High Altitude Living May Lower Risk of Common Disease, Study Finds

Living at high altitudes may lower the risk of diabetes, and scientists believe they have finally discovered why. A groundbreaking study from the Gladstone Institutes in San Francisco has revealed that red blood cells act as unexpected “sponges” for blood sugar when oxygen levels are low.

The findings, published in the journal Cell Metabolism, demonstrate that at high elevations, red blood cells begin absorbing large amounts of glucose from the bloodstream. When oxygen levels drop, these cells alter their metabolism to deliver oxygen more efficiently, simultaneously lowering circulating blood sugar levels.

This metabolic adaptation appears to explain the lower diabetes risk consistently observed in mountain-dwelling populations. A previous large-scale study involving over 285,000 adults in the United States found that people living at high altitudes (1,500-3,500 meters) had significantly lower rates of diabetes compared to those living at sea level, even after researchers adjusted for variables like diet, age, and ethnicity.

“Red blood cells represent a hidden compartment of glucose metabolism that has not been appreciated until now,” explained senior author Isha Jain, a Gladstone investigator and professor of biochemistry at UC San Francisco. “This discovery could open up entirely new ways to think about controlling blood sugar.”

The research team’s journey to this discovery began with experiments on mice to better understand hypoxia, or reduced oxygen in the blood. They observed that mice exposed to thin air cleared sugar from their bloodstream almost instantly after eating – a characteristic typically associated with reduced diabetes risk. Initially, however, the researchers were puzzled about where the sugar was going.

“We looked at muscle, brain, liver — all the usual suspects — but nothing in these organs could explain what was happening,” said Yolanda Martí-Mateos, a postdoctoral scholar in Jain’s lab and the study’s first author.

The breakthrough came when the team employed an alternative imaging method, which revealed the red blood cells themselves were the missing “glucose sink.” Under hypoxic conditions, mice produced more red blood cells, and each individual cell absorbed significantly more glucose than they did under normal oxygen conditions.

This finding represents a paradigm shift in how scientists understand glucose metabolism. While conventional diabetes research has focused on organs like the liver, pancreas, and muscle tissue, this study highlights blood cells themselves as important regulators of blood sugar.

The medical implications could be substantial. The research team has already developed an experimental drug called HypoxyStat that mimics this high-altitude effect. In laboratory tests, the drug completely reversed high blood sugar levels in diabetic mice, suggesting a potential new pathway for diabetes treatment.

This discovery is particularly significant given the global diabetes epidemic. According to the International Diabetes Federation, approximately 537 million adults worldwide were living with diabetes in 2021, a number projected to rise to 643 million by 2030. Finding new mechanisms to control blood sugar could provide alternative approaches for the millions who struggle with current treatments.

The study does have some limitations. The research focused on one specific mouse strain known for its sensitivity to blood sugar. While humans show similar results, testing other strains would confirm the universality of these findings. Additionally, to ensure consistent results, the team only studied young male mice. Because age and sex significantly impact how red blood cells are produced, more research is needed to determine whether these findings apply equally to females and older populations.

The research also raises intriguing questions about other potential health benefits of high-altitude living. Some studies have suggested correlations between elevation and reduced rates of heart disease, obesity, and certain cancers, though the mechanisms remain unclear.

“This is just the beginning,” Jain emphasized. “There’s still so much to learn about how the whole body adapts to changes in oxygen, and how we could leverage these mechanisms to treat a range of conditions.”

As research continues, this newfound understanding of red blood cells as active participants in glucose regulation may open entirely new avenues for treating metabolic disorders and potentially other conditions affected by oxygen levels in the body.