Lowering blood sugar to near-normal levels is a proven treatment for Type 1 diabetics, but it may not be the best treatment for those with Type 2 diabetes, particularly those with heart disease or multiple risk factors for heart disease, government scientists said Wednesday.
Researchers had to curtail a major clinical trial of intensive treatment for such patients after concluding that patients with the lowest blood sugar levels had an increased risk of dying compared with those with a more modest reduction of sugar levels.
The findings were a surprise to researchers, who expected to see a clear benefit from the lower sugar levels, and their source remains a mystery. Analysis has been unable to link the increased death rate to episodes of hypoglycemia -- low blood sugar -- or to any drug or combination of drugs used in the study. In particular, researchers did not find any link to the diabetes drug rosiglitazone, trade-named Avandia, which has previously been linked to deaths from heart disease among those taking it.
Dr. William T. Friedewald of Columbia University, who led the study, cautioned that most diabetes patients are not aiming to achieve such low blood sugar levels, "so this is not relevant for them." A statement issued by the American Diabetes Assn. cautioned diabetics not to alter or abandon their treatments without consulting their physicians.
An estimated 20 million Americans have Type 2 diabetes, in which tissues throughout the body become resistant to the effects of insulin. About 284,000 people die of it each year, with 65% of the deaths linked to cardiovascular disease. Type 2 diabetics have two to four times the normal risk of heart disease.
The clinical trial, called Action to Control Cardiovascular Risk in Diabetes, or ACCORD, represents an attempt to lower the incidence of cardiovascular complications in older patients at high risk. The study, at 77 sites in the United States and Canada, enrolled 10,251 people ages 40 to 82 who had had Type 2 diabetes for at least 10 years and either already had cardiovascular disease or had at least two risk factors for it, such as high blood pressure and high cholesterol levels.
Half of the patients were treated with conventional drugs and lifestyle modifications aimed at reducing their blood sugar levels to about 7% to 7.5%, the level most commonly targeted by physicians. The other half received the same drugs but in higher doses and multiple combinations to reduce sugar levels to about 6%, the same level as in healthy individuals. Most had levels of about 8.2% at entry into the study, a little higher than in the average diabetic.
Subgroups of the study are also being tested to determine whether intensive efforts to lower blood pressure or cholesterol levels can reduce risk.
The incidence of heart attacks and strokes was about 10% lower in the intensively treated group, Friedewald said in a telephone news conference. But when those events did occur in the intensively treated group, they were more likely to result in death. There were also more unexpected deaths in the group.
Overall, 257 people in the intensively treated group died over a four-year period, compared with 203 in the standard-treatment group.
"This is an important finding which shows that if you have Type 2 diabetes, very intensive treatment may be detrimental," said Dr. Elizabeth G. Nabel, director of the National Heart, Lung and Blood Institute. "There appeared to be some benefit of an overall lower death rate in both groups . . . but the harm of very intensive treatment outweighed the potential benefit."
The patients receiving intensive treatment will be switched to standard treatment as soon as possible, she said. The arms of the study investigating lowering cholesterol levels and blood pressure will continue until the trial's projected completion in June 2009.