New findings from a literature review published in Ophthalmic Research analyzed the physiological changes and clinical characteristics related to diabetic retinopathy (DR) after high altitude (HA) exposure, evaluating whether long-term exposure to HA can alleviate DR progression.
Give me some background first.
The human body undergoes a series of physiological changes to accommodate the harsh conditions in HA environments, including:
- Increased heart rate
- Hyperventilation
- Alterations in hematological features
To note, these adaptations coincide with mechanisms reported in various chronic metabolic diseases, such as diabetes mellitus (DM).
Bring this back to DR.
For example, during DR progression, retinal arteriolar dilation may be an early physiological marker of microvascular changes, and increased capillary pressure might lead to:
- Capillary wall dilation (microaneurysms)
- Leakage (edema and hard exudates)
- Rupture (hemorrhages)
What is the effect of short-term HA on DR?
The retina is very sensitive to hypoxia, so short-term exposure to HA can result in transient hyperglycemia for an initial 2-3 days and persist for over 1 week.
This rise in blood glucose may result from the stress increase in HA—with an increase in altitude, the oxygen content in the environment is diminished, leading to a stress-induced increase in blood glucose.
Consequently, a synergistic effect between HA retinopathy (HAR) and DR progression may be observed in DM patients with acute hypoxic exposure—heightening the risk of visual impairment for diabetic climbers at HAs.
Tell me more.
The study authors noted that “hyperglycemia-induced retinal damage includes the polyol pathway, advanced glycation end product accumulation, the protein kinase C pathway, and the hexosamine pathway.”
As a result, “there is no doubt that improved glycemic control and lower blood glucose might reduce the risk of DR caused by hyperglycemia in DM patients.”
What about long-term HA exposure and DR?
Studies have suggested that chronic exposure to HA may elicit glycemic control in DM patients, potentially due to the increased insulin sensitivity in highlanders compared to lowlanders.
HA hypoxia adaptation has been indicated to improve glucose tolerance in patients with type 2 DM, and long-term HA exposure leads to an increase in adiponectin levels—facilitating insulin sensitivity.
Tie it all together for me.
Per the study authors, “For those acutely exposed to HA areas, the HA hypoxic environment significantly activates transient hyperglycemia and increases the risk of diabetic microangiopathy and HAR.”
Conversely, long-term residents in HA areas are less likely to suffer from diabetic microangiopathy due to factors such as:
- Improved glucose control
- Lifestyle and nutrition selection
- Genetic adaptation
- Stronger lung function
- Increased vessel vasodilation
- Higher serum hemoglobin concentration
- Lower vascular endothelial growth factor levels
- Blunted erythropoietin response
Take home.
Exposure to HA induces layered adaptive mechanisms to protect internal homeostasis under hypoxic and low air pressure conditions.
The impact of HA environments on DR depends on the length of exposure, and a broad variety of factors.
However, long-term HA exposure potentially alleviates the risk of DR progression, while short-term exposure increases the risk of HAR and microangiopathy.
Next steps?
Future studies are warranted and should include a diverse group of participants to elucidate and confirm the potential positive impact of HA on DR.
This could potentially lead to innovative developments in new therapies for DR.