Findings Shed Light on Direct Atherogenic Effects of Hyperglycemia

Findings from a new animal study suggest how hyperglycemia can directly contribute to atherogenesis in humans.

Previous studies involving mice have failed to show that hyperglycemia, by itself, causes atherosclerosis. Dr. Ira J. Goldberg, from Columbia University in New York, and colleagues hypothesized this was because normal mice lack an enzyme that facilitates accelerated atherosclerosis with diabetes.

An enzyme, aldose reductase, is involved in the release of toxic products from glucose. This enzyme is only expressed at very low levels in mice relative to humans.

In the present study, reported in The Journal of Clinical Investigation for September 1, the researchers created mice with expression of human aldose reductase (hAR). In nondiabetic mice, this expression had little on atherosclerosis, whereas in diabetic animals, it accelerated the atherogenic process.

Further testing showed that while streptozotocin treatment alone was sufficient to promote atherosclerosis, the process was enhanced with hAR expression.

"Inhibitors of hAR or other enzymes that mediate glucose toxicity could be useful in the treatment of diabetic atherosclerosis," the investigators conclude.
J Clin Invest Aug. 2005