CDU Executive Editor

SAN DIEGO – Tight glucose control is widely known to lower cardiovascular disease (CVD) risk in Type 2 diabetics. Now, the same can be said for Type 1 diabetics, those who require daily intake of insulin via injection, inhalation or pumps. Results of a follow-up study to the landmark Diabetes Control and Complications Trial (DCCT), reported in mid-June during a “Late-Breaking Clinical Trials” session at the 65th scientific sessions of the American Diabetes Association (ADA; Alexandria, Virginia), were characterized by the ADA’s top scientific official as “the biggest news story of this meeting.”

During a press conference held prior to the presentation of results of the Epidemiology of Diabetes Interventions and Complications (EPIC) study, Richard Kahn, PhD, the association’s chief scientific and medical officer, said it was “remarkable to see this kind of substantial reduction [in CVD rates] after just six years of intensive therapy.”

The EDIC research was a follow-up to the epic DCCT study, which compared intensive management of blood glucose to conventional control in 1,441 persons with Type 1 diabetes.

DCCT and EDIC were funded by the National Institute of Diabetes and Digestive and Kidney Diseases, part of the National Institutes of Health (NIH; both Bethesda, Maryland).

The original study, which ran from 1983-1993, involved intensive treatment through at least three insulin injections a day, or via an insulin pump. “Intensive” meant keeping hemoglobin A1c (HbA1c) as close as possible to what is considered “normal” – 6% or less.

The HbA1c blood test reflects a person’s average blood sugar over a two- to three-month period and is a key diagnostic used in determining both control and compliance by both Type 1 and Type 2 diabetics.

David Nathan, MD, of Massachusetts General Hospital (Boston), who co-chaired the DCCT/EDIC research group, noted that the original DCCT study focused on eye, nerve and kidney damage of Type 1 diabetes, finding that intensive glucose control “greatly reduced” such effects.

A study of DCCT participants published in 2003 showed that tight control also lowers the risk of atherosclerosis.

The EDIC study focused on such cardiovascular events as angina, heart attack and stroke, with the most remarkable finding being the long-lasting benefit of such control.

In a statement, EDIC chair Saul Geneth, MS, of Case Western Reserve University, said, “The longer we follow patients, the more we’re impressed by the lasting benefits of tight glucose control.” He said that the earlier such therapy begins and the longer it is maintained, “the better the chances of reducing the debilitating complications of diabetes.”

The results reported at the late-breaking trials session indicate that the intensively treated patients among the roughly 1,375 persons who volunteered to continue in the study while continuing intensive therapy on their own have had less than half the number of CVD events – 46 vs. 98 – than the conventionally treated group.

Noting that the risk of heart disease is “about 10 times higher in people with Type 1 diabetes than in people without diabetes,” a proportion which he termed “much higher than in the Type 2 population.” Nathan added that tight control “is difficult to achieve and maintain, but its advantages are huge.”

He said during the press conference that “the major message” of the EDIC study after some 6-1/2 years of follow-up “is that intensive therapy should be implemented in as many Type 1 patients as possible, and as early as possible.” Such patients, Nathan added, “get a remarkably durable benefit from intensive therapy – clearly, intensive therapy is important.” And that benefit is as substantial as it is long-lasting. “For every 10% lower A1c, patients get a 21% reduction in heart disease.”

In citing the “enormous reductions” in cardiovascular events reported by the EDIC study group, the ADA’s Kahn said: “All of this makes it a ‘wow’ event that will have people talking about these results in the hallways through the rest of this meeting.”

CVD markers aid in assessing diabetics

Various new markers of cardiovascular disease (CVD) risk are helping clinicians assess such risk in their patients. Their use is proving particularly important for CVD risk assessment in diabetic patients, according to reports presented at the ADA meeting.

During a symposium that focused on non-traditional cardiovascular risk factors, Lewis Kuller, MD, professor of epidemiology at the University of Pittsburgh, said electron-beam computed tomography (EBCT) measurement of coronary artery calcium (CAC) is a valuable marker of sub-clinical atherosclerosis.

Coronary calcium scores in diabetics increase markedly, he said, in those with impaired glucose tolerance, with a score above 100 serving as strong predictor of CVD risk. The higher the CAC score in diabetics, the higher the mortality risk, Kuller said, citing “a direct linear relationship” as a predictor of mortality. He noted that the rates of atherosclerosis rise with age.

Ronald Krauss, MD, director of atherosclerosis research at Children’s Hospital Oakland Research Institute (Oakland, California), cited low-density lipoprotein (LDL, the so-called “bad” cholesterol) as a risk factor for CVD, saying it had been slowly emerging in that role over the past two decades. He said that small LDL particles – LDL-3 or LDL-4, which also are the most common – are much more capable of inducing atherosclerosis than large- (LDL-1) or medium-sized (LDL-2) particles. He added that high levels of triglycerides have been shown to produce smaller LDL and high-density lipoprotein (LDL, or “good” cholesterol) particles.

Krauss cited studies showing that diabetics with a larger concentration of small LDL particles than larger particles have a risk of cardiovascular disease triple that of those without such concentration. Measuring LDL particles and reducing small particles with therapeutics can reduce the progression of coronary artery disease, he said.

The usefulness of C-reactive protein (CRP) as part of overall CVD risk assessment for patients was discussed by Christie Ballantyne, MD, director of the Center for Cardiovascular Disease Prevention at the Baylor College of Medicine (Houston). Noting that CRP is “the best-studied marker for CVD,” he said that increased levels of CRP are indicative of a doubled risk for stroke.

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