Some people think that when it comes to diabetic complications, the only thing that matters is your hemoglobin A1c level (A1c). This is the test that is supposed to measure your average blood glucose (BG) level over the past several months.
High BG levels form what are called advanced glycation end products, or AGEs, and these long-lived products seem to gum up the works and cause diabetic complications, as well as normal aging.
Because it's an average, you can get the same A1c result if you have a constant BG level of 100 mg/dL (an unlikely event, but I'm using it to simplify), or if you spend half your time at 50 and half your time at 150 mg/dL. Because most studies of complication rates, for example the famous Diabetes Control Complications and Trial (DCCT), use only the A1c as a measure of control, many people think that's all that matters.
In fact, that's not true at all. Since then, some studies have suggested that the amount of glucose variability is as important as, or more important than, the average BG levels. Others have suggested that it's not just the AGEs but three other pathways as well that contribute to long-term diabetic complications.
And now, a new study has suggested that even short-term elevations in BG levels can cause so-called epigenetic changes in your genes that persist for a long time after you've brought your BG levels back to normal.
This would explain the persistence of beneficial effects of good BG control many years later, as well as the persistence of a higher rate of complications in people with poor control after their control had improved. For example, a follow-up study of patients in the famous DCCT study showed that the patients who had better control during the study had fewer complications years later, when their A1c levels were almost identical to those who had been in the control group.
In the new study, a group of scientists in Australia and the United States, led by Assam El-Osta, exposed human epithelial cells to high glucose levels (30 mM or about 540 mg/dL) for 16 hours. They then transferred the cells to normal glucose levels (5 mM or about 90 mg/dL) for 6 days.
When they did this, they found that even after 6 days, the expression of some genes was increased in the cells exposed to high BG levels compared with the expression of those genes in cells that had been exposed to glucose at only 90 mg/dL for the entire time.
The effect was dose-related: the higher the glucose level during the 16 hours, the greater the expression of the genes. One of the genes whose expression was increased is one that increases inflammation.
The increase in the expression of the genes did not occur under high-glucose conditions when the experimenters prevented the formation of superoxide accumulation. Superoxide is a highly reactive compound, a free radical, or reactive oxygen species (ROS), thought to cause cell damage as well as some beneficial effects like killing invading bacteria. High BG levels increase the levels of ROS.