Diabetes Risk Lower in Certain US Regions, Study Finds

Living at high elevations may lower diabetes risk by altering red blood cell behavior, a groundbreaking new study suggests.

Scientists from the Gladstone Institutes in San Francisco have discovered that red blood cells function as natural “glucose sponges” in low-oxygen environments, potentially explaining the lower diabetes rates observed among mountain-dwelling populations. The findings, published in Cell Metabolism, reveal a previously unrecognized mechanism that could revolutionize diabetes treatment approaches.

The research team examined how red blood cells respond to reduced oxygen levels, such as those experienced at high altitudes. They found that when oxygen is scarce, red blood cells dramatically increase their absorption of glucose from the bloodstream while simultaneously altering their metabolism to deliver oxygen more efficiently throughout the body.

“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 investigation builds on earlier epidemiological evidence showing significant health differences based on elevation. A previous study of over 285,000 U.S. adults found that people living at high altitudes (1,500-3,500 meters) had substantially lower diabetes rates than sea-level residents, even after accounting for variables like diet, age, and ethnicity.

To understand the mechanism behind this phenomenon, Jain’s team conducted experiments exposing mice to low-oxygen conditions similar to those at high elevations. They observed that these mice cleared sugar from their bloodstream almost instantly after eating – a characteristic typically associated with reduced diabetes risk.

Initially, the researchers were puzzled about where the glucose 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 alternative imaging techniques, revealing that red blood cells themselves were the missing “glucose sink.” Under hypoxic conditions, mice not only produced more red blood cells, but each cell absorbed significantly more glucose than under normal oxygen levels.

The implications extend beyond explaining altitude-based health differences. Researchers have developed a drug called HypoxyStat that mimics this high-altitude effect. In laboratory tests, the medication completely reversed high blood sugar levels in diabetic mice, suggesting exciting potential for human applications.

Diabetes affects hundreds of millions worldwide, with cases continuing to rise globally. Current treatments often focus on insulin regulation or limiting glucose absorption in the digestive tract. This research introduces an entirely new therapeutic target – the red blood cells themselves – which could complement existing approaches.

The study does have limitations. Researchers primarily used one specific mouse strain known for its sensitivity to blood sugar fluctuations. While preliminary human tests show similar results, more diverse animal studies would help confirm the universality of these findings. Additionally, the team focused solely on young male mice, leaving questions about how age and sex might influence these mechanisms.

“This is just the beginning,” Jain noted. “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.”

The research also highlights the unexpected health benefits of high-altitude living. Communities in mountainous regions like the Andes, Himalayas, and Rocky Mountains have long reported certain health advantages, though the underlying mechanisms remained poorly understood until now.

As global diabetes rates continue climbing, particularly in developed nations with sedentary lifestyles and processed food diets, these findings offer a promising new avenue for treatment development. By understanding how the body naturally regulates blood sugar in challenging environments, scientists may unlock novel therapeutic approaches that mimic these beneficial adaptations.