Aggressive approach to diabetes proves harmful
Attacking blood sugar levels with high drug doses can be dangerous.
Patients with type 2 diabetes, a high risk of cardiovascular disease, and who use aggressive
measures to reduce their blood sugar levels could actually be shortening their lives, according to a
large clinical trial. The results contradict the established theory that diabetics benefit from driving
down their excessively high blood sugar levels as forcibly as possible.
The trial, part of ACCORD (Action to Control Cardiovascular Risk in Diabetes), made headlines
earlier this year when this segment of the study was halted in February by a safety review board.
The results are published today by The New England Journal of Medicine
The results do not mean that diabetics should not work to keep their blood sugar under control, says
cardiologist Harlan Krumholz of Yale Medical School in New Haven, Connecticut, but they do
illustrate that taking extreme measures to lower blood sugar may not be warranted.
More than 10,000 type 2 diabetics, who either had cardiovascular disease or were at high risk for
developing the condition, were enrolled in the trial. Roughly half used standard treatments to lower
their blood sugar, and achieved an average level of `glycated haemoglobin' a measure of blood
sugar of 7.5%, which is thought to be acceptable, if higher than for a non-diabetic.
The other group used higher doses of the same drugs to lower their glycated haemoglobin, reaching
levels of 6.4% over the course of a year. They maintained these low levels for just over three years.
Over the course of three and a half years, 257 people in the high-dosing group died compared with
only 203 in the group that used standard doses.
Disturbing results
The finding shocked doctors, as they have been encouraged to lower blood sugar levels by any
means possible. "The results are disturbing," says Krumholz, who was not affiliated with the study.
"This is a treatment strategy that people have been encouraged to adopt."
Researchers have not yet worked out whether the fault lies with the methods used to lower blood
sugar levels, or with the low blood sugar levels themselves. The American Diabetes Association
recommends lowering glycated haemoglobin levels to below 7%; a non-diabetic would have levels
of 5.5-6%, says study co-author Robert Byington of Wake Forest University in Winston-Salem,
North Carolina.
Krumholz speculates that the negative effects may be a consequence of using higher doses of
medications to lower the blood sugar levels. "As you start adding complex treatment regimens, you
start offsetting the potential benefits with the added risk of adding medications," he says.
Unclear cause
The drugs used by diabetics in the study included insulin, sulphonylurea and a class of drugs known
as thiazolidinediones. That class includes rosiglitazone, marketed by GlaxoSmithKline as Avandia,
which in a recent study was linked to an increased risk of cardiovascular problems. There is no clear
link between rosiglitazone dosage and the increased death rate seen in the ACCORD study, says
Byington. "We haven't been able to identify any particular agent or treatment strategy that mediates
the higher number of deaths," says Byington.
Study 