Living at high altitudes may lower the risk of diabetes, and scientists believe they have finally figured out why.
A new study from the Gladstone Institutes in San Francisco examined how red blood cells behave in low-oxygen environments. The findings, published in the journal Cell Metabolism, reveal that at high elevations, red blood cells begin absorbing large amounts of glucose from the bloodstream, acting as a "sponge" for sugar.
When oxygen levels drop, these cells then alter their metabolism to deliver oxygen more efficiently.
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This shift also lowers circulating blood sugar, which researchers say explains the lower diabetes risk seen in mountain-dwelling populations.
A previous study of over 285,000 adults in the United States found that people living at high altitudes (1,500-3,500 meters) were significantly less likely to have diabetes than those living at sea level, even after adjusting for factors like diet, age and ethnicity.
"Red blood cells represent a hidden compartment of glucose metabolism that has not been appreciated until now," said senior author Isha Jain, a Gladstone investigator and professor of biochemistry at UC San Francisco, in the press release. "This discovery could open up entirely new ways to think about controlling blood sugar."
Previously, Jain’s team conducted experiments on mice to better understand hypoxia, or reduced oxygen levels in the blood.
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Mice exposed to thin air cleared sugar from their bloodstream almost instantly after eating, a trait typically linked to a lower risk of diabetes. Initially, however, researchers couldn't figure out 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 MartÃ-Mateos, a postdoctoral scholar in Jain’s lab and the study’s first author.
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The team discovered the answer using an alternative imaging method: the red blood cells themselves were the missing "glucose sink."
By using a different type of imaging, the team found that the red blood cells were holding onto the glucose.
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Under hypoxic conditions, the mice produced more red blood cells, and each cell absorbed significantly more glucose than they did in normal conditions.
The researchers even developed a drug, HypoxyStat, that mimics this high-altitude effect. In laboratory tests, the drug completely reversed high blood sugar in diabetic mice.
The researchers acknowledged some limitations with the study. 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 that the findings are universal.
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 hold true for females and older populations.
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"This is just the beginning," Jain said.
"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."
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