New Delhi: People who live high up in the mountains are less likely to develop type 2 diabetes than those living at sea level. The trend has been observed in populations across the Andes, the Himalayas and other high-altitude regions.
Scientists have long suspected that thinner air—where oxygen levels are lower—changes the way the body handles energy. At high altitude, the body burns more calories, produces more red blood cells and changes how it uses glucose, the main form of sugar in the blood. But the biological reason behind the lower diabetes risk has remained unclear.
Researchers at the Gladstone Institutes now believe they have an answer.
A study published 19 February in Cell Metabolism, a Cell Press journal, found red blood cells (RBCs)—best known for carrying oxygen—step in as major glucose consumers when oxygen levels fall. The discovery challenges the long-held view of RBCs as passive transporters of oxygen. Instead, the study suggests they act as a “glucose sink”, taking sugar out of the bloodstream in low-oxygen conditions and using it to improve their oxygen-delivery function.
“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 the University of California, San Francisco.
The findings, she said, open up new possibilities for managing blood sugar.
This is especially important in the context of India. According to the International Diabetes Federation’s 2022 report, at least 77 million Indians aged 20–79 years were living with diabetes, and that number was expected to increase to 134.2 million by 2045. In 2017, diabetes alone consumed about 5–25 percent of an average Indian household’s earnings, costing approximately 31 billion US dollars for diabetes management.
Also Read: Can showering in the dark before bed give you better sleep?
RBCs: A ‘glucose sink’
The idea behind the study emerged from earlier experiments in which mice were exposed to hypoxia—low-oxygen conditions—similar to those found at high altitudes. The mice initially had lower blood sugar levels.
After eating, the sugar from their blood disappeared much faster than normal. Lower blood sugar is usually associated with a lower risk of diabetes.
But there was a mystery.
When researchers checked the main organs that normally use sugar—the liver, muscles and brain—they couldn’t explain where all the sugar had gone.
With special scanning tools, scientists have now made an unexpected discovery—that RBCs soak up a lot of sugar. In low oxygen, the mice not only made more red blood cells, but each of their RBCs also used more sugar than usual.
Probing further, they found the RBCs taking up the extra sugar to increase the speed at which they carried oxygen to the body’s tissues—something that is especially important when oxygen levels are low.
In simple terms, the cells were using sugar as fuel to improve their oxygen delivery. As a result, less sugar stayed in the bloodstream.
Could this help treat diabetes?
The effects didn’t stop right away. Even after the mice were returned to an environment with normal oxygen levels, their improved blood sugar control lasted for weeks or even months.
The researchers also tested a new drug called HypoxyStat, designed to mimic some of the effects of low oxygen in the body. It was originally developed to treat mitochondrial diseases—rare genetic disorders in which cells can not produce enough energy.
By adjusting how haemoglobin, the oxygen-carrying protein in red blood cells, binds to oxygen, the Hypoxystat drug now modifies the amount of oxygen reaching tissues, helping improve cellular energy balance.
Under the new study, scientists first investigated whether the same mechanism could help control blood sugar. HypoxyStat has been observed to significantly lower high blood glucose levels in diabetic mice and log a better performance than standard treatments in some cases.
Currently, diabetes is treated using medications, such as insulin injections, including metformin, which lowers glucose production in the liver, or SGLT2 inhibitors, which aid the kidneys’ removal of excess sugar through urine, or GLP-1 receptor agonists that increase insulin release and reduce appetite.
The treatments largely target insulin functions or the pancreas, liver, and kidneys, among other organs.
“This is one of the first uses of HypoxyStat beyond mitochondrial disease,” the author said. “It opens the door to thinking about diabetes treatment in a fundamentally different way—by recruiting red blood cells as glucose sinks.”
Explaining the importance of the study, Dr Anoop Misra, chairperson, Fortis C-DOC Hospital for Diabetes and Allied Sciences in New Delhi, told ThePrint, “This appears to be an important animal study that opens a new chapter in our understanding of glucose metabolism in red blood cells.”
“Along with an intensive lifestyle, it may reflect a lower prevalence of diabetes in those living at high altitudes. However, this needs clear proof in humans to pave the way to potential new treatments,” he added.
With diabetes affecting hundreds of millions worldwide, the study is a ray of hope for blood sugar control: RBCs may hold untapped potential in the fight against the metabolic disease.
(Edited by Madhurita Goswami)
Also Read: No more tests, a bracelet-like device aims to track women’s hormones real-time