KEYSTONE, COLO. – Optimal guideline-driven management of hemoglobin A1c, blood pressure, and lipids in type 1 diabetic patients is quite effective for avoiding microvascular symptoms, but it doesn’t slow down the accelerated coronary atherosclerosis that is a disease hallmark.

That’s one of the major take-away lessons from the prospective CACTI (Coronary Artery Calcification in Type 1 Diabetes) study, Dr. Marian Rewers said at the diabetes conference sponsored by the University of Colorado and the Children’s Diabetes Foundation at Denver.

"Unfortunately, people’s CAC [coronary artery calcification] progressed equally, regardless of how many ABC goals they met. So it looks like current ABC recommendations, even if fulfilled diligently by patients and providers, do not prevent progression of CAC," according to Dr. Rewers, principal investigator for CACTI.

The "ABCs" are shorthand for the American Diabetes Association standards of medical care for nonpregnant adults with type 1 or type 2 diabetes: an A_1c below 7%, Blood pressure less than 130/80 mm Hg, and Cholesterol control with an low-density lipoprotein, or LDL, below 100 mg/dL.

These are achievable goals, yet CACTI showed that few patients with type 1 diabetes meet them. In fact, only about 10% of women and even fewer men participating in the study met all three goals, according to Dr. Rewers, who is professor of pediatrics and professor of preventive medicine as well as clinical director of the Barbara Davis Center for Childhood Diabetes at the university.

CACTI is a prospective study involving 652 adults with type 1 diabetes and 764 nondiabetic controls who averaged 38 years of age at baseline. All were asymptomatic for coronary artery disease. Half (52%) are women. They underwent measurement of CAC by electron beam CT at baseline and 3- and 6-year follow-up. The volume of CAC is a well-established marker of arterial plaque burden and a strong predictor of future coronary events.

The age-adjusted prevalence of coronary calcification proved to be 4.2-fold greater in diabetic women, compared with controls, and 2.3-fold greater in diabetic men. This sharply increased rate of subclinical atherosclerosis at a relatively early age is an important finding in light of the fact that coronary artery disease is now the leading cause of death in people with type 1 diabetes, he said.

A popular misconception is that type 1 diabetes is a childhood disease. In fact, only about half of all cases are diagnosed before age 20 years. The vast majority of individuals diagnosed with type 1 diabetes are middle aged. And they are at far greater cardiovascular risk, compared with the middle-aged nondiabetic general public.

To thwart this risk, Dr. Rewers said, the first step is to take care of the ABCs. But that’s not enough. He urged that all asymptomatic patients with type 1 diabetes undergo screening for increased coronary artery plaque burden starting at age 30 years. He favors measurement of CAC for this purpose, since it is noninvasive, far less expensive than nuclear imaging and other screening methods are, and a wealth of data show that CAC levels predict long-term risk of fatal and nonfatal cardiovascular events.

"The true cost of CAC screening without all the bells and whistles is about $100. That’s not much more than the cost of a visit to an endocrinologist. Maybe even less," he observed.

Testing should be repeated every 5 years. Rapidly progressing CAC, or a high CAC score – certainly one above 400 or perhaps even 100 – warrants referral for myocardial perfusion testing accompanied by aggressive therapy, Dr. Rewers continued.

"In CACTI, we see CAC progression in a very short time period: 3-6 years," he noted. "We don’t have to wait 15, 17, 20 years like in some of the clinical trials in nondiabetics. So this is a model to test new interventions; you can see the impact of an intervention in just 3-6 years."

Dr. Rewers urged physicians to keep an eye on emerging novel risk factors for CAD in persons with type 1 diabetes. The CACTI study has identified several promising ones associated with progressive CAC. These include low serum vitamin D; an elevated level of soluble interleukin-2 receptor, which was linked to a doubling of CAC in 3 years; and a low adiponectin.

The CACTI investigators have also reported the novel finding that subclinical atherosclerosis was associated with glycemic variability in men but not in women. The amount of time per day type 1 diabetic men spent with a blood glucose in excess of 180 mg/dL strongly correlated with CAC progression; however, time spent at less than 70 mg/dL did not (Diabet. Med. 2010;27:1436-42).

The CACTI study is funded by the National Institutes of Health. Dr. Rewers declared having no relevant financial interests.

Quelling Cardiovascular Risk in Type 1 Diabetes