A new study from Johns Hopkins Medicine has linked low blood sugar levels to a worsening of diabetic retinopathy (DR) in retinal cells cultured in low glucose.
What is tight glycemic control?
Tight glycemic control (TGC) controls the blood glucose level to within the 4.4–6.1 mmol/L range in order to avoid hyperglycemic episodes. It is usually used with the intention of preventing or delaying diabetic microvascular disease, but has also been associated with worsening DR, as have transient episodes of high and low glucose concentration.
How does it relate to diabetes?
TGC is a common strategy for diabetic management to reduce the progression of diabetic microvascular disease. However, it may also induce hypoglycemic episodes, which can paradoxically increase DR progression.
Now tell me about the study.
The study explored the effects of acute episodes of hypoglycemia on the retina and the subsequent effects on the development and progression of diabetic eye disease (DED).
Researchers analyzed the protein levels in intact retinas and retinal cells from mice and humans in low glucose.
What did they find?
First, that the glucose transporter GLUT1 is a key player in metabolic regulation of Müller cells in the retina; and second, that HIF1α accumulates during hypoglycemic episodes—increasing the chance for development of DR .
Any limitations?
As a study performed on cultured cells, the authors noted the lack of patient data as a major limitation. They were also “unable to identify the signaling pathway(s) connecting cellular detection of low glucose with the increase in nuclear accumulation of HIF-1α that remains.”
The take home.
These findings have implications for future research into methods for controlling or preventing the progression of DR.
As the authors noted: “While TGC remains essential for preventing microvascular injury in patients with diabetes, these findings suggest that this should not be achieved at the expense of glycemic stability.”