ADA 2008: Endothelial dysfunction in diabetes is marker, cause of complications

Endothelial dysfunction is both a marker for and a cause of diabetic complications. Researchers are teasing out pathways that involve oxidative stress and endothelial dysfunction, said Per-Henrik Groop, MD, PhD, Helsinki University Central Hospital, Helsinki, Finland. The challenge is in finding drugs that show the same activity in vivo that they show in cell studies or animal models.

"We know the pathways," said Dr. Groop. "The problem is that many pathways work in concert in vivo. When you observe all these pathways together in a patient, we don?t understand what is going on. We need better, more targeted drugs to deal with endothelial dysfunction."

Even short-term exposure to hyperglycemia can induce stiffness in micro and intermediate vasculature, Dr. Groop said. Vascular stiffness is both an early marker for renal damage and a manifestation of existing cellular damage.

Oxidative stress related to hyperglycemia depletes nitric oxide (NO) and disrupts normal vasodilatation pathways. Insulin resistance inhibits NO synthesis, which also contributes to endothelial dysfunction.

"Treatments that restore endothelial function may help prevent diabetic complications," Dr. Groop said. "But we don't see much effect from the drugs now in use. I think the drugs [that are currently available to clinicians] are not the right drugs."