Diabetes rates are lower in high-altitude environments — and scientists may have discovered why
Prices of diabetes are lower in high altitude areas, but researchers don’t know why. Now, a new study in mice reveals a possible explanation: Red blood cells, which play a critical role in transporting oxygen throughout the body, can lower blood sugar levels by converting glucose into a compound that helps release oxygen into tissues.
If the results can be replicated in humans, they also suggest that drugs at an early stage of development could potentially mimic this pathway.
Higher altitude, lower blood sugar
It is well known that people living at high altitudes with low oxygen levels, such as in the Andes and Himalayas, tend to have lower rates of diabetesbut the reason for the connection is unclear. In a Study 2023Scientists observed the same phenomenon in mice: When the mice were exposed to low-oxygen conditions, they developed a condition called “hypoxia,” which occurs when the oxygen supply to the tissues is insufficient and their blood sugar levels also drop.
But the glucose disappearance couldn’t be explained by the amount of glucose absorbed by muscles and other organs during the scans, so it wasn’t clear where it was going.
From high altitudes to laboratory chambers
To test whether red blood cells were responsible for the decrease in glucose, the study authors exposed mice to low-oxygen chambers containing 8% oxygen. This mimicked high-altitude air, while another group of mice was kept in air containing 21 percent oxygen, which mimicked normal atmospheric conditions, Jain said.
After several weeks, both groups of mice received glucose injections and their blood sugar levels were measured over time. Compared to mice in normal oxygen environments, mice in low oxygen conditions showed a much smaller increase in their blood sugar levels, suggesting that they might clear glucose from their blood more quickly. This effect persisted for weeks, even after the animals returned to normal oxygen levels, suggesting that a low-oxygen environment had a lasting impact on metabolism, experts say.
The researchers also performed imaging scans to track the amount of glucose absorbed by major organs and tissues, such as the liver and muscles. However, much of the disappearance of glucose could not be explained. This prompted them to investigate whether cells in the circulating blood itself could consume the glucose.
To test this idea further, they directly manipulated the number of red blood cells. The team periodically took blood from oxygen-deprived mice to keep red blood cell levels near normal, and found that this eliminated the hypoglycemic effect of hypoxia. In contrast, transfusing red blood cells into mice breathing normal air resulted in lower blood sugar levels, suggesting that the red blood cell count alone lowered blood sugar levels.
Then the team injected labeled glucose into mice and tracked it throughout the body. They found that the red blood cells of the oxygen-deprived mice absorbed significantly more glucose than those of the comparison mice. Mice in low-oxygen conditions quickly converted glucose into a molecule that binds to hemoglobin, the protein in red blood cells that carries oxygen. This bond forces hemoglobin to release oxygen more easily into tissues when oxygen levels are low.
Further analysis showed that the red blood cells produced in the oxygen-deprived mice also contained higher levels of a protein called GLUT1, which is found on the cell membrane and helps glucose enter the cell. These red blood cells contained about twice as much GLUT1 and absorbed about three times as much glucose as normal red blood cells. By marking existing red blood cells before exposing the mice to low-oxygen conditions, the researchers confirmed that only new cells produced in low-oxygen conditions showed these adaptations.
In addition to triggering an increase in red blood cells, the study shows that cells are structurally altered to consume more sugar in low-oxygen environments, said Daniel Tennantresearcher in hypoxia and metabolism at the University of Birmingham who was not involved in the work.
Lars Kaestnera red blood cell biologist at Saarland University in Germany who was not involved in the study, noted that the number of red blood cells increases when the air is rarefied, to boost the transport of oxygen throughout the body. Red blood cells use glucose as fuel. Therefore, it’s not surprising that low oxygen conditions cause blood sugar to drop because more red blood cells are there to clear it out, he told Live Science.
“From a systemic point of view, it makes a lot of sense,” he said.
It’s an “evolutionarily conserved corrective mechanism” essentially aimed at better oxygenating the body at high altitudes, Tennant told Live Science.
This opens the door to thinking about treating diabetes in a fundamentally different way.
Isha Jain, biochemist at the Gladstone Institutes and the University of California, San Francisco
The body increases its red blood cell count at high altitude by changing the expression of genes that control metabolism and producing more of a hormone called erythropoietin, which prompts the bone marrow to produce more red blood cells, said Sonia Rochabiochemist at the University of Liverpool who was not involved in the study.
This is why elite athletes train in high altitude areas for their competitions: their bodies produce more red blood cells and thus obtain “more efficient circulation to distribute oxygen to their tissues”, she told Live Science.
A diabetes drug that mimics oxygen deprivation?
In another experiment, researchers treated mice with HypoxyStat, an experimental compound developed in Jain’s lab that increases the strength with which hemoglobin binds to oxygen, preventing its release and mimicking hypoxia. The idea is that mimicking oxygen deprivation with a drug could increase red blood cell counts and help regulate blood sugar levels.
However, much more testing is needed before a drug like HypoxyStat can be tested in humans, Rocha noted.
Although red blood cell transfusion is not a practical treatment for diabetes, the results suggest potential directions such as creating red blood cells that act as better glucose sinks, the authors suggest. “This opens the door to thinking about treating diabetes in a fundamentally different way,” Jain said. said in a statement.
Martí-Mateos, Y., Safari, Z., Bevers, S., Midha, AD, Flanigan, WR, Joshi, T., Huynh, H., Desousa, BR, Blume, SY, Baik, AH, Rogers, S., Issaian, AV, Doctor, A., D’Alessandro, A., & Jain, IH (2026). Red blood cells serve as a primary glucose sink to improve glucose tolerance at altitude. Cell Metabolism, 38(3), 529-545.e8. https://doi.org/10.1016/j.cmet.2026.01.019
