Add tight lipid control to diabetes playbook

New studies show reduced coronary risks

Aggression has become the watchword in addressing complications of diabetes. Study after study shows that diabetic patients respond favorably to intensive management of the disease. But until very recently there have been few or no data available on the effects of lowering cholesterol in diabetics because patients with diabetes generally have been excluded from clinical trials.

Now a researcher at the University of Miami is preparing to publish his analysis of data from two major lipid studies — the 4S (Scandinavian Simverstatin Survival Study) and the more recent CARE (Cholesterol and Recurrent Events trial) — showing that aggressive therapy significantly reduces future coronary events and mortality among diabetics.

Ronald Goldberg, MD, chief of the division of diabetes and metabolism and professor of medicine at the University of Miami, presented results of his research at the American Diabetes Association conference in June 1998 and is preparing to publish his findings in the journal Circulation. The five-year double-blind CARE study included 4,000-plus subjects, 518 of them Type 2 diabetics, all of whom had average cholesterol levels of under 240 mg/dL. All were treated with pravastatin (Pravachol, Bristol-Myers Squibb, Princeton, NJ). The results showed:

• A 25% reduction in cholesterol in the diabetic subgroup as well as in the entire cohort.

• A 28% reduction in cardiovascular events in the diabetic group and a 27% reduction in the cohort as a whole.

• Even in patients with average cholesterol levels, cholesterol-lowering therapies substantially reduced coronary events.

In the 4S study diabetic subjects reaped even greater benefits than non-diabetics. The study included 4,000-plus members, 200 of them diabetics (mostly Type 2). All members had previous coronary events ranging from angina to myocardial infarctions, as well as cholesterol levels ranging from 200 to 300 mg/dL. The entire group was treated with simvastatin (Zocor, Merck, West Point, PA) and given dietary counseling. The results:

• The entire group under simvastatin treatment showed a mean reduction in total cholesterol of 25% and lowered LDLs by 35%. The diabetic group showed a similar reduction.

• Diabetic patients had a 45% reduction in coronary events.

• The treatment group experienced a 34% reduction in major coronary events and a 42% reduction in mortality.

"This was considered very significant and therefore at least as good, if not better than what was seen in the population as a whole," Goldberg says.

In addition, Goldberg points out, taking into account the two- to fourfold increase in the coronary heart disease risk factor for diabetics, the results weigh even more heavily in favor of aggressive cholesterol lowering treatment.

Taking a new look at cholesterol

James R. Gavin, MD, PhD, senior scientific officer at the Howard Hughes Medical Institute in Chevy Chase, MD, and until recently chairman of the ADA’s expert committee on classification and diagnosis, calls Goldberg’s results "impressive."

"What that confirms is that it is extremely important be very aggressive in achieving the therapeutic goals of cholesterol lowering in people with diabetes, even those who have already had coronary events."

The result is a re-thinking of guidelines for cholesterol levels in all diabetics, regardless of their coronary health status.

The ADA and the American Heart Association have set a goal of 130 mg/dL for all diabetics without heart disease. "But for those who have just one risk factor, which so many diabetics have — high blood pressure or smoking or kidney problems or high triglycerides or low HDL, the good cholesterol — we should presume they have heart disease and aim for an LDL of 100," Goldberg says. Although this is more aggressive than for a non-diabetic without heart disease, Goldberg insists his study supports the measures in terms of palpable declines across the entire spectrum of coronary events.

Gavin wholeheartedly agrees. Aggressive treatment "is not unreasonable because people with diabetes are at such high risk, particularly women," he says. "The good news is that in spite of that risk, you can, in fact, mitigate it. You can, in fact, achieve significant lowering of event rates in people with diabetes who are already at high risk by being aggressive with cholesterol-lowering therapy."

How long it will take such thinking to filter down into common medical practice is anybody’s guess, Gavin says.

By the demonstration of the benefits of aggressive treatment, he says, "It is hoped . . . you would in some ways change their attitude . . . and change practice. That hasn’t always happened, but at least it’s Step 1.

"We know that people benefit from cholesterol lowering therapy. For those who have had their levels determined and are known to be at risk, only about 20% are receiving treatment."

Gavin says he also hopes managed care "will understand the benefit of these kinds of interventions and exert some influence."