JDRF Research

Researchers Shed Light on Hypoglycemic Unawareness

JDRF-funded researchers have identified a potential mechanism that may shed light on why some people with diabetes lose the ability to recognize and correct hypoglycemia (low blood sugar). Gaining a better understanding of why this happens could lead to the development of treatments for this very serious complication, which can cause a loss of consciousness, and even death. In most people, the brain is able to sense warning signs when blood sugar is getting too low and react by triggering the release of hormones that bring sugar up to normal levels. But in many people with diabetes this natural mechanism becomes muted. The phenomenon, known as hypoglycemia-associated autonomic failure, makes people with diabetes who have frequent blood sugar dips unaware of impending low blood sugar and unable to take proper steps (such as eating) to prevent further episodes. Now researchers at the JDRF Yale Center for the Study of Hypoglycemia may be closer to understanding what leads to the silencing of hypoglycemic warnings. In the study, Dr. Rory McCrimmon and colleagues found that when a protein in the brain, urocortin I, is produced at abnormally high levels, it may contribute to the inability to produce a normal response to lows. The researchers demonstrated in rats that a key glucose-sensing region of the brain loses sensitivity after being exposed to urocortin I.  This loss of sensitivity persists for at least 24 hours.

The discovery, reported in the Journal of Clinical Investigation (Vol. 116, No. 6, p. 1723, 2006), is an important step toward clinical strategies that will allow diabetes patients to sense when blood sugar has dropped too low by blocking urocortin I’s effect in the brain. In a commentary accompanying the article, Philip Cryer of the Washington University School of Medicine noted that hypoglycemia caused inadvertently by insulin treatment is the “limiting factor” in good glucose control. He added that the problem will likely be solved in the short term by an artificial pancreas until the regeneration or replacement of “glucose-responsive, insulin-secreting cells becomes feasible for widespread use.”