A new German study is attempting to explain the oft-observed association between shorter people and a higher risk of developing type 2 diabetes. The research reveals short stature, in particular for men short leg length, tends to correlate with higher liver fat content and subsequently, diabetes. But before taller readers get too complacent, other research suggests increased height correlates with a greater risk of cancer.
For several years researchers have identified strange associations between height and disease. Consistently studies have found height to be inversely linked to type 2 diabetes and cardiovascular disease. This means the shorter you are, the more likely you are to develop those conditions.
New research from a team of German scientists has tried to zero in on which particular components of height can be associated with those diseases, and whether there are other biomarkers than can help explain this unusual correlation. Data from the European Prospective Investigation into Cancer and Nutrition (EPIC) was utilized, and over 2,000 subjects were included in the analysis.
After adjusting for confounding factors, the research revealed every 10 extra centimeters (3.0 in) of height conferred 41 percent less risk for diabetes in men, and 33 percent in women. The association was stronger in adults with normal weight, suggesting obesity can somewhat counteract the lowered risk of diabetes in tall people.
Looking at leg length, the research suggests longer legs in men could be associated with a reduced risk of diabetes, but this link was not seen in women. The most comprehensive observation in the study found liver fat and cardiometabolic factors seemed to significantly account for most of the enhanced diabetes risk seen in shorter people.
"We found an inverse association between height and risk of type 2 diabetes among men and women, which was largely related to leg length among men,” the researchers conclude in the study. “Part of this inverse association may be driven by the associations of greater height with lower liver fat content and a more favorable profile of cardiometabolic risk factors, specifically blood fats, adiponectin and C-reactive protein."
Of course, while the study can clearly identify an association between shorter stature and increased liver fat levels, exactly why this is the case is still unknown. The researchers do note other research has also identified a correlation between height increases and lower liver fat, but more research is needed to explain this strange association.
It is unclear why taller people seem to display more favorable cardiometabolic markers. A number of different factors are hypothesized, including potential genetic variants relating to both height and cardiometabolic conditions, as well as the tendency for taller people to have better insulin sensitivity and beta cell function. This is suggested to potentially be related to enhanced activity in taller people of certain growth proteins, such as insulin-like growth factor 1 and 2 (IGF).
However, while these specific mechanisms could help protect a tall person from diabetes and cardiovascular disease, they also may make one more prone to a number of different cancers, underpinning another long-identified association between height and disease. But this time it works the other way around. The taller a person is, the greater their risk for developing a number of different cancers. In fact, a person’s general cancer risk increases 10 percent with every 10 centimeters (3.9 in) of extra height. Several cancers in particular (kidney, breast, ovarian, colorectal, and prostate) show the greatest increased risk in relation to a person’s height.
This association between height and cancer has been observed for decades. One of the overarching hypotheses to explain this long-witnessed association is deceptively simple. Tall people simply have more cells, and more cells fundamentally increase the risk of more mutations, leading to more cancer.
In 1977 a statistical epidemiologist from the University of Oxford named Richard Peto poked a massive hole in the 'more cells equal more cancer' hypothesis. Peto asked, if incidents of cancer correlate with cell numbers, then larger organisms should display significantly higher rates of cancer compared to smaller organisms. Whales and elephants, for example, should be tortured by cancer at much higher rates than mice. But, as Peto demonstrated in his 1977 study, this was not the case. The observation was quickly dubbed Peto’s Paradox.
To explain Peto’s Paradox, it was suggested larger species of animals must have evolved specialized cancer suppression mechanisms. An interesting number of recent studies have begun to reveal some of these hidden mechanisms. Two 2015 studies revealed elephants have 20 copies of a gene called P53. Known as a tumor suppressor gene, humans only have one copy of this gene and P53 mutations are suspected to play a role in over half of all cancers in humans.
So while larger species of mammals appear to have evolved a variety of cancer suppression mechanisms, larger individuals within given species still seem to display higher rates of cancer. The most recent study verifying this observation came in 2018 from evolutionary biologist Leonard Nunney.
Nunney’s work found not all cancers showed an increased risk associated with height. While melanoma, for example, displayed the most dramatic increases in taller people, some other cancers (esophageal, stomach, and mouth) did not increase at all with height. One of Nunney’s potential explanations for this observation brings us back to insulin-growth factor levels in taller people.
The hypothesis presented is that a higher cell division rate increases the risk of mutations causing cancer, and increased cell division rates can potentially be mediated by insulin-growth factor hormones. Backing up this hypothesis, Nunney cites a condition called Laron syndrome, which is underpinned by insulin-growth factor deficiencies and manifests in those of short stature. Individuals with Laron syndrome also display incredibly low rates of cancer.
And why is skin cancer found in particularly high rates in taller people? Well, it is because skin cells are found in large numbers and divide continuously across a person's life, increasing the risk for somatic mutations leading to cancer. Nunney found cell division rates, mediated by IGF, increase by around two percent for every extra 10 cm of height.
So what does all this mean? Well, it means if you are short you may be more likely to contract type 2 diabetes and if you are tall you may be more likely to develop skin cancer. Of course, these enhanced risk levels related to height are relatively minimal compared to a multitude of environmental factors known to contribute to the disease.
It may seem dramatic to suggest that someone over seven feet tall is at double the risk of developing cancer compared to someone five feet tall. But Nunney notes these kinds of relative risk factors are nothing to worry about.
“So over the feasible range of most human height, the maximum effect you’re getting even in that extreme range is just twofold,” Nunney said to Healthline in 2018. “Whereas smoking cigarettes, even moderate smoking, is going to give you eight or nine times more risk of lung cancer than if you don’t smoke.”
The new research was published in the journal Diabetologia.
Source: Diabetologia via Eurekalert
