BMI increase a person’s chances of dying from an infectious disease?

There’s pretty much not an organ system or part of the body that’s unscathed by obesity.

The more a person weighs, the harder the cardiovascular system has to work, and the higher the risk for heart failure, heart disease, and stroke. Extra weight strains the hips, legs, and ankles, increasing the chances of developing pain and osteoarthritis. Obesity is associated with insulin resistance, which increases the risk of Type 2 diabetes. Fat cells promote inflammation and alter hormone levels in ways that doctors now think increase the risk of at least 10 types of cancer. Obesity even interferes with the brain, in ways that may increase the risk of Alzheimer’s.

Researchers have already found associations between adult obesity and sepsis and respiratory infections, as well as an increased mortality risk from bacterial infections in the blood.

“We expected obesity to be a risk factor for death attributed to infectious disease mortality, but we were surprised by the strong sex-specific differences,” Twig said.

Now they’re puzzling out why obesity in adolescence may impact a person’s risk of death from an infectious disease later in life — particularly for women. And they’ve come up with a few ideas.

People who gain weight tend to have changes in levels of certain hormones, including sex hormones like estrogen as well as insulin. These changes might alter the immune system, making them more susceptible to infections. In addition, the immune response to vaccines may be hampered by obesity, which researchers have previously found in studies on the hepatitis B, influenza, and tetanus vaccines.

Obesity is also highly related to diabetes, “and we know diabetes is a very strong risk factor for developing certain types of infection,” Twig added. “So it is possible that some of the death attributed to infections were actually mediated by development of diabetes.”

Diabetes can put people at an increased risk for other serious diseases. In another study, out this week in the Lancet, researchers linked nearly 6 percent of new cancers diagnosed globally to diabetes and excess weight. In that paper, they postulated that high insulin levels in the bodies of people with diabetes may be partially to blame: Insulin is a pro-growth hormone, so it can increase the rate of turnover in cells, including cancerous ones — helping them proliferate.

There were some important limitations to note about Twig’s study. The researchers only had data at two points in time: adolescence and cause of death later. Although people who are overweight when they're young are likely to be overweight later in life, we don't know how the study participants' bodies changed in adulthood.

It’s also possible there’s some larger reason why a person would become both obese and susceptible to diseases. The researchers didn’t have data about other risk factors with the study participants, such as smoking or diet. So there may be important associations they’re missing. Finally, this was an observational study — not an experiment — so it can't tell us whether bodyweight caused the heart problems later, just that the two are linked.

But for now, it’s a fascinating finding — and if the association turns out to be real, it means we are probably vastly underestimating obesity’s toll.

Update: This article originally mentioned HIV in the title, but it’s one example where these researchers — and others — have found an inverse association with obesity.